Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature

Tissue Eng Part A. 2009 Jun;15(6):1363-71. doi: 10.1089/ten.tea.2008.0314.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillaries / drug effects
  • Capillaries / growth & development
  • Cell Count
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Dimethylpolysiloxanes / pharmacology
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Fibrin / metabolism*
  • Humans
  • Mice
  • Neovascularization, Physiologic* / drug effects
  • Perfusion
  • Prosthesis Implantation
  • Tissue Engineering*
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects

Substances

  • Dimethylpolysiloxanes
  • Fibrin
  • Collagen