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

长期广谱预防种植体相关感染

• 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
• 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

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）：全部关节置换术后的深层伤口感染是医师和患者的毁灭性并发症，发病率的主要原因以及医疗体系的巨大经济负担。随着人口老龄化和预期寿命的增加，预计在未来20年中，关节塑料的数量将大幅增长。越来越多的高危患者接受手术进一步增加了化粪池并发症和其他不良后果的严重程度。已有30多年的历史已纳入预防和骨科应用的骨水泥中。然而，由于担心成本，长期机械性能以及最重要的是产生抗生素耐药性的潜力，因此通常不适合预防性使用抗生素。作为抗菌剂，由于其出色的安全性和有效性，对银进行了广泛的研究。此外，诱导白银广泛的细菌耐药性的风险被认为是遥远的。最近，已经研究了将银纳米颗粒（AGNP）掺入医疗设备中，但是均匀地将AGNP分散到生物材料中遇到的问题，并且需要进行复杂的过程和所需的苛刻化学物质的需求限制了其使用。得克萨斯大学圣安东尼奥分校的研究人员最近开发了一种创新的单步方法，以在丙烯酸树脂（例如多甲基丙烯酸酯（PMMA））的原位合成Agnps，不需要刺激性化学物质。初步研究表明，该材料具有与没有AGNP的树脂相当的机械性能，同时证明了分布良好的AGNP，这些AGNP提供了与几种病原体相比的Ag+离子的扩展释放。因此，该项目的目的是使用这种新颖的方法来开发一种持久的，广谱的抗菌骨水泥，以产生原位。本I阶段研究具有五个具体目的：特定目标1。机械性能的配方和评估特定目的2。在体外Ag+离子释放特定目标3。在体外抗菌活性特定目的4。生物相容性特定目的5。疲劳测试。 公共卫生相关性：全膝盖和全髋关节置换手术后的感染是患者的毁灭性并发症，对医疗保健系统的昂贵。可以将抗生素掺入骨水泥中以减少感染，但通常不预防性使用，因为它们可能会对水泥的机械​​性能产生不利影响，很昂贵，并且在微生物能够在暴露于抗生素的情况下能够生存。开发含有不会诱导耐药性并克服当前产品局限性的银纳米颗粒的安全有效的抗菌骨水泥的发展，将对公共卫生产生重大影响。