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In this 3D printing process, the little dot of blue light triggers a chemical reaction that makes the resin harden into plastic.

Credit: Tracy H. Schloemer and Arynn O. Gallegos

Making 3D printing truly 3D

Juan Siliezar

Harvard Staff Writer

Researchers from Rowland Institute eliminate need for 2D layering

Don’t be fooled by the name. While 3D printers do print tangible objects (and quite well), how they do the job doesn’t actually happen in 3D, but rather in regular old 2D.

Working to change that is a group of former and current researchers from the Rowland Institute at Harvard.

First, here’s how 3D printing works: The printers lay down flat layers of resin, which will harden into plastic after being exposed to laser light, on top of each other, again and again from the bottom to the top. Eventually, the object, such as a skull , takes shape. But if a piece of the print overhangs, like a bridge or a wing of a plane, it requires some type of flat support structure to actually print, or the resin will fall apart.

The researchers present a method to help the printers live up to their names and deliver a “true” 3D form of printing. In a new paper in Nature, they describe a technique of volumetric 3D printing that goes beyond the bottom-up, layered approach. The process eliminates the need for support structures because the resin it creates is self-supporting.

“What we were wondering is, could we actually print entire volumes without needing to do all these complicated steps?” said Daniel N. Congreve, an assistant professor at Stanford and former fellow at the Rowland Institute, where the bulk of the research took place. “Our goal was to use simply a laser moving around to truly pattern in three dimensions and not be limited by this sort of layer-by-layer nature of things.”

The key component in their novel design is turning red light into blue light by adding what’s known as an upconversion process to the resin, the light reactive liquid used in 3D printers that hardens into plastic.

In 3D printing, resin hardens in a flat and straight line along the path of the light. Here, the researchers use nano capsules to add chemicals so that it only reacts to a certain kind of light — a blue light at the focal point of the laser that’s created by the upconversion process. This beam is scanned in three dimensions, so it prints that way without needing to be layered onto something. The resulting resin has a greater viscosity than in the traditional method, so it can stand support-free once it’s printed.

“We designed the resin, we designed the system so that the red light does nothing,” Congreve said. “But that little dot of blue light triggers a chemical reaction that makes the resin harden and turn into plastic. Basically, what that means is you have this laser passing all the way through the system and only at that little blue do you get the polymerization, [only there] do you get the printing happening. We just scan that blue dot around in three dimensions and anywhere that blue dot hits it polymerizes and you get your 3D printing.”

The researchers used their printer to produce a 3D Harvard logo, Stanford logo, and a small boat, a standard yet difficult test for 3D printers because of the boat’s small size and fine details like overhanging portholes and open cabin spaces.

The researchers, who included Christopher Stokes from the Rowland Institute, plan to continue developing the system for speed and to refine it to print even finer details. The potential of volumetric 3D printing is seen as a game changer, because it will eliminate the need for complex support structures and dramatically speed up the process when it reaches its full potential. Think of the “replicator” from “Star Trek” that materializes objects all at once.

But right now, the researchers know they have quite a ways to go.

“We’re really just starting to scratch the surface of what this new technique could do,” Congreve said.

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Jonathan Weiss and Jessica Herrmann, members of the Skylar-Scott lab, run a test print using a 3D bioprinter, which allows them to print structures containing living cells. (Image credit: Andrew Brodhead)

3D printing research at Stanford

3D printing offers a world of possibilities, but it has its limitations. Stanford researchers are stretching the boundaries of current printing models and finding innovative ways to solve pressing dilemmas of design, engineering, and medicine.

The 3D printer has come a long way since the debut of consumer-friendly printers in the early 2000s. The versatile technology allows designers and engineers to forgo traditional manufacturing, opening up a world of seemingly endless possibilities. But the instrument has its limits. The process can be slow, and most objects can only be built layer by layer – with just one material at a time.

Stanford University researchers are challenging the limitations of current 3D printing technology . One innovative printing method is increasing printing speeds by 10x that of the quickest available model and allowing researchers to introduce multiple materials at once. Another group of engineers is using light to carve intricate designs into stationary mounds of resin, hoping to eliminate the need to build from the bottom up.

From creating surprisingly strong nanoscale lattices built to protect fragile satellites to fashioning heart tissue from living cells to combat congenital heart disease, these researchers are exploring the what ifs of this technology. What if our products were more resilient? What if we used biomaterials? And what if we take a moment to consider the inevitable questions that will arise as we move forward with this emerging technology?

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This 3D printer can figure out how to print with an unknown material

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While 3D printing has exploded in popularity, many of the plastic materials these printers use to create objects cannot be easily recycled. While new sustainable materials are emerging for use in 3D printing, they remain difficult to adopt because 3D printer settings need to be adjusted for each material, a process generally done by hand.

To print a new material from scratch, one must typically set up to 100 parameters in software that controls how the printer will extrude the material as it fabricates an object. Commonly used materials, like mass-manufactured polymers, have established sets of parameters that were perfected through tedious, trial-and-error processes.

But the properties of renewable and recyclable materials can fluctuate widely based on their composition, so fixed parameter sets are nearly impossible to create. In this case, users must come up with all these parameters by hand.

Researchers tackled this problem by developing a 3D printer that can automatically identify the parameters of an unknown material on its own.

A collaborative team from MIT’s Center for Bits and Atoms (CBA), the U.S. National Institute of Standards and Technology (NIST), and the National Center for Scientific Research in Greece (Demokritos) modified the extruder, the “heart” of a 3D printer, so it can measure the forces and flow of a material.

These data, gathered through a 20-minute test, are fed into a mathematical function that is used to automatically generate printing parameters. These parameters can be entered into off-the-shelf 3D printing software and used to print with a never-before-seen material. 

The automatically generated parameters can replace about half of the parameters that typically must be tuned by hand. In a series of test prints with unique materials, including several renewable materials, the researchers showed that their method can consistently produce viable parameters.

This research could help to reduce the environmental impact of additive manufacturing, which typically relies on nonrecyclable polymers and resins derived from fossil fuels.

“In this paper, we demonstrate a method that can take all these interesting materials that are bio-based and made from various sustainable sources and show that the printer can figure out by itself how to print those materials. The goal is to make 3D printing more sustainable,” says senior author Neil Gershenfeld, who leads CBA.

His co-authors include first author Jake Read a graduate student in the CBA who led the printer development; Jonathan Seppala, a chemical engineer in the Materials Science and Engineering Division of NIST; Filippos Tourlomousis, a former CBA postdoc who now heads the Autonomous Science Lab at Demokritos; James Warren, who leads the Materials Genome Program at NIST; and Nicole Bakker, a research assistant at CBA. The research is published in the journal Integrating Materials and Manufacturing Innovation .

Shifting material properties

In fused filament fabrication (FFF), which is often used in rapid prototyping, molten polymers are extruded through a heated nozzle layer-by-layer to build a part. Software, called a slicer, provides instructions to the machine, but the slicer must be configured to work with a particular material.

Using renewable or recycled materials in an FFF 3D printer is especially challenging because there are so many variables that affect the material properties.

For instance, a bio-based polymer or resin might be composed of different mixes of plants based on the season. The properties of recycled materials also vary widely based on what is available to recycle.

“In ‘Back to the Future,’ there is a ‘Mr. Fusion’ blender where Doc just throws whatever he has into the blender and it works [as a power source for the DeLorean time machine]. That is the same idea here. Ideally, with plastics recycling, you could just shred what you have and print with it. But, with current feed-forward systems, that won’t work because if your filament changes significantly during the print, everything would break,” Read says.

To overcome these challenges, the researchers developed a 3D printer and workflow to automatically identify viable process parameters for any unknown material.

They started with a 3D printer their lab had previously developed that can capture data and provide feedback as it operates. The researchers added three instruments to the machine’s extruder that take measurements which are used to calculate parameters.

A load cell measures the pressure being exerted on the printing filament, while a feed rate sensor measures the thickness of the filament and the actual rate at which it is being fed through the printer.

“This fusion of measurement, modeling, and manufacturing is at the heart of the collaboration between NIST and CBA, as we work develop what we’ve termed ‘computational metrology,’” says Warren.

These measurements can be used to calculate the two most important, yet difficult to determine, printing parameters: flow rate and temperature. Nearly half of all print settings in standard software are related to these two parameters. 

Deriving a dataset

Once they had the new instruments in place, the researchers developed a 20-minute test that generates a series of temperature and pressure readings at different flow rates. Essentially, the test involves setting the print nozzle at its hottest temperature, flowing the material through at a fixed rate, and then turning the heater off.

“It was really difficult to figure out how to make that test work. Trying to find the limits of the extruder means that you are going to break the extruder pretty often while you are testing it. The notion of turning the heater off and just passively taking measurements was the ‘aha’ moment,” says Read.

These data are entered into a function that automatically generates real parameters for the material and machine configuration, based on relative temperature and pressure inputs. The user can then enter those parameters into 3D printing software and generate instructions for the printer.

In experiments with six different materials, several of which were bio-based, the method automatically generated viable parameters that consistently led to successful prints of a complex object.

Moving forward, the researchers plan to integrate this process with 3D printing software so parameters don’t need to be entered manually. In addition, they want to enhance their workflow by incorporating a thermodynamic model of the hot end, which is the part of the printer that melts the filament.

This collaboration is now more broadly developing computational metrology, in which the output of a measurement is a predictive model rather than just a parameter. The researchers will be applying this in other areas of advanced manufacturing, as well as in expanding access to metrology.

“By developing a new method for the automatic generation of process parameters for fused filament fabrication, this study opens the door to the use of recycled and bio-based filaments that have variable and unknown behaviors. Importantly, this enhances the potential for digital manufacturing technology to utilize locally sourced sustainable materials,” says Alysia Garmulewicz, an associate professor in the Faculty of Administration and Economics at the University of Santiago in Chile who was not involved with this work.

This research is supported, in part, by the National Institute of Standards and Technology and the Center for Bits and Atoms Consortia.

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MIT researchers have developed a 3D printer  that can use “unrecognizable printing materials in real-time to create more eco-friendly products,” reports Andrew Paul for Popular Science. The engineers “detailed a newly designed mathematical function that allows off-the-shelf 3D-printer’s extruder software to use multiple materials—including bio-based polymers, plant-derived resins, or other recyclables,” explains Paul.

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Original research article, a 3d printing short course: a case study for applications in the geoscience teaching and communication for specialists and non-experts.

• Reservoir Geomechanics Research Group, Civil and Environmental Engineering Department, University of Alberta, Edmonton, AB, Canada

3D printing developed as a prototyping method in the early 1980s, yet it is considered as a 21st century technology for transforming digital models into tangible objects. 3D printing has recently become a critical tool in the geoscience research, education, and technical communication due to the expansion of the market for 3D printers and materials. 3D printing changes the perception of how we interact with our data and how we explain our science to non-experts, researchers, educators, and stakeholders. Hence, a one-day short course was designed and delivered to a group of professors, students, postdoctoral fellows, and technical staff to present the application of 3D printing in teaching and communication concepts in the geoscience. This case study was aimed at evaluating how a diverse group of participants with geoscience and engineering background and no prior experience with computer-aided modeling (CAD) or 3D printing could understand the principles of different 3D printing techniques and apply these methods in their respective disciplines. In addition, the course evaluation questionnaire allowed us to assess human perception of tangible and digital models and to demonstrate the effectiveness of 3D printing in data communication. The course involved five modules: 1) an introduction lecture on the 3D printing methods and materials; 2) an individual CAD modeling exercise; 3) a tour to 3D printing facilities with hands-on experience on model processing; 4) a tour to experimentation facilities where 3D-printed models were tested; and 5) group activities based on the examples of how to apply 3D printing in the current or future geoscience research and teaching. The participants had a unique opportunity to create a digital design at the beginning of the course using CAD software, analyze it and 3D print the final model at the end of the course. While this course helped the students understand how rendering algorithms could be used as a learning aid, educators gained experience in rapid preparation of visual aids for teaching, and researchers gained skills on the integration of the digital datasets with 3D-printed models to support societal and technical objectives.

Introduction

3D printing is a 21st century technology for transforming digital models into physical objects. This technology is rapidly evolving, with more access to 3D printing machines and materials ( Wohlers Report, 2019 ). This is an innovative tool in medical ( Baden et al., 2015 ) and biomedical sciences ( Hoy, 2013 ), engineering ( Meyers et al., 2016 ; Boyajian et al., 2020 ), and communication ( Baden et al., 2015 ; Malmström et al., 2020 ). 3D printing revolutionizes how we interact with our data and how we explain our science to non-experts ( Horowitz and Schultz, 2014 ). Creating repeatable, tangible models is emerging in the geoscience education and research as well as in the related industries, such as petroleum recovery, groundwater storage, and carbon dioxide sequestration ( Ishutov et al., 2018 ). One of the biggest advantages of 3D printing is that all the processes involved in the creation of a 3D object, from generating the design to obtaining the printed part, facilitate the learning of concepts and tools, which also develops creativity and communication skills. Earth science data are often modeled in 3D, and 3D printers can provide this 3D visualization and tangible aspect of digital data ( Figure 1 ).

FIGURE 1 . Major benefits of using 3D printing in geosciences. It is useful for developing creativity and design skills through 3D modeling. 3D printing is a convenient tool for rapid manufacture of learning and teaching aids. Any 2D or 3D model can be replicated for a better communication, especially among non-specialists. Any digital data can be reproduced with 3D printing, even if the physical sample does not exist anymore. Research ideas and concepts can be repeatedly tested on the 3D-printed samples. All data can be retrieved or repeated from the digital repositories, which include files of 3D-printed models.

3D printing or so-called additive manufacturing of an object involves deposition of a material layer by layer ( Squelch, 2017 ). Therefore, this technology enables manufacturing models in various sizes and proportions (e.g., small objects can be printed large, so that more details are visible or large objects can be scaled down, so that one can hold the planet in the hand). Sustainable learning through a tangible approach is critical for understanding of complex geologic ideas, where learners can collect, gather and evaluate information about the exterior of the model and internal structures ( Szulżyk-Cieplak et al., 2014 ). Moreover, the same model can be used to communicate these ideas to others, including non-experts in a technical subject ( Dadi et al., 2014 ). 3D printing is essential for commination with impaired people, especially students who require special needs for education ( Kostakis et al., 2015 ; Jo et al., 2016 ; Pantazis and Priavolou, 2017 ; Koehler et al., 2018 ). In the Earth science curriculum, those students can learn common topics such as volcanoes or plate tectonics by using 3D-printed models in the classroom or at home. Buehler et al. (2016) demonstrates an example of a short course for students with intellectual disabilities in an inclusive context that results in enhancing digital literacy skills and reducing stigmas about these individuals at a community level.

