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J Surg Res. 2011 Jun 1;168(1):9-15. doi: 10.1016/j.jss.2009.09.052. Epub 2009 Oct 23.

In vivo angiogenesis effect of porous collagen scaffold with hyaluronic acid oligosaccharides.

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Department of Surgery, Division of Plastic and Reconstructive Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.



Tissue engineering is a promising solution for tissue defect repair. A key problem, however, is how to keep the engineered tissue alive after implantation. The ideal scaffold for tissue engineering would be biocompatible and biodegradable and, more importantly, would exhibit good interaction with endothelial cells to promote angiogenesis.


Three different scaffolds were synthesized: collagen/hyaluronic acid (HA) (MW 6.5K), collagen/HA (MW 220K), and collagen only. The synthesized collagen/HA scaffold was analyzed for water content, pore size, and HA content. An animal model for in vivo tissue construct angiogenesis was developed using the inferior epigastric skin flap of mice and perfusion of quantum dots; the average fluorescence intensity per unit area was calculated and correlated with vessel density from histologic examination.


The pore size is not statistically different among the three groups and the HA content is not statistically different between the two collagen/HA groups. The fluorescence intensity of the collagen/HA (MW 6.5K) group is increased at day 14, 21, and 28, and is significantly higher than in the other groups. Similar results were also obtained from histologic immunohistochemistry studies. CD31-stained vessels were found co-localized with QD fluorescence and these newly formed vessels were identified at day 14 in the collagen/HA (MW 6.5K) group and increased significantly at day 21 and 28.


This study showed that collagen scaffolds with short-chain HA (MW 6.5K) revascularize faster than those with long-chain HA (MW 220K) and collagen only. The results of the new animal model for studying scaffold angiogenesis are compatible with the conventional methods of immunostaining and histological examination.

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