One-step coaxial bioprinting of aligned and vascularized 3D skeletal muscle constructs

Skeletal muscle constitutes approximately 40%-50% of total body weight and plays a vital role in human physiology; however, its regenerative capacity is insufficient in cases of volumetric muscle loss, and effective therapeutic options remain limited. To address this challenge, tissue engineering approaches have focused on constructing functional muscle grafts, with increasing attention on vascularized muscle tissues due to their enhanced integration, regeneration, and reduced fibrosis after transplantation. Nevertheless, most existing strategies rely on complex, multi-step fabrication processes requiring external scaffolds or stimulation systems, which limit practical applicability. In this study, we propose a one-step coaxial bioprinting strategy that enables the simultaneous fabrication of aligned muscle and vascular structures within a single construct. By optimizing the bioink formulation, both structural integrity and cellular functionality were achieved. Shear stress generated during coaxial printing induced myoblast alignment, promoting myogenic differentiation, while precise compartmentalization ensured effective domain separation. Furthermore, dynamic culture conditions enhanced endothelial cell maturation and vascular functionality. This scaffold-free and mechanical-stimulus-free vascularized muscle construct provides a simplified yet functional platform with strong potential for muscle disease modeling, drug screening, and regenerative therapies. The proposed fabrication strategy represents a meaningful advancement in vascularized muscle tissue engineering.