A team of researchers from Carnegie Mellon University has published a paper in Science that details a new technique allowing anyone to 3D bioprint tissue scaffolds out of collagen, the major structural protein in the human body. This first-of-its-kind method brings the field of tissue engineering one step closer to being able to 3D print a full-sized, adult human heart.
The technique, known as Freeform Reversible Embedding of Suspended Hydrogels (FRESH), has allowed the researchers to overcome many challenges associated with existing 3D bioprinting methods, and to achieve unprecedented resolution and fidelity using soft and living materials.
Each of the organs in the human body, such as the heart, is built from specialized cells that are held together by a biological scaffold called the extracellular matrix (ECM). This network of ECM proteins provides the structure and biochemical signals that cells need to carry out their normal function. However, until now it has not been possible to rebuild this complex ECM architecture using traditional biofabrication methods.
"What we've shown is that we can print pieces of the heart out of cells and collagen into parts that truly function, like a heart valve or a small beating ventricle," says Adam Feinberg, a professor of biomedical engineering (BME) and materials science & engineering at Carnegie Mellon, whose lab performed this work. "By using MRI data of a human heart, we were able to accurately reproduce patient-specific anatomical structure and 3D bioprint collagen and human heart cells."
Over 4000 patients in the United States are waiting for a heart transplant, while millions of others worldwide need hearts but are ineligible for the waitlist. The need for replacement organs is immense, and new approaches are needed to engineer artificial organs that are capable of repairing, supplementing, or replacing long-term organ function. Feinberg, who is a member of Carnegie Mellon's Bioengineered Organs Initiative, is working to solve these challenges with a new generation of bioengineered organs that more closely replicate natural organ structures.
"Collagen is an extremely desirable biomaterial to 3D print with because it makes up literally every single tissue in your body," explains Andrew Hudson, a BME Ph.D. student in Feinberg's lab and co-first author on the paper. "What makes it so hard to 3D print, however, is that it starts out as a fluid--so if you try to print this in air it just forms a puddle on your build platform. So we've developed a technique that prevents it from deforming."
The FRESH 3D bioprinting method developed in Feinberg's lab allows collagen to be deposited layer-by-layer within a support bath of gel, giving the collagen a chance to solidify in place before it is removed from the support bath. With FRESH, the support gel can be easily melted away by heating the gel from room temperature to body temperature after the print is complete. This way, the researchers can remove the support gel without damaging the printed structure made of collagen or cells.
This method is truly exciting for the field of 3D bioprinting because it allows collagen scaffolds to be printed at the large scale of human organs. And it is not limited to collagen, as a wide range of other soft gels including fibrin, alginate, and hyaluronic acid can be 3D bioprinted using the FRESH technique, providing a robust and adaptable tissue engineering platform. Importantly, the researchers also developed open-source designs so that nearly anyone, from medical labs to high school science classes, can build and have access to low-cost, high-performance 3D bioprinters.
Looking forward, FRESH has applications in many aspects of regenerative medicine, from wound repair to organ bioengineering, but it is just one piece of a growing biofabrication field. "Really what we're talking about is the convergence of technologies," says Feinberg. "Not just what my lab does in bioprinting, but also from other labs and small companies in the areas of stem cell science, machine learning, and computer simulation, as well as new 3D bioprinting hardware and software."
"It is important to understand that there are many years of research yet to be done," adds Feinberg, "but there should still be excitement that we're making real progress towards engineering functional human tissues and organs, and this paper is one step along that path."
Other collaborators on the paper include co-first author Andrew Lee, a BME Ph.D. student in Feinberg's lab; BME Postdoctoral Researcher Dan Shiwarski; BME Ph.D. students Joshua Tashman, TJ Hinton, Sai Yerneni, and Jacqueline Bliley; and BME Research Professor Phil Campbell.
About the College of Engineering:
The College of Engineering at Carnegie Mellon University is a top-ranked engineering college that is known for our intentional focus on cross-disciplinary collaboration in research. The College is well-known for working on problems of both scientific and practical importance. Our "maker" culture is ingrained in all that we do, leading to novel approaches and transformative results. Our acclaimed faculty have a focus on innovation management and engineering to yield transformative results that will drive the intellectual and economic vitality of our community, nation and world.
About Carnegie Mellon University:
Carnegie Mellon is a private, internationally ranked university with programs in areas ranging from science, technology and business to public policy, the humanities and the arts. More than 13,000 students in the university's seven schools and colleges benefit from a small faculty-to-student ratio and an education characterized by its focus on creating and implementing solutions for real world problems, interdisciplinary collaboration and innovation.
About FluidForm: Carnegie Mellon University has licensed the FRESH technology on an exclusive basis to FluidForm, Inc., located in Pittsburgh and Boston. FluidForm is focused on advancing applications of the technology in biofabrication, regenerative medicine and other industries. LifeSupport™ bioprinting support gel is used by researchers worldwide to significantly improve their ability to print cells and soft-deformable biomaterials into complex structures with high fidelity.
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