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

Abstract

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.