Lignin-based hydrogels for multifunctional wound healing applications: Roles of bulk lignin and lignin nanoparticles

Lignin, the second most abundant natural polymer, represents an underutilized renewable resource for biomaterial development. Its phenolic, aromatic, and polyfunctional structure provides antioxidant, antimicrobial, UV-absorbing, and network-forming properties that are relevant to wound healing applications. Recent advances in lignin valorization have enabled the development of lignin-based hydrogel systems using bulk lignin, chemically modified lignin, and lignin nanoparticles (LNPs). This review provides a comprehensive analysis of lignin-based hydrogels for wound healing, with particular attention to how lignin form and processing route influence hydrogel structure, mechanical performance, swelling behavior, drug loading, release kinetics, and biological activity. Key chemical modification strategies are examined in terms of their role in enhancing lignin reactivity, compatibility, and functional performance. In parallel, major nanoparticle synthesis approaches are discussed with emphasis on particle size control, stability, and scalability. The review further establishes structure-property-performance relationships governing hydrogel formation, mechanical properties, swelling behavior, drug loading capacity, and controlled release mechanisms. Characterization techniques are outlined to enable reliable evaluation of physicochemical, mechanical, and biological properties. Emerging applications in wound healing, drug delivery, and tissue engineering are critically assessed, highlighting the intrinsic antioxidant, antimicrobial, and bioactive nature of lignin-based systems. Finally, key challenges related to large-scale manufacturing, reproducibility, cost, and regulatory compliance are analyzed from a process engineering perspective. Future research directions are proposed, emphasizing standardized lignin processing, scalable fabrication strategies, and the integration of green chemistry principles to facilitate the development of clinically translatable lignin-based hydrogel technologies.