Application of 3D printing in high-school education has already shown enhanced haptic perception of the learning material. Elrod (2016) emphasized that if 3D printing would be used in the K-12 environment, students could be better prepared for careers in emerging fields of technology [e.g., science, technology, engineering, and mathematics (STEM disciplines)]. Schelly et al. (2015) demonstrated that even a 3-day short course for middle- and high-school teachers from a variety of disciplines (sciences, engineering, and arts) gained a high interest in utilizing this technology in their classrooms. Chiu et al. (2015) presented a successful model for learning, self-learning, and mastery learning approaches for freshman students with different levels of technological literacy using 3D printers. Reggia et al. (2015) suggested that providing engineering students with an opportunity to perform a project-based design course using 3D printing was an essential curricular element in many engineering programs. Chien and Chu (2018) proposed that 3D printing could enable high-school students to improve their ability to transform from STEM to STEAM (science, technology, engineering, arts, and mathematics) using 3D printers and to create a bridging curriculum with respect to high-school and college students.

Roy and Brine (2017) developed a coursework model to build intellectual capital for the next generation who would vastly depend on 3D printing, because they would shape a smart community in both developing and developed economy context. Martin et al. (2014) explained an idea of “think globally, produce locally,” where 3D printing would become more affordable with the versatility of machines and the ability to engage students with many different STEM-based activities. Gatto et al. (2015) showed that engineering education is on the course of adapting to the social and industrial revolution brought by additive manufacturing, because the latter allowed for sharing digital data in repositories and repeatedly reproducing the data to test ideas and concepts ( Figure 1 ).

For the geoscience education, not many examples are found in the literature for using 3D printing in any full-time curriculum or short courses. Ford and Minshall (2019) demonstrate how teaching models of terrains, fossils, and mineral crystals can complement digital models for a better perception of 3D features. 3D printing is currently used in four geoscience areas, primarily for research and communication: paleontology, geomorphology, porous rocks, geomechanics ( Figure 2 ). These 3D-printed models help organizing a full description, classification, and preservation of geologic specimens. Resolution of 3D printers determines the accuracy of internal and external features of 3D-printed models and hence affects the repeatability of the digital design in different materials ( Figure 2 ). These characteristics are critical not only for creating teaching aids in the Earth Science curriculum, but also for conducting experimental research with 3D-pritned specimens ( Ishutov et al., 2018 ). 3D printing also has value for communication of geoscience to non-specialist audiences to convey technical information, to support legal arguments, and to provide general knowledge of the nature. Currently, there is no universal short course that can provide fast, but positive learning experience of digital modeling and 3D printing to understand and explain geologic concepts among both experts and generalists.

FIGURE 2 . Applications of 3D printing in the geoscience research areas: (A) paleontology, (B) geomorphology, (C) porous rocks, and (D) geomechanics. A blue chart indicates the characteristics of 3D-printed models that are critical for each of the geoscience areas. Materials used in a specific application have different physical and chemical properties, which affect the resolution of a 3D-printed model. 3D printer’s hardware and post-processing of 3D-printed models determine the accuracy of external and internal features. A combination of the three previous characteristics affects the repeatability of a digital design 3D-printed in multiple copies.

This course was developed to test how a group of participants from STEM disciplines, but with various academic backgrounds could perceive the fundamentals of available 3D printing techniques and materials and their relative merits. With little or no prior knowledge of CAD modeling and 3D printing, participants learnt about applications of 3D printing in studies of reservoir rocks ( Squelch 2017 ), fossils ( Rahman et al., 2012 ), geomechanics ( Hodder et al., 2018 ), geomorphology ( Hasiuk and Harding, 2016 ), and porous media ( Ishutov, 2019 ). This one-day short course was divided into five modules and involved students, postdoctoral fellows, technicians, and professors interested in current advances of 3D printing in research and teaching. In addition, participants explored the application of 3D printing in a technical communication. The objectives of the study included: 1) to evaluate if learners with versatile educational and cultural backgrounds could perceive the basic concepts of 3D printing techniques and material properties to provide an assessment of 3D-printed models for research in their respective discipline; 2) to test if fast learning of CAD modeling and 3D printing could help the participants utilize 3D-printed models to explain geologic concepts to generalist audiences; and 3) to prove that 3D-printed models were effective tools for the geoscience education.

Materials and Methods

The short course was designed for the participants without prior experience of CAD modeling or 3D printing. In addition, the course was open for students, professors, postdoctoral fellows, technicians, and research associates from the geoscience and engineering disciplines. The short course took place at the University of Alberta, Edmonton, Canada and involved 50 participants. The course learning outcomes were: 1) to understand capabilities and limitations of different 3D printing techniques; 2) to demonstrate how to digitally design 3D-printable models using CAD software, web platforms, and computed tomography data; 3) to provide the assessment of digital models and their relative replicas 3D-printed from real data; and 4) to characterize how 3D printing can increase the effectiveness of teaching and data communication.

Course Organization and Materials

The short course was organized in five modules: 1) an introduction lecture on the 3D printing methods and materials; 2) an individual CAD modeling exercise; 3) a tour to 3D printing facilities with hands-on experience on model processing; 4) a tour to experimentation facilities where 3D-printed models are tested; and 5) group activities based on the examples of how to apply 3D printing in current or future geoscience research and teaching ( Table 1 ). Each module was taught by one of the four instructors, and facility tours were led by four instructors, two instructors per facility. All instructions on how to complete each module were organized in a digital e-book (pdf).

TABLE 1 . A brief description of topics covered in each module of the short course.

Module 1 included a lecture on the history of “rapid prototyping” and how 3D printing evolved as a tool for engineering industries. In addition, the workflow of creating a digital model and transferring it into a tangible object was covered. The model preparation for 3D printing was explained with examples of using printing specifications, such as the thickness of each layer, the vertical and horizontal dimensions, and the print speed. The lecture also contained post-processing methods, such as ultraviolet (UV) light curing or removal of support material that held the internal porous structure and external elements during printing to avoid deformation or damage of intricate designs. Instructors discussed 3D printing methods that differed by power source, resolution, precision, accuracy, build volume, materials, and price. The importance and applications of 3D-printed models were covered briefly for the areas of geoscience and engineering. At the end of the lecture, participants had a discussion session with instructors ( Figure 3A ).

FIGURE 3 . Photographs of the short course modules. (A) Module 1 “Overview of the 3D printing technology.” Course instructors presented a lecture on common additive manufacturing methods and materials and showed examples of 3D-printed models. (B) Module 2 “The art of making 3D-printable models.” Participants learned basic skills of CAD modeling using TinkerCAD. (C) Module 3 “Elko Garage Tour.” Live 3D printing process was shown to participants. (D) Module 4 “GeoPrint Tour.” Participants were shown industrial scale printing and experimental program performed with 3D-printed models. (E) Module 5 “Application of 3D printing in the geoscience.” Discussion of specific applications of geoscience models in edication and research.

Module 2 involved an individual CAD modeling exercise using an online platform on laptops or tablets ( Figure 3B ). The scale of 3D-printed models varied over the orders of magnitude: from nanometer-size features to the size of the 3D printer’s build volume. This activity was aimed at teaching the participants to create complex geological models (like rocks and fossils) using common shapes (e.g., cylinders, cubes) or multi-scale elements, which were then translated for 3D printing. At the end of this exercise, participants were able to export their model of choice for 3D printing and receive at the end of the course.

Module 3 represented a tour to the Elko Engineering Garage (University of Alberta, Edmonton, Canada) that introduced the participants to the activities associated with creating and 3D printing digital designs as well as post-processing of 3D-printed models ( Figure 3C ). Participants were exposed a variety of 3D printers and post-processing tools, as well as they had an opportunity to investigate a 3D laser scanner. Instructors made connections of the material covered in the lecture, such as material properties, 3D printing resolution, and model dimensions with the real applications in workspace. Participants were able to observe the 3D printing process of the digital models that they designed in module 2 and had a hands-on experience on post-processing their models to make give them a smooth, finished look.

Module 4 involved a visit to the GeoPRINT facility (University of Alberta, Edmonton, Canada), where an industrial-grade sand printer and a high-resolution stereolithography printer were located ( Figure 3D ). This tour introduced participants to two specific 3D printers used for geomechanical and flow research at Reservoir Geomechanics Research Group. Participants explored about the differences in material preparation, printing, and post-processing between these two technologies.

Module 5 included a group exercise on the comparison of CAD models for porous rocks, fossils and geomorphic features with their 3D-printed counterparts ( Figure 3E ). Participants assessed the differences in material finishes, accuracy of external and internal elements, and scales of 3D printing (using criteria in Figure 2 ). In addition, there was a discussion of potential application of 3D-printed models in the geoscience experiments to validate numerical simulations and complement existing laboratory tests. Instructors facilitated the discussion of 3D-printing techniques that participants have seen in modules 3 and 4 and how they could be applied to fundamental research in the areas of multi-phase fluid flow and reactive transport, discrete fracture networks, geomorphology, and paleontology ( Figure 3E ).

3D Printers and Software

Out of seven ASTM categories of 3D printing, four methods were shown in this short course: stereolithography, binder jetting, material extrusion, and material jetting. All 3D printers belonging to these categories were demonstrated in Modules 3 and 4. Materials used for demonstration of 3D printing techniques included polymers, plastics, sand, and resins.

The software used in module 2 for CAD modeling exercises was Autodesk TinkerCAD ( https://www.tinkercad.com ). It is a free online platform that requires only registration with email. The software used for processing of digital designs before 3D printing was Autodesk Meshmixer ( http://www.meshmixer.com ). It is a freeware that can be installed on most operating systems.

Post-Course Questionnaire

The course survey is proved to be one of the effective forms of analysis of the short course efficiency ( Chiu et al., 2015 ; Schelly et al., 2015 ; Meyers et al., 2016 ; Pantazis and Priavolou, 2017 ; Ford and Minshall, 2019 ; Assante et al., 2020 ). The surveys are usually conducted before and after the course to assess how learning objectives are fulfilled. In each module, the following criteria were used to build the course evaluation survey:

• fundamentals of 3D printing and its basic operating principles;

• advantages and disadvantages of 3D printing technologies;

• performance and functional constraints of 3D printing for specific applications.

• complete 3D-printing sequence of designing, fabricating, and measuring models;

• source of mismatch between digital and 3D-printed models.

• causes of errors and irregularities in 3D-printed models;

• hands-on experience of 3D printing in class for improved student understanding of subject matter.

• important 3D printing research challenges;

• resources to support experiments for teaching and classroom projects.

• understanding if humans learn better when using 3D-printed models;

• current and future 3D printing applications.

At the end of the course, instructors distributed an electronic evaluation form to all participants and asked them to complete it within 1 h. The questions in the survey were composed in a Google Docs form to allow for anonymous and individual response from each participant, who was required to indicate only their academic level. The post-course questionnaire was segmented into sections: 1) overall recommendation for the short course; 2) assessment of course materials (e-booklet, lecture slides, exercise instructions; 3) course content (cohesiveness of modules, ease of learning the material, laboratory tours, and visual aids); 4) time spent on each module; and 5) evaluation of instructors’ teaching abilities; 6) effectiveness of course learning outcomes. Section 1 responses were based on Yes/No scale. Responses in sections 2, 3, 5 were collected using the following scheme: strongly disagree, disagree, neutral, agree, and strongly agree. Responses in section 4 were registered using the following scheme: not enough, adequate, too much, no opinion. The last section was evaluated using Likert scale out of 5, where a higher value is a more positive response.

Results and Discussion

The short course involved 50 participants from geosciences and engineering ( Figure 4A ); it was expected to receive mixed comments about the course contents and organization of modules. Nonetheless, 97% of all participants responded that the course would be recommended to others ( Figure 4B ). In this case, others were referred to peer students, colleagues, and other academic staff. This outcome was positive to propose the course to various professional organizations as a customized workshop, e.g., for industry professionals interested in the use of 3D printing in research and technical communication. The instructors observed that despite the differences in age and academic background, the participants communicated with each other in a friendly manner. Based on the results of the post-course questionnaire, the short course outcomes were assessed for the adequacy and organization of the course materials, structure, and coherence of the course modules, and efficiency of the course instructors and learning objectives.

FIGURE 4 . Demographics of the short course participants. (A) Indication of the academic level and/or position. (B) Responses of participants from (A) to the question: “Will you recommend this short course to others?”

Course Materials

An e-book contained a set of short, descriptive instructions with images and figures about each module ( Figure 5 ) that was useful to most participants. Course objectives were clear, so that the short course agenda was understood by learners with different backgrounds (24 positive responses out of 32 responses in total). In addition, the survey showed that the e-book was a valuable component of the course as it helped navigating through activities and exercises (27 positive responses out of 33 responses in total). On the other hand, not all participants found the e-book visually appealing and suggested adding pseudo 3D cartoons that would visually simplify and outline different 3D printing processes (20 positive responses out of 33 responses in total; Figure 6 ). Other comments pointed out on the use of bolded text, underlining or different colors to highlight the key information in the e-book. Also, more than half of the class noted that activities were clearly defined by the instructors and suggested to include more details about the operation of software as numbered bullet points so there would be a step-by-step tutorial (21 positive responses out of 35 responses in total; Figure 6 ). A few additional notes were that the introductory lecture slides in module 1 were cohesive and well organized. For the next run of the course, instructors will prepare a short workflow with bullet points for each activity and exercise and will place them in the e-book as a support material. More images and snapshots will be added for each activity to allow the participants to navigate between the exercises.

FIGURE 5 . An example of the module instructions from the course e-book. The full version of the e-book was available for participants a day before the course. Each module contained synopsis and a set of exercises.

FIGURE 6 . Responses of participants for evaluation of the course materials, such as e-booklet and slides. All the course activities were described in the e-booklet provided on the short course day.

Course Content

The course content was developed using several approaches: lecture slides, individual exercises, group exercises, and facility tours. The majority of the class responded that modules were cohesive (29 positive responses out of 33 responses in total; Figure 7 ). Participants were mostly engaged during the visits to the Elko Garage and GeoPrint facilities (modules 3 and 4), because these tours improved their understanding of the 3D printing process (30 positive responses out of 32 responses in total). Observing the printing methods and interaction with 3D-printed models provided a motivation for the learners to incorporate this technology in their research, teaching, or other activities (29 positive responses out of 34 responses in total; Figure 7 ). In addition, the majority of participants could understand all aspects of digital design, processing, and post-processing of 3D-printed models via the CAD modeling exercise (module 2) (31 positive responses out of 34 responses it total). Instructors observed that even those participants who did not have any experience with digital modeling of simple shapes could learn it fast, because at the end of the exercise everyone was on the same level.

FIGURE 7 . Responses of participants for evaluation of the course content. Participants assessed each activity at the end of the short course. *A question about the advanced 3D printing course is whether participants would like to have a short course on the applications of 3D printing in their respective discipline (not geoscience).

