PROMOTION OF SURGICAL WOUND HEALING BY GROWTH FACTORS

手术后受损或慢性伤口患者的伤口愈合不良， 代表着一个重大的国家健康问题。大多数患者的伤口愈合情况 伤口组织缺氧引起的问题。这样做的长期目标是 建议是通过动物模型和在 体外研究，关于生长因子如何启动和维持 成功愈合，特别是在缺血组织的情况下 缺氧。这些知识将被用来开发有效的治疗方法 伤口愈合不良的患者。 显示愈合受损的缺血性皮肤溃疡模型，将 对伤口愈合率和质量进行量化评估。的作用 生长因子治疗在缺血性愈合障碍中的应用 将会被研究。上皮化、肉芽组织形成的过程 形成和血管生成将使用组织学分析进行量化， 免疫组织化学和血管灌流研究。基因的变化 表达将通过定量聚合酶链式反应进行研究 分析，重点介绍成纤维细胞生长因子和转化生长因子-β家族及其受体。 高压氧治疗将作为一种辅助治疗在 对受损愈合的管理，并可能作为生长的调节器 因子介导的基因表达。高压氧对巨噬细胞集落刺激因子和巨噬细胞集落刺激因子的影响 将对缺血创面的治疗进行检查，看看是否有协同作用 生长因子和高压氧的共同作用是一种普遍现象。 对细胞对低氧反应的体外研究将使 对参与伤口愈合的单个成分细胞进行检查， 包括成纤维细胞、内皮细胞和巨噬细胞。的作用 生长因子函数在设定可变的氧气水平时会 学习。生长因子与生长因子协同作用的机制基础 将进行间歇性高氧血症。细胞增殖与基因 用聚合酶链式反应分析的人和兔细胞的表达将被测量 以应对关键的生长因子和缺氧。

Poor wound healing in compromised post surgical or chronic wound patients, represents a major national health problem. Most patients' wound healing problems result from wound tissue hypoxia. The long term objective of this proposal is to develop further understanding through animal models and in vitro studies, of how growth factors initiate and sustain the events of successful healing, particularly in the setting of ischemic tissue hypoxia. This knowledge would be used to develop effective treatment of patients with poor wound healing. The ischemic dermal ulcer model which demonstrates impaired healing, will be quantifiably evaluated for wound healing rate and quality. The role of growth factor treatment in the setting of impaired healing due to ischemia will be studied. The processes of epithelialization, granulation tissue formation, and angiogenesis will be quantified using histologic analysis, immunohistochemistry, and vascular perfusion studies. Changes in gene expression will be studied by quantitative polymerase chain reaction analysis, focusing on the FGF and TGF-B families and their receptors. Hyperbaric oxygen therapy will be studied as an adjuvant treatment in the management of impaired healing, and as a possible regulator of growth factor mediated gene expression. The effects of HBO on GM-CSF and M-CSF treatment of ischemic wounds will be examined to see if the synergistic effects of growth factors and HBO are a general phenomena. In vitro studies of the cellular response to hypoxia will allow examination of the individual component cells involved in wound healing, including fibroblasts, endothelial cells and macrophages. The role of growth factor function in the setting of variable oxygen levels will be studied. A mechanistic basis for the synergy between growth factor and intermittent hyperoxia will be pursued. Cell proliferation and gene expression as analyzed by PCR in human and rabbit cells will be measured in response to key growth factors and hypoxia.