Bacteriophage Presenting Hydrogels to Treat Osteomyelitis

噬菌体呈递水凝胶来治疗骨髓炎

• 批准号: 9050977
• 负责人: Christopher Thomas Johnson
• 金额: $ 4.86万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-22 至 2020-02-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9050977
• 关键词: Accounting; Adverse event; Affect; Allografting; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Autologous Transplantation; Bacteria; Bacterial Counts; Bacterial Infections; Bacteriophages; Biocompatible Materials; Bone Regeneration; Bone Resorption; Cells; Chronic; Clinical Trials; Confocal Microscopy; Cytolysis; Defect; Development; Devices; Engineering; Enzymes; Equipment Malfunction; Excision; Flow Cytometry; Formulation; Gene Expression Profiling; Healed; Histology; Hydrogels; Image; Immune response; Implant; Infection; Infection prevention; Inflammatory; Inflammatory Response; Injury; Leg Ulcer; Mammalian Cell; Mediating; Medical Device Failures; Microbial Biofilms; Modeling; Monitor; Morbidity - disease rate; Mus; Nosocomial Infections; Operative Surgical Procedures; Osteomyelitis; Otitis; Outcomes Research; Phase; Phase I Clinical Trials; Play; Polymers; Population; Postoperative Period; Prevention; Process; Property; Pseudomonas aeruginosa; Radial; Regenerative Medicine; Reporting; Research; Resistance; Role; Safety; Speed; Staphylococcus aureus; System; Therapeutic; Time; Venous; Virus; Work; antimicrobial; bacterial resistance; base; bone; bone healing; bone morphogenetic protein 2; clinically relevant; clinically significant; cytokine; density; ethylene glycol; fluorescence imaging; healing; implantable device; implantation; improved; in vivo; innovation; medical implant; mortality; mouse model; novel; pathogen; public health relevance; regenerative; standard care; systemic toxicity; targeted treatment; therapeutic protein

 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.

 描述（由申请人提供）：生物材料相关感染每年造成超过一百万例医院感染，其预防是成功的再生医学策略的关键组成部分。尽管采用积极的抗生素治疗，生物材料植入物的细菌感染常常导致植入物完全移除。金黄色葡萄球菌和铜绿假单胞菌是与医疗器械故障相关的临床上最相关的革兰氏阳性和革兰氏阴性病原体。噬菌体是细菌特异性病毒，具有感染和裂解宿主细菌的能力。我们最近设计了一种基于聚乙二醇（PEG）的水凝胶系统，用于控制递送治疗性蛋白质，促进小鼠桡骨节段缺损模型中的骨修复。这些水凝胶被细菌污染会导致骨愈合、细菌持续存在和骨吸收的完全抑制。该项目的目标是设计 基于 PEG 的抗感染水凝胶。核心假设是，使用 PEG 水凝胶递送噬菌体将减少骨修复小鼠模型中的感染。目标 1：设计水凝胶以控制递送活性噬菌体以消除细菌。目标 2：检查噬菌体呈递水凝胶减少感染和改善骨修复的能力。目标 3：表征对含有噬菌体的水凝胶的体内炎症反应。拟议的研究具有创新性，因为它的重点是开发无需使用抗生素即可抵抗感染的生物材料，从而减少抗生素耐药细菌的发展，同时最大限度地减少植入设备的故障。作为这项研究的成果，我们将确定控制噬菌体释放水凝胶以减少感染和促进骨修复的可行性。这项研究将建立一种适用于各种生物医学设备的抗感染生物材料策略。