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

• Published in: The FASEB journal Vol. 21; no. 2; pp. 511 - 522
• Main Authors: Lokmic, Zerina, Stillaert, Filip, Morrison, Wayne A, Thompson, Erik W, Mitchell, Geraldine M
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01.02.2007
• Subjects: 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
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.06-6614com

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, Z., Stillaert, F., Morrison, W. A., Thompson, E. W., Mitchell, G. M. An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct.