Coordinating Center

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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.