Technology development center for integrative physiologic models of the human musculoskeletal system

The National Institutes of Health Office of the Director awarded Brigham & Women's Hospital Inc. a cooperative agreement valued at $3.516 million on March 20, 2026, under the Trans-NIH Research Support program (CFDA 93.310) to establish a Technology Development Center for Integrative Physiologic Models of the Human Musculoskeletal System. The award runs through December 31, 2030, with place of performance in Boston, Massachusetts.

The center will develop bioengineered physiologic models incorporating human cells and tissues to support disease-modifying drug development for musculoskeletal disorders affecting approximately 126.6 million U.S. adults. The award funds the creation of combinatory models for muscle, cartilage, tendon, and intervertebral disc research, with investigation of pathologies including mechanical overloading, inflammation, and injury while considering environmental exposures, aging, and hormonal effects. The center will collaborate with a Validation and Qualification Network and Consortium Steering Committee to drive innovation in New Approach Methodologies.

Sub-recipients deliver specialized components. Massachusetts Institute of Technology's Dunkel group performs statistical data analysis and develops quantitative mathematical models predicting tissue growth and regeneration, adapting computational frameworks to biomedical imaging data and validating predictions against experimental outcomes. Boston Children's Hospital's Craft laboratory produces human pluripotent stem cell-derived cartilage cells and tissues, evaluates biological relevance compared to native tissues, establishes cartilage outcomes for healthy and disease scenarios, and provides developmentally relevant progenitor cells to collaborating labs. The Spaulding Rehabilitation Hospital Corporation's Ambrosio and Wang teams establish and validate muscle organoid platforms modeling skeletal muscle aging and sex-specific effects, develop multiorgan platforms for muscle-cartilage crosstalk, and test therapeutic efficacy of extracellular vesicles. Massachusetts General Hospital provides centralized scientific, technical, regulatory, and administrative support through the Gene and Cell Therapy Institute and the Galloway laboratory, which defines tendon cell phenotypes, analyzes cellular and mechanical properties of stem cell-derived constructs, and performs validation studies on biomaterial-grown cells.

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.