3D Bioprinting Collagen Scaffolds: Engineering Functional Vascularized Tissues

Tissue engineering has long faced a fundamental challenge: creating environments where cells can organize and function as they would in natural organs.

While traditional microfluidic devices and organ-on-chip models have improved our understanding of cellular behaviour, they’ve been limited by their synthetic materials—typically silicone or plastics—which cannot yet mimic a natural cellular environment.

A research team led by Daniel Shiwarski, assistant professor of bioengineering at the University of Pittsburgh’s Swanson School of Engineering, has developed a solution that could transform tissue engineering.

Their work, published in the April 2025 edition of Science Advances, demonstrates a new approach to creating functioning tissue models using entirely biological materials.

The team’s innovation centres on “CHIPS”—collagen-based, high-resolution, internally perfusable structures. Unlike synthetic models, these scaffolds harness cells’ natural ability to organize when placed in the right environment.

“Microfluidic devices help us study cell behavior, but they’re inherently limited,” explains Shiwarski. “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.”

Collagen, the most abundant protein in the human body, provides structure and support to nearly all tissues and organs. Using it as the primary building material, the researchers created scaffolds that closely mimic natural cellular environments.

The breakthrough builds upon the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) bioprinting technique developed at Carnegie Mellon University. Through collaboration with Adam Feinberg, a professor of biomedical engineering at Carnegie Mellon, the team enhanced FRESH to achieve unprecedented resolution and quality.

The improved process can now create fluidic channels resembling blood vessels down to approximately 100 microns in diameter. This advancement enables the creation of complex vascular networks within soft tissue constructs—a critical factor in developing viable tissue models.

“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,” notes Shiwarski.

Due to manufacturing constraints, traditional microfluidic devices are restricted to flat or sequentially layered patterns. The CHIPS platform overcomes these limitations by enabling the creation of non-planar 3D networks in soft, organic materials.

The team demonstrated this capability by printing helical vascular networks modelled after DNA structures. These complex geometries would be impossible to achieve with conventional microfluidic fabrication methods.

“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 explains. “If we place cells in an environment that mimics their natural surroundings, they know exactly what to do.”

The team engineered a custom perfusion bioreactor system called VAPOR (vascular and perfusion organ-on-a-chip reactor) to support the growth and development of the 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,” says Andrew Hudson, co-founder of FluidForm Bio and co-author of the study.

Integrating CHIPS with VAPOR creates a complete tissue engineering platform that facilitates nutrient delivery and waste removal—essential functions typically performed by blood vessels in natural tissues.

The team demonstrated the platform’s capabilities by combining collagen with vascular and pancreatic cells to create a functional tissue model. This engineered tissue exhibited physiological functions, including insulin secretion in response to glucose—mimicking a key pancreas function.

Through multi-material 3D Bioprinting of extracellular matrix proteins, growth factors, and cell-laden bio-inks, the researchers created a centimetre-scale pancreatic-like tissue construct capable of glucose-stimulated insulin release that exceeds current organoid-based approaches.

This advance has significant implications for diabetes research and treatment. FluidForm Bio, a Carnegie Mellon University spinout company, has already demonstrated the ability to cure type 1 diabetes in animal models using this technology and plans to begin clinical trials in human patients within the next few years.

Looking ahead, Shiwarski’s team aims to use the CHIPS platform to study vascular diseases such as hypertension and fibrosis, modelling how these conditions affect tissue development and function. The ultimate goal is to replace animal models with more accurate, human-based systems for disease research.

“This new approach lets us bridge the gap between simplified 2D models and animal studies,” Shiwarski says. “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.”

Committed to open science principles, the team has made all models and designs from the project freely available on Shiwarski’s lab website. This open approach aims to accelerate the technology’s adoption by research groups worldwide, potentially expanding its applications to other disease areas and tissue types.

The CHIPS platform represents a significant step toward creating fully functional engineered tissues. If the current trajectory continues, this technology could transform our approach to studying disease and developing treatments.

By providing a more accurate representation of human tissue function, the platform may reduce reliance on animal testing while improving the translation of laboratory findings to clinical applications. For conditions like type 1 diabetes, where existing treatments manage symptoms but don’t address the underlying cause, engineered replacement tissues offer the potential for more effective therapies.

As researchers continue to refine these techniques, the field moves closer to the goal of manufacturing functional human tissues and potentially entire organs. While substantial challenges remain before such applications become clinical reality, the CHIPS platform demonstrates that the engineering foundations are beginning to take shape.