Enabling tissue perfusion through natural and engineered self-assembled networks

Over the past three decades, the field of tissue engineering has witnessed significant advancements. However, a persistent challenge is the development of an approach to generate rapidly perfused vascular networks at scale to support engineered tissues of appreciable size and able to adapt to changing needs. Current techniques able to create perfusable channels such as 3D printing are resource intensive and have not overcome the inherent tradeoff between vessel resolution and assembly time, limiting their utility and scalability for engineering tissues. Here we present two sacrificial self-assembly techniques that collectively develop microvascular networks and can anastomose to a variety of engineered forms. The first is vasculogenic cellular self-assembly, which leverages the innate ability of endothelial and sacrificial support cells to spontaneously form a capillary network, which we term CAMEO, or Controlled Apoptosis in Multicellular Tissues for Engineered Organogenesis. By varying the removal timing of the support cells, we determine fibroblasts are necessary for the initial vascular morphogenesis in our engineered system, and that this initial support period is sufficient for the endothelial cells to form a perfusable vasculogenic network and enhance the function of primary hepatocyte aggregates. The second is a flexible and scalable technique we term SPAN – Sacrificial Percolation of Anisotropic Networks. It uses microvascular-scale sacrificial fibers that make contacts to span a volume above a percolation density threshold and are then degraded. The resulting interconnected anisotropic voids form a perfusable fluidic network within minutes. We show that SPAN relieves hypoxia compared to bulk gels only, and the resulting voids created by SPAN can be endothelialized in a scalable way. These simple platforms can generate conduits with length scales spanning arterioles to capillaries within constructs. We show that both techniques can be used in combination with common tissue engineering processes, paving the way for rapid assembly of adaptable and perfusable tissues.2026-01-17T00:00:00