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(约占美国住院患者的10%)。这些感染中约有60%与植入的医疗设备有关，1992年造成45亿美元的医疗成本，每年造成约8万人死亡。据估计，仅在美国，每年就有超过500万个人工或假体植入。在美国国立卫生研究院的支持下，我们的目标是设计生物材料，以获得对特定细菌定植的短期和长期免疫反应。对于短期的即时防御，模型生物材料将释放融合蛋白复合体-人工调色素-旨在增强入侵细菌与单核/巨噬细胞(MO)的偶联；从而促进吞噬作用。为了长期保护，这种生物材料将转染抗原呈递细胞(特别是树突状细胞-DC)，以产生T和B细胞记忆和抗体表达，并潜在地刺激直接的自然杀伤T细胞反应。与公共健康相关：据估计，仅在美国，每年就有超过500万台人工或假肢装置被植入。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 RO1研究拨款中，我们将开发一种新型的生物材料，在促进愈合的同时防止细菌定植和后续感染。

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.