An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct

FASEB J. 2007 Feb;21(2):511-22. doi: 10.1096/fj.06-6614com. Epub 2006 Dec 16.

Abstract

A major obstacle to 3-dimensional tissue engineering is incorporation of a functional vascular supply to support the expanding new tissue. This is overcome in an in vivo intrinsic vascularization model where an arteriovenous loop (AVL) is placed in a noncollapsible space protected by a polycarbonate chamber. Vascular development and hypoxia were examined from 3 days to 112 days by vascular casting, morphometric, and morphological techniques to understand the model's vascular growth and remodeling parameters for tissue engineering purposes. At 3 days a fibrin exudate surrounded the AVL, providing a scaffold to migrating inflammatory, endothelial, and mesenchymal cells. Capillaries formed between 3 and 7 days. Hypoxia and cell proliferation were maximal at 7 days, followed by a peak in percent vascular volume at 10 days (23.20+/-3.14% compared with 3.59+/-2.68% at 3 days, P<0.001). Maximal apoptosis was observed at 112 days. The protected space and spontaneous microcirculatory development in this model suggest it would be applicable for in vivo tissue engineering. A temporal window in a period of intense angiogenesis at 7 to 10 days is optimal for exogenous cell seeding and survival in the chamber, potentially enabling specific tissue outcomes to be achieved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blood Vessels / cytology
  • Blood Vessels / growth & development*
  • Blood Vessels / ultrastructure
  • Cell Hypoxia
  • Cell Proliferation
  • Diffusion Chambers, Culture
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Microscopy, Electron, Transmission
  • Neovascularization, Physiologic*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tissue Engineering / methods*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Vascular Endothelial Growth Factor Receptor-2