Technology development center for integrative physiologic models of the human musculoskeletal system - Abstract Musculoskeletal (MSK) disorders affect approximately 126.6 million adults in the United States, accounting for more than half of the adult population. The development of disease-modifying drugs (DMDs) for these conditions remains particularly challenging due to subjective clinical assessments, the absence of reliable animal models that closely mimic human pathology, and the high costs associated with large-animal studies. MSK disorders are influenced by various factors, including environmental exposures, aging, hormonal changes, degenerative diseases, and injuries, impacting individuals across all demographics. While surgical interventions are sometimes an option, they often have high failure rates, leading to disability and progressive tissue deterioration. The financial burden is immense, with U.S. healthcare costs related to MSK conditions exceeding $400 billion annually. To overcome these challenges, innovative preclinical platforms incorporating human cells and tissues are crucial for generating reliable data to support DMD development. Our team consists of experts with a strong track record in bioengineered systems that accurately replicate human MSK structures and functions. Leveraging our extensive experience with stem cells, organoids, and advanced in vitro culture platforms, we propose the establishment of an MSK New Approach Methodologies (NAMs)Technical Development Center (TDC) to drive the innovation of combinatory physiological models for muscle, cartilage, tendon, and intervertebral disc research. Through this initiative, we will investigate MSK pathologies—including mechanical overloading, inflammation, and injury—while considering key influences such as environmental exposures, aging, and hormonal effects. Additionally, by collaborating closely with the Consortium Steering Committee, the Validation and Qualification Network (VQN), and the NAMs Data Hub and Coordinating Center (NDHCC), the MSK NAMs developed through this effort will be widely accessible to a broad range of downstream users.
