Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis

项目摘要 在美国，颅颌面（CMF）骨骼缺陷每年影响成千上万的婴儿。为 修复中度至重度骨缺损，一种称为牵引成骨（DO）的外科技术是免费的， 通常用于逐渐延长儿科患者的异常骨骼。与外部设备相比，内部 直接植入骨内的牵张装置（IDD）佩戴数月更安全， 患者舒适，没有社交不适，因此允许更长的保留时间， 提供比外部设备更好的长期稳定性。然而，它们的主要缺点是它们需要一个 在全身麻醉下进行第二次侵入性手术以取出器械。此外，分心的感染- 虎钳导致骨生长不良和需要额外翻修手术的并发症。该项目将支持- 提供了一个有前途的解决方案，生物可吸收的抗菌装置，消除了二次手术， 感染引起的并发症，从而改善临床结果。PI设计了一种新的镁合金 通过将生物相容性营养元素Mg、锌（Zn）和钙（Ca）与新的合金加工相结合， 表面处理，其不仅提供所需的机械和降解性能，而且还诱导 对骨生长和抗微生物性质的理想细胞反应。PI已证明具有抗菌性 利用病原菌体外培养的方法研究了新型纳米结构镁合金的性能和生物活性， 相关的骨髓细胞。本计画的目的是制作一个模型内牵引器 使用与纳米结构表面耦合的晶态Mg-Zn-Ca合金并验证抗菌性能， 生物活性、生物相容性和体内机械性能。中心假设是， 具有纳米结构表面的生物可再吸收合金将减少体内细菌粘附和存活力， 满足牵张成骨（DO）的力学性能和生物活性要求， PI先前的结果和镁、锌和钙作为骨修复和免疫系统必需营养素的积极作用 健康该项目具有创新性，因为合金设计，加工和纳米结构表面处理 利用材料科学四面体协同生物效益，实现机械与生物一体化 特性.此外，创造无感染IDDs的方法是创新的，因为它不依赖于抗- 益生菌，并减少抗药性细菌的出现。这个项目意义重大，因为它将超过- 生物可吸收IDDs与细菌，关键骨细胞， 和免疫细胞，从而推动新设备的临床前研究和临床转化。这 研究将为修复儿童CMF骨畸形和消除器械相关性提供新的解决方案， 并发症。

Project Summary Defects in craniomaxillofacial (CMF) skeleton affect thousands of babies every year in the United States. For repairing moderate to severe bone deficiency, a surgical technique called distraction osteogenesis (DO) is fre- quently used to gradually lengthen abnormal bones in pediatric patients. In contrast to external devices, internal distraction devices (IDD) implanted directly to the bone are safer to wear for a period of several months, more comfortable to the patients without social discomfort, and, therefore, permit greater retention periods, which provide better long-term stability than external devices. However, their major disadvantage is that they require a second invasive operation under general anesthesia for device removal. Moreover, infections of distraction de- vices cause poor bone growth and complications that require additional revision surgeries. This project will pro- vide a promising solution of bioresorbable antimicrobial devices that eliminate the secondary surgeries and in- fection-induced complications, thus improving clinical outcome. The PI has engineered a new class of Mg alloy via coupling biocompatible nutrient elements Mg, zinc (Zn) and calcium (Ca) with novel alloy processing and surface treatment, which not only provide the needed mechanical and degradation properties, but also induce desirable cellular responses for bone growth and antimicrobial property. The PI has demonstrated antibacterial property and bioactivity of the new Mg alloys with nanostructured surfaces in vitro using pathogenic bacteria and relevant bone marrow cells. The objective of this project is to fabricate a model internal distraction device (IDD) using the crystalline Mg-Zn-Ca alloys coupled with nanostructured surfaces and verify the antibacterial property, bioactivity, biocompatibility, and mechanical properties in vivo. The central hypothesis is that the IDDs made of the bioresorbable alloys with nanostructured surfaces will reduce bacterial adhesion and viability in vivo while meeting the requirements of mechanical properties and bioactivity for distraction osteogenesis (DO), built 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, processing, and nanostructured surface treatment synergize biological benefits with materials science tetrahedron to achieve integrated mechanical and biological properties. Further, the approach for creating infection-free IDDs is innovative because it does not rely on anti- biotics, and reduce the emergence of antibiotic-resistant bacteria. This project is significant because it will over- come the critical knowledge gap on the in vivo interactions of bioresorbable IDDs with bacteria, crucial bone cells and immune cells, and thus advance the new devices toward preclinical studies and clinical translation. This research will lead to new solutions for repairing CMF bone deformities in children and eliminating device-asso- ciated complications.