Coordinating Center

技术开发：摘要 为了进一步支持再生康复研究，我们将开发新的技术， 再生康复研究的医疗设备。开发的技术将集中在 功能评估（目标1）和干预策略（目标2）。 将再生康复方案转化为有意义的临床治疗的主要障碍 缺乏有意义的、敏感的和可靠的临床前功能评估可以说是应用的障碍。的 再生的大量临床前测量涉及组织学分析和/或离体/原位机械分析。 测试范例。然而，这些最终和耗时的分析排除了评估的变化， 随着时间的推移，身体功能。目标1中的研究将改善对功能恢复的分析， 使用机器学习方法来自动化步态运动学的鼠模型。算法将描述 正常值以及损伤后病理步态的模式。最终，我们将采用预测 建模以识别映射从所述步态分析软件获得的输入数据的函数， 预测骨骼肌功能的长期恢复。 再生康复的前提是，干细胞对外在的机械， 电刺激和热刺激。这些刺激的应用代表了康复临床的支柱 实践我们建议下一代再生康复研究将实施刺激- 调节局部微环境以改善组织再生的响应性生物材料。压电 材料将诸如通过运动或超声波的机械刺激转换成局部电场，该局部电场可 调节常驻干细胞增殖、迁移和分化。目标2将开展研究， 优化压电生物材料支架与机械载荷的组合使用， 急性损伤后的功能性骨骼肌再生。在未来的几年里，我们将与外部 研究人员评估压电材料用于其他适应症，如外周神经损伤。 为确保我们能迅速回应社会的需要，在第二至五年，我们会 通过我们的每月通讯和AR 3 T 2.0活动（即高级培训课程， 会议和专题讨论会），以衡量该技术的潜在用户数量 我们支持他们的发展。 最后，我们将调查我们的社区，以确定将最大限度地影响质量的技术， 再生康复研究的范围。本次调查结果将用于指导下一步 发电技术开发的努力在补助金的最后几年。

TECHNOLOGY DEVELOPMENT: ABSTRACT To further support Regenerative Rehabilitation research, we will develop novel technologies that expand the armamentarium of Regenerative Rehabilitation investigations. The technologies to be developed will focus on functional assessment (Aim 1) and interventional strategies (Aim 2). A major impediment to the translation of Regenerative Rehabilitation protocols into meaningful clinical applications is arguably the lack of meaningful, sensitive, and reliable pre-clinical assessments of function. The bulk of pre-clinical measures of regeneration involve histological analyses and/or ex vivo/in situ mechanical testing paradigms. However, these terminal and time-consuming analyses preclude the assessment of changes in physical functioning over time. The studies in Aim 1 will improve the analysis of functional recovery in a murine model using machine learning approaches to automate gait kinematics. Algorithms derived will describe normative values as well as patterns of pathologic gait after injury. Ultimately, we will employ predictive modeling to identify a function that maps input data obtained from the gait analysis software to make predictions about long-term restoration of skeletal muscle function. Regenerative Rehabilitation was borne on the premise that stem cells are responsive to extrinsic mechanical, electrical, and thermal stimuli. The application of these stimuli represents a pillar of rehabilitation clinical practice. We propose that next generation Regenerative Rehabilitation studies will implement stimuli- responsive biomaterials that modulate the local microenvironment to improve tissue regeneration. Piezoelectric materials convert mechanical stimuli, such as by exercise or ultrasound, into a local electric field that may modulate resident stem cell proliferation, migration, and differentiation. Aim 2 studies will develop and optimize a piezoelectric biomaterial scaffold used in combination with mechanical loading to promote functional skeletal muscle regeneration after an acute injury. In future years, we will work with external investigators to evaluate the use of piezoelectric materials for other indications, such as peripheral nerve injury. So as to make sure that we are highly responsive to the needs of our community, in years 2-5, we will distribute polls through our monthly newsletter and at AR3T 2.0 events (i.e. advanced training courses, conference sessions, and the Symposium) in order to gauge the number of potential users of the technology whose development we have supported. Finally, we will survey our community to identify technologies that will maximally impact the quality and scope of Regenerative Rehabilitation investigations. The results of this survey will be used to guide next generation technology development efforts in the latter years of the grant.