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.
Department of Chemical Engineering and Applied Chemistry and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9.
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Cooper
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Sefton
D000818:Animals; D001808:Blood Vessels / Q000254:growth & development*; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D016513:Mice, SCID
D005353:Fibronectins; D003094:Collagen