Modular tissue engineering is a novel approach to creating scalable, self-assembling three-dimensional tissue constructs with inherent vascularisation. 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. Subsequently, a minimally-invasive injection technique was developed to minimize surgery-related inflammation, and cell death was attributed to extensive apoptosis within 72 hours of implantation. In confirmation of in vitro results, coating collagen modules with fibronectin (Fn) was shown in vivo to reduce short-term HUVEC apoptosis by nearly 40%, while increasing long-term HUVEC survival by 30% to 45%. 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.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18244 |
| Date | 13 January 2010 |
| Creators | Cooper, Thomas |
| Contributors | Sefton, Michael |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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