Researchers at Carnegie Mellon University report that they have built a first-of-its-kind microphysiologic system, or tissue model, entirely out of collagen using their Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting technique. They say 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, noted the scientists, adding that 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, PhD, 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.”
Pancreatic-like tissue
In a study, “3D bioprinting of collagen-based high-resolution internally perfusable scaffolds for engineering fully biologic tissue systems,” published in Science Advances, the group demonstrates the use of their technique 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, PhD, 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 spinout company where co-author Andrew Hudson, PhD, 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.
“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,” said Feinberg. “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 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.”