Chitosan-based advanced biomaterials and stimuli-responsive systems for diabetic ulcer management: From principles to translational potential

Diabetic ulcers remain a significant clinical concern because of their poor healing, persistent inflammation, and increased infection risk. Chitosan and its derivatives have emerged as promising biomaterials for ulcer management due to their biocompatibility, biodegradability, mucoadhesiveness, pH responsiveness, and intrinsic properties, including hemostatic effects, antibacterial activity, anti-inflammatory properties, antioxidant capabilities, and self-healing capabilities. This review provides a comprehensive and current overview of chitosan-based approaches for diabetic ulcer management, focusing on both conventional and advanced biomaterials, including nanoparticles, hydrogels, nanofibers, microneedles, sponges, and 3D scaffolds. Special attention is given to stimuli-responsive chitosan systems designed to adjust drug release in response to specific cues, such as pH, reactive oxygen species, temperature, enzymes, or glucose levels. To underscore the translation potential, the review compiles commercialized products, recent patents, and clinical trials related to the management of diabetic ulcers based on chitosan formulations. Finally, the integration of AI-driven design with smart chitosan systems is proposed as a future direction towards personalized and predictive diabetic ulcer management.