Wrapping and Tapping Anastomosis between Engrafted Endothelial Networks and Host Vasculature

Abstract

A major obstacle in tissue engineering is poor post‐implantation cell survival due to the lack of blood perfusion. One approach is to populate the graft before implantation with endothelial or progenitor cells that can quickly organize into a network and connect with the host vasculature to achieve blood perfusion. Many types of endothelial and endothelial progenitor cells are capable of this, but the mechanism by which the implanted vascular networks anastomose with the host vasculature is unknown. Here we show that it occurs through a previously unreported process of “wrapping and tapping” (WAT). At the host‐implant interface, implanted ECs wrap around nearby host vessels, cause host vessel regression by disrupting their pericytes and basement membrane, and then completely replace segments of host vessels to divert flow into the contiguous, engrafted vascular network. This process is facilitated by high levels of MMP‐14 and MMP‐9 expressed specifically by wrapping ECs. Our results provide mechanistic understanding on this critical step of vascularization and may have implications for other physiological and pathological processes involving post‐natal vasculogenesis.