Using a 3D printer to create organic tissue models that function like living organs may sound like science fiction — but engineers at the University of Pittsburgh are making it reality.
Central to their breakthrough is a simple yet powerful idea: when provided with the right environment, cells instinctively know how to organize and function. The key lies in designing scaffolds that mimic the body's natural structures, giving cells the cues they need to grow, interact, and form tissues.
Daniel Shiwarski, assistant professor of bioengineering at the Swanson School of Engineering with a joint appointment at the School of Medicine's Vascular Medicine Institute, developed collagen-based, high-resolution, internally perfusable scaffolds—called "CHIPS"—that can integrate with a vascular and perfusion organ-on-a-chip reactor to form a complete tissue engineering platform, mimicking an organic cellular environment. In collaboration with Professor of Biomedical Engineering Adam Feinberg at Carnegie Mellon University, the findings, "3D Bioprinting of collagen-based high resolution internally perfusable scaffolds for engineering fully biologic tissue systems" (DOI: 10.1126/sciadv.adu5905 ), were published as the cover story in the April edition of Science Advances.
Shiwarski's research leverages additive manufacturing and tissue engineering to create functional replacement tissues and model diseases like diabetes and hypertension. A popular method of studying these diseases in-vitro, microfluidic modeling, uses tiny channels in a small chip to simulate blood vessel or cellular behavior. These models are typically made from silicone, and while useful, their synthetic nature has restricted scientists from utilizing these models to their full potential—until now.
"Microfluidic devices help us study cell behavior, but they're inherently limited," Shiwarski said. "Our collagen-based scaffolds change that. Since cells naturally thrive in collagen, we can print not only the structural network but also embed cells directly into that environment, allowing them to grow, interact, and form tissues."
Unlike traditionally synthetic microfluidic devices, these printed scaffolds were built entirely from collagen, allowing cells to interact with the model itself by growing and self-organizing into functional tissues within it. The team demonstrated this by combining the collagen with vascular and pancreatic cells, prompting insulin secretion in response to glucose, which mirrored natural physiological function.
To support the growth and development of cellularized collagen scaffolds, the team engineered a custom perfusion bioreactor system, VAPOR.
"This platform is unique as it securely connects the soft collagen-based tissue scaffolds to the VAPOR fluidic system by snapping the CHIPS into place around like Lego blocks." said Andrew Hudson, co-founder of FluidForm Bio and publication co-author.
Additionally, while traditional microfluidic devices are limited in design to flat or sequentially layered patterns, the team also demonstrated the ability to create non-planar 3D networks in soft, organic material by printing helical vascular networks modeled after DNA structure.
"We're taking everything that works well in microfluidics—like controlling fluid flow and setting up vascular networks—and combining it with natural biomaterials and the innate programming of cells," Shiwarski said. "If we place cells in an environment that mimics their natural surroundings, they know exactly what to do. We're recreating the right environment for them and letting the cells do their job, allowing them to adapt, evolve, and build functional tissue over time."
Shiwarski is also committed to open science with his team's work; all models and designs from the project are freely available on his lab's website . Looking ahead, Shiwarski's team aims to use this platform to study vascular diseases such as hypertension and fibrosis, modeling how these conditions affect tissue development and function. The ultimate goal is to eventually replace animal models with more accurate, human-based systems.
"This new approach lets us bridge the gap between simplified 2D models and animal studies," Shiwarski said. "Now that we've established this functional tissue environment, one of our next big goals is to study how vascular networks form alongside the development of underlying tissues—and how these processes are affected by human-specific disease variants. We can use this as a way to study complicated diseases and understand the basic biology behind them, and then we can get further insight into clinical therapies."
