Stimuli-Responsive Chitosan Hydrogels for Localized Anti-Inflammatory and Wound Healing Therapies

This research focuses on the design and development of injectable, stimuli-responsive chitosan hydrogels as smart delivery platforms for both synthetic anti-inflammatory drugs and natural plant extracts. The work builds on thermosensitive chitosan/β-glycerophosphate (CS/GP) systems, whose sol–gel transition at physiological temperature enables in situ gelation at the target site, and adapts this chemistry into a tunable carrier for localized, sustained therapy in infected, inflamed, or otherwise inaccessible regions.

A defining feature of the research is the systematic examination of how loading strategy, polymer composition, and environmental stimuli jointly govern release behavior. Parallel investigations of post-loading and in situ encapsulation demonstrate that a single chitosan platform can be tuned to deliver diclofenac sodium across a broad therapeutic window - from rapid burst release within five hours for acute pain relief to prolonged release over seven days for chronic inflammation management. This direct comparison provides a clear design rationale for matching release kinetics to clinical need without altering the underlying polymer chemistry.

The platform is further extended to natural phytochemicals, addressing the long-standing challenge of poor bioavailability and rapid metabolic degradation that limits the clinical utility of plant-derived bioactives. Ethanolic extracts of Triphasia trifolia (limeberry) and Piper betle (betel leaf) — both rich in coumarins, phenolics, and flavonoids with documented antibacterial and anti-inflammatory activities — were successfully encapsulated in the thermosensitive matrices. The resulting extract-loaded systems exhibit dual pH and temperature responsiveness, controlled release governed by Fickian or quasi-Fickian diffusion mechanisms, biodegradation under simulated physiological conditions, and potent antibacterial activity against both Gram-positive and Gram-negative pathogens. This line of work bridges traditional herbal medicine and modern controlled-release engineering, supporting plant extracts as quantifiable, well-characterized cargoes in smart material design.

To address the mechanical fragility that limits the practical injectability of pure chitosan hydrogels, a composite system reinforced with polyvinyl alcohol was developed. The CS/GP/PVA hydrogels retain full thermosensitivity, swelling capacity, and pH- and temperature-responsive release while achieving a soft-tissue-mimetic elastic modulus appropriate for injection into inflamed regions. The iterative trajectory — identifying a structural limitation and resolving it through rational composite design without compromising functional performance — reflects a coherent materials engineering progression across the research program.

Taken together, the body of work establishes a versatile and modular hydrogel platform whose release window can be engineered from hours to days, whose responsiveness can be layered across temperature, pH, and enzymatic triggers, and whose cargo scope spans both pharmaceutical and phytochemical agents. Its broader significance lies in offering a reproducible design framework for smart, functional biomaterials that align controlled delivery with the physiological cues of the wound microenvironment, contributing to the advancement of injectable therapeutic systems for localized inflammation and wound healing.