Aspiration-assisted intra-operative 3D bioprinting of scaffold-free modular units for skeletal muscle tissue regeneration

Traumatic muscle injury associated with volumetric muscle loss results in reversible muscle regeneration and function. Bottlenecks to conventional tissue engineering strategies to augment muscle regeneration are limited by low cell transplantation capacity by conventional injection of dissociated cells, the lack of customization of engineered tissues based on muscle defect geometry, as well as the feasibility of intra-operative use. Here, we developed a facile approach to engineer modular units of scaffold-free high-density muscle tissues in customizable geometric shapes and sizes with integration potential. For the first time, we describe aspiration-assisted intra-operative bioprinting of scaffold-free modular units for preclinical treatment of volumetric muscle loss. We demonstrated the ability of 3D modular muscle units to be bioprinted to the site of the muscle defect, leading to improved muscle, vascular, and neuromuscular regeneration in a mouse model of volumetric muscle loss. Transcriptional profiling revealed that the scaffold-free muscle units enable pre-formed cell-cell interactions that support myogenesis, unlike dissociated cells that lack cell-cell interactions. This technology of intraoperative modular muscle unit implantation is promising for clinical use for precise bioprinting of scalable tissues from geometrically tunable modular units.