Implanted cell-dense prevascularized tissues develop functional vasculature that supports reoxygenation after thrombosis

Tissue Eng Part A. 2014 Sep;20(17-18):2316-28. doi: 10.1089/ten.TEA.2013.0311. Epub 2014 Jun 30.

Abstract

Achieving adequate vascularization within implanted engineered tissues is a significant obstacle to maintaining viability and functionality. In vitro prevascularization of engineered tissues has been explored as a potential solution to this challenge. The traditional paradigm of in vitro prevascularization is to implant an engineered tissue with a preformed vascular network that is perfused after anastomosis with the host circulation. We investigated the efficacy of this strategy by implanting cell-dense prevascularized tissues created via cell-mediated contraction and composed of collagen and a collagen-fibrin mixture into dorsal window chambers surgically prepared on immunocompromised mice. We found that host-implant anastomosis takes place in 2-6 days and that perfusion of vessels within the implants is subsequently restricted by thrombosis. However, by day 7, a functional vascular network composed of host and implant vessels developed. Prevascularization enhanced intra-implant pO2 significantly as early as 2 days postimplantation, reaching a maximum of 55 mmHg by day 8, which was significantly greater than the maximum within cellularized control tissues (18 mmHg). By day 14, collagen tissues supported ∼ 0.51 × 10(9) implanted and host-derived cells per mL. Our findings elucidate key features of in vitro prevascularization that can be used toward the design of larger and more functionally complex engineered tissues.

Publication types

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

MeSH terms

  • Animals
  • Blood Vessels / growth & development*
  • Cell Count
  • Cells, Cultured
  • Composite Tissue Allografts / blood supply
  • Composite Tissue Allografts / growth & development*
  • Composite Tissue Allografts / physiopathology*
  • Endothelial Cells / physiology
  • Endothelial Cells / transplantation*
  • Equipment Design
  • Equipment Failure Analysis
  • Mice
  • Mice, Inbred ICR
  • Mice, SCID
  • Neovascularization, Physiologic
  • Oxygen / metabolism*
  • Thrombosis / physiopathology*
  • Thrombosis / therapy*
  • Tissue Engineering / instrumentation
  • Tissue Engineering / methods

Substances

  • Oxygen