# A Borophosphate Glass Doped with Cobalt Oxide Improves Skeletal Muscle Structure and Function in Myopathic Mice

**Authors:** Jacob A. Kendra, Alexandra G. Naman, Rebekah L. Blatt, Carla D. Zingariello, Richard K. Brow, Steven S. Segal, Aaron B. Morton

PMC · DOI: 10.3390/jfb17030155 · Journal of Functional Biomaterials · 2026-03-20

## TL;DR

A new borophosphate glass doped with cobalt oxide improves muscle strength and structure in mice with a muscle disease.

## Contribution

A novel inorganic biomaterial (CoO-TRIM) is shown to enhance muscle regeneration and function in myopathic mice.

## Key findings

- CoO-TRIM injection increased muscle force and myofiber size in myopathic mice up to 70 days post-treatment.
- VEGF levels were elevated in treated mice, leading to increased muscle vascularity.
- Inflammation markers increased temporarily but normalized by 70 days without long-term negative effects.

## Abstract

Skeletal muscle myopathy remains a significant cause of disability with limited treatment strategies. Advancements in tissue engineering have led to the development of borophosphate bioactive glasses (BPBGs) capable of enhancing skeletal muscle structure and function. Using a mouse model of severe myopathy (D2.mdx), we investigated muscle force, regeneration, angiogenesis and inflammation at 14, 70 and 140 days post-treatment (dpt). Tibialis anterior (TA) muscles of D2.mdx mice that received a single injection of cobalt oxide-doped BPBG (CoO-TRIM) particles exhibit greater active force, myofiber size, and regeneration through 70 dpt compared to control D2.mdx mice injected with Saline. Vascular endothelial growth factor (VEGF) was elevated up to 70 dpt in D2.mdx CoO-TRIM mice followed by increased muscle vascularity. As a marker of inflammation, interleukin (IL)-6 increased in D2.mdx CoO-TRIM mice compared to D2.mdx Saline controls at 14 dpt, with no differences at 70 or 140 dpt. No differences were observed in outcome measures between wild-type (WT) CoO-TRIM mice and WT Saline controls. We report that CoO-TRIM can stimulate VEGF production and promote restoration of muscle structure and function when inflammation is present. Local injection of an inorganic biomaterial alone can benefit myopathic skeletal muscle.

## Linked entities

- **Proteins:** VEGFA (vascular endothelial growth factor A), IL6 (interleukin 6)
- **Chemicals:** cobalt oxide (PubChem CID 6432046), Saline (PubChem CID 5234)
- **Diseases:** myopathy (MONDO:0005336)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Trat1 (T cell receptor associated transmembrane adaptor 1) [NCBI Gene 77647] {aka C030046M14Rik, Tcrim, Trim}, Capn12 (calpain 12) [NCBI Gene 60594] {aka CANP 12}, Pecam1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 29583] {aka CD31, Pecam}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Map1lc3b (microtubule-associated protein 1 light chain 3 beta) [NCBI Gene 67443] {aka 1010001C15Rik, Atg8, LC3b, MAP1A/MAP1B, Map1lc3}, Sptan1 (spectrin alpha, non-erythrocytic 1) [NCBI Gene 20740] {aka 2610027H02Rik, Spna-2, Spna2}, Hspa9 (heat shock protein family A (Hsp70) member 9) [NCBI Gene 15526] {aka 74kDa, Csa, Grp75, Hsc74, Hsp74, Hsp74a}, Il5 (interleukin 5) [NCBI Gene 16191] {aka Il-5}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Clgn (calmegin) [NCBI Gene 12745] {aka 4930459O04Rik, A2/6, Cln}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}
- **Diseases:** muscle damage (MESH:D009133), necrosis (MESH:D009336), cytotoxic (MESH:D064420), muscle weakness (MESH:D018908), muscle (MESH:D019042), calcification (MESH:D002114), Inflammatory (MESH:D007249), cachexia (MESH:D002100), ischemia (MESH:D007511), hyperplasia (MESH:D006965), overdose (MESH:D062787), injury to (MESH:D014947), Duchenne muscular dystrophy (MESH:D020388), autoimmune dysfunction (MESH:D001327), dislocation (MESH:D004204), VML (MESH:D009135), metabolic dysregulation (MESH:D021081), Vascular dysfunction (MESH:D002561), myositis ossificans (MESH:D009221), tissue damage (MESH:D017695), function (MESH:D003291), fibrosis (MESH:D005355), bone defects (MESH:D001847), disability (MESH:D009069), sarcopenia (MESH:D055948), atrophy (MESH:D001284), hypoxia (MESH:D000860), Skeletal muscle myopathies (MESH:D005207)
- **Chemicals:** polyphosphate (MESH:D011122), B2O3 (MESH:C042168), Na2O (MESH:C096707), acetic acid (MESH:D019342), CO2 (MESH:D002245), EU (MESH:D005063), HA (MESH:D017886), DAPI (MESH:C007293), butane (MESH:C046888), bicarbonate (MESH:D001639), platinum (MESH:D010984), graphite (MESH:D006108), PicroSirius Red (MESH:C009798), paraformaldehyde (MESH:C003043), Co (MESH:D003035), NaCl (MESH:D012965), iridium (MESH:D007495), nitrogen (MESH:D009584), Boron (MESH:D001895), silica (MESH:D012822), dithiothreitol (MESH:D004229), Al2O3 (MESH:D000537), water (MESH:D014867), CaCO3 (MESH:D002119), EDTA (MESH:D004492), Na-Ca-borophosphate (-), xylazine (MESH:D014991), TRITC (MESH:C009434), isoflurane (MESH:D007530), orthophosphate (MESH:D010710), H (MESH:D006859), PVDF (MESH:C024865), Pyrophosphate (MESH:C107241), P2 (MESH:C020845), sodium (MESH:D012964), nitric acid (MESH:D017942), Silicate (MESH:D017640), Borate (MESH:D001881), CuO (MESH:C030973), CaO (MESH:C016538), Na2CO3 (MESH:C005686), Rhodamine (MESH:D012235), CoO (MESH:C060728), calcium phosphates (MESH:D002130), phosphoric acid (MESH:C030242), Oxygen (MESH:D010100), P2O5 (MESH:C012500), P1 (MESH:C480041), Triton X-100 (MESH:D017830), ethanol (MESH:D000431)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Mutations:** K15048D
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), DBA/2J — Mus musculus (Mouse), Finite cell line (CVCL_6496)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13028039/full.md

## References

127 references — full list in the complete paper: https://tomesphere.com/paper/PMC13028039/full.md

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Source: https://tomesphere.com/paper/PMC13028039