Notre Dame Team 3D-Prints Capillary Networks for Lab-Grown Tissue

The biggest obstacle in growing replacement tissue in a lab is not shape. It is supply. Cells deep inside a thick construct starve without oxygen and nutrients. A team from the University of Notre Dame and Harvard Medical School may have cleared that bottleneck with a new bioprinting approach that builds hierarchical blood vessel networks at capillary scale.

The work, led by Yanliang Zhang in Notre Dame's Department of Aerospace and Mechanical Engineering, combines two printing techniques. Extrusion bioprinting deposits a soft gel-like scaffold for the main tissue structure. A second process, aerosol jet printing, lays down extremely fine gelatin filaments inside that matrix. Once the scaffold stabilizes, the gelatin is dissolved, leaving behind hollow channels that act as artificial capillaries.

The channels range from hundreds of micrometers down to below 10 micrometers. That lower bound sits at the scale of the body's smallest blood vessels and opens the door to thicker engineered tissue than previous methods could support. The team then tested whether these channels could do more than move fluid. They seeded select channels with endothelial cells, the specialized cells that line natural blood vessels. Those cells attached to the inner walls and formed continuous single-cell layers, creating a barrier similar to what you would find in living tissue.

Machine learning controls the process. Small adjustments in flow rate or gas pressure shift the diameter and quality of each channel. Rather than tuning by trial and error, the system maps those parameters and selects the best settings for a given design. That automation matters when a single vascular tree needs vessels of many different sizes arranged in a branching pattern.

The study, published in Nature Chemical Engineering, does not claim a printed organ. Significant hurdles remain: immune compatibility, mature blood flow, and integration with a patient's circulation. But the ability to print capillary-scale networks inside larger constructs addresses the most persistent limitation in regenerative medicine. With new NIH funding, the collaborators plan a more advanced hybrid printer that could eventually move bioprinting from tissue-shaped structures toward living, functional replacements.