Novel Methods to Assess Interfragmentary Motion: Quantifying a Critical Factor in Fracture Healing

评估骨折块间运动的新方法：量化骨折愈合的关键因素

• 批准号: 10487818
• 负责人: William Dean Lack
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10487818
• 关键词: Accounting; Animal Experimentation; Basic Science; Biomechanics; Bone Injury; Cadaver; Characteristics; Clinical; Clinical Data; Clinical Research; Clinical Trials; Complex; Computer Models; Computer Simulation; Data; Diabetes Mellitus; Distal; Environment; Femoral Fractures; Femur; Fluoroscopy; Fracture; Funding; Future; Geometry; Human; Implant; Incidence; Infection; Injury; Lead; Measurement; Measures; Mechanics; Mediator of activation protein; Metals; Methods; Motion; Movement; Observational Study; Open Fractures; Operative Surgical Procedures; Orthopedics; Outcome; Patients; Population; Positioning Attribute; Postoperative Period; Process; Protocols documentation; Rehabilitation therapy; Reporting; Research; Roentgen Rays; Series; Signal Transduction; Site; Smoking; Study models; Surgeon; Targeted Research; Techniques; Testing; Thigh structure; Translating; Translational Research; Validation; Variant; Vascular blood supply; Walking; Weight-Bearing state; Work; X-Ray Computed Tomography; base; bone; bone fracture repair; bone healing; bone quality; bone repair; clinical investigation; clinically relevant; cohort; design; healing; human subject; improved; in vivo; innovation; long bone; mechanical stimulus; mechanotransduction; novel; novel strategies; nutrition; post-operative rehabilitation; prospective; radiological imaging; repaired; response; sample fixation; translational study; treatment strategy

PROJECT SUMMARY/ABSTRACT We seek to understand how variations in surgical fixation and rehabilitation protocols for distal femur fractures impact the mechanical environment at the fracture and how this in turn influences healing. The concept of mechanotransduction, where physical forces are converted into biomechanical signals that guide cellular responses, is relevant to the healing of all human fractures. Distal femur fractures treated with locked plate fixation are an excellent model for study given a relatively high rate of healing complications (in up to 32% of cases) and a range of treatment strategies across a wide variety of mechanical conditions. The challenges faced when attempting to provide stable, yet biologically friendly (i.e., promoting secondary fracture healing) fixation at this site typify those encountered for all long bone fractures. Although the clinical importance of mechanotransduction in bone healing—in particular strain across a fracture site—has been qualitatively demonstrated, there is a lack of quantitative data. Its specific mechanisms are not fully characterized, and progress to improve related clinical outcomes [has been stagnant. A lack of quantitative clinical data limits our ability to design surgical techniques, implants, and rehabilitation protocols to optimize healing outcomes. Currently, a major obstacle in the field is an inability to assess interfragmentary strain or a clinically useful surrogate.] To overcome this, we aim to validate two novel, noninvasive, and complementary methods of quantifying clinical [fracture site motion]. Method 1) A case-specific computational model will be refined to estimate [fracture site motion] for 10 human subjects recently treated with locked plate fixation for a distal femur fracture. Method 2) Biplane fluoroscopy will be used to track [the proximal and distal bone fragments] during standing and walking for these same 10 patients. The proposed research provides two complementary methods of assessing [fracture site motion] in future translational research. These methods will be validated via cadaveric testing. Furthermore, unloaded and loaded CT measurements of [fracture site motion] in the test cohort will [allow in vivo validation]. Computational modeling provides an indirect, scalable method of estimating [fracture site motion] while biplane fluoroscopy will provide direct in vivo assessment. Both methods will support future translational research involving heretofore untestable hypotheses. This includes research into optimal fixation strategies and rehabilitation protocols, as well as the ability to control for confounding factors in studies of other aspects of fracture healing. This innovative work aims to overcome limitations in current research to develop two complementary methods of quantifying patient-specific [fracture site motion, which has been shown to be a clinically relevant surrogate for interfragmentary strain. A quantitative understanding of fracture site motion will inform observational studies and clinical trials directly targeting mechanotransduction and allow research targeting other aspects of fracture healing to account for a potential confounding effect of mechanotransduction. Further, quantifying fracture site motion is a necessary step toward future quantification of interfragmentary strain.] This translational study opens multiple avenues of mechanistic and clinical investigation with the potential for early and long-term clinical impact by decreasing the incidence of fracture [delayed union and] non-union. [The proposed work will support future Merit Review funding of a prospective observational study of optimizing fixation strategies and rehabilitation protocols for secondary fracture healing.]

项目摘要/摘要 我们试图了解股骨远端骨折手术固定和康复方案的差异。 影响骨折处的机械环境，以及这又如何影响愈合。这一概念 机械转导，将物理力转化为生物力学信号，引导细胞 反应，与所有人类骨折的愈合有关。带锁钢板治疗股骨远端骨折 固定是一种极好的研究模式，因为愈合并发症的发生率相对较高(在高达32%的 病例)和各种机械条件下的一系列治疗策略。面临的挑战 当尝试在以下位置提供稳定且生物友好的固定(即促进二次骨折愈合)时 这个部位是所有长骨骨折的典型部位。尽管在临床上重要的是 骨愈合中的机械转导--尤其是骨折部位的应变--已经被定性地 经过论证，缺乏量化数据。其具体机制尚未完全确定，而且 改善相关临床结果的进展[一直停滞不前。缺乏量化的临床数据限制了我们 能够设计手术技术、植入物和康复方案，以优化愈合结果。 目前，该领域的一个主要障碍是无法评估碎片间的应变或临床有用的 代孕。]为了克服这一点，我们的目标是验证两种新的、非侵入性的和互补的方法 量化临床[骨折部位运动]。方法1)将针对具体情况的计算模型细化为 最近接受股骨远端带锁钢板固定的10名受试者的[骨折部位运动]评估 骨折。方法2)使用双平面透视追踪[近端和远端骨块] 为同样的10名患者站立和行走。建议的研究提供了两种互补的方法 在未来的翻译研究中评估[骨折部位的运动]。这些方法将通过身体验证 测试。此外，测试队列中[骨折部位运动]的卸载和加载CT测量将[允许 体内验证]。计算建模提供了一种间接的、可扩展的方法来估计[骨折位置 运动]而双平面透视将提供直接的活体评估。这两种方法都将支持未来 涉及到迄今为止无法验证的假设的翻译研究。这包括对最佳固定的研究。 策略和康复方案，以及在其他研究中控制混杂因素的能力 骨折愈合的各个方面。这项创新性的工作旨在克服当前研究中的限制，开发出两个 量化患者特定[骨折部位运动]的补充方法，已被证明是一种 片断间菌株的临床相关替代物。对骨折部位运动的定量理解将 告知直接针对机械转导的观察性研究和临床试验，并允许研究 以骨折愈合的其他方面为目标，说明机械转导的潜在混杂效应。 此外，量化骨折部位的运动是未来量化碎块间运动的必要步骤 菌株。]这项转译研究开辟了多种机制和临床研究的途径，具有潜在的 通过减少骨折[延迟愈合]和不愈合的发生率，对早期和长期的临床影响。 [拟议的工作将支持未来功绩审查对优化的前瞻性观察性研究的资助 骨折二次愈合的固定策略和康复方案。]