ABSTRACT

Mechanical signals generated by exercise combat obesity and maintain a healthy musculoskeletal system. Age and reduced physical activity disrupt mechanical signaling and diminish the potency of stem cells within the bone marrow that replenish bone-building cells. Even though poor skeletal health is a major cause of injury and disability among aged individuals, the reason for reduced bone-building responsiveness to exercise in older individuals, compared to younger individuals, remains a knowledge gap. This project will quantify the mechanical forces that cells are subjected to in bone by using novel 3D printed tissue engineering constructs. Combining this technology with the aging conditions caused by microgravity in experiments to be conducted on the International Space Station will reveal the putative connections between aging and physical activity at the cellular level. Ultimately, these efforts may lead to non-pharmacologic, regenerative strategies to improve muscle and bone health in in older adults, in those who must undergo extended bedrest, and astronauts. The multidisciplinary approach taken in this bioengineering project will be an excellent platform to fascinate and engage the next generation of students and young scientists.

A major technical barrier in studying the mechanical environment of mesenchymal stem cells (MSCs) that reside within bone marrow is that there are no model systems currently available that can replicate the mechanical complexity of the bone marrow compartment. To close this gap, this work will develop a 3D printed bone marrow analog system that combines an in vivo environment with the accessibility of an in vitro culture system. This will permit a systematic approach of study. To study cellular mechanical environments within these marrow analogs, the approach will include an experimental setup and a complementary and validated finite element model. These mechanoactive marrow environments will provide a novel tool for mechanobiologists to systematically study the effect of the mechanical environment on cell responses in 3D. Utilization of this novel system in this project will specifically advance mechanobiology knowledge by: (1) quantifying the mechanoresponse of old MSCs in a young bone marrow geometry and vice versa, thereby identifying the contribution of mechanical stress environment to the mechanosignaling capacity of aged MSCs. (2) establishing, for the first time, how the mechanical stress environment contributes to microgravity-simulated aging of MSCs.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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