DERIVATIZED HYALURONAN FOR WOUND HEALING

描述 （改编自申请人摘要）纤维蛋白凝块提供了初始 用于创伤的实质细胞再增殖的临时基质， 组织结构已经被破坏。 然而，纯化的纤维蛋白不 支持这个功能。 事实上，纤维连接蛋白是成纤维细胞 如在伤口周围基质中发现的，从胶原环境的迁移， 变成纤维蛋白凝块 当成纤维细胞重新填充它们所取代的伤口空间时 富含纤连蛋白的纤维蛋白凝块与第二临时基质组成 透明质酸和纤维连接蛋白的混合物。 我们发现纤连蛋白也是 成纤维细胞通过组织迁移所需的浓度（2%） 透明质酸 很明显，纤连蛋白在间充质细胞中起着重要作用。 细胞募集到伤口。 最近我们发现了三种不同的 成纤维细胞迁移所需的纤连蛋白结构域。 全球目标 该建议是设计透明质酸构建体， 与纤连蛋白序列必要和足够的促进最大细胞 迁移到损伤部位。 这样的产品将在临床上是有用的。 实现止血和快速形成新组织的环境， 需要，例如新鲜清创的慢性皮肤溃疡和新鲜的 无法闭合的手术和创伤性皮肤伤口。 为此 最近设计的体外细胞迁移试验， 三维细胞外基质边界将用于筛选 潜在的候选结构。 最后将确定是否 在体外对于细胞迁移最佳的透明质酸构建体也 在体内对于皮肤伤口愈合是最佳的。

DESCRIPTION (Adapted from the applicant's abstract) The fibrin clot provides the initial provisional matrix for parenchymal cell repopulation of a wound in which the tissue architecture has been destroyed. Purified fibrin, however, does not support this function. Fibronectin, in fact, is required for fibroblast transmigration from a collagenous milieu, as found in the periwound stroma, into a fibrin clot. As fibroblasts repopulate the wound space they replace the fibronectin-rich fibrin clot with a second provisional matrix composed of hyaluronan and fibronectin. We have found that fibronectin is also required for fibroblast migration through tissue concentrations (2 percent) of hyaluronan. Clearly fibronectin plays a fundamental role in mesenchymal cell recruitment into wounds. Recently we have identified three distinct fibronectin domains required for fibroblast migration. The global aim of this proposal is to engineer a hyaluronan construct which is derivatized with fibronectin sequences necessary and sufficient to promote maximal cell migration to a site of injury. Such a product would be useful in clinical settings where hemostasis is achieved and rapid formation of new tissue are needed, for example freshly debrided chronic cutaneous ulcers and fresh surgical and traumatic cutaneous wounds that cannot be closed. To this end a recently designed in vitro assay for cell migration across three-dimensional extracellular matrix boundaries will be used for screening potential candidate constructs. Finally it will be determined whether hyaluronan constructs that are optimal in vitro for cell migration are also optimal in vivo for cutaneous wound healing.