Hybrid Bioprinting Platform Creates Capillary-Scale Vascular Networks

More than 100,000 people in the United States await organ transplants, and a new candidate is added every 10 minutes. Even when surgery succeeds, recipients face lifelong immunosuppression, infection risk and the possibility of graft rejection. For decades, scientists have sought to address these challenges by bioprinting tissues and organs from patients’ own cells.

One of the greatest barriers to producing lab-grown organs is recreating the intricate vascular networks found throughout the body, particularly tiny capillaries. These microvessels transport oxygen and nutrients to cells across every organ, making them critical to the development of functional bioengineered tissue. To overcome this barrier, researchers have developed a hybrid bioprinting approach capable of producing vascular networks with capillaries under 10 micrometers in diameter.

Researchers at the University of Notre Dame combined extrusion-based bioprinting with aerosol jet printing to create hierarchical vascular architectures. The approach forms a soft, tissue-mimicking matrix while simultaneously patterning sacrificial templates that define vessel geometry, enabling stable one-, two-, and three-dimensional networks. The work was recently featured on the cover of Nature Chemical Engineering.

The matrix is first deposited by extrusion printing to create a gel-like scaffold. Within each printed layer, aerosol jet printing places thin gelatin threads that serve as removable templates. After fabrication, the construct is immersed in warm water to liquefy the gelatin, leaving precisely arranged microchannels within the matrix. Aerodynamic focusing using a sheath flow allows dynamic control of channel diameters, ranging from hundreds of micrometers down to only several micrometers.

Because small changes in ink and gas flow can alter channel dimensions, the researchers incorporated a machine learning framework to autonomously identify optimal printing parameters. This reduced trial-and-error optimization and accelerated production of targeted geometries. Selected channels were then seeded with endothelial cells, which rapidly formed single-cell linings. The resulting structures reproduced barrier-like behavior similar to that of human capillaries without leakage.

The project, conducted with collaborators at Harvard Medical School and Brigham and Women’s Hospital, demonstrates capillary‑scale resolution while maintaining structural integrity. Potential near‑term uses include biomimetic organ‑on‑a‑chip platforms for drug safety and efficacy testing. Using patient‑specific cells could enable personalized response assessment before treatment. The team has secured new funding from the National Institutes of Health to build a more powerful hybrid bioprinter and pursue fabrication of lab‑grown organs.

“We’ve reached a major breakthrough in the field of bioprinting. Achieving capillary-scale resolution in bioprinting is an important step towards engineering fully functional tissues and complete organs,” said Yanliang Zhang, the Advanced Materials and Manufacturing Collegiate Professor in the Department of Aerospace and Mechanical Engineering at the University of Notre Dame.

“There are so many people waiting for an organ transplant, and the ability to print organs in the lab has the potential to transform lives by helping humans to live longer and live healthier. We are not simply developing better technology, but shining light on a new future for organ transplantation and human health,” said Zhang.

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