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Scheme 1 Characteristics and applications of nanomaterial-enhanced gelatin hydrogels. Schematic created by the authors. • A comprehensive overview of nanomaterial-enhanced gelatin hydrogels for microenvironment-responsive bone regeneration. • Functional nanomaterials synergistically improve mechanics, angiogenesis, osteogenesis. • Controlled drug/bioactive factor delivery systems and stem cell therapy for enhanced bone regeneration. • Critical analysis of translational challenges and future avenues to accelerate clinical translation. The repair of bone defects caused by trauma, infection, or congenital diseases faces significant challenges. In recent years, gelatin hydrogels enhanced with nanomaterials have shown great potential in the field of bone defect treatment. Due to their excellent biocompatibility, biomimetic extracellular matrix-like three-dimensional porous structure, and tunable degradation properties, gelatin hydrogels have become ideal materials for bone tissue engineering. However, their inadequate mechanical strength and limited osteoinductive properties restrict their clinical application. Studies have shown that the introduction of nanomaterials not only addresses the mechanical shortcomings of traditional hydrogels but also optimizes the bone repair microenvironment through mechanisms such as mimicking the natural bone tissue’s electrical microenvironment, scavenging reactive oxygen species (ROS), and regulating inflammatory responses. This systematic review synthesizes the latest progress in nanomaterial-enhanced gelatin hydrogels for bone regeneration, focusing on their synergistic effects across mechanical reinforcement, osteogenic differentiation, angiogenesis, immunomodulation, and controlled drug release. By elucidating how nanomaterial integration transforms gelatin hydrogels from passive scaffolds into intelligent microenvironments, it establishes a critical scientific foundation for next-generation bone regeneration strategies—providing actionable design principles to overcome clinical limitations and pioneering novel pathways for multifunctional, dynamically responsive bone repair systems.
Yang et al. (Wed,) studied this question.