Cationic Steroidal Antimicrobial-13 for Use as an Orthopedic Device Coating

用作骨科器械涂层的阳离子类固醇 Antimicrobial-13

• 批准号: 8277738
• 负责人: Kristofer D. Sinclair
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277738
• 关键词: Address; Adverse effects; Affect; Agreement; Antibiotic Resistance; Antibiotic Therapy; Award; Bacteria; Bacterial Infections; Centers for Disease Control and Prevention (U.S.); Cities; Clinical; Clinical Research; Collaborations; Control Groups; Devices; Diagnosis; Ensure; Eukaryotic Cell; Exhibits; Exposure to; Film; Fostering; Foundations; Goals; Healthcare Systems; Hospitalization; Hospitals; Hour; Human; Implant; In Vitro; Incidence; Infection; Infection prevention; Joints; K-Series Research Career Programs; Knowledge; Laboratory Research; Lead; Medial; Mentors; Modeling; Motivation; Operative Surgical Procedures; Orthopedics; Pathway interactions; Patient Care; Patients; Perioperative; Plug-in; Polymers; Predisposition; Prevention; Procedures; Production; Prokaryotic Cells; Protocols documentation; Quality of life; Rehabilitation therapy; Replacement Arthroplasty; Reporting; Research; Research Design; Resistance; Safety; Scientist; Sheep; Signal Transduction; Silicones; Sodium Chloride; Staging; Staphylococcus aureus; System; Time; Tissues; Titania; Titanium; Training; United States; Universities; Utah; Veterans; Work; abstracting; antimicrobial; bacterial resistance; bactericide; bone; career; career development; clinical care; combat; cost; experience; hip replacement arthroplasty; implant coating; implantation; improved; in vitro testing; in vivo; in vivo Model; killings; knee replacement arthroplasty; novel; prevent; programs; research study; skeletal; skeletal tissue; success; surface coating

DESCRIPTION Cationic Steroidal Antimicrobial-13 for Use as an Orthopedic Device Coating Abstract RELEVANCE: The Career Development Award-Level 1 will provide Dr. Sinclair with the mentoring and training necessary to establish him as an independent VA Career Scientist. This work, utilizing the novel polymer released antimicrobial delivery system to address the current limitations of antibiotic therapies, and the collaborations with his mentors will be the foundation on which Dr. Sinclair will establish his VA research career. The Center for Disease Control reports nearly 500,000 confirmed incidences of S. aureus and methicilin-resistant S. aureus (MRSA) occurring in the United States per year. This increasingly high number of MRSA cases can be attributed to the bacteria's evolved resistance toward antibiotic therapy. To address these issues, Cationic Steroidal Antimicrobial- 13 (CSA-13) will be incorporated into a silicone (Si) polymer coating and examined for its bactericidal potential when used as an orthopedic device coating. Preliminary in vitro testing has demonstrated greater than a 99% reduction of MRSA within 24 hours with exposure to titanium (Ti) plug implants coated with the 18% w/w Si polymer released CSA-13 antimicrobial. OBJECTIVES: 1) Provide Dr. Sinclair with the mentoring and training necessary to establish himself as a VA Career Scientist. 2) Combat resistant bacteria strain infections associated with common orthopedic device procedures through the use of the Si polymer released CSA- 13 antimicrobial. The long-term goals of this work are to foster Dr. Sinclair's continued progress toward the award of VA Career Scientist and to use the knowledge gained from his work with CSA-13 to reduce the incidence of device-related infection, minimize the time required for hospitalization, decrease the expense incurred by the VA health care system and patient, and reduce the number of stages required for revision procedures. HYPOTHESES: 1) The CSA-13 antimicrobial (18% w/w) will prevent infection caused by MRSA in vivo when eluted from the Si polymer coating on a porous coated titanium implant. 2) The rate and amount of periprosthetic bone ingrowth will not be adversely affected by the release of the CSA-13 antimicrobial. PROCEDURES: Four groups, each utilizing seven sheep, will receive a porous coated Ti bone plug in the medial aspect of the femoral condyle. Groups 1-3 will be inoculated with 200 ¿l of 1x108 planktonic MRSA. The experimental group (Group 1) will have a porous coated Ti bone plug coated with a thin film of CSA-13 in a Si polymer (18% w/w), the polymer control (Group 2) will use only the Si coating (without CSA-13), to confirm an infection signal (Group 3) will use only the bone plug without CSA-13 or the Si coating, and Group 4 will serve as the surgical control; having neither CSA-13, Si coating, or bacteria added. The results of a power analysis indicated that an effect size of seven was required for statistical significance. SIGNIFICANCE OF FINDINGS: The success of this novel antimicrobial has the potential to significantly improve VA clinical care by reducing costs associated with primary and revision surgeries caused by perioperative device related infections. This research would also greatly improve the veteran's quality of life and reduce time required for hospitalization and rehabilitation by eliminating or significantly limiting the vetera's susceptibility to preoperative device related infections. PUBLIC HEALTH RELEVANCE: Cationic Steroidal Antimicrobial-13 for use as an Orthopedic Device Coating Project Narrative. The primary goal of this Career Development Award-Level 1 is to provide Dr. Sinclair with a unique pathway to independence. This will be accomplished with expert mentoring and advising from prolific scientists in the fields of orthopedic medicine and infectious disease. With their guidance and the support of the Career Development Award, Dr. Sinclair will work to develop a unique approach to address the limitations of current antibiotic therapy. The objective of the proposed research is to combat antibiotic resistant bacterial infections associated with common orthopedic devices through the use of a synthetic bacteria eliminating surface coating. The success of this program has the potential to reduce device-related infections, time required for hospitalization, the expense incurred by the VA Health Care System and its patients, as well as the number of stages required for revision procedures.

