Antimicrobial-releasing gels for preventing infection in total joint arthroplasty

用于预防全关节置换术中感染的抗菌释放凝胶

• 批准号: 8453783
• 负责人: BRENT L VERNON
• 金额: $ 15万
• 依托单位: SONORAN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-06 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453783
• 关键词: Antibiotics; Area; Arthroplasty; Bacteria; Body Temperature; Bone Cements; Cells; Clinical Trials; Data; Development; Dose; Drug Controls; Drug Delivery Systems; Event; Fracture Healing; Future; Gel; Goals; Healed; Healthcare; Healthcare Systems; Hip region structure; Histology; Honey; Hospitals; Hydrogels; Immune; Implant; In Situ; Incidence; Infection; Infection prevention; Investments; Joints; Kidney; Knee; Lead; Liquid substance; Medicare; Metals; Microbe; Microbial Biofilms; Microspheres; Modeling; Operative Surgical Procedures; Organism; Orthopedics; Oryctolagus cuniculus; Outcome; Patients; Performance; Pharmaceutical Preparations; Polymers; Prevention; Prosthesis; Rattus; Replacement Arthroplasty; Safety; Site; Solid; Solutions; Staging; Staphylococcus aureus; Structure; Surface; Surgical wound; Suspension substance; Suspensions; Technology; Testing; Time; Ursidae Family; Viscosity; Work; Wound Healing; antimicrobial; antimicrobial drug; base; biomaterial compatibility; bone; bone healing; clinically relevant; commercialization; controlled release; cost; healing; hip replacement arthroplasty; implantation; improved; in vivo; killings; knee replacement arthroplasty; local drug delivery; meetings; novel; physical property; pre-clinical; preclinical study; prevent; public health relevance; sample fixation

DESCRIPTION (provided by applicant): Orthopaedic Surgical Site Infections (SSIs), including Prosthetic Joint Infections (PJIs), are an extremely costly health care problem, illustrated by the $70,000-$114,000 average total cost per case to treat more than 20,000 hip and knee replacement infections in the US each year. When a prosthetic joint becomes infected following arthroplasty, organisms form a biofilm on the prosthesis and become inaccessible to systemically delivered antibiotics or immune cells. There is no available option for antimicrobial delivery over the entire surface of a prosthetic joint that is press-fit directly into a bony implantation site, as the vast majority of implants are. Such a technology would provide a real benefit to patients and could decrease the current costs of treating these infections by approximately $2,000,000,000 per year. A promising approach for preventing infections following joint replacement is to use reasorbable in situ forming gels for the sustained release of antimicrobial drugs. These new gels offer the following advantages for improved prevention of prosthetic joint infections: 1) efficient and sustained antibiotic release; 2) soft yet cohesive physical structure allowing for complete surface coverage and preventing the development of biofilm in isolated crevasses, and 3) rapid degradability allowing for normal bone healing, fixing the implant in place. The goal of the proposed work is to generate critical in vivo safety and efficacy data to support future investment in pre-clinical and clinical trials on these new, synthetic, and fully resorbable antimicrobial-releasing gels. To do this, in situ forming hydrogels will be evaluated with respect to their safety and two clinically relevant outcomes-the quality of bone healing through the gel site and the efficacy of antibiotic-loaded gels in preventing infection on press-fit metal implants. Bone healing through the gel site will be evaluated by histology and load frame testing in a rabbit cancellous bone press-fit implant model. The efficacy in preventing infection will be evaluated by press-fitting textured metal implants subjected to S. aureus into a void in cancellous bone pre-filled with antimicrobial- loaded gels. Successful completion of the proposed work will provide clinically relevant proof-of- principle data regarding the safety and efficacy of these hydrogels and in particular their use on the surface of orthopaedic implants. This data will immediately be used to lead to a pre-IND meeting with the FDA and will attract future investment for the commercialization of this new drug product.

描述（由申请人提供）：骨科手术部位感染（SSI），包括假体关节感染（PJI），是一个代价极其高昂的医疗保健问题，如下所示： 在美国，每年治疗超过 20,000 例髋关节和膝关节置换感染，每例平均总费用为 70,000-114,000 美元。当假体关节在关节成形术后受到感染时，生物体在假体上形成生物膜，并且系统输送的抗生素或免疫细胞无法接触到生物膜。与绝大多数植入物一样，没有可用的选项可以在直接压装到骨植入部位的假体关节的整个表面上输送抗菌剂。这样的技术将为患者带来真正的好处，并且可以将目前治疗这些感染的成本每年减少约 20 亿美元。 预防关节置换术后感染的一种有前途的方法是使用可再吸收的原位形成凝胶来持续释放 抗菌药物。这些新型凝胶具有以下优点，可改善假体关节感染的预防：1）有效且持续的抗生素释放； 2) 柔软而有粘性的物理结构，可实现完整的表面覆盖，并防止在孤立的裂缝中形成生物膜，3) 快速降解性，可实现正常的骨愈合，将植入物固定到位。 拟议工作的目标是生成关键的体内安全性和有效性数据，以支持未来对这些新型合成且完全可吸收的抗菌释放凝胶的临床前和临床试验的投资。为此，原位形成水凝胶 将对其安全性和两个临床相关结果进行评估——通过凝胶部位的骨愈合质量以及载有抗生素的凝胶在预防压配金属植入物感染方面的功效。通过凝胶部位的骨愈合将通过兔子松质骨压配植入物模型中的组织学和负载框架测试来评估。通过将经金黄色葡萄球菌处理的有纹理的金属植入物压入预先填充有抗菌剂凝胶的松质骨的空隙中来评估预防感染的功效。成功完成拟议工作将提供有关这些水凝胶的安全性和有效性的临床相关原理验证数据，特别是它们在骨科植入物表面的使用。这些数据将立即用于与 FDA 举行 IND 前会议，并将为该新药产品的商业化吸引未来的投资。