Improved Muscle Function After Injury with the Application of a Biological Decellularized Matrix

Abstract

Background: Skeletal muscle injury leads to loss of muscle function that lasts well into recovery and can be permanent. Application of the novel bio-scaffold termed porcine-derived urinary bladder matrix (UBM) has a potential benefit to mitigate injury through tissue regeneration. To date, findings of potential benefit in animal models were limited to short assessment times. The purpose of this study was to investigate whether UBM treatment 14 days after injury sustainably improves the recovery of muscle function in injured mice. Methods: C57BL/6 adult male mice received bilateral laceration injuries on the gastrocnemius (GN) muscle under anesthesia and were then treated with vehicle or 150 µg of UBM nanoparticles. Treatment was applied immediately after injury or 14 days later. Muscle isometric force was measured 60 days after injury. Previous time course analyses have shown that muscle function did not start to improve until after 42 days after injury. Therefore, we designed a second experiment to trace the time course of UBM effects on muscle function recovery by measuring the isometric muscle force at 49 and 90 days after injury. In vitro, we analyzed the effects of UBM on muscle cell proliferation and differentiation. Results: UBM promotes muscle cell proliferation and differentiation. Twitch (Pt), tetanic (Po) force and maximal fatigue were significantly decreased in the injured mice on day 60. Muscle fatigue maximum force significantly recovered when UBM treatment was applied 14 days after injury (p<0.05) but not when UBM was applied immediately after the injury. Time course analysis demonstrated that UBM improvement of Pt and Po was evident by day 49 after injury (p<0.05). However, no further muscle function improvement was observed on day 90. Conclusions: Delayed treatment with the UBM improves muscle function recovery following laceration injury starting 49 days after injury. These effects may be mediated by improvements in muscle cell proliferation and differentiation. This animal model is suitable to test other therapeutic strategies to improve muscle function after injury.