描述 用作骨科器械涂层的阳离子甾体抗菌剂-13摘要相关性：职业发展奖-1级将为Sinclair博士提供必要的指导和培训，以使他成为独立的VA职业科学家。这项工作，利用新型聚合物释放的抗菌药物递送系统来解决目前抗生素治疗的局限性，以及与他的导师的合作将是基础 辛克莱博士将在此基础上建立退伍军人事务部的研究事业 疾病控制中心报告了近50万例确诊的S。金黄色葡萄球菌和耐甲氧西林的S.金黄色葡萄球菌（MRSA）每年发生在美国。MRSA病例数量的增加可以归因于细菌对抗生素治疗的进化耐药性。为了解决这些问题，将阳离子甾体抗菌剂-13（CSA-13）掺入硅（Si）聚合物涂层中，并检查其用作骨科器械涂层时的杀菌潜力。初步体外试验表明，暴露于涂有18% w/w Si聚合物释放CSA-13抗菌剂的钛（Ti）塞植入物后，24小时内MRSA减少99%以上。承诺：1）为辛克莱博士提供必要的指导和培训，以建立自己作为一个VA职业科学家。2)通过使用硅聚合物释放的CSA- 13抗菌剂，对抗与常见骨科器械手术相关的耐药细菌菌株感染。这项工作的长期目标是促进Sinclair博士继续获得VA职业科学家奖，并利用他在CSA-13工作中获得的知识减少器械相关感染的发生率，最大限度地减少住院时间，减少VA医疗保健系统和患者的费用，并减少翻修手术所需的阶段数量。假设：1）CSA-13抗菌剂（18% w/w）在从多孔涂层钛植入物上的Si聚合物涂层洗脱时，可预防MRSA引起的体内感染。2)CSA-13抗菌剂的释放不会对假体周围骨长入的速率和量产生不良影响。程序：4组（每组7只绵羊）将在股骨髁内侧植入多孔涂层钛骨塞。第1-3组将接种200 µ l 1 × 108抗甲氧西林金黄色葡萄球菌。实验组（第1组）将使用在Si聚合物（18% w/w）中涂覆CSA-13薄膜的多孔涂层Ti骨塞，聚合物对照组（第2组）将仅使用Si涂层（不含CSA-13），为了确认感染信号（第3组），将仅使用不含CSA-13或Si涂层的骨塞，第4组将作为手术对照;不添加CSA-13、Si涂层或细菌。功效分析的结果表明，效应量为7时才具有统计学显著性。结果的意义：这种新型抗菌剂的成功有可能通过降低与围手术期器械相关感染引起的初次和翻修手术相关的成本，显著改善VA临床护理。这项研究还将大大提高退伍军人的生活质量，并通过消除或显著限制退伍军人对术前器械相关感染的易感性来减少住院和康复所需的时间。 公共卫生关系： 用作骨科器械涂层的阳离子甾体抗菌剂-13项目叙述。 这个职业发展奖的主要目标是为辛克莱博士提供一个独特的独立途径。这将通过骨科医学和传染病领域多产科学家的专家指导和建议来实现。在他们的指导和职业发展奖的支持下，辛克莱博士将致力于开发一种独特的方法来解决目前抗生素治疗的局限性。拟议研究的目的是通过使用合成细菌消除表面涂层来对抗与常见骨科器械相关的抗生素耐药性细菌感染。该项目的成功有可能减少器械相关感染、住院所需时间、VA医疗保健系统及其患者产生的费用以及翻修手术所需的阶段数量。