Bioactive hydrogels for wound Healing: Anti-Inflammatory mechanisms and nanomaterial Integration: A review

Abstract

Chronic wounds remain a significant clinical burden due to persistent inflammation, infection risk, and delayed tissue regeneration. Bioactive hydrogels have emerged as a transformative platform by mimicking the extracellular matrix, maintaining moisture, and enabling localized, controlled delivery of therapeutics. Recent advancements have integrated nanomaterials such as silver nanoparticles, zinc oxide, and graphene oxide for enhanced antimicrobial action, reactive oxygen species (ROS) scavenging, and immunomodulation. Simultaneously, gene therapy tools, including siRNA and CRISPR systems, are now being incorporated into hydrogel matrices to precisely regulate key inflammatory pathways such as NF-kappa B, MAPK, and STAT3. This review uniquely emphasizes the anti-inflammatory mechanisms of advanced hydrogel systems, highlighting how their composition, release kinetics, and stimuli-responsiveness can be tuned for phase-specific modulation of the wound healing cascade. Key design considerations such as biodegradability, mechanical integrity, and molecular targeting are discussed with a view toward clinical translation. By offering a mechanistic and integrative perspective, this work provides a roadmap for next-generation hydrogel platforms that actively regulate inflammation and accelerate healing in chronic wounds.