While musculoskeletal tissues have multiple biological roles, their primary function is to provide mechanical support to enable the activities of daily living. With injury, aging, degeneration, or disease, musculoskeletal tissues may experience a decline in mechanical function, and this loss of function can originate at different length scales. With development, growth, and therapeutic treatment, mechanical function can improve and change across these same length scales. As such, it is essential that assessment of musculoskeletal tissue mechanics be a primary focus in both basic and translational studies of musculoskeletal tissue formation, development, degeneration, and treatment. Moreover, the innovation and sophistication of biomechanical quantification must continue to develop at a pace on par with the ever-deepening mechanistic knowledge of musculoskeletal tissue molecular biology and physiology, with advances in molecular and imaging technologies, and with new therapeutic developments in order to discern the functional outcomes in these studies. The overall objective of the Biomechanics Core (BC) is to to develop and provide a wide range of standard and innovative biomechanical approaches to evaluate musculoskeletal tissue function across length scales in the context of development, disease, injury and repair, and to provide training and funding for new projects and collaborations utilizing these assays. Over the last funding cycle, the Biomechanics Core (BC) at the Penn Center for Musculoskeletal Disorders (PCMD) has developed into a thriving resource for the musculoskeletal research community at the University of Pennsylvania and in the Philadelphia region and neighboring states. In this renewal application, we will further expand our services to meet the increased demand for specialized techniques and develop new and innovative methods that address the multi-scale mechanics of musculoskeletal tissues. The BC will continue to operate under the direction of Dr. Robert Mauck (BC Director since 2011), along with contributions and support from Dr. Snehal Shetye (BC Technical Director since 2015). Our Specific Aims are to provide guidance and training (Aim 1), to provide expertise and service for biomechanical assays (Aim 2), to develop innovative biomechanical testing techniques (Aim 3), and to provide funding for the development of novel, explorative projects and collaborations (Aim 4). Successful completion of these Aims will significantly enhance the environment and the capabilities of researchers at the University of Pennsylvania and the regional research community, leading to new approaches to address musculoskeletal disorders across length scales and stimulating new collaborations between current and new PCMD members who have not previously included analysis of biomechanical function in their musculoskeletal research programs.