Printing Tissue
Scientists at the Feinberg Lab at Carnegie Mellon University have created the first collagen-based microphysiologic system using FRESH 3D bioprinting.
Traditional human tissue models, such as organ-on-chip devices, are restricted by available manufacturing techniques. They are made from silicone rubber, plastics, or other synthetic materials. As a result, they’re unable to fully replicate natural tissue environments, so their effectiveness is limited.
However, FRESH (Freeform Reversible Embedding of Suspended Hydrogels) 3D bioprinting allows for the creation of microphysiologic systems from collagen cells and other proteins. “They’re fully biologic,” says Adam Feinberg, a professor of biomedical engineering and materials science and engineering at Carnegie Mellon. “Which means cells function better.”
In fact, according to Feinberg, the tissue models built with FRESH have “unprecedented structural resolution and fidelity.”
Researchers foresee many uses for these types of microphysiologic systems, including new treatments for Type 1 Diabetes.
FRESH 3D Bioprinting
In the FRESH method for 3D bioprinting, a support hydrogel is utilized for a temporary, thermoreversible support. This support material consists of processed gelatin microparticles with Bingham plastic. A bioink consisting of materials such as alginate, collagen, cell-laden cell slurries, and other biomaterials, is loaded into a syringe pump extruder then deposited into a support material in a layer-by-layer fashion. Later, the support material is washed away.
This combination of materials allows for the printing of biomaterials in complex geometries which previous methods were unable to attain. In addition, the support bath helps to prevent cell death, and to maintain cell viability during the printing process. And this means that the FRESH method can be used to create larger-scale models and tissue constructs that have been created previously.
A 3D Bio-Printed Human Heart
In 2020, the FRESH method was used to bioprint a full-sized model of an adult human heart. The design came from data sets consisting of patient-derived MRI data. The heart was printed using alginate. The result was a suturable high-fidelity construct, which could one day be used in future surgical training.
More recent studies are looking at whether 3D bioprinted cardiac tissue could one day be used to treat heart disease. However, there are significant limitations to the technology that would need to be overcome, including cost, the maturation state of the bioprinted tissues, and the current inability to manufacture the quantity and diversity of cell types that would be needed.
3D Bioprinted Liver Tissue
A Chinese study from January 2025 tested the use of 3D bioprinted human liver models for use in liver toxicity screening. The researchers fabricated a liver model using human-induced hepatocytes derived from human fibroblasts. The liver models exhibited mature hepatocyte functions, such as albumin expression and glycogen storage. They also demonstrated sensitivity to hepatotoxic agents like acetaminophen, and others. The study concluded that these 3D printed livers could one day be an effective, and cost-effective alternative for personalized liver toxicity screening and preclinical drug testing. They also believe the technology has the potential to improve drug development strategies and personalized liver therapies.
3D Bioprinting Pancreatic-Like Tissue
Some of the Carnegie Mellon team’s recent research uses FRESH to build complex, vascularized tissues entirely from biologic materials. This research builds on their earlier work by improving the resolution and quality of the printed tissue, creating fluidic channels that are similar to blood vessels down to about a 100-micron diameter.
The team’s most recent research has used fully biologic materials to create pancreatic-like tissue. The Carnegie-Mellon team combined FRESH with multi-material 3D bioprinting of ECM proteins, growth factors, and cell-laden bioinks and integration into a custom bioreactor platform. As a result, they were able to create a centimeter-scale pancreatic-like tissue construct. The tissue construct is capable of producing a greater level of glucose-stimulated insulin release than current organoid-based approaches are able to produce. The hope is that this tissue may one day be used to treat Type 1 Diabetes.
Daniel Shiwarski, assistant professor of bioengineering at the University of Pittsburgh and former postdoctoral fellow in the Feinberg laboratory, credits this advancement to a number of technical developments to the FRESH method. Of particular importance was the single-step fabrication process, which allowed the team to manufacture collagen-based perfusable CHIPS in a wide range of designs. The CHIPS had greater resolution and printed fidelity than any previously known bioprinting approach.
FluidForm Bio, a Carnegie Mellon University spinout company, is working to bring this technology to market. The team of Dr. Andrew Hudson, Director of Tissue Therapeutics, has already shown, via an animal model, that they can cure Type 1 Diabetes in-vivo. Clinical trials of the new technology are slated to begin in the next few years.
What’s Next
According to Feinberg, taking his team’s advanced fabrication capability and combining it with computational modeling and machine learning will hopefully give them a better idea of what they will need to print in the future.
“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,” he says.
Feinberg and his team see their research as “a base platform for building more complex and vascularized tissue systems.” The team wants to release open source designs and technologies that can be used widely within the research community. They hope other researchers will expand the capabilities of this technology to other diseases and tissue areas.