Antibacterial Biocompatible Bioresorbable Alloys for Musculoskeletal Implants

用于肌肉骨骼植入物的抗菌生物相容性生物可吸收合金

• 批准号: 9038737
• 负责人: Huinan Hannah Liu
• 金额: $ 6.9万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9038737
• 关键词: 3D Print; Address; Alloys; Aluminum; Animal Model; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Adhesion; Biocompatible; Biological; Biomechanics; Bone Growth; Bone Marrow; Bone Regeneration; Calcium; Caring; Cell Adhesion; Cell physiology; Clinical; Defect; Deposition; Devices; Elements; Engineering; Equation; Evaluation; Excision; Femur; Fracture; Fracture Fixation; Goals; Grant; Guidelines; Healed; Health; Health Care Costs; Healthcare; Histology; Immune system; Implant; In Vitro; Industry; Infection; Infection prevention; Knowledge; Lead; Ligaments; Location; Magnesium; Mechanics; Mesenchymal Stem Cells; Metals; Microbial Biofilms; Minerals; Mission; Modeling; Morbidity - disease rate; Musculoskeletal; Natural regeneration; Nutrient; Operative Surgical Procedures; Osteogenesis; Osteomyelitis; Patients; Pilot Projects; Play; Property; Rare Earth Metals; Rattus; Research; Research Personnel; Scanning Electron Microscopy; Sterility; Techniques; Technology Transfer; Toxic effect; Translations; United States National Institutes of Health; Weight-Bearing state; Work; Zinc; bactericide; base; biomaterial compatibility; bone; bone cell; bone healing; bone loss; care burden; commercialization; cost; design; follow-up; healing; implantable device; implantation; improved; in vivo; innovation; interest; materials science; medical implant; methicillin resistant Staphylococcus aureus; novel; osteogenic; pathogenic bacteria; preclinical study; public health relevance; reconstruction; repaired; response; sample fixation; scaffold; tibia; tomography

 DESCRIPTION (provided by applicant): The goal of this project is to investigate antibacterial property and biocompatibility of a new class of bioresorbable alloys for musculoskeletal repair and reconstruction. Despite advanced sterile surgical techniques and antibiotics, periprosthetic infections (PPI) still occur, and they are clinically challenging to treat. Once infected, these implants often require surgical removal because systemic administration of antibiotics does not provide adequate local antibiotic concentration and is ineffective when a biofilm forms, which leads to prolonged morbidity and significant health care burden. Thus, antibacterial biocompatible bioresorbable alloys are needed to mitigate these problems to reduce secondary surgeries, patient discomfort, and health care costs. Magnesium (Mg) alloys represent a promising new class of bioresorbable metals, providing complementary properties that are absent in implants available today. Commercially available pure Mg degrades too fast and is mechanically too weak for the surgical needs, while commercial Mg alloys contain aluminum (Al) or rare earth (RE) elements that pose serious concerns of long-term toxicity. The PI has engineered a novel class of Mg alloy composed of biocompatible elements that provide slower degradation and greater mechanical strength. The objective of this project is to determine antibacterial property and biocompatibility of the new Mg alloys for potential implant applications, e.g., fixation plates, screws, pins, and K-wires. The central hypothesis is that alloying Mg rationally with zinc (Zn) and calcium (Ca) will induce desirable biological responses in vitro and in vivo. The desirable biological responses for musculoskeletal implant applications include enhanced bone cell functions and regeneration, and reduced bacterial adhesion and viability on the new alloys, thus preventing infection. The central hypothesis is established based on the PI's prior results and positive effects of Mg, Zn, and Ca as essential nutrients for bone repair and immune system health. This project is innovative because the alloy design integrates biological benefits into the materials science tetrahedron to achieve synergistic properties for preventing infection and improving healing. Further, the approach for creating infection-free implants is innovative because it does not rely on antibiotics, and reduce the emergence of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), a common osteomyelitis-inducing pathogenic bacterium. This project is significant because it will produce critical knowledge on antibacterial property of Mg-Zn-Ca alloys and their biocompatibility for musculoskeletal implant applications, and overcome the critical gap toward preclinical studies and clinical translation.

 描述（由适用提供）：该项目的目的是研究一种新的生物渗透合金的抗菌特性和生物相容性，用于肌肉骨骼修复和重建。尽管晚期无菌手术技术和抗生素，但周围感染（PPI）仍会发生，并且在临床上挑战治疗。一旦被感染，这些即将需要手术去除，因为全身抗生素的给药不能提供足够的局部抗生素浓度，并且当生物膜形成形式时，这会导致长时间的发病率和明显的医疗保健伯恩（Burnen）。这就是需要抗菌生物相容性的生物可吸收合金来减轻这些问题以减少继发性手术，患者不适和医疗保健费用。镁（mg）合金代表了一种有希望的新型生物吸收金属，提供了当今可用的即兴中缺少的完整特性。市售的纯MG降解太快，并且在机械上对于手术需求而言太弱了，而商业MG合金含有铝（AL）或稀土（RE）元素，这些元素引起了长期毒性的严重关注。 PI设计了一种新型的MG合金，该合金由生物相容性元件组成，可提供较慢的降解和更高的机械强度。该项目的目的是确定用于潜在植入物应用的新MG合金的抗菌特性和生物相容性，例如固定板，螺丝，销钉和K线。中心假设是，与锌（Zn）和钙（CA）合理地合金MG将在体外和体内诱导理想的生物学反应。对于肌肉骨骼植入物应用的理想生物学反应包括增强的骨细胞功能和再生，以及降低了新合金对新合金的细菌粘合剂和生存能力，从而防止了感染。基于PI的先前结果和Mg，Zn和Ca作为骨修复和免疫系统健康的必需营养素的积极影响，建立了中心假设。该项目具有创新性，因为合金设计将生物学益处整合到材料科学四面体中，以实现预防感染和改善愈合的协同特性。此外，创造无感染的垂体的方法是创新的，因为它不依赖抗生素，并降低了抗生素耐药细菌的出现，例如金黄色葡萄球菌（MRSA），一种常见的骨髓炎诱导的骨髓炎诱导的致病性细菌。该项目之所以重要，是因为它将对MG-ZN-CA合金的抗菌特性及其对肌肉骨骼植入物应用的生物相容性产生关键知识，并克服临床前研究和临床翻译的关键差距。