UNS: Engineering Infection-Free Implants for Skeletal Reconstruction

全球每年有超过5000万人需要合成植入物来帮助从创伤或疾病导致的骨质流失或损伤中恢复。该项目旨在开发一种新的材料，首次具有理想植入物的所有特性：它应该支持体重和机械应力，抑制感染，促进骨愈合，并最终随着骨组织的生长而无害地溶解。虽然有100多种合成骨移植物被批准用于临床，但没有一种具有所有这些特性。这项研究不仅解决了治疗关键尺寸的大骨缺损以恢复患者的活动性和独立生活的挑战，而且还显著减少了对抗生素和昂贵生长因子的临床依赖，从而减少了相关的副作用（例如，抗生素耐药性）和医疗保健费用。这项研究的结果将导致下一代植入物，具有当前金属和聚合物植入物的综合优势，同时消除它们的问题。更广泛地说，该项目将开辟智能可吸收材料研究的新途径，为实用设计指南奠定基础，使数百万骨骼损伤或疾病患者受益，并吸引植入物行业对技术转让的重大兴趣。这些反过来将提高美国公司在全球医疗器械市场的竞争力。综合研究和教育计划还将对研究生、本科生和大学预科教育产生更广泛的影响，并提高公众对有利于医疗保健的工程解决方案的认识。在与加州，滨江的大学现有的计划合作，主要研究者将吸引代表性不足的少数民族学生和残疾学生，通过有趣的生物材料模块与阿尔法中心和梅萨学校计划激励大学预科学生，并通过与伯恩斯科学和工程日合作活动教育公众。本项目的总体目标是设计一种新型可吸收抗菌骨诱导植入物（RAOI），该植入物将承受重量并抵抗弯曲和扭转。具体而言，RAOI由生物可吸收、生物相容性和机械强度高的镁合金作为主体基材，表面上的工程纳米结构用于预防感染和增强骨再生。RAOI设计的新奇在于其集成的多功能性，首次可能满足理想植入物的所有标准。为了释放镁合金的全部潜力，我们必须解决控制其降解速率的关键科学和工程挑战。我们的新方法是在镁合金表面创建工程化纳米结构，以同时实现三个关键功能：（1）调节大块镁基质的降解速率，（2）降低致病菌的粘附和存活率，（3）增强骨髓间充质干细胞的粘附和成骨分化，以加快骨愈合。

More than 50 million people per year worldwide need synthetic implants to help recover from bone loss or injury resulting from trauma or disease. This project seeks to develop a new class of materials that, for the first time, has all of the properties of an ideal implant: it should support body weight and mechanical stress, suppress infection, enhance bone healing, and ultimately dissolve harmlessly as bone tissue grows back. While more than 100 synthetic bone grafts are approved for clinical use, none of them has all of these properties. This research not only addresses the challenges in treating critical-sized large bone defects to restore mobility and independent life of patients, but also significantly reduces the clinical dependence on antibiotics and expensive growth factors, thus reducing associated side effects (e.g., antibiotic resistance) and health care costs. The outcome of this research will lead to the next-generation implants that have the combined advantages of current metallic and polymeric implants while eliminating their problems. More broadly, this project will open up new avenues of research in smart resorbable materials, build the foundation for practical design guidelines, benefit millions of patients with skeletal injuries or diseases, and attract significant interests of implant industry for technology transfer. These, in turn, will increase the competitiveness of U.S. companies in the global medical device market. The integrated research and education plans will also have broader impacts on graduate, undergraduate, and pre-college education as well as public awareness about engineering solutions that benefit health care. In collaboration with the existing programs at the University of California, Riverside, the Principal Investigator will attract underrepresented minority students and students with disabilities, motivate pre-college students through fun biomaterial modules with ALPHA center and MESA Schools Programs, and educate the public through collaborative events with Bourns Science and Engineering Day. The overall objective of this project is to engineer a novel resorbable antibacterial osteoinductive implant (RAOI) that will bear weight and resist bending and torsion. Specifically, the RAOI consists of bioresorbable, biocompatible and mechanically strong magnesium alloys as the bulk substrate and engineered nanostructures on the surface to prevent infection and enhance bone regeneration. The novelty of RAOI design lies in its integrated multifunctionality that can potentially meet ALL criteria for an ideal implant for the first time. To unlock the full potential of magnesium alloys, we must address the critical scientific and engineering challenge of controlling their degradation rate. Our novel approach is to create engineered nanostructures on the surface of magnesium alloys to achieve the three key functions simultaneously: (1) modulate degradation rate of bulk magnesium substrates, (2) reduce adhesion and viability of pathogenic bacteria, and (3) enhance adhesion and osteogenic differentiation of bone marrow derived mesenchymal stem cells for faster bone healing.