Bioprinting strategies for skeletal muscle regeneration: Advances in bioinks, technologies, and functional reconstruction

Volumetric muscle loss (VML) presents a significant clinical challenge because the intrinsic regenerative capacity of skeletal muscle is insufficient to repair extensive defects, and current therapeutic strategies remain inadequate. Bioprinting has emerged as a transformative approach, enabling the spatially controlled deposition of cells, biomaterials, and biochemical cues to create functional, biomimetic muscle tissues. This review offers a comprehensive overview of recent advancements in bioink development, bioprinting technologies, and functional reconstruction strategies for skeletal muscle regeneration. Bioinks derived from natural, synthetic, and composite materials are examined in terms of their effectiveness in supporting myogenesis, promoting cellular alignment, and facilitating neurovascular integration. We compare key bioprinting techniques—including extrusion-based, inkjet, and laser-assisted printing—highlighting their respective strengths and limitations in achieving structural fidelity and multicellular complexity. Emerging technologies such as coaxial and microfluidic-assisted printing are also discussed for their potential to fabricate aligned, anisotropic muscle constructs with hierarchical architectures. Functional outcomes are synthesized from in vitro assays (e.g., contractility, gene expression) and in vivo studies using VML models, with a focus on vascularization, innervation, and force restoration. Despite significant progress, substantial challenges remain in achieving complete neurovascular integration, long-term functionality, and clinical scalability. Moving forward, future efforts should emphasize the development of dynamic, bioresponsive materials, integration with electrical and mechanical stimulation, and the establishment of standardized preclinical protocols. By bridging material innovation, structural design, and biological functionality, bioprinting holds great promise for next-generation, clinically relevant skeletal muscle regeneration.

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