The group exercise involving comparison of digital models with their 3D-printed counterparts and the discussion of applications in the geosciences (Module 5) was expected to be challenging, because the participants were divided into mixed groups of 10 people to avoid accumulating representatives of the same department and academic level in one group. E.g., one group might have consisted of two undergraduate students from civil engineering and geology, three professors from electrical engineering, computer engineering and geophysics, three postdoctoral fellows from mechanical engineering, and petroleum engineering, and two research associates from atmospheric science and computer science, respectively. Most of the class responded positively to such combination of groups, because it allowed them to share a broader spectrum of ideas given the versatility of backgrounds (32 positive responses out of 35 responses in total; Figure 7 ). Some participants responded that they would prefer to classify the groups by the department, so that they would share the same interest in 3D printing and might make the group work more cohesive. This model could be another option for the group activity, where the groups could be formed by the department only, but the course contents would need to be more general, rather than focusing on the geoscience and engineering applications.

Participants would also asked to have more group activities to share the knowledge learnt, which confirmed that this intentional split into mixed groups worked well for leaning the unknown concepts. A few people were not interested in the geoscience applications and would have liked to participate in the content related to their discipline only or in a more generic content. This was a viable comment, and more than half of the class responded that they would like to have an advanced 3D printing course to explore the applications in their relative subjects of interest (26 positive responses out of 30 responses in total; Figure 7 ). Perhaps a separate short course covering specific applications of 3D printing in STEM disciplines might be developed to satisfy this interest. The most expected comment was that participants were thinking of getting their own 3D printer to manufacture models for research, teaching, and communication.

Each module had a different time period for completion, because it depended on the speed of the instructor’s delivery and the pace of participants ( Figure 8 ). It was designed to spend more time on individual and group exercises (Modules 2 and 5), so that the pace between the participants could be averaged as some people needed more time to learn new tools. In general, almost all learners (29 out of 33) agreed that the 50-min lecture in module 1 was sufficient to grasp the main concepts. Some participants (12 out of 33) noted that they would need more time to go through the functionalities of the software in Module 2 to complete the CAD exercises. In future, this module could be timed in a different way, where the participants would have an extensive, detailed introduction into the software and then they would be given a set of exercises to complete. Also, for those who could complete a mandatory set of exercises faster, additional activities would be provided. For the group exercises (module 5), about half of the class completed their assignments on time, while a quarter of the class felt that the time could be reduced ( Figure 8 ). To adjust this module, more exercises would be provided, specifically a small section discussing case studies in the geoscience.

FIGURE 8 . Responses of participants for evaluation of the time spent on each module of the short course.

Efficiency of Instructors

The next set of questions in the survey was aimed at revealing any flaws in the style and structure of the instruction. It was found that the majority of the class was satisfied with the teaching style and delivery of the modules by instructors (28 positive responses out of 33 responses in total; Figure 9 ). One participant noted that it would be useful to have solutions for each exercise, mainly for the ones related to the group activity. The answers could not be compiled for each activity as they varied by the group and the amount of material covered in each case. A few participants would like to have more one-to-one communications with instructors, but it might not always possible, given the size of the class and time allocated for each activity. It is foreseen that the class size will be reduced to have more time assisting each participant in all activities, even though the majority of participants (31 out of 33; Figure 9 ) felt supported during the course.

FIGURE 9 . Responses of participants for evaluation of the instructors’ delivery of the short course.

The survey showed that instructors were knowledgeable (32 positive responses out of 33 responses in total) and well-prepared (30 positive responses out of 34 responses in total) for the course, which fulfilled the course objective of sustainable learning and communication through tangible models. It is confirmed that 3D printing promoted the curiosity among the learners and facilitated an interest in creation of a model simultaneously with the instructor. Developing creative potential entailed improving a problem-based approach to demonstrate theoretical concepts that could be accessible by different groups of participants. This short course demonstrated that diverse groups were able to assimilate, apply, and describe new knowledge more effectively, including collaborative and individual learning. There is a need in studying how these methods can complement traditional instruction in terms of retention of material and motivating learners to study and develop their communication and problem-solving skills.

Efficiency of Learning Objectives

The course learning objectives were evaluated during interactive exercises of the course as well as post-course questionnaire. After completion of each module, participants were asked to complete the same set of three questions based on the course objectives. Their responses were averaged using Likert scale, where more positive responses were approaching 5 and less positive responses were approaching 1 ( Table 2 ). Participants were scoring how each of the three objectives was fulfilled when they completed modules subsequently. It was evident that more confidence was gained toward the end of the short course when all three course objectives were assessed (increasing scores from Module 1 to Module 5 in Table 2 ). While not all participants had geoscience background, collaborative learning is proven to be effective in enhancing creativity and hence enabling a large class to adopt the new technology. Post-course questionaries demonstrated that faculty, students, research fellows, and technicians could effectively work in teams to understand basic concepts of 3D printing techniques and material properties. They used this information to provide an assessment of 3D-printed models and to generate ideas for research in their respective disciplines.

TABLE 2 . Comparison of student responses on fulfilling the course learning objectives.

Individual CAD modeling exercise (module 2) helped the participants understand how geological and engineering models could be designed and utilized to explain ideas and concepts to generalist audiences. In module 5, instructors provided an example of 3D-printed porous rock created from a digital model ( Figure 10 ). All participants were asked to use this workflow to characterize how the rock porosity could have been formed and to explain why the rock grains had angular or rounded geometry and how they were transported to form a larger formation. Participants with a geoscience background were assessing responses of participants that did not have any background in the geoscience. It was noted that comparison of images, 3D digital models, and 3D-printed samples altogether provided better understanding of the rock properties rather than each model separately. Also. participants with good technical background in CAD within the team could help teaching other teammates, providing additional peer learning element in the process.

FIGURE 10 . Workflow for generation of 3D-printed samples from digital models. Source data are either optical or CT images of natural rocks (e.g., Berea sandstone). Images are segmented into pores and grains; the grain volume is transferred to 3D printing software as a CAD model. Selected 3D printer creates a tangible model layer-by-layer (polymer in this example). Pore space is filled with support material (soft polymer) that is removed by post-processing.

Module 5 was very useful for synthesizing previous modules and providing exercises linking CAD modeling from module 2 with 3D printing methods presented in module 1 and materials observed in modules 3 and 4. Participants were asked to choose one model for which both CAD and 3D-printed models were available ( Figure 11 ). Their task was to prepare a 1-min presentation of the model intended for general audience. The exercise was aimed at evaluating if 3D-printed models could improve geoscience learning for non-specialists. This collaborative learning approach demonstrated that expertise from students with different backgrounds could contribute to the cognitive process. Instead of learning under the instructions of tutors, participants collaboratively worked and learnt together. Participants noted that those teammates without geoscience background provided more intuitive and comprehensive description of selected models. It might be due to the fact that specialists could not often formulate higher-level explanation of concepts and phenomena.

FIGURE 11 . Examples of 3D-printed models used in course exercises. (A) Fossil and rock specimens. (B) Geomorphology and porous models.

Post-course questionnaire showed that 3D printing was an efficient tool in teaching and communication geological data and hypotheses to many types of diverse audiences. This study proved that non-specialists could learn, understand, and explain scientific concepts without prior knowledge about them. This finding is important because 3D printing can be used in many university curricula where students with any background can learn sciences in any environment. In particular, tangible aspect of 3D-printed models is vital for the geoscience education where most of the data are in a 3D format. Future development of the short course will involve several examples of non-geoscience data (e.g., engineering, medicine) to challenge participants in interpretation of concepts that are far beyond their expertise. This approach will help identifying if 3D-printed models are useful in communicating more complex phenomena to non-specialist audience.

3D printing is an emerging technology in the geoscience that provides additional teaching support, enhances technical communication using visual aids, and enables repeatable experimentation in research. While the process of incorporating this technology into the regular curriculum in academic institutions may take years, short courses can help this process by improving student and faculty engagement and by developing skills for a more qualitative knowledge acquisition. The short course presented in this study was useful for a diverse group of participants including professors, students, postdoctoral fellows, and technicians from the geoscience and engineering disciplines, because it allowed them to communicate geological concepts using digital models and their tangible counterparts. Participants demonstrated that this technology allowed them having the capacity for modification and sharing digital data and supporting educators who wanted to produce teaching models without prior expertise and in a rapid manner.

While this one-day short course had five modules, participants acknowledged that the time spent on each module was adequate as the modules contained the right amount of instructions and activities. It was designed in a way that participants would create their digital model, learn about different 3D printing techniques, observe how these techniques worked live and how 3D-printed models were experimented with in the laboratory, and finally 3D print their own model and discuss its properties. It was noted by the participants that course materials, such as e-booklet and slides with instructions, helped them digesting technical information in a cohesive way.

The main objectives of the short course was fulfilled, because the majority of participants responded that they would start using 3D printing for their research, teaching, or communication. Moreover, many participants had an interest in taking an advanced short course on the applications of this technology in their respective disciplines and to recommend this short course to others. Each module can certainly be modified and adjusted according to the background of the audience. This short course can be a primer for educators willing to introduce creative modeling in their teaching schedule and prepare students for problem-solving skills using tangible models. Making testable analogs of natural phenomena for the geoscience researchers is critical and can be achieved through acquiring CAD modeling skills in this course. Besides creating visual and teaching aids, this technology is a powerful tool in communication, as shown in the short course, because the participants with diverse academic backgrounds could discuss ideas and concepts without prior knowledge about them, only using 3D-printed models.

Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics Statement

Written informed consent was obtained from the relevant individuals for the publication of any potentially identifiable images or data included in this article.

Author Contributions

SI was the primary designer of the short course contents and the paper outline. He presented a poster at 2019 American Geophysical Union Conference on that study. SI developed exercises for the short course and prepared introduction and methods sections. KH developed presentation slides for the short course and wrote sections on results and discussion. RC was responsible for the introduction and conclusions. Figures were collected and analyzed by all authors. GZ-N was responsible for the lab tours.

The course was partially funded by MIP-CONACYT-280097 Grant, Mexico and NSERC 549236, Natural Sciences and Engineering Research Council of Canada. The funds covered the costs of 3D-printed models for participants of the short course.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We would like to thank the University of Alberta and Faculty of Engineering for the opportunity to host this short course on campus. Our special gratitude is to the Elko Engineering Garage for providing a demonstration tour and 3D printing the short course models. We are grateful to the Reservoir Geomechanics Research Group [RG] 2 for support in preparation of this course. We also thank NSERC for support in continuous running of GeoPRINT GeoInnovation Environment at the Department of Civil and Environmental Engineering.

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Keywords: 3D printing, learning aid, visualization, reservoir, porous rock, geomodeling, fossils, geomorphology

Citation: Ishutov S, Hodder K, Chalaturnyk R and Zambrano-Narvaez G (2021) A 3D printing Short Course: A Case Study for Applications in the Geoscience Teaching and Communication for Specialists and Non-experts. Front. Earth Sci. 9:601530. doi: 10.3389/feart.2021.601530

Received: 01 September 2020; Accepted: 13 May 2021; Published: 28 May 2021.

Reviewed by:

Copyright © 2021 Ishutov, Hodder, Chalaturnyk and Zambrano-Narvaez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Sergey Ishutov, [email protected]

This article is part of the Research Topic

3D Printing in Geology and Geophysics: A New World of Opportunities in Research, Outreach, and Education

3D bioprinting: current status and trends—a guide to the literature and industrial practice

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• Published: 02 December 2021
• Volume 5 , pages 14–42, ( 2022 )

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• Silvia Santoni 1 , 2 ,
• Simone G. Gugliandolo 1 , 2 ,
• Mattia Sponchioni   ORCID: orcid.org/0000-0002-8130-6495 2 ,
• Davide Moscatelli 2 &
• Bianca M. Colosimo 1  

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The multidisciplinary research field of bioprinting combines additive manufacturing, biology and material sciences to create bioconstructs with three-dimensional architectures mimicking natural living tissues. The high interest in the possibility of reproducing biological tissues and organs is further boosted by the ever-increasing need for personalized medicine, thus allowing bioprinting to establish itself in the field of biomedical research, and attracting extensive research efforts from companies, universities, and research institutes alike. In this context, this paper proposes a scientometric analysis and critical review of the current literature and the industrial landscape of bioprinting to provide a clear overview of its fast-changing and complex position. The scientific literature and patenting results for 2000–2020 are reviewed and critically analyzed by retrieving 9314 scientific papers and 309 international patents in order to draw a picture of the scientific and industrial landscape in terms of top research countries, institutions, journals, authors and topics, and identifying the technology hubs worldwide. This review paper thus offers a guide to researchers interested in this field or to those who simply want to understand the emerging trends in additive manufacturing and 3D bioprinting.

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Introduction

Bioprinting is a collection of additive manufacturing (AM) technologies, whose aim is to fabricate parts imitating real tissue and organ functionalities by combining both living and non-living materials in a specific three-dimensional (3D) spatial organization structure. As in traditional 3D printing or AM, the target is achieved through the use of computer-aided design (CAD) that represents the fundamental configuration of the target tissue or organ, in order to produce bioengineered structures that have various applications in regenerative medicine, tissue engineering, reconstructive surgery, drug discovery, pharmacokinetics, medical and basic cell-biology research [ 1 ]. Compared to traditional 3D printing or AM processes, bioprinting brings a main innovative feature, namely the printing of living cells within a specific medium called bioink, which adds many different challenges, such as how to avoid the deterioration of living cells while printing constructs that have a 3D volumetric shape similar to the ones of natural tissues and organs.

In light of the application of such manifolds and the growing interest towards personalized medicine, bioprinting methods have attracted increasing attention in recent years from both academia and industry, which has translated into extensive research efforts. During the last decade, many novel procedures and technologies related to biomanufacturing have emerged, ranging from dedicated 3D bioprinters [ 2 ] to specific “raw biomaterials” named bioinks [ 3 , 4 ].

A bioprinter is a 3D printer that realizes biological tissue constructs by the layerwise deposition of living cells. To achieve this aim, bioprinters generally use bioinks, which are soft biomaterials loaded with living cells manipulated according to specific protocols to build biological constructs. The use of secondary dissolvable materials is an additional option to vertically support and protect cells during the printing process.

Although many bioprinting review papers focusing on describing techniques or bioink classifications have been published in recent years [ 3 , 5 , 6 , 7 ], a systematic and quantitative investigation of the actual landscape has not been performed, including the analysis of papers, patents and companies with the aim of highlighting the actual distribution of key players in academia and industry, as well as the main topics currently under study. To the best of our knowledge, the first and only scientometric review on 3D bioprinting cannot be considered up-to-date including the latest scientific innovations in this area, as it was published in 2017 [ 8 ] based on data retrieved from 2000 to mid-2016. In fact, two-thirds of the total publications related to bioprinting to date have been published since 2016.

