Physical properties and cytotoxicity of antimicrobial dental resin adhesives containing dimethacrylate oligomers of Ciprofloxacin and Metronidazole.

OBJECTIVE: Antimicrobial oligomers synthesized from ciprofloxacin (CF) and metronidazole (MN) were investigated for their potential use in dental adhesives. METHODS: Susceptibility of the cariogenic bacterium Streptococcus mutans UA159 to CF, MN, and CF/MN combination was evaluated. Hydrolytic stability and drug release from the oligomers was studied in buffer and simulated human salivary esterase conditions. Cytotoxicity of films with 15wt% drug oligomers co-polymerized with commercial monomers were assessed using human gingival fibroblasts (HGFs). In-house adhesives were prepared and characterized for viscosity. Polymerized films were analysed for gel content and water swelling. Interfacial fracture toughness (KIC) of composites bonded to dentin by either a 2 or 3-step etch-and-rinse approach using the in-house formulated adhesives was measured. RESULTS: The respective minimum inhibitory concentration for CF and MN against S. mutans was 0.7 and 2400µg/mL, with the combination having an additive effect (0.35µg/mL CF with 1200µg/mL MN). Antibiotics were released upon hydrolysis of the oligomers. Films containing the drug oligomers were not cytotoxic against HGFs. Replacing 2-hydroxyethyl methacrylate with the drug oligomers increased the viscosity of the experimental adhesives, reduced gel content, and decreased swelling of films in water. Antimicrobial adhesives demonstrated bonding to dentin with interfacial KIC values comparable to the in-house control in the 2-step application, and with slightly lower KIC values in the 3-step approach. SIGNIFICANCE: The antimicrobial oligomers can be incorporated into dental adhesive systems using formulations that show comparable fracture toughness to commercial materials, and may provide a means to deliver local antimicrobial drug release at the marginal interface.

Synthesis and characterization of Ciprofloxacin-containing divinyl oligomers and assessment of their biodegradation in simulated salivary esterase.

OBJECTIVE: Two leading causes contributing to dental restoration replacement are the marginal breakdown at the composite/dentin interface and secondary caries mediated by bacteria. The objective of the present study was to synthesize oligomers which incorporated enhanced bio-stability but would also be able to generate antimicrobial function if they underwent degradation. METHODS: Stability was incorporated into the oligomers by generating structural features that would physically hinder the availability of hydrolytically sensitive groups in the oligomers. As a proof-of concept for the antibacterial feature, antimicrobial function was achieved by covalently incorporating Ciprofloxacin (CF) into the backbone of cross-linking divinyl oligomers (referred to as EDV and HLH-CFPEG). The hydrolytic stability of the oligomers was studied in simulated human salivary esterase and compared to the commercial monomer 2,2-bis[4(2-hydroxy-3-methacryloxypropoxy)-phenyl]propane (BisGMA). RESULTS: Both drug oligomers were found to be significantly more stable than BisGMA. Upon degradation, both drug oligomers released CF differentially in free form. Polymer synthesis from resin formulations containing 15wt% HLH-CFPEG showed a high degree of vinyl group conversion and gel content, and under hydrolytic conditions showed the release of CF during a 28-day monitoring study period. SIGNIFICANCE: HLH-CFPEG can be used in dental resin adhesive systems for local delivery of CF to the marginal interface. Minimizing the growth of Streptococcus mutans at the marginal site can improve longevity by reducing esterase activity derived specifically from S. mutans.

Biodegradation Studies of Novel Fluorinated Di-Vinyl Urethane Monomers and Interaction of Biological Elements with Their Polymerized Films.

