Bacteriophage Presenting Hydrogels to Treat Osteomyelitis

 描述（由申请人提供）：生物材料相关感染每年造成超过100万例医院感染，其预防是成功的再生医学策略的关键组成部分。生物材料植入物的细菌感染经常导致植入物的完全移除，尽管积极的抗生素治疗。金黄色葡萄球菌和铜绿假单胞菌是与医疗器械失效相关的最具临床相关性的革兰氏阳性和革兰氏阴性病原体。噬菌体是具有感染和裂解宿主细菌的能力的细菌特异性病毒。我们最近设计了一种基于聚乙二醇（PEG）的水凝胶系统，用于控制治疗蛋白的递送，以促进小鼠桡骨节段性缺损模型中的骨修复。这些水凝胶被细菌污染导致骨愈合、细菌持续存在和骨吸收的完全抑制。本项目的目标是设计 抗感染的聚乙二醇水凝胶。中心假设是使用PEG-水凝胶递送噬菌体将减少用于骨修复的小鼠模型中的感染。目的1：设计水凝胶，用于控制活性噬菌体的递送以消除细菌。目的2：检查噬菌体呈递水凝胶减少感染和改善骨修复的能力。目的3：表征对含有噬菌体的水凝胶的体内炎症反应。这项研究具有创新性，因为它专注于开发在不使用抗生素的情况下抵抗感染的生物材料，从而减少抗生素耐药性细菌的发展，同时最大限度地减少植入设备的故障。作为本研究的成果，我们将建立控制噬菌体释放水凝胶的可行性，以减少感染和促进骨修复。这项研究将建立一个抗感染的生物材料，适用于各种生物医学设备的战略。

 DESCRIPTION (provided by applicant): Biomaterial-associated infections account for over one million nosocomial infections per year, and their prevention is a critical component to successful regenerative medicine strategies. Bacterial infection of biomaterial implants frequently results in complete removal of the implant despite aggressive antibiotic therapy. Staphylococcus aureus and Pseudomonas aeruginosa are the most clinically relevant gram positive and gram negative pathogens associated with medical device failure. Bacteriophages are bacteria-specific viruses that have the ability to infect and lyse host bacteria. We have recently engineered a poly (ethylene glycol) (PEG)-based hydrogel system for controlled delivery of therapeutic proteins that facilitates bone repair in a murine radial segmental defect model. Contamination of these hydrogels with bacteria leads to complete inhibition of bone healing, persistence of bacteria, and bone resorption. The objective of this project is to engineer PEG- based hydrogels that are infection resistant. The central hypothesis is that delivery of bacteriophage using a PEG-hydrogel will reduce infection in a mouse model for bone repair. Aim 1: Engineer hydrogels for controlled delivery of active bacteriophage to eliminate bacteria. Aim 2: Examine the ability of phage presenting hydrogels to reduce infection and improve bone repair. Aim 3: Characterize the in vivo inflammatory response to bacteriophage containing hydrogels. The proposed research is innovative because it focuses on developing biomaterials that resistant infection without the use of antibiotics, thereby reducing the development of antibiotic resistant bacteria while minimizing implanted device failure. As outcomes of this research, we will establish the feasibility of controlled bacteriophage release hydrogels to reduce infection and promote bone repair. This research will establish a strategy for infection-resistant biomaterials that is applicable to various biomedical devices.