The Maturation of Tissue-Engineered Skeletal Muscle Units following 28-Day Ectopic Implantation in a Rat.

Volumetric muscle loss (VML) is a loss of skeletal muscle that results in a sustained impairment of function and is often accompanied by physical deformity. To address the need for more innovative repair options, our laboratory has developed scaffold-free, multiphasic tissue-engineered skeletal muscle units (SMUs) to treat VML injuries. In our previous work, using the concept of the "body as a bioreactor", we have shown that implantation promotes the maturation of our SMUs beyond what is possible in vitro. Thus, in this study we sought to better understand the effect of implantation on the maturation of our SMUs, including the effects of implantation on SMU force production and cellular remodeling. We used an ectopic implantation so that we could more easily dissect the implanted tissues post-recovery and measure the force contribution of the SMU alone and compare it to pre-implantation values. This study also aimed to scale up the size of our SMUs to enable the replacement of larger volumes of muscle in our future VML studies. Overall, implantation resulted in extensive maturation of the SMUs, as characterized by an increase in force production, substantial integration with native tissue, innervation, vascularization, and the development of structural organization similar to native tissue.