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

Zerina Lokmic^*, Filip Stillaert, Wayne A. Morrison^*, Erik W. Thompson^* and Geraldine M. Mitchell^*,1

^* Bernard O’Brien Institute of Microsurgery and University of Melbourne Department of Surgery, St. Vincent’s Hospital, Melbourne, Australia; and

Department of Plastic and Reconstructive Surgery Unit, University Hospital, UZ Gent, Belgium

¹ Correspondence: Bernard O’Brien Institute of Microsurgery, 42 Fitzroy St., Fitzroy, 3065, Melbourne, Victoria, Australia. E-mail: mitcg{at}unimelb.edu.au

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.

Key Words: chamber space • macrovascular loop • angiogenesis • growth and remodeling • in vivo tissue engineering

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