Degradable orthopedic hardware

可降解矫形硬件

• 批准号: 8881483
• 负责人: DAVID L. KAPLAN
• 金额: $ 36.2万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8881483
• 关键词: Address; Alloys; Animal Model; Animals; Biocompatible Materials; Biological Assay; Biomechanics; Biomedical Engineering; Bone Regeneration; Bone remodeling; Child; Clinical; Data; Deposition; Device Removal; Devices; Diagnostic radiologic examination; Drug Formulations; Evaluation; Excision; Fracture Fixation; Goals; Gold; Healed; Histologic; Histology; Image Analysis; In Vitro; Infection; Inflammatory; Kinetics; Lead; Mechanics; Metals; Modeling; Modification; Molecular Weight; Morphology; Operative Surgical Procedures; Orthopedics; Osteolysis; Outcome; Patients; Polyglycolic Acid; Porosity; Process; Property; Proteins; Rattus; Reaction; Recording of previous events; Research; Research Personnel; Role; Running; Silk; Stress; Surgeon; System; Testing; Time; TimeLine; Tissues; Titania; Titanium; Variant; Work; X-Ray Computed Tomography; base; biodegradable polymer; bone; design; healing; implantation; improved; in vivo; insight; interest; meetings; nano; osteogenic; poly(lactic acid); poly-L-lactic acid; public health relevance; repaired; response; retinal rods; screening; single photon emission computed tomography

 DESCRIPTION: Degradable orthopedic repair devices would provide significant clinical benefits to overcome current limitations in bone remodeling, degradation kinetics and bone integration. Current options are limited primarily to nondegradable metals which have become the gold standard for orthopedic repairs due to robust mechanical properties and ease of implantation, while limitations of stress shielding, infections, bone remodeling and second surgical removals have shifted significant interest toward degradable devices. Orthopedic screws and plates composed of polylactic and polyglycolic acids have become lead candidates for degradable hardware with a reduced need for removal and improved bone remodeling. However, polylactic and polyglycolic acid screws and plates are associated with inflammatory reactions due to degradation products, osteolysis and incomplete bone remodeling. Thus, orthopedic hardware that has appropriate mechanical properties, tunable and full degradation and is pro-osteogenic would have a major impact on orthopedic repairs in promoting accelerated healing, reducing second surgeries and improving long-term patient outcomes. Our long term goal is to develop fully degradable screws, plates and rods using silk protein functionalized by bioactive molecules to promote healthy bone remodeling and integration. The objective of the proposed research is to determine the ability of the proposed silk format to meet the structural needs of degradable orthopedic systems and successfully direct pro-osteogenic remodeling. We hypothesize that functionalized silk orthopedic hardware can be tuned to fully degrade over a 6-12 month time while promoting osteointegration to optimize utility in orthopedic repairs and meeting mechanical requirements. Our extensive preliminary in vitro and in vivo data support this hypothesis. The rationale for this research is to gain fundamental insight into the role of functionalized and degradable orthopedic screws and plates in accelerating healing and directing successful bone remodeling. The anticipated outcomes are expected to have a substantial positive impact on orthopedic repairs by presenting hardware designs capable of meeting mechanical needs of fracture fixation and addressing current limitations and complications. An interdisciplinary team of investigators who have a history of collaborative efforts will conduct the studies [David Kaplan - silk biomaterials, bioengineering, Ara Nazarian - biomechanics/biomiaging and animal studies, Sam Lin and Brian Snyder - orthopedic surgeons].

 描述：可降解的骨科修复装置将为克服骨重塑，降解动力学和骨骼整合的当前局限性提供重大临床益处。当前的选择主要限于不可降解的金属，由于强大的机械性能和易于植入的易用性，这已成为骨科修复的金标准，而应力屏蔽，感染，骨骼重塑和第二手术切除的局限性已将重大兴趣转移到可污染的设备上。由多乳酸和聚乙醇酸组成的骨科螺钉和板已成为可降解硬件的铅候选者，并减少了去除和改善骨骼重塑的需求。然而，聚乳酸和多乙醇酸螺钉和板与由于降解产物，骨溶解和不完全骨重塑而引起的炎症反应有关。这是具有适当的机械性能，可调节和充分降解且具有促核化的骨科硬件，将对骨科修复产生重大影响，以促进加速的愈合，减少第二次手术并改善长期患者的结局。我们的长期目标是使用通过生物活性分子功能化的丝蛋白来开发完全降解的螺钉，板和杆，以促进健康的骨骼重塑和整合。拟议研究的目的是确定所提出的丝绸格式满足可降解骨科系统的结构需求并成功地指导亲核重塑的能力。我们假设可以调节功能化的丝绸骨科硬件，以在6-12个月的时间内完全降级，同时促进取整组，以优化骨科维修中的效用并满足机械要求。我们广泛的体外初步和体内数据支持这一假设。这项研究的基本原理是对功能化和可降解的骨科螺钉和板在加速愈合中的作用并指导成功的骨骼重塑的基本见解。预计预期的结果有望通过提出能够满足骨折固定机械需求并解决当前局限性和并发症的机械需求的硬件设计，对骨科维修产生重大积极影响。有合作努力历史的研究人员的跨学科团队将进行研究[David Kaplan-丝绸生物材料，生物工程，ARA Nazarian-生物力学/生物学和动物研究，Sam Lin和Brian Brian Snyder-正骨外科医生]