TRAUMA, INFECTION, AND PROSTHETIC BIOMATERIALS

人工设备和器官的植入总是伴随着 创伤性的组织破裂。长期的成功目前是 因炎症组织中不可接受的感染发生率而受阻 在假肢周围。这项提案旨在调查一个方面 这种感染的发病机制。我们将在体外和体内检测 部分假体生物材料与细胞和组织的体内相互作用 创伤性伤口的体液成分。我们假设这一接触 某些生物材料与中性粒细胞和/或血浆之间的关系会导致 最初的激活和由此导致的宿主防御系统的耗尽 感染。激活和由此导致的宿主防御系统的耗尽 抗感染。细胞(中性)成分的激活 会导致氧化代谢的活性中间产物的释放 以及可导致组织坏死的溶酶体成分。 随之而来的是，这种相互作用将使中性粒细胞无法 对感染的进一步有效反应。此外，我们假设 体液成分的激活将导致对 补充有效的宿主-微生物相互作用所必需的成分。 具体地说，拟议的工作将描述采取的变化 放置在中性粒细胞和血浆中，作为体外暴露于这些物质的结果 通常用于假肢装置的生物材料；然后，使用动物 模型，我们将确定这些缺陷是否也是 在体内的假体生物材料周围。这项研究将进一步记录 这些缺陷与增加的传染性有关 假体周围间隙与观察到的激活和 随后中性粒细胞和血浆功能受损。修改 通过在生物材料上涂覆物质(层粘连蛋白，纤维连接蛋白， Vitronectin，毛细血管内皮细胞)已知对 然后将进行中性粒细胞或较少激活补体。 然后，将未改性和改性的生物材料与以下各项进行比较 与细胞和体液宿主防御系统接触引起的损伤 以及它们在体内对假体周围间隙的感染性。 这次调查不仅应该增进我们对 种植后感染的机制，但它也应该有助于 通过提供体外实验来设计和预测未来的生物材料 传染性的相关因素。

The implantation of artificial devices and organs is always accompanied by the traumatic disruption of tissue. Long term success is currently hampered by an unacceptable incidence of infection in the inflamed tissue around the prosthesis. This proposal is designed to investigate one aspect of the pathogenesis of such infection. We will examine the in vitro and in vivo interaction of selected prosthetic biomaterials with cellular and humoral components of the traumatic wound. We hypothesize that contact between certain biomaterials and neutrophils and/or plasma will cause initial activation and resultant depletion of the host defenses against infection. The activation and resultant depletion of the host defenses against infection. The activation of the cellular (neutrophilic) component will result in release of activated intermediates of oxidative metabolism and of lysosomal constituents which can induce tissue necrosis. Concomitantly, the interaction will render the neutrophil incapable of effective further response to infection. Additionally, we hypothesize that activation of the humoral component will cause utilization and depletion of complement components necessary for effective host-microbe interaction. Specifically, the proposed work will characterize the changes that take place in neutrophil and plasma as a result of in vitro exposure to those biomaterials commonly used in prosthetic devices; then, using an animal model, we will determine whether or not these defects also are produced around prosthetic biomaterial in vivo. The study will further document that these defects are associated with increased infectivity in the periprosthetic space in proportion to the observed activation and subsequent impairment of neutrophil and plasma function. Modification of the biomaterials by coating them with substances (laminin, fibronectin, vitronectin, capillary endothelial cells) known to be less damaging to neutrophils or less activating to complement will then be carried out. Unmodified and modified biomaterials can then be compared with respect to the damage induced by contact with cellular and humoral host defenses in vitro as well as their infectivity of the periprosthetic space in vivo. This investigation should not only enhance our understanding of the mechanisms of postimplantation infections but it should also help in the design and predictive testing of future biomaterials by providing in vitro correlates of infectivity.