Long-Term Broad-Spectrum Prevention of Implant-Related Infections

长期广谱预防种植体相关感染

基本信息

批准号：
8251429
负责人：
Gregg Siegel
金额：
$ 16.23万
依托单位：
BIOMEDICAL DEVELOPMENT CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-30 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8251429
关键词：
Acinetobacter baumannii Acrylic Resins Antibiotic Resistance Antibiotics Area Arthroplasty Biocompatible Materials Biomedical Engineering Bone Cements Chemicals Clinical Complex Complication Data Development Devices Doctor of Medicine Doctor of Philosophy Drug Formulations Drug resistance Economic Burden Engineering Ensure Evaluation Exposure to FDA approved Fatigue Free Radicals Future Goals Hardness Health Sciences Healthcare Healthcare Systems Implant In Situ In Vitro Infection Intramuscular Ions Joints Knee Lead Legal patent Libraries Life Life Expectancy Materials Testing Measures Mechanics Medical Device Methods Modeling Morbidity - disease rate Operative Surgical Procedures Orthopedics Oryctolagus cuniculus Patients Performance Physicians Plant Resins Polymers Polymethyl Methacrylate Porosity Prevention Preventive Principal Investigator Process Production Property Prophylactic treatment Pseudomonas aeruginosa Public Health Reducing Agents Regulation Reproducibility Research Research Personnel Risk Safety Sampling Scientist Severities Silver Spectroscopy, Fourier Transform Infrared Spectrum Analysis Stabilizing Agents Staging Surface System Technology Tensile Strength Testing Texas Total Hip Replacement Universities Water Wound Infection absorption adverse outcome aging population antimicrobial antimicrobial drug bacterial resistance bactericide biomaterial compatibility commercialization cost cytotoxicity density efficacy evaluation high risk implantation in vivo innovation methicillin resistant Staphylococcus aureus microorganism nanoparticle nanoparticulate novel pathogen phase 1 study polymerization prevent prophylactic scale up septic

项目摘要

DESCRIPTION (provided by applicant): Deep wound infection following total joint arthroplasty is a devastating complication for physician and patient, a leading cause of morbidity, and a significant economic burden to the healthcare system. With an aging population and increased life expectancies, the number of arthroplasties is expected to rise dramatically over the next 20 years. The growing number of high-risk patients undergoing surgery further increases the severity of septic complications and other adverse outcomes. Antibiotics have been incorporated into bone cement for prophylaxis and orthopedic applications for more than 30 years. However, antibiotic laden bone cement is not generally indicated for prophylactic use due to concerns about cost, long-term mechanical performance, and most importantly, the potential for developing antibiotic resistance. As an antimicrobial agent, silver has been extensively researched because of its exceptional safety and efficacy. Further, the risk of silver inducing widespread bacterial resistance is considered to be remote. Recently, the incorporation of silver nanoparticles (AgNP) into medical devices has been investigated, but problems encountered with homogeneously dispersing AgNPs into biomaterials and the need for complex processes and harsh chemicals required for synthesis have limited its use. Researchers at the University of Texas Health Science Center at San Antonio have recently developed an innovative single-step method to synthesize AgNPs in situ in acrylic resins such as polymethylmethacrylate (PMMA) that requires no harsh chemicals. Preliminary studies show that this material possesses mechanical properties comparable to resins without AgNPs, while demonstrating well-distributed AgNPs that provide extended release of Ag+ ions that are biocidal to several pathogens. Thus, the goal of this project is to develop a long-lasting, broad-spectrum, antimicrobial bone cement using this novel method to generate AgNPs in situ. This Phase I study has five Specific Aims: Specific Aim 1. Formulation and Evaluation of Mechanical Properties Specific Aim 2. In Vitro Ag+ Ion Release Specific Aim 3. In Vitro Antimicrobial Activity Specific Aim 4. Biocompatibility Specific Aim 5. Fatigue Testing PUBLIC HEALTH RELEVANCE: Infection following total knee and total hip replacement surgery is a devastating complication for patients and very costly to the healthcare system. Antibiotics can be incorporated into bone cement to reduce infection, but are generally not used preventively because they can adversely impact the mechanical properties of the cement, are expensive, and can cause drug resistance where a microorganism is able to survive exposure to the antibiotic. The development of a safe and effective antimicrobial bone cement containing silver nanoparticles that would not induce drug resistance and would overcome the limitations of current products would have a significant impact on public health.

描述（由申请人提供）：全关节置换术后的深部伤口感染对医生和患者来说是一种毁灭性的并发症，是发病的主要原因，也是医疗保健系统的重大经济负担。随着人口老龄化和预期寿命的延长，预计未来 20 年关节置换术的数量将急剧增加。接受手术的高危患者数量不断增加，进一步增加了脓毒症并发症和其他不良后果的严重程度。抗生素被纳入骨水泥用于预防和骨科应用已有 30 多年的历史。然而，由于成本、长期机械性能以及最重要的是产生抗生素耐药性的可能性，含有抗生素的骨水泥通常不用于预防性使用。作为一种抗菌剂，银因其卓越的安全性和功效而受到广泛的研究。此外，银引发广泛细菌耐药性的风险被认为很小。最近，人们对将银纳米颗粒 (AgNP) 纳入医疗器械进行了研究，但将银纳米颗粒均匀分散到生物材料中遇到的问题以及合成所需的复杂工艺和刺激性化学品限制了其使用。德克萨斯大学圣安东尼奥健康科学中心的研究人员最近开发了一种创新的单步方法，可以在聚甲基丙烯酸甲酯 (PMMA) 等丙烯酸树脂中原位合成纳米银颗粒，无需使用刺激性化学品。初步研究表明，该材料具有与不含 AgNP 的树脂相当的机械性能，同时证明 AgNP 分布均匀，可延长释放 Ag+ 离子，对多种病原体具有杀菌作用。因此，该项目的目标是使用这种原位生成银纳米粒子的新方法开发一种持久、广谱、抗菌骨水泥。该第一阶段研究有五个具体目标：具体目标 1. 机械性能的制定和评估具体目标 2. 体外 Ag+ 离子释放具体目标 3. 体外抗菌活性具体目标 4. 生物相容性具体目标 5. 疲劳测试公共卫生相关性：全膝关节和全髋关节置换手术后的感染对患者来说是一种毁灭性的并发症，并且对医疗保健系统来说成本高昂。抗生素可以掺入骨水泥中以减少感染，但通常不用于预防性使用，因为它们会对骨水泥的机械性能产生不利影响，价格昂贵，并且可能导致微生物在接触抗生素后存活下来的耐药性。开发一种安全有效的含有银纳米粒子的抗菌骨水泥，不会引起耐药性，并克服现有产品的局限性，将对公众健康产生重大影响。