Advanced Antimicrobial and Anti-Infective Strategies to Manage Peri-Implant Infection: A Narrative Review.

Despite reductions in bacterial infection and enhanced success rate, the widespread use of systemic antibiotic prophylaxis in implant dentistry is controversial. This use has contributed to the growing problem of antimicrobial resistance, along with creating significant health and economic burdens. The basic mechanisms that cause implant infection can be targeted by new prevention and treatment methods which can also lead to the reduction of systemic antibiotic exposure and its associated adverse effects. This review aims to summarize advanced biomaterial strategies applied to implant components based on anti-pathogenic mechanisms and immune balance mechanisms. It emphasizes that modifying the dental implant surface and regulating the early immune response are promising strategies, which may further prevent or slow the development of peri-implant infection, and subsequent failure.

The Role of Bacterial, Dentinal, Salivary, and Neutrophil Degradative Activity in Caries Pathogenesis.

Until recently, it was widely accepted that bacteria participate in caries pathogenesis mainly through carbohydrate fermentation and acid production, which promote the dissolution of tooth components. Neutrophils, on the other hand, were considered white blood cells with no role in caries pathogenesis. Nevertheless, current literature suggests that both bacteria and neutrophils, among other factors, possess direct degradative activity towards both dentinal collagen type-1 and/or methacrylate resin-based restoratives and adhesives, the most common dental restoratives. Neutrophils are abundant leukocytes in the gingival sulcus, where they can readily reach adjacent tooth roots or gingival and cervical restorations and execute their degradative activity. In this review, we present the latest literature evidence for bacterial, dentinal, salivary, and neutrophil degradative action that may induce primary caries, secondary caries, and restoration failure.

Simulating the Intraoral Aging of Dental Bonding Agents: A Narrative Review.

Despite their popularity, resin composite restorations fail earlier and at higher rates than comparable amalgam restorations. One of the reasons for these rates of failure are the properties of current dental bonding agents. Modern bonding agents are vulnerable to gradual chemical and mechanical degradation from a number of avenues such as daily use in chewing, catalytic hydrolysis facilitated by salivary or bacterial enzymes, and thermal fluctuations. These stressors have been found to work synergistically, all contributing to the deterioration and eventual failure of the hybrid layer. Due to the expense and difficulty in conducting in vivo experiments, in vitro protocols meant to accurately simulate the oral environment's stressors are important in the development of bonding agents and materials that are more resistant to these processes of degradation. This narrative review serves to summarize the currently employed methods of aging dental materials and critically appraise them in the context of our knowledge of the oral environment's parameters.

Interfacial Biomaterial-Dentin Bacterial Biofilm Proliferation and Viability Is Affected by the Material, Aging Media and Period.

Biomaterial−dentin interfaces undergo degradation over time, allowing salivary, tissue fluid, and bacterial movement between the root filling or restoration and dentin. This study aims to investigate the effect of aging in simulated human salivary/bacterial/blood esterases (SHSE) on proliferation and viability of Enterococcus faecalis biofilm within the dentin interface with four materials used to fill/restore the endodontic space. Root canals of human anterior teeth were prepared and filled with gutta-percha and one of the following: self-cured resin composite (BisfilTM 2B, Bisco, Schaumburg, IL, USA) with either self-etch (SE) (EasyBond) or total-etch (TE) (ScotchbondTM, 3M, Saint Paul, MN, USA) methacrylate-based adhesives, epoxy-resin sealer (AH Plus®, Dentsply Sirona, York, PA, USA), or bioceramic sealer (EndoSequence® BC Sealer™, Brasseler USA, Savannah, GA, USA). Specimens were aged in SHSE or phosphate-buffered saline (PBS) for up to 360 days, followed by cultivation of steady-state E. faecalis biofilm. Depth and viability of interfacial bacterial biofilm proliferation were assessed by confocal laser scanning microscopy and live/dead staining. Data were analyzed using three-way ANOVA and Scheffe's post hoc analyses. Initial depths of biofilm proliferation were similar among material groups (p > 0.05). All groups showed significantly deeper biofilm proliferation with increased aging period (p < 0.05). SHSE aging increased interfacial biofilm depth for TE, SE and BC (p < 0.05) but not AH. For unaged interfaces, BC exhibited the lowest ratio of live bacteria, followed by AH, TE, and SE (p < 0.05). Interfacial bacterial biofilm proliferation and viability were dependent on the biomaterial, aging media, and period.

