Combined photobiomodulation and exosome therapy for muscle and tendon regeneration: an experimental rabbit study

Achilles tendon injuries are common, especially among athletes, and their treatment remains challenging. Reduced muscle strength and immobility can exacerbate tendon stiffness, leading to disability. This study investigated the effects of adipose tissue-derived mesenchymal stem cell exosomes and low-level laser therapy (LLLT) on muscle and Achilles tendon elasticity in a rabbit model. Twelve New Zealand white rabbits underwent ultrasound imaging of Achilles tendons and gastrocnemius muscles with a 40 MHz probe during flexion and dorsiflexion. Foot stress during movement was measured. To create a partial tendon injury, a 5 mm longitudinal incision, 3 mm deep, was made in the Achilles tendon. Male rabbits were randomly divided into four groups: control, LLLT (830 nm, 15 mW, 3 J/cm²), exosome injection (200 µg/mL), and combined LLLT with exosomes. Treatments were applied on days 1, 8, and 15. Ultrasound evaluations were performed before injury, immediately after, and on days 8 and 21. Tendon and muscle samples were analyzed histologically with hematoxylin-eosin staining. On day 21, the force applied to induce flexion and dorsiflexion of the Achilles tendon and gastrocnemius muscle significantly increased in the combined treatment group compared to the others (P < 0.05). The thickness strain of both muscle and tendon improved significantly with combination therapy (P < 0.05). Histology showed compact, parallel collagen fibers and a well-organized extracellular matrix in tendons treated with LLLT and exosomes. No inflammation was observed, and muscle atrophy was reduced. Combining low-level laser therapy with exosomes derived from ADSCs enhanced the histological, ultrasound-derived, and mechanical aspects related to Achilles tendon repair. This included improvements in tendon and gastrocnemius strain, as well as flexion and dorsiflexion force.