Treatment of volumetric muscle loss in mice using nanofibrillar scaffolds enhances vascular organization and integration.
Traumatic skeletal muscle injuries cause irreversible tissue damage and impaired revascularization. Engineered muscle is promising for enhancing tissue revascularization and regeneration in injured muscle. Here we fabricated engineered skeletal muscle composed of myotubes interspersed with vascular endothelial cells using spatially patterned scaffolds that induce aligned cellular organization, and then assessed their therapeutic benefit for treatment of murine volumetric muscle loss. Murine skeletal myoblasts co-cultured with endothelial cells in aligned nanofibrillar scaffolds form endothelialized and aligned muscle with longer myotubes, more synchronized contractility, and more abundant secretion of angiogenic cytokines, compared to endothelialized engineered muscle formed from randomly-oriented scaffolds. Treatment of traumatically injured muscle with endothelialized and aligned skeletal muscle promotes the formation of highly organized myofibers and microvasculature, along with greater vascular perfusion, compared to treatment of muscle derived from randomly-oriented scaffolds. This work demonstrates the potential of endothelialized and aligned engineered skeletal muscle to promote vascular regeneration following transplantation.
['Nakayama|Karina H|KH|', 'Quarta|Marco|M|', 'Paine|Patrick|P|', 'Alcazar|Cynthia|C|', 'Karakikes|Ioannis|I|', 'Garcia|Victor|V|', 'Abilez|Oscar J|OJ|0000-0002-9991-400X', 'Calvo|Nicholas S|NS|', 'Simmons|Chelsey S|CS|', 'Rando|Thomas A|TA|', 'Huang|Ngan F|NF|0000-0003-2298-6790']
D000818:Animals D002460:Cell Line D018920:Coculture Techniques D016207:Cytokines D042783:Endothelial Cells D006801:Humans D051379:Mice D018485:Muscle Fibers, Skeletal D018482:Muscle, Skeletal D032448:Myoblasts, Skeletal D057139:Nanofibers D012038:Regeneration D023822:Tissue Engineering D054457:Tissue Scaffolds
Tissues Regeneration Cell therapies Musculoskeletal models Tissue engineering