Molecular stenting with a crosslinked hyaluronan derivative inhibits collagen gel contraction
Molecular stenting with a crosslinked hyaluronan derivative inhibits collagen gel contraction
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DOI：
10.1038/sj.jid.5700380
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发表时间：
2006-10-01
影响因子：
6.5
通讯作者：
Clark, Richard A. F.
中科院分区：
文献类型：
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作者：
Mehra, Tanuj D.;Ghosh, Kaustabh;Clark, Richard A. F.
成人烧伤创面，缺乏透明质酸（HA），经常经历过度的组织重塑和收缩。相反，含有大量透明质酸的胎儿伤口经过重塑，最终形成无疤痕的修复或再生。因此，在烧伤创面中添加透明质酸衍生物能更好地模拟胎儿细胞外基质，并能减少收缩。为了验证这一假设，我们确定了透明质酸及其两种衍生物对成纤维细胞介导的胶原凝胶收缩的影响，胶原凝胶收缩是一种广泛用于模拟体内伤口收缩的实验。有趣的是，高分子量HA （HMW HA）促进胶原凝胶收缩，而巯基衍生物HA- dtph则弱抑制收缩。相反，聚乙二醇二丙烯酸酯(PEGDA)-交联HA-DTPH （HA-DTPH-PEGDA）以浓度依赖的方式强烈抑制收缩。细胞肌动蛋白的免疫荧光染色显示这种抑制不是由于细胞附着或扩散减少。此外，收缩的胶原- hmv HA凝胶的上清液比胶原-HA- dtphpegda凝胶的上清液含有更多的HA，这表明HMW HA通过有效地扩散到胶原凝胶中来促进收缩。因此，结果表明，HA-DTPH交联增强了胶原/HA-DTPH复合材料的结构力学，从而抵抗成纤维细胞的收缩力，因此可能能够减少病理状态下观察到的过度伤口收缩。
Adult burn wounds, which lack hyaluronan (HA), often undergo excessive tissue remodeling and contraction. In contrast fetal wounds, which contain large amounts of HA, undergo remodeling that culminates in a scarless repair or regeneration. Therefore, adding a HA derivative to burn wounds would better mimic the fetal extracellular matrix and could reduce contraction. To test this hypothesis, we determined the effects of HA and its two derivatives on fibroblast-mediated, collagen gel contraction, an assay widely used to mimic in vivo wound contraction. Interestingly, high molecular weight HA (HMW HA) facilitated collagen gel contraction, whereas a thiol-functionalized derivative HA-DTPH weakly inhibited contraction. In contrast, polyethylene glycol diacrylate (PEGDA)-crosslinked HA-DTPH (HA-DTPH-PEGDA) strongly inhibited contraction in a concentration-dependent manner. Immunofluorescence staining of cellular actin showed that this inhibition was not owing to reduced cell attachment or spreading. Furthermore, the supernatant of contracted collagen-HMV HA gels contained greater amounts of HA than those found in the supernatant of collagen-HA-DTPHPEGDA gels, suggesting that HMW HA facilitates contraction by effectively diffusing out of the collagen gels. Therefore, the results suggest that the crosslinking of HA-DTPH enhances the structural mechanics of collagen/HA-DTPH composites, which resists the fibroblast contractile forces and may, therefore, be able to reduce excessive wound contraction observed in pathological conditions.