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(The FASEB Journal. 1998;12:1331-1340.)
© 1998 FASEB


RESEARCH COMMUNICATION

In vitro reconstruction of a human capillary-like network in a tissue-engineered skin equivalent

Annie F. Black1,a, François Berthoda, Nicolas L'heureux2,a, Lucie Germaina, and François A. Augera,1

a Laboratoire d'Organogénèse Expérimentale/LOEX, Centre Hospitalier Affilié, Pavillon Saint-Sacrement and Department of Surgery, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada G1S 4L8

For patients with extensive burns, wound coverage with an autologous in vitro reconstructed skin made of both dermis and epidermis should be the best alternative to split-thickness graft. Unfortunately, various obstacles have delayed the widespread use of composite skin substitutes. Insufficient vascularization has been proposed as the most likely reason for their unreliable survival. Our purpose was to develop a vascular-like network inside tissue-engineered skin in order to improve graft vascularization. To reach this aim, we fabricated a collagen biopolymer in which three human cell types—keratinocytes, dermal fibroblasts, and umbilical vein endothelial cells—were cocultured. We demonstrated that the endothelialized skin equivalent (ESE) promoted spontaneous formation of capillary-like structures in a highly differentiated extracellular matrix. Immunohistochemical analysis and transmission electron microscopy of the ESE showed characteristics associated with the microvasculature in vivo (von Willebrand factor, Weibel-Palade bodies, basement membrane material, and intercellular junctions). We have developed the first endothelialized human tissue-engineered skin in which a network of capillary-like tubes is formed. The transplantation of this ESE on human should accelerate graft revascularization by inosculation of its preexisting capillary-like network with the patient's own blood vessels, as it is observed with autografts. In addition, the ESE turns out to be a promising in vitro angiogenesis model.—Black, A. F., Berthod, F., L'Heureux, N., Germain, L., Auger, F. A. In vitro reconstruction of a human capillary-like network in a tissue-engineered skin equivalent. FASEB J. 12, 1331–1340 (1998)


Key Words: angiogenesis • endothelial cell • extracellular matrix • inosculation • skin substitute




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