GROWTH FACTOR MEDIATION OF HEALING OF VASCULAR GRAFTS

植入血液的化学和生物力学参数- 接触的生物材料引发和/或调制结果 炎症反应、再生反应和血栓反应。这些 组织反应最终决定了临床治疗的成功 植入的血管假体。生物可吸收丙交酯/乙交酯 被巨噬细胞吞噬的共聚假体 导致广泛的肌成纤维细胞和内皮细胞的再生。 目前的议定书试图澄清 动脉壁各成分的再生能力 分析假体组合物的作用机制 生物力学特性会影响组织的反应。 具体目标包括：(1)成分和 下颌骨可吸收假体的生物力学特性 血管内皮细胞成纤维细胞再生的速度和程度 细胞、胶原和弹性蛋白、持续蛋白和细胞范围 再生细胞的增殖活性和功能 组织；(2)特定生长因子的作用和鉴定 作为人工血管修复的介体 植入；(3)巨噬细胞-生物材料相互作用 特异性巨噬细胞衍生生长因子的释放 血管愈合的中介物；以及(4)外源性 生长因子在优化血管愈合中的作用。 这项提议将利用生物可再吸收和不可再吸收 根据井中定义的可重复参数编织的假体 特有的纱线。假体将被植入兔体内并 犬类模型和外植体稍后将通过组织学进行分析， 免疫细胞化学和超微结构技术， 放射自显影、胶原蛋白测定和功能分析 依从性、强度和前列环素产生率。 对移植组织的Northern印迹分析将鉴定出mRNA 对于特定的增长因素。其中生长因子的含量 接受淋洗技术的移植组织将被 由生物测定、生化和免疫化学检测 增长因素分析，结果表示为以下函数 植入后时间。这些结果将是暂时的 与组织学分析和组织培养有关 巨噬细胞-生物材料相互作用的研究。这些 并发分析将记录差异激活 生物材料导致滞留巨噬细胞的产生 生长因子(S)的生物测定和特异性 生长因子鉴定将利用生化和 免疫化学技术。一项相关的研究将检查 对血管愈合的调节作用 特定生长因子，HBGF-1，应用于生物材料。 对这些问题的澄清应该会带来新的一代 具有更大临床疗效的小口径血管假体 以及选择性地刺激或抑制某些方面的能力 适当使用生长因子及其受体促进血管愈合 对抗者。

The chemical and biomechanical parameters of implanted blood- contacting biomaterials initiate and/or modulate the resultant inflammatory, regenerative, and thrombotic reactions. These tissue reactions ultimately determine the clinical success of implanted vascular prostheses. Bioresorbable lactide/glycolide copolymeric prostheses which are phagocytized by macrophages lead to extensive myofibroblast and endothelial cell regeneration. The current protocol attempts to clarify the extent of the regenerative capacities of the components of the arterial wall and to analyze the mechanisms by which the prosthetic composition and biomechanical characteristics affect the tissue responses. Specific aims include (1) the effects of compositional and biomechanical characteristics of bioresorbable prostheses on the rate and extent of regeneration of myofibroblasts, endothelial cells, collagen and elastin, the duratin and extent of cellular proliferative activity, and functionality of these regenerated tissues; (2) the role and identification of specific growth factors as mediators of vascular healing following prosthetic implantation; (3) macrophage-biomaterial interactions inducing release of specific macrophage derived growth factors as mediators of vascular healing; and (4) the efficacy of exogenous growth factors in optimization of vascular healing. This proposal will utilize bioresorble and non-resorbable prostheses woven to defined reproducible parameters from well characterized yarns. Prostheses will be implanted into rabbit and canine models and explants will later be analzyed by histologic, immunocytochemical, and ultrastructural techniques, autoradiography, collagen assays, and functional analyses of compliance, strength, and prostacyclin production rates. Northern blot analyses of explanted tissues will identify mRNA for specific growth factors. The content of growth factors within explanted tissues subjected to elutriation techniques will be determined by bioassays and by biochemical and immunochemical growth factor analyses with results expressed as a function of time following implantation. These results will be temporally related to the histologic analyses and to corrobation tissue culture studies of macrophage-biomaterial interactions. These concurrent analyses will document the differential activation of resident macrophages by biomaterials resulting in their production of growth factor(s) as documented by bioassays and specific growth factor identification will utilize biochemical and immunochemical techniques. A related study will examine the modulation of vascular healing in response to the application of a specific growth factor, HBGF-1, applied to biomaterials. The clarification of these issues should lead to a new generation of small caliber vascular prostheses with greater clinical efficacy as well as an ability to selectively stimulate or inhibit aspects of vascular healing by appropriate use of growth factors and their antagonists.