SUMMARY The overall goal of the South Carolina COBRE for Translational Research Improving Musculoskeletal Health (SC-TRIMH) is to advance our understanding of musculoskeletal diseases and their management by enhancing and expanding the biomedical research capacity at Clemson University. Phase I SC-TRIMH successfully established and implemented the new scientific paradigm of Virtual Human Trials (VTH) for translational research. Virtual Human Trials consists of powerful computational modeling combined with quantitative functional validation and in vivo assessment to expedite the development of new therapeutics, interventions, and devices for musculoskeletal health. The overarching SC-TRIMH Phase II approach is to continue promoting outstanding multidisciplinary and collaborative research to improve patient care using this new paradigm. SC- TRIMH is a multidisciplinary and interactive center promoting translational research for musculoskeletal health which supports junior investigators and enhances their research competitiveness. The specific aims are to: 1) expand the critical mass of funded investigators conducting musculoskeletal research by implementing the concept of VHT for the development of new devices, interventions, and therapeutics for musculoskeletal disorders; 2) strengthen innovative scientific cores that support and advance musculoskeletal research to provide SC-TRIMH researchers with the best support to move their research forward to patient care; and 3) advance the ongoing development of an independent, sustainable, multidisciplinary thematic program by promoting the planning of program project and center grants at the institution level by building teams of PIs in niche areas, establishing a platform for technology transfer and commercialization through collaborations with Clemson University Research Foundation and the South Carolina Research Authority for academic startups, and develop a strategy for administrative infrastructure and financial recovery for SC-TRIMH resources. The Center is led by a leadership team with multidisciplinary expertise coalescing resources and disciplines from Clemson University School of Health Research (CUSHR) and its clinical partner, PRISMA Health System (PHS). The scientific cores include: 1) Multi-scale Computational Modeling Core providing cluster computing, bioengineering, bioinformatics, and systems biology expertise to model patient/specimen specific musculoskeletal system at body, tissue, and cellular levels for the development of novel technology; 2) Advanced Fabrication and Testing Core to generate, refine, and optimize the function and performance of technology using the advanced micro and macro fabrication technologies; and, 3) Preclinical Assessment Core to provide animal testing and human cadaver analysis to assess the in vivo function of novel devices, interventions, and therapeutics. These cores will support Phase II Research Project Leaders (RPLs) to advance musculoskeletal health and facilitate their competitiveness for national research awards. Extensive institutional support including flexible funds and three new tenure-track faculty positions will contribute to the Center's long-term success and viability.

NARRATIVE Musculoskeletal disease is one of the leading causes of disability and health care expenses where an estimated 126.6 million Americans (one in two adults) are affected by a musculoskeletal condition costing an estimated $213 billion each year in treatment and lost wages. With an aging population, this figure is only set to increase and become worse since research is hampered by a low and slow rate of translation of basic discoveries into clinical practice, e.g. only 25% of highly promising biomedical discoveries resulted in a published randomized clinical trial and less than 10% were established in clinical practice within 20 years. This COBRE center implements a new concept for translational research, i.e. Virtual Human Trials, to expedite the process from concept development to new deliverable therapeutics, interventions, and devices for musculoskeletal health.