Effect of Chitosan-Alginate Polyelectrolyte Complex Formation and Multilayer Polymer Configuration on the Characteristics of 3D-Printed Metronidazole-Loaded Periodontal Films.

This study aimed to prepare six different metronidazole-loaded film formulations by 3D printing for periodontal treatment. Chitosan (CH) and alginate (ALG) gels were prepared separately and printed layer-by-layer, varying polymer type and number of layers. Polyelectrolyte complex (PEC) gels were prepared by mixing CH and ALG (1:1) at different polymer concentrations to investigate the effect of complexation strength on film performance. Films were characterized by thickness measurements, drug content analysis, Micro-CT and SEM imaging, swelling, adhesion, antimicrobial activity, release kinetics, and cumulative drug release. Increasing ALG layers significantly enhanced swelling and accelerated metronidazole release, whereas CH-dominant films exhibited lower swelling and slower release. Overall, PEC films modified the drug release profile. Layer-by-layer printing promoted more uniform diffusion, whereas stronger polyelectrolyte complexation slowed drug release due to increased structural irregularity. All films were confirmed to exhibit microbiological activity. Micro-CT analysis in conjunction with SEM enabled precise evaluation of the layered film structure produced by 3D printing and detailed assessment of layer definition, internal heterogeneity, and their relationship with swelling and drug release behaviour. These findings suggest that tailoring the structural design via polymer layering or complexation represents a promising strategy for local drug delivery systems in periodontal therapy.