Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis

项目摘要 牵引成骨（DO）是一种修复中度至重度先天性和获得性骨折的技术。 颅颌面（CMF）骨骼畸形。牵引装置经常用于固定和拉长血管。 有目的地进行截骨术的骨骼，并允许身体的自然成骨过程产生 以1-3 mm/天的速度填充膨胀间隙的新骨。与外部装置相比，内部牵引装置 (IDD)直接植入骨骼，佩戴数月更舒适， 社会不适，并允许更长的保留期，这导致比外部更好的长期稳定性 装置.然而，IDD的主要缺点是它们需要在一般情况下进行第二次侵入性手术。 因为目前的IDD是由不可降解的钛（Ti）合金制成的。IDDs 已经尝试了可降解聚酯如聚-L-乳酸（PLLA）及其衍生物，但临床上 由于其固有的机械强度低于金属，导致过早坍塌， 的设备。此外，牵引器通常突出穿过皮肤用于转动，因此面临更高的风险， 感染.预防引起的骨生长不良和并发症需要全身使用抗生素 并且经常需要额外的翻修手术。该项目将为生物可吸收抗微生物药物提供一个有前途的解决方案。 消除二次手术和感染引起的并发症，从而改善临床 结果。PI通过将生物相容性营养元素Mg、Zn (Zn)和钙（Ca）的新型合金加工和表面处理，这不仅提供了所需的 机械和降解性能，而且还诱导骨生长和抗- 微生物特性PI证明了新型镁合金的抗菌性能和生物活性， 使用病原菌和相关骨髓细胞体外纳米结构表面。的目的 本计画是利用结晶Mg-Zn-Ca合金与奈米结构表面结合来制作一个IDD模型 并在体内验证其抗菌性能、生物活性、生物相容性和力学性能。中央 假设由具有纳米结构表面的生物可吸收合金制成的IDD将减少细菌感染， 在满足DO力学性能和生物活性要求的同时， 建立在PI的先前结果和镁，锌，钙作为骨修复的必需营养素的积极作用， 免疫系统健康该项目具有创新性，因为合金设计，加工和纳米结构 表面处理协同生物效益与材料科学四面体，以实现综合机械， 化学和生物性质。这个项目意义重大，因为它将克服关键的知识差距， 生物可吸收IDDs与细菌、关键骨细胞和免疫细胞的体内相互作用表明， 生物可吸收IDD的承载能力，从而推动新器械向临床转化。这 研究将为CMF骨畸形的修复和减少并发症提供新的解决方案。

Project Summary Distraction Osteogenesis (DO) is a technique for repairing moderate to severe congenital and acquired cra- niomaxillofacial (CMF) skeletal deformities. Distraction devices are frequently used to secure and elongate the bones where an osteotomy is created purposely, and allow the body's natural osteogenic processes to produce new bone to fill the expanding gap at 1-3 mm/day. In contrast to external devices, internal distraction devices (IDD) are implanted directly to the bone, are more comfortable to wear for a long period of several months without social discomfort, and permit greater retention periods, which lead to better long-term stability than external devices. However, the major disadvantage of IDD is that they require a second invasive operation under general anesthesia for device removal, because current IDDs are made out of non-degradable titanium (Ti) alloys. IDDs of degradable polyesters such as poly-L-lactic acid (PLLA) and derivatives have been attempted, but clinically abandoned because their inherently lower mechanical strength than that of metals caused premature collapse of device. Moreover, distractors normally protrude through the skin for turning and thus face a higher risk for infections. Infection-induced poor bone growth and complications require systemic administration of antibiotics and often additional revision surgeries. This project will provide a promising solution of bioresorbable antimicro- bial devices that eliminate the secondary surgeries and infection-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 anti- microbial 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 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 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 mechan- ical and biological properties. This project is significant because it will overcome the critical knowledge gap on the in vivo interactions of bioresorbable IDDs with bacteria, crucial bone cells and immune cells, demonstrate load-bearing capacity of bioresorbable IDDs, and thus advance the new devices toward clinical translation. This research will lead to new solutions for repairing CMF bone deformities and reducing complications.