Antibacterial Biocompatible Bioresorbable Alloys for Musculoskeletal Implants

 描述（由申请人提供）：本项目的目的是研究用于肌肉骨骼修复和重建的新型生物可吸收合金的抗菌性能和生物相容性。尽管有先进的无菌手术技术和抗生素，但假体周围感染（PPI）仍会发生，并且在临床上难以治疗。一旦感染，这些植入物通常需要手术切除，因为全身给予抗生素不能提供足够的局部抗生素浓度，并且在生物膜形成时无效，这导致长期发病和显著的医疗保健负担。因此，需要抗菌生物相容性生物可吸收合金来缓解这些问题，以减少二次手术、患者不适和医疗保健成本。镁（Mg）合金代表了一类有前途的新型生物可吸收金属，提供了目前可用植入物中缺乏的互补特性。市售的纯镁降解太快，机械性能太弱，无法满足手术需求，而市售镁合金含有铝（Al）或稀土（RE）元素，会造成严重的长期毒性问题。PI设计了一种新型镁合金，由生物相容性元素组成，可提供更慢的降解和更大的机械强度。本项目的目的是确定新型镁合金的抗菌性能和生物相容性，用于潜在的植入物应用，例如，固定板、螺钉、骨针和克氏针。中心假设是，镁与锌（Zn）和钙（Ca）合理合金化将在体外和体内诱导理想的生物学反应。肌肉骨骼植入物应用的理想生物学反应包括增强骨细胞功能和再生，以及减少新合金上的细菌粘附和存活力，从而防止感染。中心假设是基于PI的先前结果以及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作用而建立的。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，创建无感染植入物的方法是创新的，因为它不依赖于抗生素，并减少了耐药性细菌的出现，如耐甲氧西林金黄色葡萄球菌（MRSA），一种常见的骨髓炎诱导病原菌。该项目意义重大，因为它将产生关于Mg-Zn-Ca合金抗菌性能及其用于肌肉骨骼植入物应用的生物相容性的关键知识，并克服临床前研究和临床转化的关键差距。

 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.