Bioprinting Tissue Engineered Vascular Conduits for Treating Single Ventricle Defects

Tissue engineered vascular conduits (TEVCs) offer high potential for treating cardiovascular diseases, such as single ventricle defects, by repairing damaged tissues and improving circulation. Conduits made of realistic tissue components present as long-lasting solutions capable of adapting with the body and integrating with host cells, thus offering enhanced, physiologically mimicking functionality. Bioprinting is an enabling approach toward generating user-designable tissues, with potential for maximizing accommodation for patient- specific needs. However, current bioprinting techniques are restricted in the types of materials that can be used as bioinks, typically relying on artificial materials/modifiers in bioink solutions or extremely high concentrations and acidity to enable printability, which limit biocompatibility and versatility. Many natural, physiological materials remain unprintable, especially with direct inclusion of cells within the bioinks. Moreover, key limitations in existing TEVCs (which are typically not bioprinted) include high incidence of stenosis in patients, thus elevating the risks of utilizing such products as the clinical gold standard. In this proposed study, we will develop highly tunable and customizable TEVCs utilizing a novel bioprinting method capable of directly printing fully physiological materials, including cell-laden tissues. Our method is fast, enabling rapid production of TEVCs with custom features. We will further incorporate universal immunocompatible human induced pluripotent stem cell (iPSC)-derived cells, including endothelial cells, in our bioprinted TEVCs to generate highly biomimicking living vessels with a functional endothelium, which will be conditioned and matured to enhance vessel function prior to implantation experiments. Matured TEVCs will subsequently be implanted in vivo into humanized rats to evaluate performance enhancements. Our study will produce a new generation of TEVCs with significantly enriched functions – custom bioprinted, immunocompatible living vessels for personalized and off-the-shelf capable regenerative therapeutic applications. We aim to develop fundamental advances in tissue engineered vessels for treating single ventricle defects. Project Number: 1R21HL173807-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Michael MAK | Institution: YALE UNIVERSITY, NEW HAVEN, CT | Award Amount: $460,625 | Activity Code: R21 | Study Section: Therapeutic Development and Preclinical Studies Study Section[TDPS] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21HL17380701A1