Given the rapid growth of this special field, the present work is aimed at stimulating the interest of scientists and experts already involved in traditional 3D printing or AM by highlighting the emerging trends and the most recent advancements [ 1 , 9 , 10 , 11 , 12 ]. This review presents a rational roadmap to the scientific and patenting results produced to date, which can be especially useful for researchers new to the field, as they can quickly obtain the geographical distribution of laboratories and companies actively involved in 3D bioprinting combined with a critical analysis of their output in terms of publications, patents, new tools and manufacturing techniques.

The paper is organized as follows: the literature review results are presented and discussed in “ The academic research trends ” section with a detailed analysis of the most productive authors and active research networks worldwide. “ Market and patent landscape ” section describes the market and patent landscape to identify both emerging and established technology hubs. Finally, the main conclusions are drawn in “ Conclusions ” section.

The academic research trends

Trends in the relevant scientific literature: critical data analysis and classification of applications and trends.

Following previous scientometric studies and AM [ 8 , 12 ], we based our literature analysis considering all research and review papers published in scientific journals included in Scopus (Elsevier) and Web of Science (WoS) in the past 20 years (from 2000 to 2020). We also used SciVal ( https://www.scival.com/ ) as a supporting tool in our query. The latter was focused on bioprinting processes, materials and bioapplications according to the latest definition of bioprinting, and is a modified version of the one used by Rodríguez-Salvador et al. (details in the Supplementary Information). In order to better highlight the most recent trends, a detailed analysis was further performed with reference to scientific results published in the last four years, i.e., since 2016.

A total number of 13,111 papers (11,683 research articles and 2537 review papers) were initially collected using both the Scopus and WoS databases. An extensive cleaning and deduplication process was subsequently performed through EndNote (X9, Clarivate Analytics, Philadelphia, USA), leading to 9314 unique documents, consisting of 7574 research articles and 1740 review papers).

It is worth noting that 79% of these papers were published after 2014 and nearly 53% of total publications were published after 2017. Specifically, 61% (4620 out of 7574) of research articles and 74% (1288 out of 1740) of review papers have been published since 2016, showing an exponential growth of attention on this topic in the scientific literature. Figure  1 shows the total number of publications retrieved from Scopus for the last 20 years, where the steady rise during the past 10 years is clearly visible. This growing number of scientific papers led to a 143% increase in the number of review papers in a single year for 2016. Since then, due to the continuous evolution and rapid innovation in this field, a constant annual growth rate of (28 ± 9)% in review papers has been reported.

3D bioprinting publications by year: articles, blue; reviews, light blue

In order to select the most relevant venues for 3D bioprinting papers, SciVal ( https://www.scival.com/ ) was used to research on the topic T.8060 (Bioprinting; Printability; Tissue Engineering) together with InCites Journal Citation Reports to include information on Impact Factor, Article Citation Median and Review Citation Median focusing on 2018 and 2019 (details are also given in Table S1 of the Supplementary Information).

The number of papers published (usually referred to as ‘scholarly output’ Footnote 1 ) in the past five years was specifically used to select the twenty most productive journals in the bioprinting field. Figure  2 presents the main results of this ranking. As clearly seen in the figure, Biofabrication (with 319 publications, namely 297 articles and 22 review papers), Biomaterials (with 184 publications, namely 166 articles and 18 review papers), and Acta Biomaterialia (with 162 publications, consisting of 124 articles and 38 review papers) are the most prolific journals in this field. Moreover, the percentage of publications focusing on bioprinting with respect to the overall number of papers from 2000 to 2020 was used as an additional indicator of the level of attention to this topic (data retrieved from Scopus), and are shown as dots in Fig.  2 . As expected, Bioprinting (66%), Biofabrication (43%), International Journal of Bioprinting (42%), and Bio-Design and Manufacturing (26%) are the top-focalized journals. Most of these are young journals (founded in 2009, 2015, 2016, and 2018, respectively) focusing on this novel field, with impact factors (IF) revealing their age and their specific field of focus (IF values ranging from 4.10 for Bio-Design and Manufacturing to 8.21 of Biofabrication, compared with older and more generic journals such as Advanced Materials with IF equal to 27.4 Footnote 2 ).

The top twenty journals focusing on 3D bioprinting (SciVal-Scopus). The bars represent the number of publications (blue: articles, light blue: reviews) retrieved from Scopus, while the yellow dots represent the percentage of publications focusing on 3D bioprinting with regards to the total number of publications. The examined time interval is 2000–2020

With regard to review papers, a different classification can be outlined depending on the specific 3D bioprinting technology each paper refers to [ 13 , 14 ]. As for traditional AM processes, different bioprinting techniques vary in the technique of layerwise deposition of biomaterial. Even if the bioprinting literature does not assume the proper terminology defined in the AM standards (ISO/ASTM 52900), AM technologies similar to the ones used for polymers are often adopted. The first class of technologies is based on nozzle-deposition [ 11 , 15 , 16 , 17 , 18 , 19 ], which can have different printing resolutions and speed depending on the precision of the bioprinting head, the nozzle diameter size and the droplet formation mechanism (Fig.  3 a). A second main class of technologies are optical-based, namely the vat photopolymerization (always referred to as stereolithography in the literature on bioprinting [ 11 , 20 , 21 ]) both in its traditional setting and the two-photon polymerization version.

a Different procedures of 3D bioprinting, adapted from Derakhshanfar et al. and Loai et al. [ 22 , 23 ]. b Number of publications for each bioprinting technique (extrusion, stereolithography, laser-assisted and inkjet) for publication years 2000 to 2020; inset: 5-year publication trend for 2016–2020

Figure  3 b shows that extrusion-based bioprinting is the most studied approach in the literature, potentially because it is the most affordable solution for an entry-level bioprinter, and the least expensive technology that allows the use of a wide range of printable biomaterials [ 2 ]. The second and third most widespread techniques are vat photopolymerization and inkjet bioprinting. The former is characterized by many benefits, i.e., higher resolution, a wide variety of bioink viscosities and higher cell density [ 24 , 25 ]. Eventually, thanks to the drop-on-demand (DOD) patterning method available in most bioprinters, jetting is often used for printing smaller features.

The extrusion-based technique is rapidly becoming popular likely because of the great number of entry-level bioprinters that have entered the market in recent years. Meanwhile, vat photopolymerization 3D bioprinting is emerging as a prominent bioprinting method for complex tissues.

Bioprinting research landscape: main applications and emerging topics

The main utilities of 3D bioprinting are in basic medical/cell biology research, the production of pathology models, mini-tissue production for drug screening, and the field of regenerative medicine for the future replacement of tissues and organs [ 5 ]. Within this framework, the ideal workflow of bioprinting should start from retrieving patient-specific cells through biopsy, designing the morphology of the organ or tissue to be replaced, and going back to the patient at the end for the transplantation of a functional organ [ 26 , 27 , 28 , 29 , 30 , 31 ]. To the best of our knowledge, this ideal workflow cannot be yet completed from end to end, as different challenges [ 1 , 32 ] need to be overcome. Among the most important ones, vascularization and multi-material printing are the most relevant. Vascularization consists of printing tiny vessels and capillaries that are specifically designed to enable the survival of living cells by the delivery of nutrients and oxygen. Multiple materials are needed to allow different types of cells and hydrogels to be combined in the 3D structure, as it occurs in real biological tissues.

Considering the long-term goals and driving factors, research on 3D bioprinting is now progressing in three major areas:

Application-driven research focusing on specific utilities of 3D bioprinting, i.e., distinct tissues, pathology models or organ-on-a-chip for drug discovery.

Biomaterials research to develop novel bioink formulations that improve printability or support tissue differentiation and maturation, and allow the study of cells to be bioprinted in the construct.

Process-driven research focusing on the printing technology to improve the resolution and accuracy of 3D bioprinting while avoiding cell damage, support the design of complex shapes, reduce printing time and costs, and allow specific functionalities, i.e., multi-material printing.

In order to highlight the main trends in the literature, we clustered papers published since 2000 based on text analytics keywords. The number of articles related to each topic is shown together with its evolution over time in Fig.  4 .

Trends of publication topics on 3D bioprinting over the years. The number of publications relative to each topic are shown over time. The graph was created by counting at most one keyword in each topic class for each publication while having an average of two topics of interest in each publication

A considerable number of publications, especially review papers, are focused at the fundamental aspects of 3D bioprinting, and are included within the class of process-driven papers. For instance, a basic theme such as biomimicry shows steady growth from 2010, while there are newer ideas, including four-dimensional (4D) bioprinting that first appeared in 2016 and is already the subject of 28 papers [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Some publications show the bioprinting workflow [ 27 , 28 , 29 ] and areas [ 42 ], while the ethical aspects of bioprinting are still relatively underrepresented [ 43 ].

Regarding the applications of 3D bioprinting, about 40% of all publications refer to a specific tissue or organ starting with their title (as shown in Table 1 and the Supplementary Information). Many review papers are directed at the bone, cartilage (in particular, articular cartilage), vascularized tissue, cardiac tissues, liver, neural tissue, skin, pancreas, cornea, kidney and muscle, where the first classes mentioned are also the most frequently studied ones (see Fig.  5 ). On the other hand, some emerging topics have received increased attention in the last few years, such as dental tissue, nerve regeneration, lung, intestine, thyroid gland [ 44 ], urethra [ 45 ], and encapsulated T-cells [ 46 ]. This trend might continue in the near future.

Catalogue of all publications based on the automatic assignment of keywords extracted from the titles relative to the tissues and organs (others: articulation, nerve regeneration, kidney, adipose tissue, lung, dental, trachea, ear, pancreas, cornea, aortic valve, esophagus, retina, neural tissue, thyroid gland, urethra, intestine, eye, T-cells). The sum is not equivalent to the total number of publications, since each paper can focus on more than one tissue

Among other applications, graft and implants, pathology models, and organs-on-a-chip are also addressed, with a relative role (i.e., percentage of reviews over the total number of publications) showing an upward trend for the past 10 years. In this area, we can observe studies on traditional topics, such as bioglues, grafts and implants, but also new solutions including the BioPen (which is a handheld device invented by Wallace and co-workers [ 72 ] for printing cartilage in vivo) or the application of bioprinting to cryopreservation.

Since the beginning (the first papers date back to 2002), 3D bioprinting has also been subject to pathology models for in vitro studies of diseases. In particular, 3D-bioprinted cancer models have been described for breast cancer [ 115 , 116 , 117 , 118 , 119 , 120 , 121 ], mammary ductal carcinoma [ 115 ], appendiceal cancer [ 122 ], mesothelioma [ 123 ], glioblastoma and metastasis. Other types of diseases that have been modeled through bioprinting include epilepsy [ 124 ], diabetes [ 110 , 125 ], degenerative diseases, immune-enhanced organoids for immunotherapy screening [ 126 ], and wound healing [ 127 , 128 ]. In all these applications, 3D bioprinting has been utilized for drug discovery, drug screening, and pharmaceutical applications, especially after 2011. On the one hand, the production of pathological tissues and organs using cells from patients leads to a personalized approach on drug discovery [ 129 ]. On the other hand, the serial production of mini-tissues in a standardized manner can be highly useful for the high-throughput screening of large libraries of drugs already available on the market (drug screening [ 130 , 131 ] or novel drug discovery [ 132 ]). In the future, the main target is to 3D print patient-specific models using the patient’s own cells to test different chemotherapeutic drugs in vitro for selecting the most efficient patient-specific therapy. Translational medicine and the implications of 3D bioprinting in regenerative medicine, as well as the clinical translation of 3D bioprinted constructs [ 50 , 133 , 134 ], are certainly becoming hot topics in the near future.

Compared to other applications, publications on translational medicine occurred fairly lately (starting in 2009), adding up to 117 publications with more than 60% classified as review papers. In fact, the application of 3D-bioprinted tissues in medicine is still being implemented; to the best of our knowledge, no tissues or organs produced by 3D bioprinting have been implanted in vivo in real patients. However, the 3D printing of biomaterials [ 135 , 136 , 137 ] is increasingly common in medicine, especially for the production of bone and dental implants and grafts, but also in surgery for the production of patient-specific 3D models on which surgeons can train before the actual procedure.

Microfluidics and organs-on-a-chip are some of the latest areas in 3D bioprinting, and, even though the first occurrence dates back to 2004, most of the relevant publications have been published after 2010. At present, only about 100 publications refer to this topic by the title. Publications on organ-on-a-chip models focus either on modeling healthy or pathologic organs [ 138 ], where bioprinting can be useful for studying gene expression and cell differentiation in different healthy conditions by controlling the microfluidics and the microenvironment, or can be used to realize in vitro models for drug screening in pathology studies.

Concerning biomaterials, one of the most exciting field of research relates to bioinks, with about 25% of the whole number of publications on bioprinting focusing on the development of novel bioinks to obtain specific biological, mechanical, and chemical characteristics. This stream of research is fairly new, as research on bioinks was rather limited before the rise of 3D bioprinting. Nowadays, the number of reviews on bioprinting is growing together with the rising need of information to standardize tests on 3D cultures. On this subtopic, the literature focuses on imaging (73 publications), biological characterization (726 publications), resolution (49 publications) and printability (32 publications), with an increasing interest in rheology (21 publications) and structural integrity (9 articles).

Most of the recent papers on bioinks outline the need to find the best compromise between printability and specialization for the specific cell or tissue under study [ 139 , 140 ]. In fact, each cell type requires highly specific conditions in addition to a number of standard requirements (e.g., aqueous environment, sufficient oxygen and nutrient diffusion, appropriate pH, physiological osmolarity of key vitamins and minerals). For example, certain cell types require appropriate sites for attachment, specific substrate properties and space in order to proliferate and produce their extracellular matrix (ECM) [ 141 ]. Bioinks can be classified depending on their origin (natural or synthetic), the type of 3D printing process they can be used in (e.g., bioinks for material extrusion, jetting or photopolymerization differ in their rheological characteristics, shape fidelity and printability features) or the gelation kinetics: ionic, stereocomplex, thermal, photocrosslinking, enzymatic and click chemistry [ 142 ].

Overall, about 15% of all publications focus on innovative cell types in 3D bioprinting, such as stem cells, spheroids, and organoids. This rate is yet to increase mostly because innovative cell types are still under investigation in biology with the aim to overcome open challenges concerning differentiation and maturation. With reference to stem cells in 3D bioprinting [ 143 , 144 ], Skeldon et al. outlined that the main types of stem cells used in this context are mesenchymal stem cells, neural stem cells, and human induced Pluripotent Stem Cells (iPSCs) [ 143 ]. However, our search found that general multipotent human Adipose Stem Cells (hASCs), as well as nasal and bone marrow stem cells, have also been used. Spheroids have been used in 3D bioprinting since 2003, mostly as the living components of bioinks. Finally, organoids have become one of the latest cell sources used in 3D bioprinting since their first occurrence in 2017 [ 145 ].

