Multifunctional smart hydrogels: Spatiotemporal delivery networks for osteogenic microenvironment engineering and regenerative design paradigms

Bone defects arising from trauma, tumor resection, diabetes, and various other factors pose significant challenges in clinical treatment. Compared with traditional static bone grafts, smart hydrogels possess the ability to respond to external and internal stimuli such as temperature, pH, light, and enzymes. They can dynamically regulate their structure and function while further integrating with cutting-edge technologies like exosomes, functionalized nanomaterials, and gene therapy, demonstrating the advantages of intelligence, precision, and functional integration in treatment. This review provides a comprehensive summary of the response mechanisms and drug delivery modalities associated with smart hydrogels. It also explores their underlying mechanisms and applications in bone defect repair while establishing a multidimensional analytical framework encompassing “ Bone Repair Process - Material Design - Clinical Translation.” Furthermore, it highlights existing challenges within this field and offers new perspectives for bone regeneration efforts. Ultimately, this aims to guide with a structured approach for the practical application of these innovative materials. Smart targeted controlled release systems may represent an appealing next-generation platform within the realms of bone tissue engineering and regenerative medicine.