Pre-Innervated Tissue Engineered Muscle Promotes a Pro-Regenerative Microenvironment Following Volumetric Muscle Loss
| Autor: | Joseph C. Maggiore, Halimulati Kaisaier, D. Kacy Cullen, Zarina S. Ali, Carlos A. Aguilar, Kevin D. Browne, Franco A Laimo, Foteini Mourkioti, Suradip Das |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Tissue engineered business.industry Regeneration (biology) Cell migration Fibril Neuromuscular junction Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Tissue engineering In vivo Medicine Myocyte business 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/840124 |
| Popis: | Volumetric Muscle Loss (VML) is defined as traumatic or surgical loss of skeletal muscle tissue beyond the inherent regenerative capacity of the body, generally leading to a severe functional deficit. Autologous muscle grafts remain the prevalent method of treatment whereas recent muscle repair techniques using biomaterials and tissue engineering are still at a nascent stage and have multiple challenges to address to ensure functional recovery of the injured muscle. Indeed, appropriate somato-motor innervations remain one of the biggest challenges for both autologous muscle grafts as well as tissue engineered muscle constructs. We aim to address this challenge by developing Pre-Innervated Tissue Engineered Muscle comprised of long aligned networks of spinal motor neurons and skeletal myocytes. Here, we developed methodology to biofabricate long fibrils of pre-innervated tissue engineered muscle using a co-culture of myocytes and motor neurons on aligned nanofibrous scaffolds. Motor neurons lead to enhanced differentiation and maturation of skeletal myocytes in vitro. These pre-innervated tissue engineered muscle constructs when implanted in vivo in a rat VML model significantly increase satellite cell migration, micro-vessel formation, and neuromuscular junction density in the host muscle near the injury area at an acute time point as compared to non-pre-innervated myocyte constructs and nanofiber scaffolds alone. These pro-regenerative effects can potentially lead to enhanced functional neuromuscular regeneration following VML, thereby improving the levels of functional recovery following these devastating injuries. |
| Databáze: | OpenAIRE |
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