Surprisingly, the characterization or development of new process technologies for 3D bioprinting has received rather limited attention in the literature. The rate of publications on this topic decreased from around 30% in 2010 to 15% in 2019. This can be mainly ascribed to the increasing focus on biology, medicine, or material science rather than engineering driving the increase of attention to bioprinting. Secondly, most of the processes used in this field are those borrowed from the traditional 3D printing of polymers with modifications to achieve the desired results. However, a lot of research is lacking, especially for most of the complex technologies. This is clearly visible in the literature, where most of the studied techniques are the laser-based ones (144 articles and 14 reviews) and stereolithography (83 articles and 18 reviews). Inkjet was introduced in 2006 and is among the oldest techniques, while extrusion 3D bioprinting first appeared in 2001, but expanded especially after 2015 with the entry of commercial bioprinters to the market.

Moreover, the application categories include printing techniques that simply exploit existing printing technologies and processes in innovative ways to meet the needs of a specific application (e.g., creating channels to form vascularized tissue). Such is the case of bioprinting in a suspension bath, primarily developed to create vascularized tissues. Among others, one of the most recent techniques is called freeform reversible embedding of suspended hydrogels (FRESH), which has now progressed to its second version and consists of extruding a bioink in a dissolvable suspension bath usually made of a gelatin microparticle slurry, which enables the 3D bioprinting of constructs with higher resolution and is useful for the production of vessels of very small diameters (5 to 10 µm) [ 146 ]. This technique has been used very recently for the 3D bioprinting of a full-size human heart [ 147 ]. An alternative utility of this type of technique is sacrificial writing in functional tissues (SWIFT), which enables the production of small vessels and vascularization through extrusion bioprinting directly inside a functional and vital tissue, which simultaneously acts as a suspension bath [ 63 ].

Moreover, a further highly innovative branch of applications is the magnetic levitation approach, introduced in 2020 by Mironov et al. (also affiliated to the company 3D Bioprinting Solutions [ 148 ]). However, the first experiments with magnetic-based bioprinters showed a limitation that the bioinks have to withstand the pull of Earth’s gravity. Regarding this aspect, space agencies like ESA or NASA are also investigating the idea of using microgravity to improve the 3D printing of soft human tissues, such as blood vessels and muscles. This means using a scaffold-free, nozzle-free and label-free approach (i.e., without magnetic nanoparticles). Enabling in-space bioprinting may not only help improve bioprinting research to face organ shortage on Earth but would also have repercussions in long-term/long-distance human space missions (including Moon and Mars programs). The increased risk of injuries in such distant missions impose the need to develop the ability to print replacement tissues or organs for astronauts in emergency situations. In this context, 3D bioprinting could be considered as a mission enabler for such kinds of projects (i.e., space exploration and planet colonization) [ 149 ].

Worldwide distribution of the most prolific academic institutions

In order to highlight countries and institutions currently involved in 3D bioprinting research, the geographical distribution of affiliations declared in the publications were analyzed. A preliminary analysis was performed on the aggregated data retrieved from SciVal. The United States (USA), China, South Korea, Germany, United Kingdom (UK), and Canada scored as the most relevant countries where research on 3D bioprinting is currently ongoing. Similar results were obtained by ranking the countries depending on the authors’ affiliations (see Fig.  6 a Footnote 3 for further details). As seen in Fig.  6 b, the US has an obvious leading role in terms of absolute performance (number of authors and institutions involved in bioprinting research), which shows a more diffused attention to this topic (with an average of 4.6 top authors in each of the leading institutions). Meanwhile, China has a second leading position but is characterized by a more focused profile, where only a handful of institutions are currently hosting the most prolific authors on 3D bioprinting (with 7.5 authors on average in each of the top institutions).

a Geographic localization of the current affiliation of the 100 most relevant authors (blue), and the most relevant affiliations (green) according to SciVal based on the Scholarly output. The ten most relevant universities are highlighted. The interactive map can be viewed at https://ggle.io/3kuZ . Map data ©2021 Google. b Number of the most prolific universities (retrieved by considering the affiliations in papers) and top authors per country. The number of the most relevant authors, in blue, and the number of the most relevant institutions per country, in green, were retrieved from SciVal on the topic T.8060 (Bioprinting; Printability; Tissue Engineering) . The countries are listed following the SciVal ranking based on the Scholarly output. China, South Korea, and Germany have the highest number of authors per affiliation. The fraction of authors over the number of institutions per country is represented in yellow, and the data are shown on the secondary y axis on the right

In Table 2 , the number in the parentheses after the research institute refers to the relative position of the institution/author in the worldwide ranking obtained by considering the number of published products (called ‘scholarly output’ in SciVal). In particular, products are associated to the institution depending on the affiliation of the authors of each product.

The table lists the top ten affiliations; it can be observed that the University of California at San Diego (1) and Harvard University (2) in the USA, and Nanyang Technological University (3) in Singapore are the three leading institutions in this field (see also Table S2 for a complete list of top affiliations and authors per country). A similar geographical distribution is shown for the most prolific authors (shown in blue in Fig.  6 b).

A more complete analysis of the top-leading laboratories and scientists is presented in Table 3 , with specific attention to the investigated topics. For the most inclusive analysis possible, these authors were selected as the 20 researchers with the highest scholarly output and/or citation count within the topic of 3D bioprinting according to SciVal. Moreover, the network of collaborations between universities defined by considering co-authorships is shown in Fig.  7 , from which it can be inferred that, despite global collaborations, the highest number of publications in collaborations are also geographically clustered. The clusters identified from this graph are also discussed in Table 4 .

Network graph showing collaborations between the most prolific authors; the authors’ names and relative affiliations are presented in color and black, respectively. The size of the node (circle) is directly proportional to the number of publications on 3D bioprinting retrieved from that author, while the color indicates the country of affiliation. The links between the nodes denote the number of collaborations (only collaborations on at least 10 publications are shown); the thickness of a link is proportional to the number of articles produced in collaboration between the two authors. Twelve clusters of collaborations can be identified from this graph, in which 5 are prominent in terms of the number of publications of authors and the number of collaborations

Within the US, three clusters of collaborations can be recognized. The most relevant group in the USA per number of publications can be referred to as the “Harvard cluster ” in which a strong collaboration between PIs affiliated to Harvard can be seen; the PIs involved are Khademhosseini, Ali, whose current first affiliation is Terasaki Institute for Biomedical Innovation, and Zhang, Yu Shrike, who is currently affiliated to Harvard Medical School. Considering authors’ multiple affiliations, this cluster also has a connection with Massachusetts Institute of Technology (6). Within this cluster, vascularization and heart [ 75 , 150 , 151 , 152 , 153 ] are the types of tissue attracting the greatest interest. In the US, another group of collaborations can be identified as the “ Wake Forest cluster ”, in which a network of connections can be recognized within the university with the affiliations of Atala, Anthony, Yoo, James, and Lee, Sangjin. Within this cluster, the focus is mainly on process [ 154 ], cartilage [ 155 ] and articulations [ 156 ].

A further research facility worth mentioning is the UC San Diego (1), which is the leading university in the world on 3D bioprinting, to which Chen, Shaochen is affiliated. Publications by this university are mainly focused on the optimization of the bioprinting process, particularly inkjet [ 157 , 158 , 159 , 160 ], and the evaluation of printability [ 161 , 162 ]; regarding the type of tissues, the recurrent topic is the creation of tubular structures and vasculature [ 163 ].

Within Asia, China is ranked second in terms of the number of publications (1036 papers), with leading institutions such as Zhejiang University (5), Tsinghua University (8) and the Chinese Academy of Sciences (9). Notably, while the USA has mainly academic players, among the 14 top institutions in China, two are government-run and one is a medical institution (see Fig. S1 in the Supplementary Information for further details). Interestingly, most of the collaborations in Asia occur within universities.

Within Zhejiang University (5), a strong collaboration can be noticed between Fu, Jianzhong, He, Yong, and Gao, Qing, with the main focus of publications on vascularization [ 164 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 183 ]. Other universities worth mentioning are Tsinghua University and the Ministry of Education, where Sun, Wei and Li, Xinda are the most prolific authors, respectively. The focus of these collaborations is on topics such as the inkjet process [ 184 , 185 ], biomaterials [ 186 ], with targeted efforts on tumor model preparation [ 187 ], especially regarding glioma [ 188 ] and lung cancer [ 189 ], the use of stem cells [ 190 ], and the formation of vasculature [ 191 ].

South Korea is ranked third in terms of published products (scholarly output from SciVal). The main academic institutions here are Pohang University of Science and Technology (7), Konkuk University (15), and Sungkyunkwan University (14). The Pohang University of Science and Technology (7) can be considered as the center of a relative cluster to which the Korea Polytechnic University also belongs. To the first affiliation, Cho, Dongwoo and Jang, Jinah are active and mainly focused on the liver [ 192 , 193 ], cardiac repair [ 194 , 195 ], cartilage [ 196 ], vascularization [ 197 , 198 ], and cornea [ 111 , 199 ].

Within Asia, further notable institutions are located in Singapore (6), which is globally ranked the sixth in terms of number of publications, with the main participating institutions of Agency for Science, Technology and Research (40), to which Naing, May Win is affiliated, and the Singapore University of Technology and Design, to which Chua, Chee Kai is affiliated. Moreover, the most prolific institution in Russia is the Sechenov First Moscow State Medical University, to which Mironov, Vladimir A. is affiliated.

In Europe, Germany (4) and the UK (5) are the two leading countries in terms of publications, number of top authors and top institutions. However, the most productive institution on bioprinting in Europe is Utrecht University in the Netherlands (10). Four clusters of collaborations can be identified within Europe, one being the “ Utrecht University cluster ”, which primarily links Malda, Jos and Levato, Riccardo from Utrecht University (10), and Groll, Jürgen from University of Würzburg in Germany (4), with a main focus on the general aspects of 3D bioprinting [ 14 , 31 , 200 , 201 , 202 ]. Two additional clusters of collaborations can be identified in Germany within the Technische Universität Dresden with researchers Lode, Anja and Ahlfeld, Tilman, and Friedrich-Alexander University Erlangen-Nürnberg to which Boccaccini, Aldo R. and Detsch, Rainer are affiliated. In addition, a cluster of collaboration can be identified in Poland with a collaboration between the Warsaw University of Technology (Święszkowski, Wojciech) and the Polish Academy of Sciences (Costantini, Marco).

Finally, it is worth noting that some leading universities are also located in Oceania; the University of Wollongong in Australia, to which Wallace, Gordon G. and Yue, Zhilian are affiliated, and the University of Otago in New Zealand, to which Woodfield, T. B.F. and Lim, K. S. are affiliated.

Market and patent landscape

In recent years, interest in 3D bioprinting has been gathering momentum not only in academia, but also in the industry. Between 2014 and 2015, numerous 3D bioprinting companies have entered the market, and new start-ups, spin-offs and subsidiaries continue to emerge. Bioprinting could become a new standard for the biofabrication of tissues in the field of regenerative medicine; many bioprinter manufacturers have started to commercialize their proposals and services in research or other professional fields. Most of these companies sell materials (bioinks and cells), bioprinters and consulting services.

According to the latest market research by Mordor Intelligence [ 260 ], the global bioprinting industry was valued at USD 586.13 million in 2019 and is expected to reach USD 1,949.94 million by 2025, which is equivalent to a compound annual growth rate (CAGR) of 21.91% for the period of 2020–2025 [ 261 ]. These values were confirmed by another report, in which the value of 3D bioprinting market was projected to reach USD 1,647.4 million by 2024 at a CAGR of 20.4% for 2019–2024.

The growth of the 3D bioprinting industry, which is mainly driven by technological improvements on biomaterials and 3D bioprinters, has pushed business players to develop and enhance their existing manufacturing and distribution capabilities.

To review and analyze the companies and start-ups currently on the market, we used commercial magazines, newsletters and specialized blogs to retrieve 70 legally claimed bioprinting companies (latest update in July 2020). The analysis excluded 3D printing or biotechnology companies which announced their entrance into the market with no actual 3D bioprinting-related commercial products or services offered. The list of these companies, together with the available basic information regarding their business and their bioprinter models are reported in Table S3.

Based on the analysis, the business models of such companies could be classified as follows: (a) those selling commercial bioprinters and/or bioinks (63% of the whole market), (b) those providing bioprinting services (such as CAD modelling, specific tissue or cell culture constructs, scaffolds, grafts, or only consulting) with their own proprietary technology or commercially unavailable bioprinters (37% of the industry) and/or starting custom tissue partnership with clients (usually cosmetics or pharmaceutics industries) that have specific requests, as well as granting technology access partnerships (Table 5 ).

Around 80% of the market is composed of established companies, while 20% are start-ups with strong economic growth, mainly stemming from university spin-offs.

Table 6 reports the bioprinter market composition classified by technique, based only on the available information from manufacturer’s websites. Once again, it is possible to see that extrusion-based models are the most widespread ones, as their popularity is guaranteed by the lower cost and ease of use. Inkjet-based bioprinters consist the second most common technology. Nowadays, the inkjet technology is included in most of the extrusion-based bioprinters commercially available as an additional printing head. Despite the fact that stereolithography was the first technology in AM, stereolithography-based bioprinters are a new addition to the bioprinting industry, some of which only appeared at the time of writing of this paper or have yet to be announced. Laser-assisted bioprinters are among the most expensive bioprinters, which are usually part of more sophisticated systems. These are among devices capable of reaching the highest resolutions on the market. Only two-photon stereolithography has even better resolution, but it is not always categorized as a pure bioprinter, as this system is mainly useful for printing scaffolds for cells to attach to rather than printing cells and using bioink at the same time.

Based on the previous analysis, the industry is obviously growing at a fast rate not only in terms of quantity, but also in terms of diversification of the technologies developed and offered. Even though there are some polarizing countries, the companies that develop and commercialize bioprinting technologies are relatively dispersed across nearly all continents (Fig.  8 a).

a Worldwide distribution of 3D bioprinting companies. The interactive map can be viewed at https://ggle.io/3kuZ . Map data ©2021 Google. b 3D bioprinting market composition by continent

Mapping the companies making up this industry is essential to find potential technology hubs.

Considering single countries, the retrieved data suggests that USA remains the most significant player with 39% of all companies, exceeding all the other countries by one order of magnitude, whose percentages vary between 7 and 1%. In terms of continents, apart from the 40% share of North America, consisting basically of USA and Canada, Europe harbors 36% of all companies, with countries like Germany, UK and France representing nearly half of all European companies. The continents that follow are Asia (14%), Latin America (8%) and Oceania (1%) (Fig.  8 b).

As far as we are concerned, there is a multitude of university start-ups, especially in China and in Latin America, that prefer to use their own custom-designed bioprinting technologies.

