GelMA-Based Nanocomposites for Bone Defect Regeneration: Design, Performance, and Clinical Translation Potential

This narrative review summarizes recent advances in gelatin methacryloyl (GelMA)-based nanocomposites for bone defect regeneration, addressing the persistent clinical need for effective and customizable bone repair strategies. As an extracellular matrix (ECM)-mimicking hydrogel, GelMA offers favourable biocompatibility, tunable mechanics, and photo-crosslinkability, enabling integration with light-based 3D printing platforms to fabricate patient-specific scaffolds and, more recently, skeletal organoid-inspired constructs. Nevertheless, key barriers to translational advancement remain, including limited load-bearing capacity without reinforcement, insufficient vascularization, lack of intrinsic antibacterial activity, and a shortage of large-animal validation and well-designed clinical trials. We synthesize how formulation and processing parameters translate into scaffold properties and biological outcomes, and we discuss representative optimization strategies-such as composite reinforcement with hydroxyapatite/bioglass, bioactive molecule delivery, and immunomodulatory design-to address these limitations. We further highlight application-oriented evidence across major bone-loss-related conditions and summarize practical translational bottlenecks, including batch-to-batch reproducibility, scalable, GMP-compliant pathways that may be required, sterilization compatibility, and the need to synchronize degradation kinetics with new bone formation. By integrating material design, mechanistic considerations, and translational constraints, this review provides a framework to guide the rational development of GelMA-based systems toward clinically relevant bone regeneration.