Antibacterial and osteogenic activities of clindamycin-releasing mesoporous silica/carboxymethyl chitosan composite hydrogels

Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against Streptococcus sanguinis for at least 14 days in vitro. In vitro assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.