Scarless Wound Repair

描述(由申请人提供)： 瘢痕形成是一个具有重要临床意义的问题。成人皮肤伤口有疤痕愈合，而妊娠早期胎儿皮肤有愈合无疤痕的能力。利用胎鼠创伤模型，我们已经确定了几个参与无疤痕伤口修复的内源性分子。一种特定的分子完全抑制妊娠晚期胎儿伤口的疤痕形成，这些伤口通常会修复疤痕，并显着改善成人伤口的疤痕形成。此外，伤口炎症也明显减轻。 在这项第一阶段的研究中，我们建议：1)证实分子介导的瘢痕减少与损伤的伤口愈合无关，2)完善创伤(即切开创面与切除创面)分子使用的适应症，3)完善皮肤炎症中分子使用的适应症，4)为第二阶段重组分子生产方法提供理论基础。 在第二阶段，我们将建议设计和构建以及测试所产生的分子的体外生化活性和体内生物活性。我们的长期目标是开发内源性蛋白多糖，作为治疗皮肤疤痕和炎症的有效药物。

DESCRIPTION (provided by applicant): Scar formation is a problem of great clinical importance. Adult skin wounds heal with scar while early gestation fetal skin has the capacity to heal without scar. Using a fetal rat wound model, we have identified several endogenous molecules involved in scarless wound repair. Administration of a specific molecule completely inhibits scar formation in late gestation fetal wounds that normally repair with scar and significantly ameliorates scar formation in adult wounds. In addition, wound inflammation was also significantly reduced. In this Phase I study we propose to: 1) confirm that molecule-mediated scar reduction is not associated with impaired wound healing, 2) refine the indications for molecule usage in wounds (i.e., incisional vs. excisional wounds), 3) refine the indications for molecule usage in skin inflammation, and 4) provide a rationale for the method of recombinant molecule production in Phase II. In Phase II, we will propose to design and construct as well as test the in vitro biochemical activity and in vivo bioactivity of the produced molecule. Our long-term goal is to develop endogenous proteoglycans as an effective treatment for cutaneous scar and inflammatory conditions.