Combined Regenerative and Rehabilitation Therapies for Extremity Trauma

四肢创伤的再生与康复联合疗法

• 批准号: 10724267
• 负责人: Nick J Willett
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10724267
• 关键词: 3-Dimensional; Amputation; Angiography; Animals; Athletic Injuries; Attenuated; Autologous Transplantation; BMP2 gene; Blood Vessels; Bone Tissue; Bone structure; Caring; Cell Therapy; Cells; Chronic; Clinical; Collagen; Communication; Consultations; Data; Defect; Dose; Encapsulated; Engineering; Exercise; Extracellular Matrix; Family; Fiber; Gait; Histology; Hydrogels; Impairment; Implant; Injury; Intervention; Isometric Exercise; Limb Salvage; Limb structure; Literature; Mechanical Stimulation; Mechanics; Methods; Military Personnel; Modeling; Muscle; Muscle Fibers; Muscle satellite cell; Muscular Atrophy; Natural regeneration; Neurologic Dysfunctions; Operative Surgical Procedures; Outcome; Outcome Measure; Pain; Pathology; Patient-Focused Outcomes; Patients; Physical therapy; Pre-Clinical Model; Production; Protocols documentation; Publications; Publishing; Quality of life; Rattus; Regenerative Medicine; Regenerative engineering; Regimen; Rehabilitation therapy; Research; Role; Running; Series; Severities; Soldier; System; Testing; Thick; Tissue Engineering; Tissues; Torque; Transplantation; Trauma; Traumatic Arthropathy; Treatment Efficacy; Treatment Protocols; Vascularization; Veterans; Work; analytical method; battlefield injury; bone; bone fracture repair; bone healing; chronic pain; combat casualty; combat injury; combat wound; daily functioning; efficacy evaluation; efficacy testing; exercise intensity; exercise intervention; exercise training; functional disability; functional improvement; functional outcomes; healing; improved; insight; limb injury; member; microCT; muscle regeneration; muscular structure; nerve supply; physical therapist; quadriceps muscle; regenerative; regenerative approach; regenerative rehabilitation; regenerative therapy; reinnervation; repaired; restoration; scaffold; service member; severe injury; stem; tissue injury; tissue regeneration; tissue trauma; treadmill; treatment group; volumetric muscle loss

Description: Extremity trauma has been the predominant cause of combat casualties for U.S. armed forces members in recent military conflicts. These injuries often result in long-term functional disabilities, pain, and neurologic dysfunction. This proposal will utilize preclinical models of extremity trauma and test new tissue engineered therapies in combination with rehabilitation regimens. The overall objective of the proposed study is to establish an integrated regenerative medicine and rehabilitation therapy treatment protocol to enhance restoration of limb function following severe extremity trauma. The hypothesis is that treatment of large volume multi-tissue injuries with regenerative engineering strategies that improve revascularization in combination with low intensity rehabilitation regimens will enhance tissue regeneration, integration, and long term functional outcomes. Research Plan: We propose the following Aims: Aim 1: Engineer regenerative muscle constructs using muscle stem (satellite) cells and microvascular fragments for Volumetric Muscle Loss (VML) injuries; Aim 2: In a VML model alone, determine if treadmill running rehabilitation enhances the regeneration of large muscle loss treated with muscle stem cell constructs; Aim 3: In a multi-tissue extremity trauma model, assess the efficacy of combined treadmill running rehabilitation and regenerative therapies on muscle and bone healing Methods: We will use preclinical models of extremity trauma, including VML and multi-tissue bone and muscle defects. In Aim 1 VML injuries will be treated with regenerative muscle therapies including muscle stem cells or microvascular fragments which will be delivered in collagen hydrogels or decellularized muscle matrices. In Aim 2, treadmill based exercise will be used to test the role of key rehabilitation parameters including timing of initiation and intensity on graft integration and function. In Aim 3, rehabilitation and regenerative therapies (as determined in Aim 2 for re-vascularization potency or muscle regeneration potency) will be tested in a multi- tissue injury model of composite bone and muscle trauma. Outcome measures will include assessments of muscle and limb structure and function (Aim 1-3) and bone structure and function (Aim 3). We anticipate the proposed work will result in new insights on rehabilitation protocols for severely injured limbs and will be communicated through publications and our clinical consultants to impact military and veterans care.

描述：肢体创伤一直是美国武装部队战斗人员伤亡的主要原因 最近的军事冲突成员。这些伤害通常会导致长期功能障碍，疼痛和 神经功能障碍。该建议将利用肢体创伤的临床前模型并测试新组织 工程疗法与康复方案结合使用。拟议研究的总体目标 是建立综合的再生医学和康复治疗治疗方案，以增强 严重肢体创伤后肢体功能的恢复。假设是大量的处理 通过再生工程策略的多组织伤害，可改善血运重建 低强度康复方案将增强组织再生，整合和长期功能 结果。 研究计划：我们提出以下目的：目标1：使用肌肉的工程师再生肌肉结构 茎（卫星）细胞和微血管碎片，用于体积肌肉损失（VML）损伤；目标2：在VML中 仅模型，确定跑步机进行康复是否会增强所治疗的大肌肉损失的再生 肌肉干细胞构建体；目标3：在多组织的肢体创伤模型中，评估的功效 在肌肉和骨骼愈合方面的跑步机恢复和再生疗法的结合 方法：我们将使用四肢创伤的临床前模型，包括VML和多组织骨和肌肉 缺陷。在AIM 1中，VML损伤将通过再生肌肉疗法（包括肌肉干细胞或 微血管碎片将在胶原凝胶或脱细胞肌肉基质中递送。目标 2，基于跑步机的运动将用于测试关键康复参数的作用，包括 移植整合和功能的起始和强度。在AIM 3中，康复和再生疗法（作为 在AIM 2中确定的重新血管化效力或肌肉再生效力）将在多个 复合骨和肌肉创伤的组织损伤模型。结果指标将包括评估 肌肉和肢体结构和功能（AIM 1-3）以及骨结构和功能（AIM 3）。 我们预计拟议的工作将为肢体严重受伤的康复方案提供新的见解 并将通过出版物和我们的临床顾问进行传达，以影响军事和退伍军人护理。