Combined Regenerative and Rehabilitation Therapies for Extremity Trauma

描述：创伤一直是美国武装部队战斗伤亡的主要原因。 在最近的军事冲突中。这些损伤通常会导致长期的功能障碍，疼痛， 神经功能障碍这项提案将利用临床前模型的四肢创伤和测试新的组织 工程治疗与康复方案相结合。拟议研究的总体目标 是建立一个综合的再生医学和康复治疗方案，以提高 严重肢体创伤后肢体功能的恢复。假设是大体积的治疗 多组织损伤与再生工程策略，改善再血管化结合 低强度的康复方案将增强组织再生、整合和长期功能， 成果。 研究计划：我们提出以下目标：目标1：利用肌肉工程师再生肌肉结构 干（卫星）细胞和微血管碎片用于容积性肌肉丧失（VML）损伤;目的2：在VML中 单独模型，确定跑步机跑步康复是否增强了治疗的大肌肉损失的再生 目的3：在多组织肢体创伤模型中，评估肌肉干细胞构建体的疗效。 结合跑步机跑步康复和再生疗法对肌肉和骨骼愈合的影响 方法：我们将使用临床前四肢创伤模型，包括VML和多组织骨和肌肉 缺陷在目标1中，VML损伤将用再生肌肉疗法治疗，包括肌肉干细胞或 微血管片段，其将在胶原水凝胶或脱细胞肌肉基质中递送。在Aim中 2、基于跑步机的运动将用于测试关键康复参数的作用，包括时间的选择。 引发和强度对移植物整合和功能的影响。在目标3中，康复和再生疗法（如 在目标2中确定的血运重建效力或肌肉再生效力）将在多- 复合性骨骼肌肉损伤的组织损伤模型。成果衡量标准将包括以下评估： 肌肉和肢体结构和功能（目标1-3）以及骨结构和功能（目标3）。 我们预计，拟议的工作将导致对严重受伤的肢体康复协议的新见解 并将通过出版物和我们的临床顾问进行沟通，以影响军队和退伍军人护理。

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.