Fibronectin coating of collagen modules increases in vivo HUVEC survival and vessel formation in SCID mice

Modular tissue engineering is a novel approach to creating scalable, self-assembling, three-dimensional tissue constructs with inherent vascularization. Under initial methods, the subcutaneous implantation of human umbilical vein endothelial cell (HUVEC)-covered collagen modules in immunocompromised mice resulted in significant host inflammation and limited HUVEC survival. A minimally invasive injection technique was used to minimize surgery-related inflammation, and cell death was attributed to extensive apoptosis within 72 h of implantation. Coating collagen modules with fibronectin (Fn) was shown in vivo to reduce short-term HUVEC TUNEL staining by nearly 40%, while increasing long-term HUVEC survival by 30–45%, relative to collagen modules without fibronectin. Consequently, a ∼100% increase in the number of HUVEC-lined vessels was observed with Fn-coated modules, as compared to collagen-only modules, at 7 and 14 days post-implantation. Furthermore, vessels appeared to be perfused with host erythrocytes by day 7, and vessel maturation and stabilization was evident by day 14.