Drug-Templated Mesoporous Silica for Dental Adhesive Applications
Stewart, Cameron 1 ; Hong, Jenny 2 ; Hatton, Benjamin 3 ; Finer, Yoav 2
1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Faculty of Dentistry, University of Toronto; 3. Department of Materials Science and Engineering, University of Toronto
Composite fillings have relatively high failure rates, mainly due to recurrent caries caused by bacterial microleakage at restoration margins. Release of antimicrobial drug from mesoporous silica nanoparticles (MSNs) in this area could reduce bacterial load and extend restoration lifetime. However, past attempts have failed due to inefficient post-synthesis drug loading, fast release, limited efficacy and deterioration of physical properties.
Herein we develop and characterize antimicrobial-drug-templated MSNs (DMSNs) through a novel one-pot synthesis with inherently maximized drug loading and long-term controlled release and assess their performance in a drug-eluting dental adhesive.
Novel MSNs (DMSNs) were produced through a one-pot synthesis resulting in pores inherently filled with drug. Particles were characterized via electron-microscopy, energy dispersive X-ray, and thermogravimetric analysis. Drug release from free DMSNs and MCM, and DMSN-filled commercial adhesive was monitored in buffer or simulated human salivary esterase (SHSE). Miniature short-rod resin-dentin fracture toughness samples with commercial or DMSN-adhesive (N=10/group) were tested for adhesive-dentin interfacial bond strength. Ex-vivo restored teeth incubated with SHSE were monitored for drug release from the restoration margin. Cariogenic Streptococcus mutans biofilm inhibition by DMSN-adhesive was assessed via colony forming unit (CFU) assay as well as confocal laser microscopy (CLSM).
Cumulative drug release from DMSN-filled adhesive over 90 days occurred at a rate of 1.185 µg days-0.5 cm-2 in buffer and 1.813 µg days-0.5 cm-2 in SHSE, demonstrating biodegradation-triggered release. In a model restoration, this correlates to 65% of the loaded drug released over 5 years, at levels sufficient to inhibit cariogenic bacteria S. mutans’ growth. No significant differences between the fracture toughness of the bond to human dentin between commercial (1.10 ±0.144 MPa m0.5) and experimental adhesives (1.08 ±0.127 MPa m0.5) immediately post restoration and following 30-days incubation with SHSE. However, at 180-days incubation with SHSE, experimental group (1.31±0.166 MPa*m0.5) had a significantly higher fracture toughness than commercial group (0.86±0.303 MPa*m0.5, P<0.05). S. mutans biofilm growth on DMSN-adhesive had a log reduction of 4.39 at 24 hr and 4.41 at 30-days pre-incubation to reach steady-state drug release. CLSM observations confirmed no growth of biofilms over the drug-adhesive vs. control after 72 hr.
Antimicrobial MSNs with superior properties and a simplified synthesis were produced and successfully used to form an antimicrobial-eluting restorative adhesive with long term efficacy, potentially reducing cariogenic biofilm load at the restoration-tooth interface and producing a clinically significant impact on restoration service life.