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Musculotendinous Project

Differentiated C2c12 cells form multinucleated skeletal muscle myotubes in vitro

The reconstruction of skeletal muscle tissue either lost by traumatic injury, tumor ablation or due to congenital abnormalities is hampered by the lack of availability of functional substitutes to this native tissue. Satisfactory repair of a severed muscle relies upon good apposition of the cut ends with regeneration of the motor nerve branches serving the muscle. However, in the case of multiple lacerations or debridement of traumatized muscle there is frequently a loss of muscle tissue. This a particular problem in the context of military combat wounds where the morbidity associated with severe soft tissue injury can be significant, accounting for over 80% of all  surgical amputations.

While Skeletal, smooth and cardiac muscle neogenesis has been noted using the ECM bioscaffolds developed in the lab, the source of cells that contribute to this new muscle tissue formation has not been investigated, nor has the full potential of muscle reconstruction been investigated.  This project aims to develop an ECM scaffold that can facilitate restoration of a functional skeletal muscle-tendon unit and ultimately a complete muscle compartment.

Our initial studies have focused on the use of small intestinal submucosa scaffolds to replace partial lost gastrocnemius muscle and achillies tendon. These studies have shown that this material is capable of stimulating restoration of significant muscle mass and restitution of the musclulotendinous junction restoring functionality to a damaged limb. This new muscle growth is both contractile and innervated and comprises a mixed muscle fiber population similar to the native muscle that was lost.

Future studies will further develop this implant to replace larger muscular defects. We are identifying appropriate techniques to seed the scaffold with mesechymal stem cells that will allow regeneration of entire muscle units where no native skeletal muscle remains.

The Badylak laboratory contains a full range of equipment for testing both the mechanical characteristics of regenerating muscle including ex vivo tissue baths as well as equipment to determine innervation of the muscle via electromyography both in vivo and ex vivo.

C2C12 myoblasts migrating into a scratch wound in vitro over and 18 hour perido in response to pepsin digested SIS-ECM Differentiated C2C12 cells form myotubes in vitro

 

 

 

Updated 16-May-2011