Metronidazole-laden silk fibroin methacrylated scaffolds for managing periapical lesions

Abstract

This study aimed to develop and characterize silk fibroin methacrylated/SilkMA electrospun scaffolds associated with metronidazole/MET to control infection in root-end resected periapical lesions while supporting bone regeneration. SilkMA-based formulations (10% w/v) incorporating MET (0—control; 5, 15, or 30% w/w) were electrospun into fibrous scaffolds and photocrosslinked. Scaffolds’ morphology, chemical composition, swelling/degradation profiles, mechanical properties, cytocompatibility with alveolar bone-derived mesenchymal stem cells/aBMSCs and stem cells from apical papilla/SCAPs, anti-inflammatory potential, and antibacterial efficacy (direct contact assay against Aggregatibacter actinomycetemcomitans/Aa and Fusobacterium nucleatum/Fn; Aa biofilm model) were assessed. Statistical analysis was conducted using a significance level of 5%. Morphological analysis revealed that MET content influenced fiber diameters post-crosslinking, while the chemical composition analysis confirmed MET integration within the scaffolds. 30%MET-laden scaffolds demonstrated reduced swelling capacity compared to SilkMA/control scaffolds, while complete degradation was observed after 42 days for the formulated scaffolds. Mechanical testing indicated enhanced stiffness and tensile strength in 30%MET-laden scaffolds compared to SilkMA/control (p < 0.05). Cytocompatibility evaluations showed non-cytotoxic effects across all formulations for aBMSCs and SCAPs. Anti-inflammatory assays demonstrated decreased pro-inflammatory cytokine interleukin-6 synthesis by aBMSCs treated with SilkMA + MET30% and Escherichia coli LPS, comparable to negative control (p > 0.05). Antibacterial efficacy assays revealed significant inhibition of Aa and Fn, with 30%MET-laden scaffolds demonstrating biofilm inhibition against Aa (p < 0.05). These findings underscore the potential of SilkMA scaffolds laden with MET as a promising strategy for managing periapical lesions, offering enhanced structural support, antimicrobial properties, and biocompatibility crucial for effective tissue regeneration and infection control after endodontic surgery.