More than 100,000 people in the United States are currently waiting for an organ transplant, while another potential recipient joins the list roughly every 10 minutes. For those who receive a donated organ, the procedure is only the beginning of a lifelong medical challenge. Immunosuppressive drugs are required to prevent rejection, but these medications can weaken the immune system and increase susceptibility to infection. The transplanted organ may still fail, and the shortage of donated organs leaves many patients waiting for years. A new advance in bioprinting could eventually help address this crisis by making it possible to construct living tissues with the intricate blood-vessel systems needed to keep them alive.
Researchers at the University of Notre Dame and collaborators at Harvard Medical School and Brigham and Women’s Hospital have developed a hybrid bioprinting strategy capable of producing vascular networks with capillaries less than 10 micrometers in diameter. These structures are narrower than the width of a human hair and approach the scale of the smallest blood vessels found in the body. The work, led by Yanliang Zhang, Advanced Materials and Manufacturing Collegiate Professor in Notre Dame’s Department of Aerospace and Mechanical Engineering, represents a significant step toward fabricating tissues that can exchange oxygen and nutrients throughout their internal volume. The study, published in Nature Chemical Engineering, describes a system that combines two printing methods with machine-learning-assisted process control.
The central difficulty in building functional organs outside the body is not simply creating the correct shape. Living cells require a continuous supply of oxygen, glucose and other nutrients, as well as a route for removing carbon dioxide and metabolic waste. In natural organs, this exchange is handled by a hierarchical vascular network that begins with large arteries and branches repeatedly into smaller arterioles, capillaries and venules. Capillaries are particularly important because they bring blood close enough to individual cells for diffusion to occur. Without a comparable microvascular network, cells in the interior of a thick engineered tissue rapidly become starved of oxygen and die, limiting the size and usefulness of most lab-grown organs.
Zhang’s team addressed this problem by integrating extrusion bioprinting with aerosol jet printing. In the first stage, extrusion printing deposits a soft, gel-like biomaterial in successive layers to form the main tissue matrix. This matrix acts as a supportive, hydrated scaffold designed to resemble some of the mechanical and biological characteristics of living tissue. Within the printed matrix, the researchers use aerosol jet printing to place extremely fine gelatin filaments. The gelatin functions as a temporary sacrificial material. Once the surrounding matrix has stabilized, the gelatin can be removed, leaving behind hollow channels that form the internal architecture of the artificial vascular system.
Aerosol jet printing gives the process a level of control that conventional extrusion systems cannot easily achieve. The technique uses a carrier gas and a surrounding sheath flow to aerodynamically focus an aerosolized stream of material. By changing the flow conditions, researchers can adjust the diameter of the deposited filament while maintaining a finely controlled trajectory. In the Notre Dame system, the approach allows channel dimensions to be varied from hundreds of micrometers down to only a few micrometers. That range is essential because biological vascular systems are not composed of tubes with a single uniform diameter; they contain large vessels that gradually divide into dense networks of microscopic branches.
The researchers also incorporated machine learning to reduce the trial-and-error traditionally required to tune the printing process. Small changes in the gelatin ink’s flow rate or in the sheath gas can significantly alter the final channel diameter, continuity and structural quality. Instead of testing every combination manually, the computational framework analyzes the relationship between printing parameters and the resulting structures. It then identifies promising operating conditions for a desired channel size and configuration. This automated optimization is particularly valuable when a single vascular design contains vessels of many different dimensions. By rapidly adjusting the parameters, the system can produce complex architectures with greater efficiency and consistency than conventional manual calibration.
Using the combined platform, the team fabricated hierarchical vascular structures in one, two and three dimensions. These included networks designed to reproduce the branching organization found in biological tissues rather than isolated, straight channels. After the temporary gelatin was removed, selected channels were seeded with endothelial cells, the specialized cells that line blood and lymphatic vessels in the human body. The cells attached to the inner surfaces of the printed channels and spread to form continuous single-cell layers. This lining is crucial because endothelial cells regulate the exchange of materials between blood and tissue, control vessel permeability and contribute to the barrier function that prevents uncontrolled leakage.
The successful formation of endothelial layers suggests that the channels were not merely geometric features but could support a basic biological function. According to the researchers, the cells rapidly adhered to the channel walls and developed a barrier resembling the lining of natural capillaries. Demonstrating this behavior is an important milestone because artificial vessels must do more than transport fluid: they must interact with living tissue and maintain an environment in which other cell types can survive. The study’s results indicate that the hybrid-printed networks may provide a platform for constructing more sophisticated tissue models, although additional work will be required to test long-term stability, blood compatibility, flow behavior and integration with larger tissue systems.
The technology could also accelerate drug development through improved organ-on-a-chip models. Many existing laboratory models lack the three-dimensional structure and microvascular complexity of human organs, making it difficult to predict how a drug will behave in patients. A printed vascular network populated with living cells could help researchers study drug transport, toxicity and therapeutic response under more realistic conditions. If patient-derived cells are incorporated, the same system might eventually be used to compare how a particular individual’s tissue responds to different treatments before a therapy is administered. Such personalized models could be especially useful for diseases involving the heart, liver, kidneys and blood vessels, where vascular behavior strongly influences treatment outcomes.
Zhang’s longer-term goal is to develop an autonomous bioprinting system capable of manufacturing fully functional tissues and, ultimately, organs such as hearts, kidneys and livers. The current work does not represent a complete printed organ, and significant scientific and engineering barriers remain, including the development of multiple interacting cell types, mature blood-flow systems, immune compatibility and reliable connections to a patient’s circulation. Nevertheless, the ability to print capillary-scale channels within larger, hierarchical networks addresses one of the most persistent obstacles in regenerative medicine. Supported by new National Institutes of Health funding, the Notre Dame and Harvard collaborators plan to build a more advanced version of the hybrid printer. If the approach can be scaled and shown to function over long periods, it could help transform bioprinting from the fabrication of tissue-shaped structures into the production of living, physiologically active replacements.
Subject of Research: Hybrid bioprinting of hierarchical vascular networks containing capillary-scale channels.
Article Title: Hybrid bioprinting of hierarchical vascular networks at capillary-scale resolution
News Publication Date: 28-May-2026
Web References: University of Notre Dame Department of Aerospace and Mechanical Engineering: https://ame.nd.edu/ ; Yanliang Zhang: https://engineering.nd.edu/faculty/yanliang-zhang/ ; Nature Chemical Engineering: https://www.nature.com/natchemeng/volumes/3/issues/6
References: Nature Chemical Engineering, DOI: 10.1038/s44286-026-00396-x
Image Credits: Photo by Wes Evard / University of Notre Dame’s College of Engineering
Keywords: Bioprinting, 3D printing, vascular networks, capillaries, tissue engineering, organ engineering, regenerative medicine, aerosol jet printing, machine learning, endothelial cells, organ-on-a-chip, personalized medicine, transplantation
