DERIVATIZED HYALURONAN FOR WOUND HEALING

描述 (改编自申请人的摘要)纤维蛋白凝块提供了最初的 创面实质细胞再繁殖的临时矩阵 组织结构已经被摧毁。然而，纯化的纤维蛋白不会 支持此功能。事实上，纤维连接蛋白是成纤维细胞所必需的 从伤口周围的基质中发现的胶原环境中的轮回， 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 富含纤维粘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。我们发现纤维连接蛋白也是 成纤维细胞通过组织浓度迁移所需的(2%) 透明质酸。显然，纤维连接蛋白在间充质中起着重要作用 细胞在伤口中的募集。最近我们发现了三个不同的 成纤维细胞迁移所需的纤维连接蛋白结构域。的全球目标 这项提议是设计一种衍生化的透明质酸结构 具有促进最大细胞生长的必要和充分的纤维连接蛋白序列 迁移到受伤的地方。这样的产品在临床上是有用的 止血和快速形成新组织的环境是 需要，例如新鲜清创的慢性皮肤溃疡和新鲜的 无法闭合的外科和创伤性皮肤伤口。为此， 最近设计的一种细胞跨细胞迁移的体外实验 三维细胞外基质边界将用于筛选 潜在的候选构造。最后，将确定是否 在体外最适合细胞迁移的透明质酸结构也是 最适合在体皮肤伤口愈合。

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.