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

• Published in: Acta biomaterialia Vol. 7; no. 3; pp. 1072 - 1083
• Main Authors: Cooper, T.P., Sefton, M.V.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2011
• Subjects: Animals; apoptosis; Blood Vessels - growth & development; Cell Survival; Cells, Cultured; coatings; collagen; Collagen - metabolism; Endothelial cells; Endothelium, Vascular - cytology; erythrocytes; Fibronectin; fibronectins; Fibronectins - metabolism; Humans; In Situ Nick-End Labeling; inflammation; Male; Mice; Mice, SCID; Modular tissue engineering; SCID mice; severe combined immunodeficiency; tissue engineering; Vascularization; Modular tissue engineering; SCID mice; Endothelial cells; Fibronectin; Vascularization
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2010.11.008

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 72h 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 14days post-implantation. Furthermore, vessels appeared to be perfused with host erythrocytes by day 7, and vessel maturation and stabilization was evident by day 14.