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.

项目概要 牵引成骨 (DO) 是一种修复中度至重度先天性和后天性骨折的技术。 颌面（CMF）骨骼畸形。牵引装置经常用于固定和拉长 故意进行截骨术的骨骼，并允许身体的自然成骨过程产生 新骨以每天 1-3 毫米的速度填补不断扩大的间隙。与外部设备相比，内部干扰设备 (IDD) 直接植入骨骼，长时间佩戴更舒适，无需担心 社会不适，并允许更长的保留期限，这比外部的长期稳定性更好 设备。然而，IDD的主要缺点是在一般情况下需要进行第二次侵入性手术。 装置移除时需要麻醉，因为目前的 IDD 是由不可降解的钛 (Ti) 合金制成。国际直拨电话 已经尝试了可降解聚酯，例如聚-L-乳酸（PLLA）及其衍生物，但临床上 被放弃是因为它们固有的机械强度低于金属，导致过早塌陷 设备的。此外，牵引器通常会穿过皮肤进行转动，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施用抗生素 并且经常进行额外的翻修手术。该项目将为生物可吸收抗微生物提供一个有前途的解决方案 生物装置消除了二次手术和感染引起的并发症，从而改善了临床 结果。 PI 通过耦合生物相容性营养元素镁、锌设计了一种新型镁合金 (Zn)和钙(Ca)采用新颖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，而且还诱导骨生长和抗骨生长所需的细胞反应 微生物特性。 PI展示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在体外研究纳米结构表面。此举的目的 该项目是使用结晶 Mg-Zn-Ca 合金与纳米结构表面结合来制造 IDD 模型 并验证其抗菌性能、生物活性、生物相容性和体内力学性能。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 体内粘附和活力，同时满足 DO 的机械性能和生物活性要求， 基于 PI 先前的结果以及镁、锌和钙作为骨骼修复和骨修复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 表面处理与材料科学四面体协同生物效益，实现机械集成 化学和生物学特性。该项目意义重大，因为它将克服关键的知识差距 生物可吸收 IDD 与细菌、关键骨细胞和免疫细胞的体内相互作用，证明 生物可吸收 IDD 的承载能力，从而推动新设备走向临床转化。这 研究将带来修复 CMF 骨畸形和减少并发症的新解决方案。