Biomaterials that Promote Infection Immunity

描述（由申请人提供）：医院感染是美国第四大死亡原因，每年有> 200万例病例（或约10%的美国医院患者）。这些感染中约有60%与植入式医疗器械有关，1992年造成> 45亿美元的医疗费用，每年约有80，000人死亡。据估计，仅在美国每年就有超过500万个人工或假体部件被植入。在NIH的支持下，我们的目标是设计生物材料，以寻求对特定细菌定植的短期和长期免疫反应。对于短期即时防御，模型生物材料将释放融合蛋白复合物-人工调理素-旨在增强入侵细菌与单核细胞/巨噬细胞（MO）的偶联;从而促进吞噬作用。对于长期保护，生物材料将抑制抗原呈递细胞（特别是树突状细胞-DC）产生T细胞和B细胞记忆和抗体表达，并可能刺激直接的天然杀伤T细胞反应。公共卫生相关性：据估计，仅在美国每年就有超过500万件人工或假体装置植入。然而，70%的医院获得性感染与植入物或留置医疗器械有关，病死率在5- 50%之间。在这项为期5年的NIH RO 1研究资助中，我们将开发一类新型生物材料，促进愈合，同时防止细菌定植和随后的感染。

DESCRIPTION (provided by applicant): Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). About 60% of these infections are associated with an implanted medical device causing >$4.5 billion medical costs in 1992 and ~80,000 deaths annually. It is estimated that over 5 million artificial or prosthetic parts are implanted per annum in the U.S. alone. Our goal, with NIH support, is to engineer biomaterials that will solicit a short- and long-term immune response to specific bacterial colonization. For short-term immediate defense, model biomaterials will release fusion protein complexes - artificial opsonins - designed to enhance the coupling of invading bacteria to monocyte/macrophage (MO); thus promoting phagocytosis. For long-term protection, the biomaterial will transfect antigen-presenting cells (specifically dendritic cells - DCs) to produce T- and B-cell memory and antibody expression, and potentially stimulate direct native killer T-cell responses. PUBLIC HEALTH RELEVANCE: It is estimated that over 5 million artificial or prosthetic devices are implanted per annum in the U.S. alone. However, 70% of hospital-acquired infections are associated with implants or indwelling medical devices, with the case-to-fatality ratio between 5-50%. In this 5-yr NIH RO1 research grant, we will develop a novel class of biomaterials that promote healing while preventing bacterial colonization and subsequent infections.