PHAGOCYTE-SURFACE INTERACTIONS

描述：这些调查的目的是确定 炎性和纤维化改变的机制通常 由植入的生物材料触发。虽然植入的医疗器械 代表着一种日益重要的治疗方式，很少是 已知生物相容性的决定因素。急慢性疾病 涉及早期吞噬细胞的种植体的炎症反应 植入物表面的再吸收通常伴随着纤维化 令人费解的是，MOST一般都是惰性和无毒的 植入性材料。申请人最近发现 纤维蛋白(原)的表面吸附是 巨噬细胞和中性粒细胞对细胞表面的吸引作用 聚合物植入物，很可能是后来的纤维化改变。尽管 现在确定了表面纤维蛋白原吸附的要求， 次要事件(例如，结合纤维蛋白(原)的可能修改， 可能与可能放大纤维蛋白原的辅助蛋白结合- 依赖炎症反应，吞噬细胞募集机制， 绑定和激活，以及负责最终 纤维化改变的发生仍不清楚。因此，第一个目标是 建议的工作之一是确定新的表位 纤维蛋白(原)，可能出现在表面吸附和 可能是这种复杂蛋白质的构象变化。他们将在那时 试图确定吞噬细胞黏附于 蛋白质涂层的植入物表面，以及这种细胞的影响： 蛋白质：代谢和促炎的表面相互作用 贴壁吞噬细胞的活性。最后，初步研究将是 开展了蛋白质吸附和早期初级研究的重要性 吞噬细胞聚集波对后续种植体相关性纤维化的影响 改变。希望更好地了解这些复杂的宿主： 植入物的相互作用可能会改善我们目前对 构成了生物相容性，并导致了设计的改进 生物材料表面。

DESCRIPTION: These investigations are aimed at determining the mechanisms responsible for the inflammatory and fibrotic changes often triggered by implanted biomaterials. Although implanted medical devices represent an increasingly important therapeutic modality, little is known of the determinants of biocompatibility. The acute and chronic inflammatory responses to implants involving the early phagocyte recruitment to the implant surface often followed by fibrosis are puzzling in view of the generally inert and non-toxic nature of most implantable materials. The Applicants have recently found that the surface adsorption of fibrin(ogen) is a necessary precedent to the attraction of both macrophages and neutrophils to the surfaces of polymeric implants and, probably to later fibrotic changes. Although the requirement for surface fibrinogen adsorption is now established, the secondary events (e.g., possible modifications of bound fibrin(ogen), possible binding of ancillary proteins which may amplify fibrinogen- dependent inflammatory responses, mechanisms of phagocyte recruitment, binding and activation, and processes responsible for the ultimate occurrence of fibrotic changes remain unclear. Therefore, the first aim of the proposed work is that of identifying novel epitopes of fibrin(ogen) which may appear following the surface adsorption and probably conformational change of this complex protein. They shall then attempt to determine the mechanisms involved in phagocyte adhesion to protein-coated implant surfaces, as well as the effects of such cell: protein:surface interactions on the metabolic and pro-inflammatory activities of adherent phagocytes. Finally, preliminary studies will be carried out on the importance of the primary protein adsorption and early wave of phagocyte accumulation on subsequent implant associated fibrotic changes. It is hoped that a better knowledge of these complex host: implant interactions may improve our present understanding of what constitutes biocompatibility and lead to improvements in the design of biomaterial surfaces.