Using their novel Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting technique, which allows for the printing of soft living cells and tissues, researchers built a first-of-its-kind microphysiologic system, or tissue model, entirely out of collagen.
(Nanowerk News) 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, the 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 and engineering. “Most importantly, these models are fully biologic, which means cells function better. This advance in FRESH bioprinting builds off of the research we published in Science in 2019
(“3D bioprinting of collagen to rebuild components of the human heart”), by improving the resolution and quality to create little fluidic channels that are like blood vessels down to about 100-micron diameter. Just as a frame of reference, the human hair is roughly 100 microns in diameter, so we’re able to engineer very tiny features that are almost capillary scale. By recreating this complex architecture, it allows us to build tissues that mimic different organ and disease types.”
“There were several key technical developments to the FRESH printing technology that enabled this work,” explained 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 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. “What we’re hoping is that very quickly, almost immediately, other labs in the world will be able to adopt and use this capability to expand it to other disease and tissue areas,” Feinberg said. “We see this as a base platform for building more complex and vascularized tissue systems, which has broad applications.”
