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

描述（由申请人提供）：全关节置换术后的深部伤口感染是医生和患者的毁灭性并发症，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增加，关节成形术的数量预计将在未来20年内急剧增加。越来越多的高危患者接受手术，进一步增加了脓毒性并发症和其他不良后果的严重性。抗生素已被纳入骨水泥预防和骨科应用超过30年。然而，由于对成本、长期机械性能的担忧，以及最重要的是，抗生素骨水泥通常不适用于预防性使用。作为一种抗菌剂，银因其特殊的安全性和有效性而得到广泛研究。此外，认为银诱导广泛细菌耐药性的风险很小。最近，已经研究了将银纳米颗粒（AgNP）掺入医疗装置中，但是将AgNP均匀分散到生物材料中所遇到的问题以及合成所需的复杂工艺和苛刻化学品的需要限制了其使用。位于圣安东尼奥的德克萨斯大学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，可以在丙烯酸树脂（如聚甲基丙烯酸甲酯（PMMA））中原位合成AgNP，不需要苛刻的化学品。初步研究表明，这种材料具有与不含AgNP的树脂相当的机械性能，同时证明了良好分布的AgNP，其提供对几种病原体具有生物杀灭作用的Ag+离子的延长释放。因此，本项目的目标是使用这种新方法原位生成AgNPs来开发一种持久、广谱、抗菌的骨水泥。本I期研究有五个具体目标：具体目标1。机械性能的制定和评价具体目标2。体外Ag+离子释放特定目标3。体外抗菌活性特定目标4.生物相容性特定目标5.疲劳试验 公共卫生相关性：全膝关节和全髋关节置换手术后的感染是患者的毁灭性并发症，对医疗保健系统来说非常昂贵。抗生素可以掺入骨水泥中以减少感染，但通常不用于预防，因为它们可能对骨水泥的机械性能产生不利影响，价格昂贵，并且可能导致耐药性，其中微生物能够在暴露于抗生素的情况下存活。开发一种安全有效的含银纳米颗粒的抗菌骨水泥，这种骨水泥不会诱导耐药性，并将克服现有产品的局限性，这将对公众健康产生重大影响。

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.