Nanocellulose-templated ZnO via RSM-guided synthesis from Calophyllum inophyllum biomass for hydrogel-based applications

The valorization of biomass waste into high-value functional materials is an important strategy for sustainable bioeconomy development. This study presents an integrated approach utilizing nanocellulose (NC) derived from Calophyllum inophyllum shell waste as both a renewable matrix and a structure-directing template for the green synthesis of ZnO nanoparticles. Response surface methodology (RSM) was employed to optimize synthesis conditions, revealing that NC concentration, temperature, and pH significantly influenced ZnO crystallite size as determined by X-ray diffraction (XRD). The model showed an excellent fit (R 2 = 99%). The ZnO crystallite size ranged from 82.37 to 271.83 Å. Morphological comparison showed that ZnO synthesized without NC at pH 8.5 exhibited larger particles (82-451 nm) with agglomeration whereas NC-assisted ZnO showed more uniform nanospherical particles (20-75 nm), supporting the role of NC in regulating particle growth and dispersion. The optimized ZnO was incorporated into an NC-based hydrogel, yielding a zeta potential of −37.92 ± 1.82 mV, rheological behavior (∼31.82 mPa·s), antioxidant activity (IC 50 = 68.29 mg mL −1 ), and antibacterial activity against Staphylococcus aureus and Escherichia coli . MTT-based biocompatibility testing showed cell viability above 100% under the tested conditions. Release kinetics showed the Korsmeyer-Peppas model provided the highest R 2 for NC/ZnO hydrogels with 10 and 100 ppm initial ZnO loadings (0.9898 and 0.9374, respectively). In vivo studies achieved 98.61 ± 1.35% wound closure within 14 days, supported by improved re-epithelialization, collagen deposition, and reduced inflammation. Overall, this work demonstrates the potential of a biomass-derived NC/ZnO hydrogel for wound-healing applications.