Notre Dame Team 3D Prints Capillary Networks Smaller Than 10 Micrometers

A team at the University of Notre Dame has built a hybrid bioprinter that can print capillary networks narrower than 10 micrometers. That is thinner than the finest human hair, and it is exactly the scale that has blocked bioprinting from moving beyond thin tissue samples toward full organs.

The system combines two 3D printing methods. Extrusion printing lays down the soft tissue matrix. Aerosol jet printing deposits a gelatin-based sacrificial material in much finer channels. Once the print finishes, warm water dissolves the gelatin, leaving behind a network of tubes that mimic blood vessels.

Machine learning ties the two processes together. The researchers used Bayesian optimization to tune ink flow rate and sheath gas pressure for each target channel size. The system usually finds the right settings in about eight test rounds, replacing trial and error with a repeatable workflow.

The result is stable one-dimensional, two-dimensional, and three-dimensional vascular structures. When the team seeded the channels with endothelial cells, the cells formed single-cell layers similar to those in real human tissue. That barrier function is critical: it is what keeps blood contained and tissues alive.

The work, led by Yanliang Zhang and collaborators at Harvard Medical School, appears in Nature Chemical Engineering. A four-year NIH grant already funds a follow-up system aimed at larger, more complex organ-like constructs.

What makes this different from earlier bioprinting efforts is the resolution. Most extrusion-based systems can print vessel-like channels, but they stall at the capillary scale. Adding aerosol jet printing closes that gap without abandoning the material properties that make extrusion useful for bulk tissue.

The immediate applications are in drug discovery and disease modeling, where thin tissue slices are already useful but limited. The longer-term goal is functional organs for transplant. That is still years away, but the capillary barrier is one of the hardest problems to solve, and this system clears it.