CYR61 improves muscle force recreation in a rabbit trauma model

Abstract

BACKGROUND: Critically elevated compartment pressures after complicated tibial fractures may result in fibrosis and therefore scarring of muscles with impaired function. Several studies have shown a relationship between angiogenesis and more effective muscle regeneration. Cysteine-rich angiogenic inducer 61 (CYR61) is associated with angiogenesis but it is not clear whether it would restore muscle force, reduce scarring or improve angiogenesis after acute musculoskeletal trauma. OBJECTIVE: We researched whether local application of CYR61 (1) restores muscle force, (2) reduces scar tissue formation, and (3) improves angiogenesis. METHODS: We generated acute soft tissue trauma with temporary ischemia and increased compartment pressure in 22 rabbits and shortened the limbs to simulate surgical fracture debridement. In the test group, a CYR61-coated collagen matrix was applied locally around the osteotomy site. After 10 days of limb shortening, gradual distraction of 0.5 mm per 12 hours was performed to restore the original length. Muscle force was measured before trauma and on every fifth day after trauma. Forty days after trauma we euthanized the animals and histologically determined the percentage of connective and muscle tissue. Immunohistology was performed to analyze angiogenesis. RESULTS: Recovery of preinjury muscle strength was significantly greater in the CYR61 group (2.8 N; 88%) as compared to the control (1.8 N; 53%) with a moderate reduction of connective tissue (9.9% vs. 8.5%). Immunohistochemical staining showed that blood vessel formation increased significantly (trauma vs. control 38.75 ± 27.45 mm2 vs. 24.16 ± 19.81 mm2). CONCLUSIONS: Local application of CYR61 may improve restoration of muscle force and accelerate muscle force recovery by improving angiogenesis and moderately reducing connective tissue.