Emerging technological trends

The fact that several 3D bioprinting companies across the globe currently manufacture commercially available 3D bioprinters is a clear indication that the field of AM and the bioengineering industry are evolving at a rapid pace. Along with the number of companies, the abundance of technological innovations associated with bioprinters and bioinks is also growing rapidly. In fact, the main leading bioprinting companies are trying to break into the market with increasingly peculiar technologies.

Most of the companies try to produce all-in-one extrusion-based bioprinting platforms with support for multi-materials (viscous pastes, gels and hydrogels, ABS/PLA and other filaments or polymer powders, liquids, ceramics and foods), multi-tools (laser system for ultra-high-precision cutting and engraving, CNC milling machine, photo-crosslinking UV LED, microscope, HD cameras for monitoring, autocalibration tools, 3D electronics printer, built-in incubator) and custom-made software (e.g. AI powered automatic organ and tissue segmentation software), often available in different versions according to customer requirements [ 153 , 220 , 244 , 245 , 262 , 263 , 264 , 265 ].

This panorama also includes firms that invest their resources in developing more refined solutions that aim to solve specific problems. A possible starting trend is to develop methods capable of using tissue spheroids and managing them, for example, through magnetic bioprinting such as the Organ.Aut, a magnetic bioprinter from the Russian company 3D Bioprinting Solutions [ 266 ], also delivered to the ISS on board the Soyuz MS-11 spacecraft. Furthermore, the Japanese company Cyfuse Biomedical [ 267 ] developed a platform that allows to create scaffold-free tissues using the Kenzan bioprinting method to manipulate spheroids. In this method, the production of 3D constructs is achieved by placing cellular spheroids in a temporary array of needles through a cell-dispensing robotic mechanism. On the other hand, there are companies, such as the Germany-based Cellbricks, that prefer to produce complex 3D-printed cell culture structures with a proprietary non-commercial stereolithography-based bioprinting platform [ 268 ].

Moreover, some enterprises try to propose bioprinters with more degrees of freedom to increase system flexibility and the range of printable features, like the American company Advanced Solutions [ 269 ], which patented a six-axis robotic extrusion-based bioprinter arm capable of loading up to ten independent biomaterials during a single print run. Other companies decided to focus on unusual features of their 3D bioprinters, such as the Rollovesselar™ module of the Chinese company Revotek for printing scaffold-free 3D cylindrical structures with a proprietary bio-ink to create vessels. This company claimed to have successfully replaced a short segment of the abdominal artery in 30 rhesus monkeys [ 270 ].

The bioprinting industry is not only driven by extrusion-based platforms. Other technologies to achieve the single cell deposition accuracy are under development, such as the Image Based Single Cell Isolation (IBSCI) developed by the French company Cellenion [ 271 ], which is a high-resolution-based technology consisting of automated image acquisition, processing and advanced algorithms to automatically isolate single cells from a cell suspension. Another French company, Poietis [ 272 ] focuses on laser-assisted bioprinting combined with extrusion-based and inkjet technologies supported via a proprietary PIA™ software to reconstitute the 3D representation of an entire tissue, layer after layer. Yet other companies, such as the Canada-based Aspect Biosystems, attempt to achieve improved accuracy in the development of microfluidic platforms equipped with an on-printhead crosslinking system that is able to print bioinks with a coaxial shell.

Some new business entities aim to increase their market share by widening the offer, producing affordable systems and collaborating with other entities. This is the case of CELLINK [ 273 ] that provides a wide range of solutions, both in terms of affordable bioprinters (extrusion-based and DLP-based) and various specific bioinks. In connection with Prellis Biologics, they have just released one of the first systems using two-photons stereolithography to the market, named the Holograph X™, with a special solution to increase the 3D printing speed by using a parallel set of photons, i.e., a multiphoton technology, in order to simultaneously cure millions of points in the bioink, and in turn achieve bioprinting speeds of up to 250,000 voxels per second.

Pioneering bioprinting companies like Organovo [ 274 ] instead prefer to provide services or products (like liver and kidney tissue models histologically and functionally similar to the native ones [ 241 , 275 ]) along with their proprietary technology.

It is also worth mentioning BIOLIFE4D, an upcoming biotech firm founded in 2015, with headquarters in Illinois (USA). The company is dedicated to produce a patient-specific, fully functioning heart through 3D bioprinting and with a patient’s own cells. In 2018, BIOLIFE4D successfully constructed a 3D-bioprinted vascularized and contractile cardiac patch made of iPSC. In 2019, they claimed that their next milestone would be to produce a human mini-heart, which would constitute the 3D-bioprinted mini version of a full-sized heart [ 276 ].

Evolution of patent trends

The industrial interest toward 3D bioprinting can be quantified in terms of number of deposited patents, which reflects the propensity of a company to protect its ideas and solutions. In this work, the Espacenet website [ 277 ] was used to identify the patents submitted in this field.

A new version of the global query matching the syntax and other specifications of this different database was made. A patent search was conducted in July 2020, and a total of 309 patent abstracts were found since the year of 2000. The abstracts of all patent records were carefully reviewed and grouped into the following categories: “bioprinting method”, “bioink”, “scaffold”, “bioprinter technology”, and “marginal involvement of 3D printing”.

At first glance, it is apparent that the number of patents published shows exponential growth, just as the number of scientific publications. Two-thirds of all patents found were published in the last 3 years (Fig.  9 a). This further confirms the growing number of companies and researchers entering this market.

a 3D bioprinting patent publication by year; b 3D bioprinting patent landscape composition per continent

Despite the fact that, as the previous analysis has highlighted, nearly all of the main bioprinting-related companies are based in the USA and Europe, more than two-third of the patents originate from Asia (Fig.  9 b). It is important to underline that most of these patents were published recently, which is a good sign that Asian companies are expected to soon break into the market. Among the Asian countries, China is leading the field of 3D bioprinting with 58% of all patents published so far (against 19% of USA), followed by South Korea (14%).

Another interesting aspect concerns the topic of patents (Table 7 ). Nearly half of them are about new bioprinting methods for specific functions (bone, vascular, trachea graft), for describing novel 3D bioprinting techniques, or to patent new bioprinter technologies. One-third is instead relative to biomaterials: novel bioink formulations rather than specific applications for specific bioink.

Intriguingly, patents regarding scaffold production or bioprinter technologies were more common in the early years, while those concerning bioinks or specific applications became more prevalent later. This is probably an indication that current technologies have been somewhat established, and new solutions in this area can more easily concern new material developments for organ- or tissue-specific customization.

Figure  10 demonstrates that over two-thirds of the considered patents came from universities or unaffiliated scientists. It is clear that, in recent years, the number of academic applicants (i.e., universities, hospitals and research centers) is growing much faster than those coming from the industrial sector, whose number stays fairly constant. A more in-depth analysis of the patent origin (Figs. 10 , 11 ) indicates that about 56% of those in the academic field and 61% of those in the industry come from China, which means that research output on bioprinting in this country is still booming. It is thus possible to justify the huge discrepancy between the high number of Chinese patents and the low number of Chinese companies. The next few years will probably see the birth of a growing number of Chinese companies focused on bioprinting.

Distribution of patent applicants by year since 2011: Universities/Hospitals/Research centers, blue; Companies/Corporations, orange; Scientists with no affiliation, grey

Country distribution of patent applicants by year: a Universities/Hospitals/Research centers patent; b Companies/Corporations patent. Top countries: China, blue; USA, orange; South Korea, grey

Conclusions

The field of 3D bioprinting, which represents a novel area within AM technologies, shows a great potential for future expansion. In the last few years, this discipline has received an impressive level of interest in the scientific literature, attracting many innovators and creating new exciting markets. All these signals outline that we are possibly observing the expansion of a long-term research direction. Instead of preparing an additional review paper, the aim of this study was to provide the reader with a comprehensive overview of the academic and industry landscape of 3D bioprinting, in order that unfamiliar researchers have a compass to venture into exciting emerging technologies, and experienced academics are provided with an updated snapshot of the current status of this fast-changing field.

In the first part, a scientometric review of the literature was provided, with an analysis of all of the impressive literature (almost 10,000 papers, with most of them published in the last few years) to highlight the globally most relevant applications and key actors in terms of laboratories and research networks.

In the second part, the associated companies and emerging technologies were described to highlight the upcoming innovations and the most relevant players that consider the technology for new market developments.

It was confirmed that both paper and patent publications exhibited exponential growth in this sector, with the USA leading the level of scientific output while China showing an impressive growth in the whole number of patents, which clearly highlights its possible future position as a leading country in the bioprinting industry.

Many open challenges highlighted in this study call for new technological solutions that can be possibly borrowed from traditional AM research. The enhancement of printing resolution and speed, as well as cost reduction are common challenges to be faced in the near future. Remarkably though, bioprinting has certain unique features, such as the requirement of avoiding the mistreatment of cells during printing, and taking multi-material printing as a key asset for future technological developments.

To achieve this aim, multidisciplinary research should combine engineering expertise in AM, biological knowledge on cell growth and differentiation, material science for biomaterial developments, and expertise in biomedicine and pharmaceutics to highlight and solve relevant research questions. With such a multidisciplinary approach, we might see a flourishing area that can have a relevant impact on successful future technologies aimed at the improvement of human wellbeing.

The Scholarly Output measures the number of research outputs [ 278 ].

IF data refer to 2019.

Data from SciVal, map created using Google MyMaps.

Abbreviations

Two-dimensional

Three-dimensional

Four-dimensional

Acrylonitrile butadiene styrene

Artificial intelligence

• Additive manufacturing

Computer-aided design

Compound annual growth rate

Computerized numerical control

Digital light processing

Drop-on-demand

Extracellular matrix

Gelatin methacryloyl

Human adipose stem cells

High-definition

Image-based single cell isolation

Impact factor

Induced pluripotent stem cell

International space station

Polycaprolactone

Polylactic acid

Poly (lactic-co-glycolic acid)

United Kingdom

United States

United States Dollar

Ultraviolet light emitting diode

Web of science

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This study was partially supported by the collaboration agreement between the Italian Space Agency and Politecnico di Milano, “Attività di Ricerca e Innovazione” Agreement n. 2018-5-HH.0.

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Santoni, S., Gugliandolo, S.G., Sponchioni, M. et al. 3D bioprinting: current status and trends—a guide to the literature and industrial practice. Bio-des. Manuf. 5 , 14–42 (2022). https://doi.org/10.1007/s42242-021-00165-0

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DOI : https://doi.org/10.1007/s42242-021-00165-0

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The UF-licensed technology has been granted two patents, and its development was supported through funding from federal agencies, including the National Science Foundation and the Department of Energy.

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Imagine someone needs a heart transplant and scientists take cells from that person to create an entire new heart for them. Research on the International Space Station is helping to bring that dream closer to reality.

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In Earth’s gravity, bioprinting requires a scaffold or other type of structure to support tissues, but in the near-weightlessness of the space station’s orbit, tissues grow in three dimensions without such support. Redwire Corporation developed the BioFabrication Facility (BFF) as a part of the larger goal of using microgravity to bioprint human organs. Popular Science magazine recently awarded the BFF a 2023 Best of What’s New Award in the Health Category. These awards, handed out since 1988, recognize “groundbreaking innovations changing our world,” according to Popular Science, and “radical ideas that are improving our everyday lives and our futures.”

A current investigation, BFF-Cardiac , uses the BFF to evaluate the printing and processing of cardiac tissue samples. Cardiovascular disease is the number one cause of death in the United States. Adult heart tissue is unable to regenerate, so damaged heart tissue is mostly replaced with scar tissue, which can block electrical signals and prevent proper cardiac contractions. This investigation could support the development of patches to replace damaged tissue – and eventually the creation of replacement hearts. The work represents a big step toward addressing the significant gap between the number of transplant organs needed and available donors.

The BFF-Meniscus investigation and the follow-up BFF-Meniscus-2 investigation resulted in the first successful bioprinting of a human knee meniscus in orbit using the space station’s BioFabrication Facility, announced in September 2023. Musculoskeletal injuries, including tears in the meniscus, are one of the most common injuries for the U.S. military and this milestone is a step toward developing improved treatments on the ground and for crew members who experience musculoskeletal injuries on future space missions. After initial printing and a period of growth in microgravity, the tissues returned to Earth for additional analysis and testing.

The Russian state space agency ROSCOSMOS launched equipment in 2018, 3D MBP, that included a magnetic printer called Organ.Aut. A series of experiments from 2018 through 2020 showed that this approach could create tissue constructs, helping to pave the way for additional research on producing artificial organs.

Bioprinting technology also could create artificial retinas to help restore sight for the 30 million people worldwide who suffer from degenerative retinal diseases. One way to manufacture artificial retinas is a technique that alternates layers of a light-activated protein and a binder on a film. On Earth, gravity affects the quality of these films, but researchers suspected that films created in microgravity would be more stable and have higher optical clarity. Protein-Based Artificial Retina Manufacturing is one of several investigations by LambdaVision Inc. in partnership with developer Space Tango Inc. to develop and validate space-based manufacturing methods for artificial retinas. The company has consistently manufactured multiple 200-layer artificial retina films in microgravity and now is working to commercialize its hardware and strategies for development of other therapies and drugs.

Bioprint FirstAid , a study from ESA (European Space Agency) and the German Space Agency (DLR), demonstrated the function of a prototype for a portable handheld bioprinter that creates a patch from a patient’s own skin cells. Space causes changes in the wound healing process, and such customized bandages could accelerate healing on future missions to the Moon and Mars. Using cultured cells from the patient reduces the risk of rejection by the immune system, and the device offers greater flexibility to address wound size and position. Because the device is small and portable, health care workers could take it almost anywhere on Earth. The investigation showed that the device works as intended in microgravity, and researchers are studying the space-printed patches and comparing them with samples printed on the ground before taking the next step.

Bioprinting in microgravity also could make it possible to produce food and medicine on demand on future space missions. Such capabilities would reduce the mass and cost of materials needed at launch and help maintain the health and safety of crew members throughout a mission.

The 3D Printing In Zero-G investigation, which started in 2014, demonstrated that the process of 3D printing with inorganic materials such as plastic worked normally in microgravity. 1 3D printing could reduce the need to pack costly spare parts on future long-term missions and help solve the problem of trying to predict every tool or object that might be needed on a mission. With the addition of bioprinting capabilities, crews eventually may be able to 3D print almost anything they need – from a replacement screwdriver to a replacement knee.

John Love, ISS Research Planning Integration Scientist

Expedition 70

Search this database of scientific experiments to learn more about those mentioned above.

1 Prater TJ, Bean QA, Werkheiser N, Grguel R, Beshears RD, Rolin TD, Huff T, Ryan RM, Ledbetter III FE, Ordonez EA. Analysis of specimens from phase I of the 3D Printing in Zero G Technology demonstration mission. Rapid Prototyping Journal. 2017 October 6; 23(6): 1212-1225. DOI: 10.1108/RPJ-09-2016-0142.

