BIOMATERIAL MEDIATED INFLAMMATION AND FIBROSIS

大多数类型的植入生物材料通过在很大程度上仍不清楚的机制来触发炎症和纤维化反应。吞噬反应已被证明影响纤维化反应(即成纤维细胞的增殖和胶原的产生)。我们建议的研究旨在阐明炎症和纤维化之间的相互关系(S)，从而开发控制生物材料介导的纤维化反应程度的策略。组织接触生物材料会在不同程度上引发纤维化反应。纤维反应不足或过度往往会导致医用植入物的失败。例如，人工韧带经常因为缺乏足够的组织整合而失败，而活跃的纤维化反应可能导致可植入传感器的失败。由于生物材料介导的组织反应的机制在很大程度上仍不清楚，我们仍然不知道如何控制材料植入物周围纤维组织的形成。在这笔赠款的前三年，我们阐明了与生物材料介导的炎症反应有关的一系列事件。(1)实施后不久，吞噬细胞通过移行和趋化过程被招募到腹膜腔。(2)吞噬细胞在种植体上的聚集是由吸附的纤维蛋白原介导的，吞噬细胞被激活以产生许多促纤维化的产物，包括细胞因子和组织因子。(4)黏附的吞噬细胞产生组织因子导致纤维蛋白凝块在种植体表面聚集，为成纤维细胞的迁移、增殖、胶原的产生提供了基础，通过改变吞噬细胞的募集和激活，我们可以有目的地调节纤维化反应，以适应不同材料装置的目的。对于HIS，使用不同的特异性抗体、拮抗剂、化学物质、药物来研究(1)吞噬细胞募集，(2)吞噬细胞黏附，(3)吞噬细胞相互作用，(1)吞噬细胞募集，(2)吞噬细胞黏附，(3)吞噬细胞黏附，(3)吞噬细胞激活，(4)吞噬细胞介导的凝血对生物材料植入物上纤维组织形成程度的影响。总体而言，这些研究将第一次提供详细和具体的新知识，为未来合理设计具有期望的组织反应性和可能的伤口愈合反应的植入式医疗设备提供所需的新知识。

Most types of implanted biomaterials trigger both inflammatory and fibrotic responses through mechanisms which are still largely unknown. Phagocytic responses have been demonstrated to influence fibrotic responses (i.e., fibroblast proliferation and collagen production). Our proposed investigations are aimed at elucidating the interrelation(s) between inflammation and fibrosis and consequently developing strategies which control the extent of biomaterial-mediated fibrotic responses. Tissue contact biomaterials trigger, to varying degrees, fibrotic responses. Both insufficient and excessive fibrotic responses an often lead to the failure of medical implants. For example, artificial ligaments often fail because of the lack of adequate tissue integration whereas exuberant fibrotic reactions can lead to the failure of implantable sensors. Because the mechanisms involved in biomaterial-mediated tissue responses remain largely unknown, we still do not know how to control fibrotic tissue formation surrounding material implants. During the first three years of this grant, we elucidated a sequence of events involved in biomaterial- mediated inflammatory responses. (1) Shortly after implementation, phagocytes are recruited to peritoneal cavity via transmigration and chemotactic processes. (2) Phagocyte accumulation on implants is mediated by the adsorbed fibrinogen, phagocytes are activated to produce many pro-fibrotic products, including cytokines and tissue factor. (4) The generation of tissue factor by adherent phagocytes causes the accumulation of fibrin clot on implant surfaces, providing a foundation for fibroblast immigration, proliferation, collagen production, and by changing phagocyte recruitment and activation, we may purposefully modulate fibrotic reactions to suit the purpose of different material devices. For his, using different specific antibodies, antagonists, chemicals, drug investigate the influences of (1) phagocyte recruitment, (2) phagocyte adhesion, (3) phagocyte interactions, we shall investigate the influences of (1) phagocyte recruitment, (2) phagocyte adhesion, (3) phagocyte adhesion, (3) phagocyte activation, and (4) phagocyte- mediated coagulation on the extent of fibrotic tissue formation on biomaterial implants. Overall, these studies will provide, for the first time, detailed and specific new knowledge required for the future rational design of implantable medical devices with desired tissue reactivity and, possibly wound healing responses.