3D-printed chitosan-starch mesh filled with minocycline-alginate hydrogel for dual anti-Staphylococcus aureus and...

Bone infections, particularly those caused by Staphylococcus aureus, pose clinical challenges due to biofilm formation and association with bone loss. To address this, we developed a three-dimensional (3D) printed hydrogel-based drug delivery device composed of a chitosan-starch mesh filled with a minocycline-alginate hydrogel. We hypothesize that this novel 3D-printed device can deliver the drug with dual therapeutic effects - anti-S. aureus activity and osteogenesis. To optimize the mesh formulation composition and printing parameters, we applied a neurofuzzy logic-based data-driven approach. The model identified that higher polysaccharide concentrations and reduced flow speed improved mesh printing quality. The presence of minocycline within the device was confirmed by FTIR-ATR through the identification of characteristic functional group, while DSC analysis provided additional evidence of its crystalline state. The device's structure led to a biphasic drug release profile. Antibiofilm assays showed a 2.7-log reduction in methicillin resistant S. aureus biofilm formation with minocycline-loaded devices, compared to 0.59-log reduction in unloaded devices, indicating effective antibiofilm activity on early biofilm formation. Cytocompatibility was confirmed in human osteoblastic-like cells and the minocycline-devices promoted bone regeneration in an ex vivo organotypic bone defect model.