Background: Traumatic musculoskeletal injuries are highly prevalent among civilians, athletes, and warfighters causing skeletal muscle degeneration and muscle dysfunction. Time-release ion matrices (TRIM) are promising inorganic biomaterials, restoring damaged tissue following injury through local ion release, stimulating regenerative gene expression. It is currently unknown if effects of TRIM are exerted on all muscles within the same muscular compartment. Following our previous work in the tibialis anterior (TA) muscle, the purpose of this study was to investigate the dissolution effects of a novel biomaterial, Cobalt Oxide (CoO)-TRIM, to enhance muscle regeneration and microvascular density within the underlying extensor digitorum longus (EDL) muscle following BaCl2-induced injury. Hypothesis: 8 days post injury (dpi), CoO-TRIM will: 1) increase muscle fiber cross-sectional area (CSA) and muscle regeneration of the EDL muscle; and 2) enhance EDL muscle vascularity. Methods: The left or right TA muscle of adult (4-month-old) male and female C57BL/6J mice were randomly injected with 70 µl of BaCl2. Following the acute inflammatory phase post-BaCl2 (3 dpi), mice were randomly separated into two groups (n=8) and injected with 70 µl sterile saline alone (vehicle control) or 70 µl CoO-TRIM (5 µg/µl) into the previously injured TA muscles. At 8 dpi, the underlying EDL was isolated and frozen for histological analysis. Muscle cross-sections were immunostained for laminin (myofiber borders), embryonic myosin heavy chain (eMyHC, active regeneration), CD31 (endothelial cells), and DAPI (nuclei). Results: Cross-sectional analysis revealed a 25% increase in regenerating muscle fiber CSA (means ± SEM: TRIM, 640 ± 42 µm2, Saline, 510 ± 24 µm2; P = 0.02), with a reduction of small area fibers (1000 µm2) (TRIM, 33.7 ± 5.7%; Saline, 17.9 ± 2.3%; P = 0.02) following CoO-TRIM injection to TA. 8 dpi, EDL muscles underlying CoO-TRIM treated TAs had a 31% increase in muscle regeneration (eMyHC+ fibers/muscle area (mm2); TRIM, 755 ± 86 fibers/mm2; Saline, 575 ± 46 fibers/mm2; P = 0.09), and a 35% increase in muscle vascularity (CD31 staining; µm2/muscle fiber; TRIM, 64.4 ± 6.2 µm2/fiber; Saline, 47.7 ± 3.1 µm2/fiber; P=0.03). Conclusion: Results support the hypothesis that CoO-TRIM enhances muscle fiber CSA and muscle regeneration in EDL muscles following TA treatment. Moreover, CoO-TRIM increased muscle vascularity, suggesting the angiogenic effects of CoO-TRIM complement those of myogenesis. Based on previous work from our group in the TA muscle, these results support CoO-TRIM’s potential as a clinically relevant therapeutic following skeletal muscle injury, with regenerative effects on tissues within the same muscular compartment. Support: Sydney and J.L. Huffines Institute for Sports Medicine and Human Performance Graduate Research Award (J.A.K., J.W.), ACSM Texas Chapter Student Research Development Award (J.A.K.), Texas A&M Department of Kinesiology and Sport Management (J.A.K., J.W., A.B.M), Texas A&M College of Education and Human Development (J.A.K., A.B.M.), NIH-NIAMS LRP Award (A.B.M.) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Hao et al. (Fri,) studied this question.