The two dominant approaches to vascularization of engineered tissues-angiogenesis and vasculogenesis-require several days to generate perfusion in implanted constructs. This proposed R03 pilot study seeks to develop a third approach, in which microsurgical anastomosis of a prevascularized microfluidic tissue to host vessels provides an immediate, physical route to perfusion. This work will implant endothelialized microfluidic collagen- and fibrin-based tissues using the rat femoral artery and vein as recipients, and will analyze the maintenance of perfusion and tissue viability in the construct. The constructs will be densely seeded with adipocytes to model soft tissue replacements. This proof-of-principle study is an important requisite step before such a physical strategy for vascularization can realize its potential as an alternative to angiogenesis and vasculogenesis. This work will provide a broad enabling tool for generating vascularized tissues and a concrete path to engineering vascularized adipose tissue for treatment of large soft tissue defects, as is often seen after tumor resection or major trauma.
Reconstructing a large tissue defect (e.g., after tumor resection or major trauma) requires the ability to graft and sustain a large living tissue at the defect site. The proposed work will test a new approach to tissue reconstruction, in which engineered tissues that contain functional vessels are surgically linked with host vessels to provide immediate blood flow. This approach has the potential to create clinically relevant tissue volumes that can be implanted without loss of viability.