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One of the drawbacks to 3D printing, which has been hyped as a revolutionary technology for more than a decade, is that changing the printed medium can require lengthy adjustments to the machinery, in something of a trial and error process.

A collaboration between MIT's Center for Bits and Atoms (CBA), the US National Institute of Standards and Technology (NIST), and the National Center for Scientific Research in Greece (Demokritos) has attempted to address that problem.

The team used a 3D printer they had already developed to capture data and provide feedback as it operates. They added three instruments to the machine's extruder – the part that pushes the printing medium along, melts it, and squirts it on the item being printed. The additional instruments were designed to take measurements as the printer did its thing, which are used to calculate parameters.

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The technique essentially allows 3D printers to automatically optimize their fused filament fabrication (FFF) printing process when using a new material.

In a paper published in the journal Integrating Materials and Manufacturing Innovation, the researchers said: "Our method allows us to successfully find process parameters, using one set of input parameters, across all of the machine and material configurations that we tested, even in materials that we had never printed before.

"Rather than using direct parameters in FFF printing, which is time-consuming to tune and modify, it is possible to deploy machine-generated data that captures the fundamental phenomenology of FFF to automatically select parameters."

In an interview with MIT News , senior author Neil Gershenfeld, who leads CBA, said: "In this paper, we demonstrate a method that can take all these interesting materials that are bio-based and made from various sustainable sources and show that the printer can figure out by itself how to print those materials. The goal is to make 3D printing more sustainable." ®

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• NATURE PODCAST
• 15 November 2023

How to 3D print fully formed robots

• Benjamin Thompson &

Shamini Bundell

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00:46 Machine vision enables multi-material 3D printing

3D printers are capable of producing complex shapes, but making functioning objects from multiple materials in a single print-run has proved challenging. To overcome this, a team has combined inkjet printing with an error-correction system guided by machine vision, to allow them to print sophisticated multi-material objects. They used this method to make a bio-inspired robotic hand that combines soft and rigid plastics to make mechanical bones, ligaments and tendons, as well as a pump based on a mammalian heart.

Research article: Buchner et al.

News & Views: Multi-material 3D printing guided by machine vision

Video: The 3D printer that crafts complex robotic organs in a single run

07:49 Research Highlights

Citizen-scientists help identify an astronomical object that blurs the line between asteroid and comet, and how a Seinfeld episode helped scientists to distinguish the brain regions involved in understanding and appreciating humour.

Research Highlight: Citizen scientists find a rarity: an asteroid trying to be a comet

Research Highlight: One brain area helps you to enjoy a joke — but another helps you to get it

10:31 Assessing the effectiveness of lifestyle interventions for diabetes

Type 2 diabetes affects hundreds of millions of people around the world and represents a significant burden on health-care systems. But behaviour change programmes — also known as lifestyle interventions — could potentially play a large role in preventing people from developing type 2 diabetes. This week in Nature a new paper assesses how effective this kind of intervention might be. Looking at a huge amount of data from the NHS Diabetes Prevention Programme, the paper concludes that these interventions represent a viable diabetes prevention strategy.

Research article: Lemp et al.

News & Views: Diabetes prevention programme put to the test

17:35 Briefing Chat

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Welcome back to the Nature Podcast. This week, the 3D printer that creates complex bio-inspired robots...

Benjamin Thompson

...and assessing the effectiveness of lifestyle interventions at preventing diabetes. I'm Benjamin Thompson...

... and I'm Shamini Bundell.

First up in the show, Nick Petrić Howe finds out how to 3D print a robot hand.

Nick Petrić Howe

If you look at your hand, from a mechanical perspective, it's quite complicated. It has bits of soft material, muscles and ligaments, combined with hard material, the bony skeleton that sits beneath. Together this allows us to do everything from banging with a hammer to threading a tiny needle. So, to make something like this, artificially, is quite a challenge. But a new paper in Nature has managed it using 3D printing. By overcoming a key limitation of inkjet 3D printing, a team has produced an artificial hand, with synthetic bones, ligaments and tendons capable of grasping different objects.

Robert Katzschmann

So, we could really show that we can get a functional, human hand inspired structure that we can pull on the tendons and then the structure moves and shows its range of motion.

Now, you could make an artificial hand using conventional techniques, where you cast materials into moulds to form the desired shape, and then combine them with other materials. But these methods require tedious calibrations. And it's difficult to incorporate lots of materials with different properties, limiting what the final robot can do. Also, they lack the very fine details you would need to make something as complex as a synthetic human-hand. So, researchers have been interested in using 3D printing to do the job, as it can be incredibly precise and quick. But it has its own problems, such as the difficulty of combining different kinds of materials together, as Thomas Buchner, another of the paper's authors, explains.

Thomas Buchner

If we were trying to 3D print robots, we always had to use maybe different separate printers and then assemble the robot, or we had to do a little bit of 3D printing, and then cast around those 3D printed parts to get those different material properties that we were looking for to actually have a functional robot in the end.

So, the team has been trying to streamline this process. Rather than multiple printed elements being combined together, they wanted to create a system that could print a complex robot in one go. To achieve this, they were working with a type of 3D printing known as inkjet printing, which sprays liquid from a nozzle — similar to home printers. The big advantage of inkjet printing is that it's faster than other kinds of 3D printing whilst still being precise, but there's a downside too. When something is inkjet printed, droplets of material can accumulate, so the surface becomes quite uneven. Typically, this is dealt with by using some kind of scraper to get rid of the extra material and get your would-be robot ready for the next layer of printing. But this extra scraping step can be a problem. For one thing, it limits what kinds of materials you can use — some materials can accumulate and kind of gunk up the scraper. So the team made a printer that could... keep an eye on the process.

Here, we have a printer that kind of has eyes. So there is a laser scanner that scans the whole print bed then understands where there's too much and too little material and automatically corrects for that in the next layer that is deposited, so that it kind of fills up those unevenness in those lower spots.

Instead of scraping away the excess, it doesn't make the excess in the first place. If one bit is too thick, the robotic eye can see that and make the next layer that little bit thinner, removing the need for a scraper at all. Which means a lot more materials can be used, which in turn means they can make all sorts of complicated bio-inspired robots. Here's Robert again.

We also build a little walking robot that has little arm with a gripper on top that can pick up boxes and other items. And also, we build a heart, sort of like a pump that is like a human heart with ventricles that we pressurise, and then we can make a fluid flow go through these ventricles.

And all these robots were printed in one go, without needing to go back and add different materials for the different parts. They did, however, need to connect some electronics externally to do things like sense pressure in the hand, but nonetheless, the method detailed in this paper, impressed mechanical engineer and 3D printer aficionado, Yong Lin Kong.

Yong Lin Kong

I thought it was very impressive, and it's fascinating to bring a breakthrough into a technology that many have felt that is sort of in the mature state – it is already commercially available for decades. I think a lot of us might assume that, oh, this is the best this machine can do. But this paper show that just by incorporating machine-vision, one can bring material compatibilities that was otherwise not possible into this type of process and, and allows us to create not just multi-material construct, but in high-resolutions and higherthroughput approach.

Yong Lin would like to see more materials being used in this approach in the future. For example, they could attempt to incorporate electronic components during the printing process, further speeding up the path from idea to robot. The team are already looking at this as they progress this research, and Robert is optimistic that this technique, even beyond robots, could help make medical implants... and even jazz up your shoes.

You could think of medical implants, you could think of much more intricate shoes, for example, intelligent shoes, or you could also use this in terms of prototyping things for tissue engineering, and provide structures in this direction. So the technology itself will only grow by now people developing more and more materials that can be printed on this contact-free printer. And the more you bring different materials in it, suddenly the systems or just the designs that are being printed, they become relevant for all kinds of fields, that's at least what I imagined will happen.

That was Robert Katzschmann from ETH Zurich, in Switzerland. You also heard from Thomas Buchner, also from ETH Zurich, and Yong Lin Kong, from the University of Utah, in the US. For more on this paper, check out the show notes and we'll also put up a link to a video we've made about it showing that the robots in action.

Later in the show, testing the effectiveness of diabetes lifestyle interventions. Right now, though, it's time for the Research Highlights with Dan Fox.

<Music>

Astronomers have teamed up with citizen scientists to identify an object that blurs the line between asteroid and comet. Quasi-Hildas are asteroids located beyond our Solar System’s asteroid belt, but within Jupiter's orbit. Around 300 have been spotted, but only a few are known to be active, displaying comet-like behaviour like having a tail made of dust or gas. As part of the Active Asteroids project, researchers worked with volunteers from the public to identify an active Quasi-Hilda by examining archive images. A thorough image search and follow up observations then revealed that this asteroid was active when was closest to the Sun in March 2016 and April this year. The researchers conclude that these periods of activity probably occurred as the Sun's heat converted solid forms of compounds like water and CO 2 into gas. They say that this finding could improve our understanding of the distribution of these chemicals in the solar system. Read that research in full in the Astrophysical Journal Letters .

Sometimes, you don't need to understand the joke to find it funny, and sometimes no amount of explanation can make a gag work for you. Now neuroscientists know that understanding a joke and finding it funny are distinct processes in the human brain. Researchers studied the brain activity of 26 people as they consumed humorous material. The participants first listened to 40 jokes and 14 neutral sentences that were played in a random order. After hearing each clip, participants had to decide whether it was a joke and rate how funny it was. Next, they watched an episode of the sitcom Seinfeld and completed a questionnaire to assess whether they enjoyed the comedy. Brain activity during both experiments showed that understanding a joke involves activity in two brain areas, the dorsal striatum, which has a role in memory and cognition, and, the ventral striatum, which responds to reward, but actually enjoying the joke only involved the ventral striatum. Both areas are rich in the chemical messenger dopamine, and the team suggests that dopamine signalling could play an important role in humour processing, opening avenues for further investigation. What's the deal with that research? Find out in the Journal of Neuroscience .

Type 2 diabetes is a leading cause of morbidity and mortality. Estimates suggest that type 2 diabetes affects hundreds of millions of people around the world, significantly burdening health systems. But behaviour change programmes – also known as lifestyle interventions – could potentially play a large role in preventing people from developing type 2 diabetes. And this week in Nature , there is a paper assessing just how effective this kind of intervention might be. Joining me to talk about the work is George Caputa, a senior editor for the journal Nature who handles a lot of papers involving metabolism and physiology. George, thank you so much for being on the show.

George Caputa

No, it's really great to be here, Ben.

So, we've got this new paper then focusing on lifestyle behaviours and clinical trials have shown that behavioural interventions can make a difference in preventing folk from going from being pre-diabetic, where someone has elevated blood sugar, to full type 2 diabetes.

Yeah, this is not the first epidemiological study or even just a scientific study in general, showing that behavioural interventions can help individuals lose weight or even prevent the development of full type 2 diabetes. I think that something that we have gotten to, especially at this point in time, is that we do we have access to huge amounts of data. And so we can start to make potentially more definitive conclusions. And these are important, obviously, because a lot of these studies are the basis for public policy, public health, governments, they decide about what to fund depending on these types of studies.

And in this case, then the researchers behind the paper and looked at a data set gathered from health data from folk who referred to different interventions, but primarily England's NHS Diabetes Prevention Pprogramme. What do we know about that?

Yeah, so the NHS Diabetes Prevention Programme is a behavioural change programme with weight loss, diet, physical activity goals, and this consists of 13 group sessions over the course of nine months.

And overall, what was the big question that the researchers wanted to answer in this paper?

Yeah, so the question is, if an individual is diagnosed with pre-diabetes, if they are provided with a behavioural change programme, can we prevent them developing full diabetes? Can we kind of stop the progression.

And so in this work, then they take the anonymized patient records from about 2 million people to analyse the effectiveness of behavioural change programmes. And they've done a lot of statistics, in particular, something called a regression discontinuity design. So broadly, what have they done to show the effectiveness of behavioural programmes?

Obviously, in an epidemiological study, you have to be looking apples to apples, because you have to make sure that the groups that you're looking at are being intervened in the same way that they all qualify the same, because then you start to get behavioural and environmental factors that can confound your analysis. And regression discontinuity design, very generally, it is a way to within this population be able to make potentially statistically significant claims about the changes that they see, and that they are very much influenced specifically by the intervention of this programme. And not because the individuals that they're looking at are different groups or influenced in different ways. And one of the reasons that we considered this paper is because it is using state-of-the-art statistical analyses. So this is something that was very appreciated by the reviewers that what was being done here was using some very new and modern techniques.

And what's the headlines of what they saw then in terms of folk taking part in these programmes?

So, I think to say that they saw a very dramatic results is not the case. But what they did see is that there was statistically significant changes in the measures that they were using to qualify these individuals for pre-diabetes. They're looking at HbA1c which is a blood marker for how high your blood sugar has been basically over the past month, and so it's a good indication of whether your body over the past month has been able to properly maintain its blood glucose, which is a measure of how pre-diabetic you are. And what they saw was a decrease in the levels of HbA1c in the individuals who participate in this programme, they also saw a decrease in body weight, and they also saw a slight decrease in blood pressure and these associated metabolic measures. And I think what the researchers were able to definitively say is that this intervention had an effect. Obviously, in a situation like this, for some individuals, it probably was a big effect. And for some individuals, it probably was quite small. That's why when you get the average, it tends to be more modest.

And as someone who is an editor who looks at science papers then, what is this paper done maybe differently to things you've seen before?

What I tend to see as an editor is a lot of proposed pharmacological treatments. So like new drugs, new targets, new potential pills that people can take. And so to see a study that's really looking at another type of intervention, that can be just as powerful as putting someone on another drug, or even combined can be very powerful. That is something as an editor, that's really important, because this is a space that we don't talk about enough in terms of public health, in terms of these types of behavioural interventions. I think that as a society, we're kind of very focused, and we associate the most effectiveness with a drug.

I'm sure, though, that it's not the case that this is kind of everything sort of wrapped up with a neat little bow, there are those who doubt the effectiveness of behavioural intervention programmes. And I'm sure there are questions that remain to be asked when other people get their eyes on this paper.

Yeah, I mean, you know, I think there are people who will look at this paper and say, we're not seeing the same dramatic changes in blood glucose levels in this HbA1c that we would see if we were to immediately put these people on, we would consider frontline, first choice, diabetes drugs. The truth is, the individuals that they're looking at in this study aren't diabetic, they're pre diabetic. And usually, in many countries, the clinical intervention here is that your doctor says you have pre-diabetes, you need to change your behaviour, maybe gives them access to some information, but that's probably it. You know, this is like a full programme. I think the critics of the paper would say that this change is not so big. But when you're looking at the numbers of people who have diabetes, if you can reduce maybe 2% of those cases, that is a huge amount of savings for a public health programme, and for people's lives.

