Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis

用于牵引成骨的具有纳米结构表面的营养衍生合金

• 批准号: 9895281
• 负责人: Huinan Hannah Liu
• 金额: $ 15.27万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895281
• 关键词: 3-Dimensional; Address; Alloys; Aluminum; Animals; Anodes; Anti-Bacterial Agents; Antibiotics; Bacteria; Bacterial Adhesion; Bacterial Antibiotic Resistance; Biological; Bone Diseases; Bone Growth; Bone Marrow Cells; Bone Regeneration; Bone callus; Calcium; Cells; Clinical; Clinical Trials; Complement; Coupled; Coupling; Deformity; Dependence; Device Removal; Devices; Dimensions; Disadvantaged; Distraction Osteogenesis; Elements; Engineering; Equipment Malfunction; Face; Future; General Anesthesia; Goals; Histology; Image; Immune; Implant; In Vitro; Infection; Infection prevention; Inflammatory Response; Knowledge; Lead; Magnesium; Mandible; Measures; Mechanics; Metals; Methods; Microscopy; Miniature Swine; Modeling; Monitor; Nanostructures; Nutrient; Operative Surgical Procedures; Osteogenesis; Osteotomy; Outcome; Oxides; Performance; Physiologic calcification; Pilot Projects; Plants; Polyesters; Process; Property; Rare Earth Metals; Rattus; Research; Rod; Roentgen Rays; Secure; Side; Skin; Spectrum Analysis; Sterility; Stress; Surface; Surgical complication; Techniques; Technology Transfer; Testing; Time; Titanium; Toxic effect; Trauma; Weight-Bearing state; X-Ray Computed Tomography; Zinc; age group; antimicrobial; bactericide; bioimaging; biomaterial compatibility; bone; bone cell; bone healing; clinical translation; cost; craniofacial; craniomaxillofacial; crystallinity; design; developmental disease; distraction; experience; healing; high risk; immune health; implantable device; improved; in vivo; infection risk; innovation; interest; materials science; mechanical properties; meetings; novel; operation; osteogenic; pathogenic bacteria; poly-L-lactic acid; premature; public health relevance; reconstruction; repaired; response; skeletal; social; tool; tumor

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.

项目摘要 牵引成骨(DO)是一种修复中重度先天性和获得性CRA的技术。 颌面(CMF)骨骼畸形分心装置经常被用来固定和拉长 有目的地进行截骨术的骨骼，允许身体的自然成骨过程产生 新骨以1-3 mm/天的速度填充不断扩大的间隙。与外部设备相比，内部分心设备 (IDD)直接植入骨骼，长时间佩戴几个月更舒适 社会不适，并允许更长的保留期，这导致了比外部环境更好的长期稳定性 设备。然而，IDD的主要缺点是在一般情况下需要二次侵入性手术 麻醉取出装置，因为目前的IDDS是由不可降解的钛(钛)合金制成的。IDDS 一些可降解的聚酯，如聚L-乳酸(PLLA)及其衍生物，已经尝试过，但在临床上 废弃是因为其固有的机械强度比金属低，导致过早坍塌 设备的一部分。此外，干扰物通常会通过皮肤突出以进行旋转，因此面临更高的风险 感染。感染引起的骨骼生长不良和并发症需要全身使用抗生素 通常还会进行额外的翻修手术。该项目将为生物可再吸收抗微生物提供一种有前景的解决方案。 消除二次手术和感染引起的并发症的BAL装置，从而改善临床 结果。PI通过偶联生物相容的营养元素镁、锌，设计出了一种新型的镁合金 (锌)和钙(钙)采用新的合金加工和表面处理，不仅提供了所需的 机械和降解特性，但也诱导理想的细胞反应骨生长和抗 微生物特性。等电点显示了新型镁合金的抗菌性能和生物活性 纳米结构表面在体外使用病原菌和相关的骨髓细胞。这样做的目的是 该项目是利用晶态的镁锌钙合金与纳米结构的表面相耦合来制作IDD模型 并在体内验证其抗菌性、生物活性、生物相容性和力学性能。中环 假设由具有纳米结构表面的生物可吸收合金制成的IDDS将减少细菌 在满足DO的机械性能和生物活性要求的同时， 基于PI的先前结果和镁、锌和钙作为骨修复和骨修复所必需的营养物质的积极作用 免疫系统健康。这个项目是创新的，因为合金的设计、加工和纳米结构 表面处理与材料科学四面体协同生物效益，实现机械一体化-- 生理和生物学特性。这个项目意义重大，因为它将克服 可生物吸收的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IDDS的承载能力，从而将新型装置推向临床。这 研究将为修复CMF骨畸形和减少并发症找到新的解决方案。