Multifunctional transdermal nanocomposite patch based on phenolated lignin-chitosan reinforced with MgO nanoparticles for wound healing

This study reports the fabrication of chitosan-based nanocomposite films containing lignin and MgO nanoparticles for in vitro and in vivo wound-healing applications. Phenolated lignin nanoparticles (100 nm, ζ = −29 mV) enhanced antioxidant functionality, while MgO nanoparticles (192 nm, ζ = −14 mV) were incorporated as an inorganic reinforcing component. FTIR, XRD, and XPS analyses suggested changes in intermolecular interactions and local chemical environments following incorporation of lignin and MgO nanoparticles. The nanocomposites exhibited favourable physicochemical properties, including a high swelling ratio (91.6%), reduced water contact angle (41.40°), and improved tensile strength (80 MPa). They also showed strong antioxidant activity (ABTS: 325 ± 8 µg TE mL⁻¹; DPPH: 152 ± 5 µg TE mL⁻¹), high protein adsorption (2.3 g BSA g⁻¹), robust UV shielding, and > 95% inhibition of Escherichia coli and Staphylococcus aureus. Biological evaluation demonstrated high biocompatibility (> 90% viability in HaCaT and HDF cells), low hemolysis (< 12%), and favorable blood-clotting indices (~ 40%). In vitro scratch assays showed complete wound closure within 48 h, indicating enhanced fibroblast migration. In a mouse wound model, the lead film achieved 74.1% wound closure after 15 days, compared with 63.8% for DuoDerm and 60.1% for the untreated control. Histological and immunohistochemical analyses further showed reduced residual granulation tissue, increased collagen deposition, and a nonsignificant trend toward reduced CD45-positive inflammatory-cell infiltration. The integrated formulation therefore combines structural reinforcement with antioxidant, antibacterial, cytocompatibility, and wound-repair-supporting functions in a single bio-based platform system. Overall, these findings suggest that phenolated lignin–chitosan/MgO nanocomposites are promising sustainable, multifunctional wound-dressing materials. Engineering of a multifunctional phenolated lignin-chitosan/MgO nanocomposite transdermal patch for enhanced wound healing. Phenolated kraft lignin-derived nanoparticles and MgO nanoparticles were integrated into a chitosan matrix to obtain bioactive patches with reactive oxygen species-scavenging, antibacterial, and inflammation-modulating properties, resulting in improved wound healing performance. Fakhar, A. (2026). https://BioRender.com/nvpivp4 .