Nature's George Caputa there, to read the paper we chatted about by Lemp et al . and an associated News and Views article. Look out for links in the show notes.

Finally, on the show, it's time for the Briefing Chat, where we discuss a couple of articles that have been featured in the Nature Briefing . So Ben, why don't you go first this time?

Yeah, I've got an article this week that I read about in Wired , and it's based on a paper in Science , and it's looking at a potential explanation for why an estimated 10 billion snow crabs disappeared from the Bering Sea off the coast of Alaska. Now, this is a climate-change related story, but maybe not in the way you might expect.

Ooh, I haven't actually heard of snow crabs. Can you paint me up a visual description?

Yeah, so this species of snow crab we're talking about in this case are about maybe 10-15 centimetres across, look like a crab and they live on the sea floor. And they are an extensively monitored species and they're economically very important for fisheries and so forth–

– but populations, as I say, absolutely crashed following marine heat waves in 2018 and 2019, like 90% of the population, which had previously been quite healthy. And this corresponded with water temperatures rising by three degrees.

So, these marine heat waves were particularly impactful on these crabs.

Well, absolutely. And it turns out, it's not just that it was too hot for the crabs, which is what I think you might expect hearing that –

– that's what I would assume, yeah –

– well, actually, no. So, it turns out that these crabs actually might have starved. So the researchers pulled together a bunch of models and different strands of evidence. And what they've shown is that is likely what happened is, as the temperature went up, so did the crabs’ metabolism, okay, so they needed energy, and estimates suggest that the three degree rise then in this water temperature, potentially doubled the amount of calories that these crabs needed to consume. So there's obviously a lot of competition for food. And it turns out that in fact, before the heat waves, the population had been bigger than usual, right? So, a record high. So the amount of competition was astonishing for scarce resources, because of course, these crabs were just really, really hungry.

Ah okay, so double bad luck there of the heatwave coming at peak population time in an accidentally not very adaptive response there.

Well, not just double bad luck, Shamini, there's multiple layers of bad luck –

– ah right –

– so other problems of this article discusses suggests that warmer waters can alter the movement of nutrients up and down the water column, and that affects the food chain. So less food in general for the crabs to eat. And as we've discussed before, food chains are astonishingly complex webs of different things. And if you sort of lean on one part or nudge one bit in the wrong way, it can have some quite serious effects much further away, for example.

And this is a specific example of like, they figured out why this snow crab population crashed in this specific point in time. But obviously, marine heat-waves linked to climate change are gonna get more common, this work must have quite sort of broad implications.

Well, absolutely. And in terms of the snow crab, I think researchers estimate that it could take years of normal, I guess, sea temperature levels before the populations come back. But as you say, it seems like that might not necessarily be the case. But there is lots to understand in general about this, because there are other negative effects as well of warming seas on different organisms, right? Like, for example, making eggs is very energy intensive. Okay. So it could be that for some species, they just don't have enough energy to breed. And changing temperatures of the sea could mean that populations move to different places to be at the right temperature they like to be at, and this could introduce animals to new predators, or it can introduce predators to new areas, of course, as well, or invasive species and what have you. But it's not necessarily all bad for all animals, some fish seem to do better in warmer waters. So it's a super complicated one.

And you mentioned fishing as well. So I guess there's a more immediate impact on this local area of this snow crab population crash.

Yes, snow crabs are eaten by people and I think fishing seasons have been closed or curtailed recently, which is obviously having an economic impact on the fishers who are out there. So climate change is having multiple effects on multiple different areas once again.

Yeah, I feel like we're gonna be seeing a lot more of these complex and kind of unpredictable at times effects of the different elements of climate change –

– I don't think my story is gonna help, although it's to do with humans sort of escaping and living on Mars, which is not, not what we're going for.

There's the obvious segue, right. Okay, go ahead.

It's a fun story. Now, we have talked before about robot chemists, and AI robot chemists that basically, you know, you send them away, and they can do a whole bunch of experiments. They can work out what experiments to do, they have a little robotic arm to do the chemistry with. This is a slightly different twist on this story. I was reading about this in Nature , and it's a Nature Synthesis paper. And these researchers in China, they've developed this particular robot chemist with the aim of basically helping us settle Mars, or at least for humans travelling and working on Mars, or potentially other planets.

And what can this AI chemist do then? Why do we need it on Mars, I suppose?

Well, so it turns out that having things on Mars is very important. If we're working there, if humans are there, you know, they need particular resources and one in particular that is very useful is oxygen, not just for humans to breathe, but also rocket propulsion. If you want to get something off the surface of Mars via rocket, you actually need quite a lot of oxygen. And oxygen, like various other resources, you don't want to be having to take it there with you, you want to be able to get it from resources that you already have there. So, this particular robot chemist was set a task, which was basically looking at different ways where you might be able to get a set of chemical reactions that allow you to extract oxygen, using only stuff that's already on Mars, chemicals that it could literally get from the surface, if it was there.

And I'm imagining then on the surface, you've got what regolith is the name of Martian soil?

– Ooh, well done –

– I think we've talked in the past, there are lots of different sorts of rocks, right. But I think that's what researchers are learning now.

Yeah, so, if we were to go to Mars, one thing, yeah, we know we would have is whatever rock was at our feet. The other thing that we know Mars has is water. So ice under the surface, at the poles and that's pretty convenient. If we want to make oxygen, we could theoretically break down H 2 O into oxygen. Now, the way that you would do that is you would need some sort of a catalyst, you know, some sort of chemical processes going on, that takes water and produces oxygen out the other end. And it's this catalyst that the AI robot has to basically invent from scratch. Now, if we were here on Earth, we could be like, here, great, catalyst go. But again, we don't want to have to be loading up our rockets with loads of catalysts and sending it over. These researchers wanted a robot that could go to a bit of rock on Mars, and see what's in that material and invent a catalyst and create a catalyst from what it's actually got there.

Ah, okay, I'm presuming that it's not testing it on Mars. As far as I'm aware, there isn't a robot AI chemist on the surface of Mars right now.

No, they haven't sent it to Mars. This particular little robot may never go to Mars, but it is a proof of principle and in order to sort of demo it, they gave us some meteorites, either meteorites that are from Mars, or that are sort of equivalent to the Martian surface. That was the test basically, it was like okay, if you had this chunk of material, can you develop a new catalyst? And yeah, their robot AI developed a new chemical that acts as a catalyst that produces oxygen. It did a bunch of modelling simulations, it did a bunch of experiments, the kind of thing that a real, human chemist could do, but it would take a long time. Now, some people think this robot chemists going to Mars is actually very unlikely, because there's a NASA project that's working also on making oxygen on Mars, which uses a different method, which is basically producing oxygen from the Martian air, which is mostly carbon dioxide. And the lead investigator on that project says, you know, we can scale this up, we can produce loads of oxygen. So maybe this robot chemist will be set to other tasks, again, using local materials, whether it's Mars, whether it's the Moon, whether it's, you know, some other exciting planet in the far future.

Well, there's a story that combines a lot of things we've talked about a lot in the past, we got AI, we've got robots, we've got Mars, this is right in the centre of this Venn diagram and let's keep an eye on how it goes. But let's call it there for today's Briefing Chat, and listeners for more stories like these, and where you can sign up for the Nature Briefing to have more like them delivered directly to your inbox, check out the show notes for some links.

And that's all for this week. As always, you can keep up with us on X we're @naturepodcast, or you can send us an email to [email protected]. I'm Shamini Bundell...

...and I'm Benjamin Thompson. See you next time.

doi: https://doi.org/10.1038/d41586-023-03570-w

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Journal of Materials Chemistry B

Application of 3d/4d/5d and 6d bioprinting in cancer research: how does the future look like.

The application of Three- and four-dimensional (3D/4D) printing in cancer research represents a significant advancement in understanding and addressing the complexities of cancer biology. 3D/4D materials provide more physiologically relevant environments compared to traditional two-dimensional models, allowing for a more accurate representation of the tumor microenvironment. This enhanced fidelity enables researchers to study tumor progression, drug responses, and interactions with the surrounding tissues in a manner closer to in vivo conditions. The dynamic nature of 4D materials introduces the element of time, allowing for the observation of temporal changes in cancer behavior and response to therapeutic interventions. The use of 3D/4D printing in cancer research holds great promise for advancing our understanding of the disease and improving the translation of preclinical findings to clinical applications. Accordingly, this review aims to have a brief description about 3D/4D printing and their beneficial and limitations in the field of cancer. Moreover, 5D/6D printing as well as artificial intelligence (AI) were introduced in recent years that could overcome the limitations of 3D/4D printing and open promising avenue for the diagnosis and treatment of cancer.

• This article is part of the themed collection: Journal of Materials Chemistry B Recent Review Articles

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3D Printed Watch Straps Steal the Show at Watches and Wonders

April 15, 2024

Switzerland’s prestigious ECAL University of Art and Design, in partnership with Alloyed Ltd based in Oxford, UK, have recently unveiled a captivating array of titanium watch straps.

Designed by talented students enrolled in the Master of Advanced Studies in Design for Luxury and Craftsmanship program, these watch straps have pushed the boundaries of conventional design methodologies. Leveraging advanced 3D modeling techniques and titanium 3D printing, the students transcended the limitations of traditional craftsmanship to create truly unique pieces that captivated the imagination.

Out of the diverse range of concepts proposed by the students, a select few were chosen for production, utilizing high-grade titanium (TI6AI4V) powder. The designs were prominently featured at the prestigious Watches and Wonders exhibition in Geneva, Switzerland this April drawing admiration and acclaim from industry professionals and enthusiasts alike.

This collaborative endeavor not only exemplifies the seamless integration of cutting-edge engineering and timeless craftsmanship but also highlights the potential for creative exploration within the realm of luxury accessory design. By bringing together the technical prowess of materials scientists and the artisanal expertise of jewelers, this initiative has set a new standard for innovation in contemporary horology.

Source: designboom.com

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Tremendous turnout demonstrates USF’s growth in undergraduate research

• April 16, 2024

Research and Innovation

By: Cassidy Delamarter , University Communications and Marketing

Nearly 600 undergraduate students across the Tampa, St. Petersburg and Sarasota-Manatee campuses showcased their ingenuity at the university’s OneUSF Undergraduate Research Conference . The 16% increase in student participation from the last year reflected the university’s commitment to fostering collaborative discovery and the pivotal role student researchers play in shaping a brighter future.

“The Undergraduate Research Conference is an exciting opportunity to celebrate the hard work and dedication of student researchers and their faculty mentors,” Provost Prasant Mohapatra said. “The conference provides a platform for undergraduate students to showcase their research and engage meaningful discussions with their peers and mentors. Research experiences support student success through hands on learning opportunities and contribute to our mission as an AAU institution."

students talking by posters

Posters filled the Marshall Student Center Ballroom at the Tampa conference.

welcome sign at the conference

The Office of High Impact Practices and Undergraduate Research greeted students as they arrived.

students collaborating on cell phone to review presentation

Throughout the Marshall Student Center, students could be found helping their peers prepare for their research presentations. 

the president and provost

(left to right): Allison Crume, dean of undergraduate studies and AVP for student success, Provost Prasant Mohapatra, Joy Harris, Director of HIPUR, President Rhea Law

anna by her poster

The OneUSF conference marked the second time Anna Alieva presented her research on cold war propaganda. Now, looking ahead to the future, she is exploring ways to expand the research.

Hosted by the Office of High Impact Practices and Undergraduate Research , the conference served as a platform for students on each campus to present their research and engage in discussion with peers and mentors. The event highlighted USF’s unique effort to offer an abundance of research opportunity to students, representing almost every college.

Elliot Santaella Aguilar, who’s double majoring in psychology and biomedical sciences , fell in love with research his freshman year during an internship at the Mote Marine Laboratory and Aquarium in Sarasota. Now in his third year at USF, Santaella Aguilar has dedicated his research to opioid misuse in adolescents and is about to submit a research paper to a premiere scientific journal. His research is focused on examining the relationship between different types of supervised activities, such as athletics, hobby clubs and volunteer organizations, and their protective effect against opioid use among juvenile delinquents –  an area that has yet to be tested in the field.

Santaella Aguilar presenting his research at the Tampa campus conference | Photo by: Cassidy Delamarter

In addition to presenting at the Tampa campus’s conference, he plans to present this summer at the College on Problems of Drug Dependence , one of the most prestigious conferences in the field, according to his faculty mentor Micah Johnson , assistant professor in the College of Behavioral and Community Sciences .

While Johnson says Santaella Aguilar is a superstar, Santaella Aguilar credits his passion and early success to the opportunities with Johnson that he found through USF’s Office of High Impact Practices and Undergraduate Research.

“I am happy that through USF HIPUR, I was able to find this opportunity and learn more about the research field that I am now very passionate about,” Santaella Aguilar said. “The research opportunities available to students at USF are extensive and diverse, making it an exciting environment for prospective students interested in research.”

“I used to think of research as something that typically happens in STEM-related fields, with physical data, gathering and examination. As a non-STEM major, I feel like this is an opportunity that makes research accessible to anyone regardless of their career interests or major and encourages students to make their hard work known.” – Anna Alieva, international studies major 

At the USF St. Petersburg conference, Victoria Drew, a first-year student majoring in biomedical sciences , shared that she has also grown to appreciate the process of research from this experience. As an aspiring anesthesiologist, Drew dedicated her project to examining the impact of various anesthetics and their roles in regulating cancer and preventing neurotoxicity in children and animals.

“Hopefully, in the future, we will be able to look at a patient’s genetic standing, their condition and demographics and create more patient-centered care using anesthetics that work best for them,” she said. Drew’s research won one of USF St. Petersburg’s awards for best project and poster.

The USF Sarasota-Manatee campus expanded the conference by welcoming graduate students. For Leah Burger, doctoral student and research assistant in the College of Education , the opportunity gave her a chance to share her work on expanding literacy and access to STEM knowledge among kids through engagement with virtual reality games – an effort that could lay the foundation for the next generation in STEM.

A recipient of the Trailblazers Research Scholarship , Burger said presenting her findings has provided hands-on experience with the research process.

“I am amazed and honored to have the freedom to see the vast depth of knowledge kids have about their interests and the way their interests can be incorporated into writing games,” she shared. “Research is knowledge creation, and that is not easy. But with this experience, I feel more confident going into my dissertation process."

For students interested in research, information on how to get started is available here , as well as free resources, such as workshops to learn citation management. Several research experiences for undergraduates in chemistry, engineering, geosciences and physics are available to provide students with practical hands-on experience, including one that allows students pursuing weather-related careers to learn about beach ecosystems and hurricane hunting .

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Cassidy Delamarter , MyUSF

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April 10, 2024

NPR: A professor worried no one would read an algae study. So she had it put to music

April 4, 2024

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