TRAUMA, INFECTION, AND PROSTHETIC BIOMATERIALS

人工装置和器官的植入总是伴随着 组织的创伤性破坏 长期成功目前 由于发炎组织中不可接受的感染发生率而受阻 在假肢周围。 本提案旨在调查一个方面 这种感染的发病机制。 我们将检查体外和体内 选择的假体生物材料与细胞和 创伤伤口的体液成分 我们假设接触 某些生物材料与中性粒细胞和/或血浆之间的相互作用将导致 宿主防御系统的初始激活和最终耗尽， 感染 宿主防御系统的激活和随之而来的损耗 抵抗感染 细胞（亲脂性）成分的活化 将导致氧化代谢的活化中间体的释放 以及可诱导组织坏死的溶酶体成分。 同时，这种相互作用将使中性粒细胞不能 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 补充有效宿主-微生物相互作用所必需的成分。 具体而言，拟议的工作将描述 由于体外暴露于那些 通常用于假体装置的生物材料;然后，使用动物 模型，我们将确定是否这些缺陷也产生 在生物修复材料周围 该研究将进一步记录 这些缺陷与感染性增加有关， 假体周围空间与观察到的激活成比例， 随后中性粒细胞和血浆功能受损。 改性 通过用物质（层粘连蛋白，纤连蛋白， 玻连蛋白，毛细血管内皮细胞），已知对 然后进行中性粒细胞或更少的补体活化。 然后可以比较未改性和改性的生物材料， 与细胞和体液宿主防御接触引起的损伤， 以及它们在体内对假体周围空间的感染性。 这次调查不仅应该加强我们对 植入后感染的机制，但它也应该有助于 设计和预测性测试未来的生物材料， 与传染性相关

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.