Optical imaging in musculoskeletal systems can provide dynamic cellular-resolution analysis of biological tissues and regenerative processes. Here, we advance multiphoton imaging and analysis techniques to explore therapeutic cell homing in the bone, mitochondrial dynamics during regeneration in muscle and bone, and collagen organization in metabolic bone disorders. We develop aberration correction approaches to recover high-resolution imaging of cell dynamics deep in the bone marrow and in muscle. We leverage our imaging techniques to explore single mitochondrial dynamics in skeletal muscle, and the disruptions in mitochondrial order that occur after volumetric muscle loss. Finally, we have developed second harmonic generation imaging using polarized light for analysis of bone collagen assembly into lamella sheet structures and have investigated collagen organization in metabolic bone disorders. Our findings could provide insight into dynamic processes driving musculoskeletal homeostasis and fragility disorders.
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