Stimuli-responsive polysaccharide-based smart hydrogels for diabetic wound healing: Design aspects, preparation methods and regulatory perspectives

Diabetes adversely affects wound-healing responses, leading to the development of chronic infected wounds. Such wound microenvironment is characterized by hyperglycaemia, hyperinflammation, hypoxia, variable pH, upregulation of matrix metalloproteinases, oxidative stress, and bacterial colonization. These pathological conditions pose challenges for the effective wound healing. Therefore, there is a paradigm shift in diabetic wound care management wherein abnormal pathological conditions of the wound microenvironment is used as a trigger for controlling the drug release or to improve properties of wound dressings. Hydrogels composed of natural polysaccharides showed tremendous potential as wound dressings as well as stimuli-responsive materials due to their unique properties such as biocompatibility, biodegradability, hydrophilicity, porosity, stimuliresponsiveness etc. Hence, polysaccharide-based hydrogels have emerged as advanced healthcare materials for diabetic wounds. In this review, we presented important aspects for the design of hydrogel-based wound dressings with an emphasis on biocompatibility, biodegradability, entrapment of therapeutic agents, moisturizing ability, swelling, and mechanical properties. Further, various crosslinking methods that enable desirable properties and stimuli responsiveness to the hydrogels have been mentioned. Subsequently, state-of-the-art developments in mono- and multi- stimuli-responsive hydrogels have been presented along with the case studies. Finally regulatory perspectives, challenges for the clinical translation and future prospects have been discussed.