Journal
TISSUE ENGINEERING PART A
Volume 15, Issue 6, Pages 1363-1371Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2008.0314
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Funding
- National Institutes of Health [R01 HL067954, R01 HL085339, R01 HL086959]
- Whitaker Foundation
- University of California, Irvine
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One critical obstacle facing tissue engineering is the formation of functional vascular networks that can support tissue survival in vivo. We hypothesized that prevascularizing a tissue construct with networks of well-formed capillaries would accelerate functional anastomosis with the host upon implantation. Fibrin-based tissues were prevascularized with capillary networks by coculturing human umbilical vein endothelial cells (HUVECs) and fibroblasts in fibrin gels for 1 week. The prevascularized tissue and nonprevascularized controls were implanted subcutaneously onto the dorsal surface of immune-deficient mice and retrieved at days 3, 5, 7 and 14. HUVEC-lined vessels containing red blood cells were evident in the prevascularized tissue by day 5, significantly earlier than nonprevascularized tissues (14 days). Analysis of the HUVEC-lined vessels demonstrated that the number and area of perfused lumens in the prevascularized tissue were significantly larger compared to controls. In addition, collagen deposition and a larger number of proliferating cells were evident in the prevascularized tissue at day 14. Our results demonstrate that prevascularizing a fibrin-based tissue with well-formed capillaries accelerates anastomosis with the host vasculature, and promotes cellular activity consistent with tissue remodeling. Our prevascularization strategy may be useful to design large three-dimensional engineered tissues.
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