Regenerative Rehabilitation of Complex Musculoskeletal Injuries

复杂肌肉骨骼损伤的再生康复

• 批准号: 10367370
• 负责人: ROBERT E GULDBERG
• 金额: $ 63.33万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367370
• 关键词: Accidents; Area; Biocompatible Materials; Biological; Biological Markers; Biological Products; Biomechanics; Blood Vessels; Bone Regeneration; Cohort Studies; Complex; Complication; Coupled; Coupling; Custom; Data; Defect; Dose; Elements; Environment; Experimental Designs; Feedback; Female; Functional Regeneration; Funding; Gait; Goals; Histology; Individual; Injury; Interdisciplinary Study; Knowledge; Limb structure; Lower Extremity; Maps; Measurement; Measures; Mechanics; Methodology; Modeling; Multivariate Analysis; Muscle; Musculoskeletal; Natural regeneration; Outcome; Pain; Patients; Physical Rehabilitation; Physicians; Physiological Processes; Pre-Clinical Model; Procedures; Prospective Studies; Protocols documentation; Rattus; Recovery of Function; Regimen; Rehabilitation therapy; Second Look Surgery; Severities; Testing; Time; Tissues; Translating; Trauma patient; Treatment Protocols; Variant; Weight-Bearing state; Work; X-Ray Computed Tomography; base; biomechanical test; bone; clinical practice; cohort; combat; design; disability; evidence base; functional outcomes; functional restoration; gait examination; healing; implanted sensor; improved; instrument; limb injury; male; mechanical signal; mechanical stimulus; microCT; muscle regeneration; musculoskeletal injury; new technology; non-invasive monitor; novel; predictive marker; predictive modeling; prospective; quadriceps muscle; radiological imaging; regeneration model; regenerative; regenerative rehabilitation; regenerative treatment; repaired; response; response biomarker; restoration; sample fixation; sensor; sex; skeletal; tissue regeneration; treatment strategy; wireless

SUMMARY Complex musculoskeletal trauma is common both in combat and high energy civilian accidents and often leads to prolonged disability or skeletal nonunion. Regenerative rehabilitation is an emerging field with the potential to improve functional outcomes for lower limb musculoskeletal trauma patients. Our overall objectives are to (i) investigate rehabilitative loading as a regenerative rehabilitation treatment strategy for severe complex musculoskeletal trauma and (ii) understand the relationship between rehabilitative loading, local regenerative niche mechanics, and the biological response. We will meet these objectives through the following specific aims. Specific Aim 1: Determine the effects of rehabilitative loading, injury severity and sex on regenerative niche mechanical signals and functional regeneration. In a rat model of a femoral bone defect, we will employ a factorial experimental design to determine effective rehabilitative loading protocols in critically sized injuries, and determine the effects of rehabilitation on local and systemic biological responses and functional regeneration as a function of sex and injury size. Specific Aim 2: Integrate sensor-enabled real-time feedback into rehabilitation protocols and test the ability to accelerate bone and muscle functional recovery following severe extremity injury. This aim will use wireless implantable strain sensors to provide noninvasive monitoring of mechanics in the regenerative niche throughout the progression of healing under rehabilitative loading. Sensor mechanical data will be used to identify strain ranges that serve as early indicators of healing status and are used as a criterion for dynamically adjusting the rehabilitation regimen on a subject-specific basis to accelerate functional regeneration of musculoskeletal tissue. Specific Aim 3: Build predictive multivariate models based on co-dependent relationships among local regenerative niche mechanical parameters, systemic biomarkers, and functional regeneration. Finite element modeling will be used to generate simulated strain maps showing local variations in regenerative niche mechanical signals using implantable sensor measurements as time-varying boundary conditions. Linear multivariate analyses will be used to map spatial and temporal relationships between the biological responses and local regenerative niche mechanics under rehabilitative loading regimens. Integrating early mechanical data and systemic biomarker data from the previous aims, nonlinear symbolic regression will be used to develop predictive models of bone and muscle functional outcomes for subjects of both sexes. These models will be tested in a prospective study using an additional cohort of both sexes to validate whether models developed in one sex can be predictive of healing outcomes in both the same and the opposite sexes.

概括 复杂的肌肉骨骼创伤在战斗和高能量平民事故中都是常见的，并且经常导致 长时间的残疾或骨骼骨不连。再生康复是一个新兴领域，有可能 改善下肢肌肉骨骼创伤患者的功能结果。我们的总体目标是（i） 研究康复负荷作为严重复合物的再生康复治疗策略 肌肉骨骼创伤和（ii）了解康复载荷，局部再生之间的关系 利基力学和生物反应。我们将通过以下特定目标达到这些目标。 特定目标1：确定康复负荷，伤害严重性和性别对再生的影响 利基机械信号和功能再生。在股骨缺陷的大鼠模型中，我们将采用 一种阶乘实验设计，以确定急性伤害中有效的康复负荷方案， 并确定康复对局部和系统生物学反应和功能再生的影响 作为性别和伤害大小的函数。特定目标2：将启用传感器的实时反馈集成到 康复方案并测试加速骨骼和肌肉功能恢复的能力 严重的肢体伤害。此目标将使用无线植入应变传感器提供无创监测 在康复负荷下，在整个康复过程中，在再生生态位中的力学。传感器 机械数据将用于识别作为治愈状况早期指标的应变范围，并且 用作特定于主题的动态调整康复方案的标准，以加速 肌肉骨骼组织的功能再生。特定目的3：建立基于多元模型的预测性多元模型 关于局部再生利基机械参数之间的共依赖关系 生物标志物和功能再生。有限元建模将用于生成模拟应变 图显示了使用可植入传感器测量的局部变化的局部变化 作为时变边界条件。线性多元分析将用于绘制空间和时间。 康复中的生物学反应与局部再生利基机制之间的关系 加载方案。从上一个目标整合早期的机械数据和全身生物标志物数据， 非线性符号回归将用于开发骨骼和肌肉功能结果的预测模型 对于男女的主题。这些模型将在一项前瞻性研究中进行测试 性别以验证一种性别中开发的模型是否可以预测两者的愈合结果 和异性。