Streptococcus mutans Proteases Degrade Dentinal Collagen.

Here, we explored the role of S. mutans's whole cell and discrete fractions in the degradation of type I collagen and dentinal collagen. Type I collagen gels and human demineralized dentin slabs (DS) were incubated in media alone or with one of the following: overnight (O/N) or newly inoculated (NEW) cultures of S. mutans UA159; intracellular proteins, supernatant or bacterial membranes of O/N cultures. Media from all groups were analyzed for protease-mediated release of the collagen-specific imino acid hydroxyproline. Images of type I collagen and DS were analyzed, respectively. Type I collagen degradation was highest for the supernatant (p < 0.05) fractions, followed by intracellular components and O/N cultures. Collagen degradation for DS samples was highest for O/N samples, followed by supernatant, and intracellular components (p < 0.05). There was lower detectable degradation for both type I collagen and DS from NEW culture samples (p < 0.05), and there was no type I collagen or DS degradation detected for bacterial membrane samples. Structural changes to type I collagen gel and dentinal collagen were observed, respectively, following incubation with S. mutans cultures (O/N and NEW), intracellular components, and supernatant. This study demonstrates that intracellular and extracellular proteolytic activities from S. mutans enable this cariogenic bacterium to degrade type I and dentinal collagen in a growth-phase dependent manner, potentially contributing to the progression of dental caries.

Minimally Invasive Therapies for the Management of Dental Caries-A Literature Review.

In recent years, due to a better understanding of the caries pathology and advances in dental materials, the utilization of non-invasive and minimally invasive techniques that delay/obviate the need for traditional restorations has started gaining momentum. This literature review focuses on some of these approaches, including fluoride varnish, silver diamine fluoride, resin sealants, resin infiltration, chemomechanical caries removal and atraumatic restorative treatment, in the context of their chemistries, indications for use, clinical efficacy, factors determining efficacy and limitations. Additionally, we discuss strategies currently being explored to enhance the antimicrobial properties of these treatment modalities to expand the scope of their application.

Assessment of Root Canal Sealers Loaded with Drug-Silica Coassembled Particles Using an In Vitro Tooth Model.

INTRODUCTION: The purpose of this study was to assess the antimicrobial activity of root canal sealers modified with novel highly loaded antimicrobial drug-silica coassembled particles (DSPs) on Enterococcus faecalis-infected root canal dentin. METHODS: DSPs were synthesized through coassembly of silica and octenidine dihydrochloride (OCT) surfactant drug (35% w/w OCT). DSPs (1% wt of the total mass of the sealer) were mixed homogenously with either epoxy resin sealer (AH Plus [AH]; Dentsply Sirona, Tulsa, OK) or calcium silicate-based sealer (EndoSequence BC Sealer [BC]; Brasseler, Savannah, GA). To assess the antimicrobial activity of DSP-loaded sealers, the apical third of single-rooted teeth was obtained and infected with E. faecalis for 3 weeks followed by the application of experimental (DSP-loaded) sealers or corresponding controls for up to 28 days. Microbiological analysis and laser scanning confocal and scanning electron microscopy were used to determine the colony-forming unit (CFU)/mL, the percentage of live bacteria, and the intratubular bacterial and sealer penetrations. Factorial analysis of variance and Tukey post hoc tests were used to assess the antimicrobial effect of DSPs on different sealers. RESULTS: All experimental groups showed significant reductions in CFUs at all-time points compared with positive controls (P < .05). The addition of DSPs to BC significantly reduced the CFUs (2.11 ± 0.13, 2.22 ± 0.19, and 2.25 ± 0.17 at 1, 7, and 28 days, respectively) compared with the unmodified sealer (3.21 ± 0.11, 4.3 ± 0.15, and 4.2 ± 0.2 at 0, 7, and 28 days). DSPs enhanced the antimicrobial performance of AH only at 1 day (4.21 ± 0.17 vs 5.19 ± 0.12, P < .05). AH and AH + DSPs showed higher bacterial viability compared with BC and BC + DSPs at all incubation periods (P < .05). CONCLUSIONS: Loading endodontic sealers with DSPs had a material-dependent effect on the antimicrobial properties and could reduce the incidence of secondary infections.

