Perfusability and immunogenicity of implantable pre-vascularized tissues recapitulating features of native capillary network

Vascularization is a key pre-requisite to engineered anatomical scale three dimensional(3-D)constructs to ensure their nutrient and oxygen supply upon implantation.Presently,engineered pre-vascularized 3-D tissues are limited to only micro-scale hydrogels,which meet neither the anatomical scale needs nor the complexity of natural extracellular matrix(ECM)environments.Anatomical scale perfusable constructs are critically needed for translational applications.To overcome this challenge,we previously developed pre-vascularized ECM sheets with long and oriented dense microvascular networks.The present study further evaluated the patency,perfusability and innate immune response toward these pre-vascularized constructs.Macrophage-co-cultured prevascularized constructs were evaluated in vitro to confirm micro-vessel patency and perturbations in macrophage metabolism.Subcutaneously implanted pre-vascularized constructs remained viable and formed a functional anastomosis with host vasculature within 3 days of implantation.This completely biological pre-vascularized construct holds great potential as a building block to engineer perfusable anatomical scale tissues.