Fig. 1: Concept of pre-innervated tissue-engineered muscle.

The present study was focused on exploring the role of pre-innervation on myocytes in vitro and host neuromuscular environment in vivo following implantation. a For in vitro studies, our overarching hypothesis was that innervation would augment skeletal myocyte fusion, maturation, and formation of Neuromuscular Junctions (NMJs). b Volumetric Muscle Loss (VML) is defined as frank loss of muscle volume that is accompanied by chronic motor axotomy leading to denervation of the injured area. We used a standardized rat model of VML where >20% of the Tibialis Anterior (TA) muscle volume was resected to create a defect leading to potential damage to intramuscular branches of the host nerve and loss of motor end plates (or NMJs) near the injury area. For in vivo studies, our overarching hypothesis was that implantation of pre-innervated constructs would facilitate preservation of muscle volume, accelerate angiogenesis, enhance Acetylcholine Receptor (AchR) clustering and promote innervation of AchRs (mature NMJs) near the implant site at acute time point.