DEVELOPMENT OF AN ARG-GLY-ASP-BASED WOUND HEALING AGENT

基于 ARG-GLY-ASP 的伤口愈合剂的开发

• 批准号: 3498299
• 负责人: JAMES W POLAREK
• 金额: $ 5万
• 依托单位: TELIOS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3498299
• 关键词: burns; cell migration; chemical conjugate; collagen; decubitus ulcer; extracellular matrix; fibroblasts; fibronectins; peptide chemical synthesis; polymers; protein sequence; wound healing

The slow healing or lack of healing of wounds such as decubitus ulcers, severe burns and diabetic ulcers is a serious medical problem in this country, affecting millions of individuals and causing severe pain or death in many patients. A major factor contributing to the poor healing response seen in these patients is the destruction of specific extracellular matrix proteins. Cells interact with these matrix components through Arg-Gly-Asp sequences present in such molecules as fibronectin, vitronectin, collagen, and tenacin. Such attachment allows the cells to move through the matrix, as in fibroblast migration into wounds. By providing a synthetic matrix, we believe that we can influence the healing process in wounds such as the type mentioned above. This work is designed to develop a synthetic matrix composed of RGD- containing peptides coupled to a biodegradable polymer, thereby providing a method of stimulating cell migration into the wound in a time expected to be shorter than if the cells were required to synthesize the matrix themselves. We will analyze each of three components (peptide, polymer, and coupling chemistry) to achieve a compound which behaves best in in vitro assays designed for this purpose. The material will then be tested in an accepted animal wound healing model to determine if healing time and integrity of the healing wound bed can be affected.

伤口愈合缓慢或不愈合，如褥疮溃疡， 严重烧伤和糖尿病溃疡是一个严重的医疗问题， 影响数百万人并造成严重疼痛或死亡 在许多患者中。 导致愈合不良的主要因素 在这些患者中看到的是特定细胞外基质的破坏， proteins. 细胞通过Arg-Gly-Asp与这些基质成分相互作用 存在于诸如纤连蛋白，玻连蛋白，胶原蛋白， 和tenacin。 这种附着允许细胞移动通过基质， 如成纤维细胞迁移到伤口中。 通过提供合成基质， 我们相信，我们可以影响伤口的愈合过程， 上述类型。 本工作旨在开发一种由RGD- 含有与生物可降解聚合物偶联的肽，从而提供 一种在预期的时间内刺激细胞迁移到伤口中的方法， 比需要细胞合成基质的时间短 自己 我们将分析三种成分（肽，聚合物， 和偶联化学）以获得在以下方面表现最佳的化合物： 为此目的设计的体外试验。 然后将对材料进行测试 在公认的动物伤口愈合模型中， 会影响愈合伤口床的完整性。