Enhancing the Vascularization Properties of Skin Tissue

描述（由申请人提供）： 皮肤溃疡每年折磨美国约450万患者，据估计，美国15%的老年人患有慢性、难以愈合的皮肤伤口。这些伤口中的许多无法愈合，通常导致严重的并发症，包括截肢和危及生命的感染。这些伤口的愈合通常会受到缺氧的影响，因此增强血管形成并同时刺激多个修复过程的策略有可能显着改善慢性伤口的治疗和愈合。 Stratatech Corporation正在开发一系列工程皮肤组织产品，以改善慢性皮肤伤口的管理和愈合。虽然施用单个血管生成因子可以刺激血管生成的某些方面，但是需要多种因子的同时表达来促进形态和功能正常的血管。该I期提案旨在测试角质形成细胞可以被工程化以协调表达升高水平的多种治疗因子的假设。这将通过使用非病毒载体将低氧诱导的伤口愈合反应的主调节剂稳定地引入专有角质形成细胞来源中并表征生物活性血管生成因子的表达和分泌来实现。如果成功，拟议的研究将最终导致改进治疗的开发和商业化，以促进慢性伤口和其他严重皮肤缺损的愈合。

DESCRIPTION (provided by applicant): Cutaneous ulcers afflict approximately 4.5 million patients in the United States each year and it is estimated that 15% of older adults in the United States suffer from chronic, hard-to-heal skin wounds. Many of these wounds fail to heal, often resulting in severe complications including amputations and life-threatening infections. The healing of these wounds is often impaired by hypoxia, so strategies to enhance vascularization and simultaneously stimulate multiple repair processes have the potential to significantly improve the treatment and healing of chronic wounds. Stratatech Corporation is developing a portfolio of engineered skin tissue products to improve the management and healing of chronic skin wounds. While administration of individual angiogenic factors may stimulate some aspects of angiogenesis, the simultaneous expression of multiple factors is required to promote morphologically and functionally normal vessels. This Phase I proposal is designed to test the hypothesis that keratinocytes can be engineered to coordinately express elevated levels of multiple therapeutic factors. This will be accomplished by stably introducing a master regulator of hypoxia-induced wound healing responses into a proprietary keratinocyte cell source using non-viral vectors and characterizing the expression and secretion of biologically-active angiogenic factors. If successful, the proposed research will ultimately lead to the development and commercialization of improved treatments to promote the healing of chronic wounds and other severe skin defects.