Reviewed by Lexie CornerApr 28 2025
Engineers at the University of Pittsburgh are working to develop 3D-printed organic tissue models that mimic the behavior of living organs.
Online cover of Science Advances, April issue. A collagen-based 3D-bioprinted tissue scaffold perfused within a 3D printed bioreactor to achieve vascular-like nutrient delivery in engineered tissues. Previous designs posed bioengineering challenges as they traditionally used plastic and elastomers that are stiff and difficult to engineer. Shiwarski et al. developed a 3D bioprinting method to create soft, living tissues that develop internal vascular networks. They printed pancreatic tissues that can sense glucose and release insulin, potentially transforming treatments for type 1 diabetes and human organ manufacturing. Image Credit: Daniel Shiwarski
The core concept behind their discovery is simple yet powerful: cells have an inherent ability to organize and function when provided with the right conditions. The key is to create scaffolds that mimic the natural structures of the body, offering cells the necessary signals to proliferate, communicate, and form tissues.
To develop a comprehensive tissue engineering platform that replicates an organic cellular environment, Daniel Shiwarski, an Assistant Professor of Bioengineering at the Swanson School of Engineering with a joint appointment at the School of Medicine's Vascular Medicine Institute, created collagen-based, high-resolution, internally perfusable scaffolds known as “CHIPS.”
These scaffolds can be integrated with a vascular and perfusion organ-on-a-chip reactor. Adam Feinberg, a Biomedical Engineering Professor at Carnegie Mellon University, collaborated on the study.
Shiwarski's research applies tissue engineering and additive manufacturing to model conditions like diabetes and hypertension and produce functional replacement tissues. Microfluidic modeling, a widely used in vitro method for studying these diseases, simulates blood vessel or cellular behavior using small channels in a chip.
Typically made of silicone, these models have been useful but limited in scope due to their synthetic nature. However, with this development, scientists are now able to utilize them fully.
Microfluidic devices help us study cell behavior, but they are inherently limited. 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.
Daniel Shiwarski, Assistant Professor, Swanson School of Engineering, University of Pittsburgh
Since these printed scaffolds were made entirely of collagen, rather than the synthetic materials typically used in microfluidic devices, cells were able to interact with the model by proliferating and self-organizing into functional tissues within it. By combining the collagen with vascular and pancreatic cells, the team was able to replicate natural physiological processes, such as insulin secretion in response to glucose.
The team developed a unique perfusion bioreactor system called VAPOR to support the development and growth of cellularized collagen scaffolds.
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.
Andrew Hudson, Co-Founder and Study Co-Author, FluidForm Bio
Additionally, by printing helical vascular networks modeled after DNA structures, the team demonstrated the creation of non-planar 3D networks in soft, organic materials. This contrasts with traditional microfluidic devices, which are limited to flat or sequentially layered patterns.
We are 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. If we place cells in an environment that mimics their natural surroundings, they know exactly what to do. We are recreating the right environment for them and letting the cells do their job, allowing them to adapt, evolve, and build functional tissue over time.
Daniel Shiwarski, Assistant Professor, Swanson School of Engineering, University of Pittsburgh
Shiwarski's team is also committed to open science; all project models and designs are publicly available on the lab’s website. Looking ahead, Shiwarski’s group aims to model the effects of vascular disorders, such as fibrosis and hypertension, on tissue growth and function using this platform. The long-term goal is to replace animal models with more accurate human-based systems.
Shiwarski said, “This new approach lets us bridge the gap between simplified 2D models and animal studies. Now that we have 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.”
Journal Reference:
Shiwarski, D. J., et al. (2025). 3D bioprinting of collagen-based high-resolution internally perfusable scaffolds for engineering fully biologic tissue systems. Science Advances. doi.org/10.1126/sciadv.adu5905.