An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct.
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.
Lokmic
Zerina
Z
Bernard O'Brien Institute of Microsurgery and University of Melbourne Department of Surgery, St. Vincent's Hospital, Melbourne, Victoria, Australia.
Stillaert
Filip
F
Morrison
Wayne A
WA
Thompson
Erik W
EW
Mitchell
Geraldine M
GM
D000818:Animals; D017209:Apoptosis; D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development* / Q000648:ultrastructure; D015687:Cell Hypoxia; D049109:Cell Proliferation; D015194:Diffusion Chambers, Culture; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D040301:Vascular Endothelial Growth Factor Receptor-2