3D-alginate/chitosan/cannabidiol hydrogel: a pH-responsive platform for controlled local drug delivery

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with anti-inflammatory, antimicrobial, and osteoanabolic properties, making it a promising agent for regenerative uses. However, delivering it locally in a controlled way remains a challenge. This study aimed to design and characterize a 3D-bioprinted alginate/chitosan hydrogel loaded with CBD as a platform for controlled local drug delivery. Matrices with CBD concentrations from 0 to 24 mg ml −1 were produced with a BioX printer (Cellink®) using a standardized protocol. The alginate–chitosan polyelectrolyte complex, reinforced by Ca 2+ crosslinking, provided a consistent architecture, uniform CBD distribution and adequate mechanical stability. Biocompatibility (L929 fibroblasts, ISO 10993-5), antimicrobial activity against oral ( S. gordonii, F. nucleatum, P. gingivalis ) and common pathogens ( S. aureus, E. coli, P. aeruginosa ), and CBD release (HPLC-DAD) were evaluated. Ex vivo mucoadhesion was quantified on porcine mucosa with a TA-XTplus texture analyzer. Structures with CBD concentrations up to 12 mg ml −1 maintained cell viability above 70% for 72 h, whereas 24 mg ml −1 was cytotoxic. The interaction between chitosan and CBD resulted in enhanced antimicrobial effects against S. gordonii and F. nucleatum , with limited activity against other bacteria. The 12 mg ml −1 formulation showed the highest ex vivo detachment force (0.473 ± 0.024 N) compared with the control hydrogel (0.374 ± 0.014 N). Over the 120-h evaluated, the release patterns showed a biphasic behavior: an initial burst (0–48 h, pH 5. 5), releasing approximately 25% of CBD (1. 504 mg ml −1 ), followed by sustained release (48–120 h, pH 7.4), reaching approximately 27. 5% (1. 648 mg ml −1 ), retaining approximately 72.5% of the CBD within the matrix at the end of the observation period. The bioprinted alginate/chitosan/CBD hydrogel combines a safe cytocompatibility profile, pH-responsive controlled release, and targeted antimicrobial activity, establishing a promising mucoadhesive platform for controlled local CBD delivery, with potential relevance to future bone-related applications.