Collagen is well-known as an important component of our skin, but its impact is much greater, as it is the most abundant protein in the body, providing structure and support to nearly all tissues and organs. Using their novel Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting technique, which allows for the printing of soft living cells and tissues, Carnegie Mellon's Feinberg lab has built a first-of-its-kind microphysiologic system, or tissue model, entirely out of collagen. This advancement expands the capabilities of how researchers can study disease and build tissues for therapy, such as Type 1 diabetes.
Traditionally, tiny models of human tissue that mimic human physiology, known as microfluidics, organ-on-chip, or microphysiologic systems, have been made using synthetic materials such as silicone rubber or plastics, because that was the only way researchers could build these devices. Because these materials aren't native to the body, they cannot fully recreate the normal biology, limiting their use and application.
"Now, we can build microfluidic systems in the Petri dish entirely out of collagen, cells, and other proteins, with unprecedented structural resolution and fidelity," explained Adam Feinberg, a professor of biomedical engineering and materials science & engineering at Carnegie Mellon University. "Most importantly, these models are fully biologic, which means cells function better."
In new research published in Science Advances, the group demonstrates the use of this FRESH bioprinting advancement, building more complex vascularized tissues out of fully biologic materials, to create a pancreatic-like tissue that could potentially be used in the future to treat Type 1 diabetes. This advancement in FRESH bioprinting builds on the team's earlier work published in Science , by improving the resolution and quality to create fluidic channels that are like blood vessels down to about 100-micron diameter.
"There were several key technical developments to the FRESH printing technology that enabled this work," described Daniel Shiwarski, assistant professor of bioengineering at the University of Pittsburgh and prior postdoctoral fellow in the Feinberg lab. "By implementing a single-step bioprinting fabrication process, we manufactured collagen-based perfusable CHIPS in a wide range of designs that exceed the resolution and printed fidelity of any other known bioprinting approach to date. Further, when combined with multi-material 3D bioprinting of ECM proteins, growth factors, and cell-laden bioinks and integration into a custom bioreactor platform, we were able to create a centimeter-scale pancreatic-like tissue construct capable of producing glucose-stimulated insulin release exceeding current organoid based approaches."
This technology is currently being commercialized by FluidForm Bio , a Carnegie Mellon University spinout company where co-author Dr. Andrew Hudson, Director of Tissue Therapeutics, and his team have already demonstrated in an animal model that they can cure Type 1 diabetes in-vivo. FluidForm Bio plans to start clinical trials in human patients in the next few years.
"It is paramount for everyone to understand the importance of team-based science in developing these technologies and the value that varied expertise, ranging from biology to materials science, brings both to the project, and our impact on society," elaborated Feinberg.
"Going forward, the question is not, can we build it? It's more of, what do we build? The work we're doing today is taking this advanced fabrication capability and combining it with computational modeling and machine learning, so that we can hopefully better understand what we need to print. Ultimately, we want the tissue to better mimic the disease of interest or ultimately, have the right function, so when we implant it in the body as a therapy, it'll do exactly what we want."
Feinberg and his collaborators are committed to releasing open-source designs and other technologies that allow for broad adoption within the research community. "We're hoping that very quickly, other labs in the world will adopt and expand this capability to other disease and tissue areas," Feinberg added. "We see this as a base platform for building more complex and vascularized tissue systems."
Learn more by viewing Prof. Feinberg's research explanation on CMU Engineering's YouTube page .
