ADVANCED BIOMATERIALS FOR WOUND MANAGEMENT: A COMPREHENSIVE REVIEW OF PH-RESPONSIVE CHITOSAN HYDROGELS AND INTEGRATED PHYTOCHEMICAL THERAPIES

The physiological process of wound healing is intricate and susceptible to disruption, often leading to chronic, non-healing wounds that impose a considerable global health and economic burden. Traditional wound dressings, while offering basic protection, frequently lack the capacity to actively modulate the complex wound microenvironment or address the underlying biological dysfunctions. This comprehensive review examines the significant advancements in wound care, focusing on the evolution from passive coverings to sophisticated, functional biomaterials. Particular emphasis is placed on chitosan-based hydrogels, which have garnered substantial interest due to chitosan's inherent biocompatibility, biodegradability, antimicrobial efficacy, and haemostatic capabilities. The advent of "smart" hydrogel systems, particularly those engineered to respond to specific physiological cues such as the pH fluctuations characteristic of different wound states, represents a paradigm shift towards targeted therapeutic interventions. This review critically analyses the rationale for employing pH as a trigger for controlled drug release within the wound bed. Furthermore, it explores the therapeutic potential of incorporating bioactive phytochemicals, notably Umbelliferone (UMB) and Resveratrol, into these advanced chitosan hydrogel matrices. These plant-derived compounds possess a spectrum of beneficial properties, including potent anti-inflammatory, antioxidant, and antimicrobial activities, which are directly relevant to mitigating the complex pathology of non-healing wounds. Strategies to overcome the inherent physicochemical limitations of these phytochemicals, such as poor solubility and instability, through hydrogel encapsulation techniques are discussed. The synergistic interplay between the pH-responsive chitosan delivery vehicle and the multifaceted therapeutic actions of encapsulated phytochemicals is highlighted as a promising frontier for developing more efficacious and targeted wound healing therapies. Finally, current research gaps are identified, and future perspectives for the clinical translation of these advanced wound management systems are presented.