GROWTH FACTOR MEDIATION OF HEALING OF VASCULAR GRAFTS

生长因子对血管移植物愈合的调节

• 批准号: 3358929
• 负责人: HOWARD P GREISLER
• 金额: $ 21.08万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358929
• 关键词: autoradiography; biomaterial interface interaction; biomaterials; biomechanics; blood vessel prosthesis; cell growth regulation; collagen; dogs; elastin; fibroblasts; growth factor; histology; immunochemistry; laboratory rabbit; macrophage; nonsurgical revascularization; regeneration; surgical wound; vascular endothelium; wound healing

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.

植入血液的化学和生物力学参数- 接触生物材料引发和/或调节所产生的 炎症、再生和血栓形成反应。 这些 组织反应最终决定了 植入的人造血管 生物可吸收丙交酯/乙交酯 被巨噬细胞吞噬的共聚物假体 导致广泛肌成纤维细胞和内皮细胞再生。 目前的协议试图澄清的程度 动脉壁成分的再生能力， 来分析假体成分 和生物力学特性影响组织响应。 具体目标包括（1）成分和 生物可吸收假体的生物力学特性 肌成纤维细胞、内皮细胞的再生速率和程度 细胞、胶原蛋白和弹性蛋白、细胞内 增殖活性和功能，这些再生 组织;（2）特定生长因子的作用和鉴定 作为修复后血管愈合的介质 巨噬细胞-生物材料相互作用诱导 释放特定的巨噬细胞衍生的生长因子， 血管愈合介质;（4）外源性 生长因子在血管愈合的优化。 该提案将利用生物可吸收和不可吸收 根据井中确定的可重现参数编织假体 特征纱线。 将假体植入家兔体内， 随后通过组织学分析犬模型和外植体， 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 依从性、强度和前列环素生产率。 对冷冻组织的北方印迹分析将鉴定mRNA 特定的生长因子。 体内生长因子的含量 将采用淘析技术处理的组织 通过生物测定、生物化学和免疫化学测定 生长因子分析，结果表示为 植入后的时间。 这些结果将在时间上 与组织学分析和腐蚀组织培养有关 巨噬细胞-生物材料相互作用的研究。 这些 同步分析将记录以下差异激活： 生物材料导致巨噬细胞产生 通过生物测定和特定的 生长因子鉴定将利用生物化学和 免疫化学技术。 一项相关的研究将审查 调节血管愈合，以响应应用 特异性生长因子HBGF-1在生物材料中的应用。 这些问题的澄清应导致新一代的 小口径人造血管的临床效果更好 以及选择性地刺激或抑制 通过适当使用生长因子及其 对手。