Controlled Synthesis of ZnO Nanomaterials via Central Composite Design for Biomedical Applications

The development of biomedical materials at the nano and microscale requires precise control over synthesis conditions in order to obtain structures with tailored properties. To this end, chemometrics provides a set of statistical and mathematical methods for the systematic design and interpretation of experiments. Such approaches are increasingly applied in materials science, where they allow the control and optimization of complex synthetic processes at the nanoscale. In particular, Design of Experiments (DoE) combined with Response Surface Methodology (RSM) enables a rigorous evaluation of the effects and interactions of different variables while reducing the number of experiments required. Within this framework, we applied a Central Composite Design (CCD) to investigate three key factors: reaction time, zinc precursor concentration, and KCl concentration. This strategy was used for the controlled synthesis of zinc oxide (ZnO) materials. ZnO is widely employed in biomedical contexts because of its unique properties, including photocatalytic activity, biocompatibility, and antibacterial activity. Through the central composite design approach, we identified optimal synthesis conditions that yielded ZnO structures with good morphology, high surface area, and optimal crystallinity. Moreover, the resulting material exhibited dual functionality. Under simulated solar irradiation it effectively photodegraded a model dye molecule, methylene blue, while in dark conditions it showed significant bactericidal activity against E. coli and S. aureus. The antibacterial effect is likely mediated by cellular uptake of the released zinc ions, that were quantified using Anodic Stripping Voltammetry (ASV). Ongoing studies are now directed towards integrating the optimized ZnO with different cellulose-based supports, including cellulose acetate, microcrystalline cellulose, and cellulose derived from plant fibers. This approach aims to design advanced biomaterials that combine controlled zinc release with enhanced photocatalytic performance, thereby expanding the potential applications of ZnO in the biomedical field. Acknowledgements: Financial support from MIUR is acknowledged: grants PRIN 2022 "2022WZK874 - Smart biopolymeric ZnO Nanowires composites for enhanced antibacterial activity (Soteria)", PRJ-1310, CUP: B53D23015730006 and PNRR “Network 4 Energy Sustainable Transition – NEST”, code PE0000021, CUP B73C22001280006, Spoke 1, Mission 4, by EU – NextGenerationEU.