PROMOTION OF SURGICAL WOUND HEALING BY GROWTH FACTORS

通过生长因子促进手术伤口愈合

• 批准号: 2180796
• 负责人: THOMAS Anthony MUSTOE
• 金额: $ 13.94万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2180796
• 关键词: angiogenesis; colony stimulating factor; extracellular matrix proteins; fibroblast growth factor; fibroblasts; gene expression; growth factor; growth factor receptors; histology; hyperbaric oxygen therapy; hyperoxia; hypoxia; immunocytochemistry; ischemia; laboratory rabbit; macrophage; platelet derived growth factor; polymerase chain reaction; protein biosynthesis; receptor expression; surgical wound; tissue /cell culture; transforming growth factors; vascular endothelium; wound healing

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.

手术后受损或慢性伤口患者的伤口愈合不良， 这是一个严重的国家健康问题。大多数患者的伤口愈合 伤口组织缺氧会导致问题。这一长期目标 建议是通过动物模型和 体外研究，生长因子如何启动和维持的事件， 成功愈合，特别是在缺血组织的情况下 缺氧这些知识将用于开发有效的治疗方法， 伤口愈合不良的患者。 显示受损愈合的缺血性皮肤溃疡模型将 可定量评价伤口愈合速度和质量。的作用 生长因子治疗在由于局部缺血导致的愈合受损的情况下 将被研究。 上皮化，肉芽组织 形成和血管生成将使用组织学分析来定量， 免疫组织化学和血管灌注研究。基因变化 表达将通过定量聚合酶链反应进行研究 分析，重点是FGF和TGF-B家族及其受体。 高压氧治疗将作为一种辅助治疗进行研究， 管理受损的愈合，并作为一个可能的调节生长 因子介导的基因表达。高压氧对GM-CSF和M-CSF的影响 将检查缺血性伤口的治疗以观察是否协同 生长因子和高压氧的影响是一种普遍现象。 细胞对缺氧反应的体外研究将使 检查参与伤口愈合的单个组分细胞， 包括成纤维细胞、内皮细胞和巨噬细胞。的作用 生长因子在可变氧水平设置中的功能将是 研究了生长因子和细胞因子之间协同作用的机制基础 将继续间歇性高氧。细胞增殖以及基因 将测量通过PCR分析的人和兔细胞中的表达 对关键生长因子和缺氧的反应