Antimicrobial antidegradative dental adhesive preserves restoration-tooth bond.

OBJECTIVE: Assess the ability of an antimicrobial drug-releasing resin adhesive, containing octenidine dihydrochloride (OCT)-silica co-assembled particles (DSPs), to enhance the biostability and preserve the interfacial fracture toughness (FT) of composite restorations bonded to dentin. Enzyme-catalyzed degradation compromises the dental restoration-tooth interface, increasing cariogenic bacterial infiltration. In addition to bacterial ingress inhibition, antimicrobial-releasing adhesives may exhibit direct interfacial biodegradation inhibition as an additional benefit. METHODS: Mini short-rod restoration bonding specimens with total-etch adhesive with/without 10% wt. DSPs were made. Interfacial fracture toughness (FT) was measured as-manufactured or post-incubation in simulated human salivary esterase (SHSE) for up to 6-months. Effect of OCT on SHSE and whole saliva/bacterial enzyme activity was assessed. Release of OCT outside the restoration interface was assessed. RESULTS: No deleterious effect of DSPs on initial bonding capacity was observed. Aging specimens in SHSE reduced FT of control but not DSP-adhesive-bonded specimens. OCT inhibited SHSE degradation of adhesive monomer and may inhibit endogenous proteases. OCT inhibited bacterial esterase and collagenase. No endogenous collagen breakdown was detected in the present study. OCT increased human saliva degradative esterase activity below its minimum inhibitory concentration towards S. mutans (MIC), but inhibited degradation above MIC. OCT release outside restoration margins was below detection. SIGNIFICANCE: DSP-adhesive preserves the restoration bond through a secondary enzyme-inhibitory effect of released OCT, which is virtually confined to the restoration interface microgap. Enzyme activity modulation may produce a positive-to-negative feedback switch, by increasing OCT concentration via biodegradation-triggered release to an effective dose, then subsequently slowing degradation and degradation-triggered release.

Biostable, antidegradative and antimicrobial restorative systems based on host-biomaterials and microbial interactions.

OBJECTIVES: Despite decades of development and their status as the restorative material of choice for dentists, resin composite restoratives and adhesives exhibit a number of shortcomings that limit their long-term survival in the oral cavity. Herein we review past and current work to understand these challenges and approaches to improve dental materials and extend restoration service life. METHODS: Peer-reviewed work from a number of researchers as well as our own are summarized and analyzed. We also include yet-unpublished work of our own. Challenges to dental materials, methods to assess new materials, and recent material improvements and research directions are presented. RESULTS: Mechanical stress, host- and bacterial-biodegradation, and secondary caries formation all contribute to restoration failure. In particular, several host- and bacterial-derived enzymes degrade the resin and collagen components of the hybrid layer, expanding the marginal gap and increasing access to bacteria and saliva. Furthermore, the virulence of cariogenic bacteria is up-regulated by resin biodegradation by-products, creating a positive feedback loop that increases biodegradation. These factors work synergistically to degrade the restoration margin, leading to secondary caries and restoration failure. Significant progress has been made to produce hydrolytically stable resins to resist biodegradation, as well as antimicrobial materials to reduce bacterial load around the restoration. Ideally, these two approaches should be combined in a holistic approach to restoration preservation. SIGNIFICANCE: The oral cavity is a complex environment that poses an array of challenges to long-term material success; materials testing conditions should be comprehensive and closely mimic pathogenic oral conditions.

