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

基本信息

批准号：
10306931
负责人：
Huinan Hannah Liu
金额：
$ 8.43万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10306931
关键词：
Address Affect Alloys Anti-Bacterial Agents Antibiotics Bacteria Bacterial Adhesion Bacterial Antibiotic Resistance Biological Bone Diseases Bone Growth Bone Marrow Cells Bone Regeneration Calcium Cells Child Clinical Coupled Coupling Defect Deformity Device Removal Devices Disadvantaged Distraction Osteogenesis Engineering Equipment Malfunction General Anesthesia Immune In Vitro Industry Infection Knowledge Magnesium Mechanics Medical Device Modeling Nanostructures Nutrient Operative Surgical Procedures Outcome Patients Property Research Skeleton Surface Surgical complication Techniques Technology Transfer United States Zinc antimicrobial biomaterial compatibility bone bone cell clinical translation craniomaxillofacial crystallinity design developmental disease distraction immune health implantable device improved in vivo innovation interest materials science mechanical properties meetings novel operation pathogenic bacteria pediatric patients preclinical study public health relevance repaired response social

项目摘要

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.

项目摘要颅颌面（CMF）骨骼的缺陷在美国每年都会影响成千上万的婴儿。为了修复中度至重度骨缺乏，一种称为分散成骨的手术技术（DO）是Fre-fre- 与外部设备相反，内部设备直接植入骨骼的干扰设备（IDD）可以安全磨损几个月，更多对没有社会不适的患者感到舒适，因此允许更长的保留期，这与外部设备相比，提供更好的长期稳定性。但是，他们的主要灾难是他们需要一个在全身麻醉下进行的第二次侵入性手术，用于拆除设备。此外，分心的感染恶化导致骨骼生长和并发症不佳，需要进行额外的修订手术。这个项目将支持视频是可消除可消除生物吸收的抗微生物器件的有望解决方案派系引起的并发症，从而改善了临床结果。 PI设计了新的MG合金类通过将生物相容性的营养元素Mg，锌（Zn）和钙（CA）耦合，并与新型合金加工和表面处理，不仅提供了所需的机械和降解特性，还会影响骨生长和抗菌特性的理想细胞反应。 PI已显示抗菌使用病原细菌和相关的骨髓细胞。该项目的目的是制造模型内部干扰设备（IDD）使用结晶MG-ZN-CA合金与纳米结构表面结合并验证抗菌特性，体内生物活性，生物相容性和机械性能。中心假设是由具有纳米结构表面的可生物可吸收合金将降低细菌的粘附和生存能力，而满足机械性能的要求和生物活性对分散注意力造成的要求（DO），建立在 PI的先前结果和Mg，Zn和Ca作为骨修复和免疫系统的必需营养素的积极影响健康。该项目具有创新性，因为合金设计，加工和纳米结构的表面处理与材料科学四面体协同生物学益处，以实现综合机械和生物学特性。此外，创建无感染IDD的方法是创新的生物剂，并减少抗生素耐药菌的出现。该项目很重要，因为它将过度出现对生物可吸收IDD与细菌，关键骨细胞的体内相互作用的关键知识差距和免疫细胞，从而将新设备推向临床前研究和临床翻译。这研究将导致新的解决方案来修复儿童的CMF骨畸形，并消除设备 - 评估粘结并发症。