The purpose and objectives of the training program proposed for continued support remain to prepare bioengineers for an impactful career in orthopaedic research as part of a focused program leading to the Ph.D. degree in Bioengineering. Training a diverse cohort of bioengineers side-by-side with orthopaedic surgeons and life scientists at various levels of training, will continue to foster an environment conducive to research and education in the orthopaedic arena. Indeed, this has been the formula that has been very successful in our training program thus far and, in today's complex and interdisciplinary research world, this approach is more essential than ever. Trainee research areas represent a wide range of musculoskeletal problems including, but not limited to, the cellular and molecular biology of bone growth, repair, ossification, and maintenance; the etiology and pathogenesis of tendon and ligament injury, repair, and regeneration; mechanical loading effects on articular cartilage; and biomaterials to promote tissue repair and regeneration. In addition to formal didactic coursework outlined in our enhanced Orthopaedic Bioengineering curriculum, training opportunities include seminar series, journal clubs, and other enrichment and outreach activities. The primary participating departments in this training program are the Department of Orthopaedic Surgery in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania. Both departments have grown significantly over the past five years in terms of numbers of faculty, grant funding, and trainees. Six predoctoral trainees are requested in this continuation grant. It should be noted that the predoctoral trainees work in a structured, yet flexible environment while completing course requirements toward the Ph.D. degree in Bioengineering. Despite the fact that the Ph.D. program is typically five years in total duration, typically, only two years, and not the first year, will be supported by this training grant so that positions can be made available for new trainees to grow the program. There are three primary training sites for this training grant. The first primary site is the McKay Orthopaedic Research Laboratory in Stemmler Hall in the Department of Orthopaedic Surgery, the second is the Translational Musculoskeletal Research Center at the Philadelphia VA Medical Center, and the third is the orthopaedic research unit in Skirkanich Hall in the Department of Bioengineering. These facilities represent >85% of the dedicated training space for the program. Finally, it should be noted that the University of Pennsylvania operates a large number of state-of-the-art, sophisticated core facilities that are available to faculty and trainees.