Drug self-assembly for synthesis of highly-loaded antimicrobial drug-silica particles.

Antimicrobial drug release from biomaterials for orthopedic repair and dental restorations can prevent biofilm growth and caries formation. Carriers for drug incorporation would benefit from long-term drug storage, controlled release, and structural stability. Mesoporous silica, synthesized through a co-assembly of silica and surfactant template, is an ideal drug encapsulation scaffold that maintains structural integrity upon release. However, conventional loading of drug within meso-silica pores via concentration-gradient diffusion limits the overall payload, concentration uniformity, and drug release control. Herein we demonstrate the co-assembly of an antimicrobial drug (octenidine dihydrochloride, OCT), and silica, to form highly-loaded (35% wt.) OCT-silica nanocomposite spheres of 500 nm diameter. Drug release significantly outlasted conventional OCT-loaded mesoporous silica, closely fit Higuchi models of diffusive release, and was visualized via electron microscopy. Extension of this concept to the broad collection of self-assembling drugs grants biomedical community a powerful tool for synthesizing drug-loaded inorganic nanomaterials from the bottom-up.

Responsive antimicrobial dental adhesive based on drug-silica co-assembled particles.

Most dental resin composite restorations are replacements for failing restorations. Degradation of the restoration-tooth margins by cariogenic bacteria results in recurrent caries, a leading cause for restoration failure. Incorporating antimicrobial agents in dental adhesives could reduce interfacial bacterial count and reduce recurrent caries rates, inhibit interfacial degradation, and prolong restoration service life, while minimizing systemic exposure. Direct addition of antimicrobial compounds into restorative materials have limited release periods and could affect the integrity of the material. Attempts to incorporate antimicrobial within mesoporous silica nanoparticles showed theoretical promise due to their physical robustness and large available internal volume, yet yielded short-term burst release and limited therapeutic payload. We have developed novel broad-spectrum antimicrobial drug-silica particles co-assembled for long-term release and high payload incorporated into dental adhesives. The release of the drug, octenidine dihydrochloride, is modulated by the oral degradative environment and mathematically modeled to predict effective service life. Steady-state release kills cariogenic bacteria, preventing biofilm formation over the adhesive surface, with no toxicity. This novel material could extend dental restoration service life and may be applied to other long-term medical device-tissue interfaces for responsive drug release upon bacterial infection. STATEMENT OF SIGNIFICANCE: This study describes a novel dental adhesive that includes a broad-spectrum antimicrobial drug-silica co-assembled particles for long-term antimicrobial effect. The release of the drug, octenidine dihydrochloride, is modulated by the oral degradative environment and mathematically modeled to predict effective release throughout the service life of the restoration. Steady-state drug-release kills caries-forming bacteria, preventing biofilm formation over the adhesive surface, without toxicity. This novel material could extend dental restoration service life and may be applied to other long-term medical device-tissue interfaces for responsive drug release upon bacterial infection. Since recurrent cavities (caries) caused by bacteria are the major reason for dental filling failure, this development represents a significant contribution to the biomaterials field in methodology and material performance.

Selective molecular transport through intrinsic defects in a single layer of CVD graphene.

We report graphene composite membranes with nominal areas more than 25 mm(2) fabricated by transfer of a single layer of CVD graphene onto a porous polycarbonate substrate. A combination of pressure-driven and diffusive transport measurements provides evidence of size-selective transport of molecules through the membrane, which is attributed to the low-frequency occurrence of intrinsic 1-15 nm diameter pores in the CVD graphene. Our results present the first step toward the realization of practical membranes that use graphene as the selective material.