The monomeric components of resin composites in dental restorative materials are susceptible to hydrolysis in the oral cavity. The main objective of this study was to assess the bio-stability of fluorinated urethane dimethacrylates and determine the nature of fluoro-chemistry interactions with protein and bacterial adhesion (both sources of hydrolytic activity) onto cured resin. Degradation studies were performed in the presence of either albumin (in a mildly alkaline pH) or cholesterol esterase (CE). The surface chemistry of the polymers was assessed by water contact angle measurements, pre- and post- incubation with albumin. Adhesion of Streptococcus mutans to cured resin was investigated. The fluorinated monomers were more stable against degradation when compared to the commercial monomer bisphenol A-diglycidyl methacrylate (BisGMA). While fluorinated monomers showed hydrolytic stability with respect to CE, all fluorinated monomers underwent some degree of degradation with albumin. The fluoro-chemistry did not reduce protein and/or bacterial adhesion onto the surface, however post incubation with albumin, the fluorinated surfaces still presented hydrophobic character as determined by the high contact angle values ranging from 79° to 86°. These monomers could potentially be used to increase the hydrophobicity of polymeric composites and provide a means to moderate esterolytic degradation associated with the monomeric component of the polymers within the oral cavity.

Biodegradation of composite resin with ester linkages: identifying human salivary enzyme activity with a potential role in the esterolytic process.

OBJECTIVES: The ester linkages contained within dental resin monomers (such as Bisphenol A-glycidylmethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA)) are susceptible to hydrolytic degradation by salivary esterases, however very little is known about the specific esterase activities implicated in this process. The objective of this work was to isolate and identify the dominant proteins from saliva that are associated with the esterase activities shown to be involved in the degradation of BisGMA. METHODS: Human whole saliva was collected and processed prior to separation in a HiPrep 16/60 Sephacryl S-200 HR column. The fraction with the highest esterase activity was further separated by an anion exchange column (Mono-Q (10/100G)). Isolated fractions were then separated by gel electrophoresis, and compared to a common bench marker esterase, cholesterol esterase (CE), and commercial albumin which has been reported to express esterase activity. Proteins suspected of containing esterase activity were analyzed by Mass Spectroscopy (MS). Commercially available proteins, similar to the salivary esterase proteins identified by MS, were used to replicate the enzymatic complexes and confirm their degradation activity with respect to BisGMA. RESULTS: MS data suggested that the enzyme fraction with the highest esterase activity was contained among a group of proteins consisting of albumin, Zn-α2-glycoprotein, α-amylase, TALDO1 protein, transferrin, lipocalin2, and prolactin-induced protein. Studies concluded that the main esterase bands on the gels in each fraction did not overlap with CE activity, and that albumin activity emerged as a lead candidate with significant esterase activity relative to BisGMA degradation, particularly when it formed a complex with Zn-α2-glycoprotein, under slightly basic conditions. SIGNIFICANCE: These enzyme complexes can be used as a physiologically relevant formulation to test the biostability of composite resins.

Biodegradation of resin composites and adhesives by oral bacteria and saliva: a rationale for new material designs that consider the clinical environment and treatment challenges.

OBJECTIVE: To survey the recent literature from the late 1980s to recent years in order to assess the relationship between resin degradation, catalyzed by biological factors, and clinical failure outcomes such as marginal breakdown. METHODS: The literature shows that degradation occurs in many manufacturers' products despite varied vinyl acrylate compositions. The authors examine salivary enzyme activity and their ability to degrade the polymeric matrix of resin composites and adhesives, as well as oral microorganisms that can promote demineralization of the tooth surface at the marginal interface. A survey of recent research relating matrix metalloproteinase (MMPs) to the degradation of the exposed collagen at the dentin adhesive interface is also discussed in the context of marginal breakdown. RESULTS: The literature provides strong support that together, the above factors can breakdown the marginal interface and limit the longevity of resin composite restorations. The authors have found that the field's current understanding of resin biodegradation in the oral cavity is just beginning to grasp the role of bacteria and enzymes in the failure of resin-based restorations. SIGNIFICANCE: Knowledge of these biodegradation processes is pertinent to areas where innovative strategies in the chemistry of restorative materials are anticipated to enhance the longevity of resin composites.