Advances and Application Potential of Functional and Stimuli-Responsive Hydrogels in Diabetic Bone Repair

Impaired bone healing in diabetes continues to present a major challenge in orthopedic and regenerative medicine. The compromised osseous regeneration typically stems from a complex pathological cascade—namely, persistent local hyperglycemia, excessive reactive oxygen species (ROS), impaired neurovascular coupling, sustained low-grade inflammation, altered insulin signaling, and the deleterious deposition of advanced glycation end products. Together, these systemic and microenvironmental anomalies impede endogenous repair, potentially culminating in delayed union or frank non-union. To overcome these limitations, functional and stimuli-responsive (smart) hydrogel networks have emerged as a versatile therapeutic platform. These matrices provide sustained local delivery, while selected responsive chemistries couple release or degradation to glucose, ROS, proteases, pH, or externally applied light. Temperature-dependent gelation, antioxidant activity, and electrical conductivity are distinguished from pathological-signal-triggered release. In this review, we summarize current progress in the rational design and implementation of functional and stimuli-responsive hydrogels for diabetic bone repair. We evaluate their biological mechanisms together with responsive chemistry, tested trigger levels, release and degradation kinetics, mechanical properties, and the relevance of each experimental model, concluding with prospective strategies to guide subsequent biomaterial innovation and clinical translation in this domain.