Novel 3D Printed Biodegradable Polyurethane-Urea Elastomer Recapitulate Skeletal Muscle Structure and Function

Effective skeletal muscle tissue engineering relies on the control over the scaffold architecture for providing the muscle cells with required directionality, together with mechanical property match with the surrounding tissue. Although recent advances in 3D printing fulfills the first requirement, the available synthetic polymers are either too rigid or show unfavorable surface and degradation profiles for the latter. In addition, natural polymers that are generally used as hydrogels, lack the required mechanical stability to withstand the forces exerted during muscle contraction. Therefore, one of the most important challenges in the 3D printing of soft and elastic tissues such as skeletal muscle is the limitation of the availability of elastic, durable and biodegradable biomaterials. Herein, we have synthesized novel, biocompatible and biodegradable, elastomeric, segmented polyurethane and polyurethane-urea (TPU) copolymers which are amenable for extrusion 3D printing and show high elasticity, low rigidity, controlled biodegradability and improved wettability, compared to conventional polycaprolactone (PCL) and PCL based TPUs. The degradation profile of the 3D printed TPU scaffold was in line with the potential tissue integration and scaffold replacement process. Even though TPU attracts macrophages in 2D configuration, its 3D printed form showed limited activated macrophage adhesion and induced muscle-like structure formation by C2C12 mouse myoblasts <i>in vitro</i>, while resulting in a significant increase in muscle regeneration <i>in vivo</i> in a tibialis anterior defect in a rat model. Effective muscle regeneration was confirmed with histopathological assessment as well as gait analysis and micro-CT evaluation. These results demonstrate that matching the tissue properties for a given application via use of tailor-made polymers can substantially contribute to the regenerative outcomes of 3D printed tissue engineering scaffolds.