a b s t r a c tMicrobial infections affect humans worldwide. Many quaternary ammonium compounds have been synthesized that are not only antibacterial, but also possess antifungal, antiviral and anti-matrix metalloproteinase capabilities. Incorporation of quaternary ammonium moieties into polymers represents one of the most promising strategies for preparation of antimicrobial biomaterials. Various polymerization techniques have been employed to prepare antimicrobial surfaces with quaternary ammonium functionalities; in particular, syntheses involving controlled radical polymerization techniques enable precise control over macromolecular structure, order and functionality. Although recent publications report exciting advances in the biomedical field, some of these technological developments have also been accompanied by potential toxicological and antimicrobial resistance challenges. Recent evidenced-based data on the biomedical applications of antimicrobial quaternary ammonium-containing biomaterials that are based on randomized human clinical trials, the golden standard in contemporary medicinal science, are included in the present review. This should help increase visibility, stimulate debates and spur conversations within a wider scientific community on the implications and plausibility for future developments of quaternary ammonium-based antimicrobial biomaterials.Published by Elsevier B.V.
Objectives Remineralization of demineralized dentin is important for improving dentin bonding stability and controlling primary and secondary caries. Nevertheless, conventional dentin remineralization strategy is not suitable for remineralizing completely-demineralized dentin within hybrid layers created by etch-and-rinse and moderately aggressive self-etch adhesive systems, or the superficial part of a caries-affected dentin lesion left behind after minimally invasive caries removal. Biomimetic remineralization represents a different approach to this problem by attempting to backfill the demineralized dentin collagen with liquid-like amorphous calcium phosphate nanoprecursor particles that are stabilized by biomimetic analogs of noncollagenous proteins. Methods This paper reviewed the changing concepts in calcium phosphate mineralization of fibrillar collagen, including the recently discovered, non-classical particle-based crystallization concept, formation of polymer-induced liquid- precursors (PILP), experimental collagen models for mineralization, and the need for using phosphate-containing biomimetic analogs for biomimetic mineralization of collagen. Published work on the remineralization of resin-dentin bonds and artificial caries-like lesions by various research groups was then reviewed. Finally, the problems and progress associated with the translation of a scientifically-sound concept into a clinically-applicable approach are discussed. Results and Significance The particle-based biomimetic remineralization strategy based on the PILP process demonstrates great potential in remineralizing faulty hybrid layers or caries-like dentin. Based on this concept, research in the development of more clinically feasible dentin remineralization strategy, such as incorporating poly(anionic) acid-stabilized amorphous calcium phosphate nanoprecursor-containing mesoporous silica nanofillers in dentin adhesives, may provide a promising strategy for increasing of the durability of resin-dentin bonding and remineralizing caries-affected dentin.
Mineralisation of fibrillar collagen with biomimetic process-directing agents has enabled scientists to gain insight into the potential mechanisms involved in intrafibrillar mineralisation. Here, by using polycation- and polyanion-directed intrafibrillar mineralisation, we challenge the popular paradigm that electrostatic attraction is solely responsible for polyelectrolyte-directed intrafibrillar mineralisation. Because there is no difference when a polycationic or a polyanionic electrolyte is used to direct collagen mineralisation, we argue that additional types of long-range non-electrostatic interactions are responsible for intrafibrillar mineralisation. Molecular dynamics simulations of collagen structures in the presence of extrafibrillar polyelectrolytes show that the outward movement of ions and intrafibrillar water through the collagen surface occurs irrespective of the charges of polyelectrolytes, resulting in the experimentally verifiable contraction of the collagen structures. The need to balance electroneutrality and osmotic equilibrium simultaneously to establish Gibbs-Donnan equilibrium in a polyelectrolyte-directed mineralisation system establishes a new model for collagen intrafibrillar mineralisation that supplements existing collagen mineralisation mechanisms.
Effective control of oral biofilm infectious diseases represents a major global challenge. Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells. The present review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years. Antimicrobial dental materials based on antimicrobial agent release, contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface. Among the therapeutic approaches for managing biofilms in clinical practice, antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms, and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches. Nevertheless, more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data. The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.
Objective Antibacterial primer and adhesive are promising to help combat biofilms and recurrent caries. The objectives of this study were to compare novel bonding agent containing quaternary ammonium dimethacrylate (QADM) with bonding agent containing nanoparticles of silver (NAg) in antibacterial activity, contact-inhibition vs. long-distance inhibition, glucosyltransferases (gtf) gene expressions, and cytotoxicity for the first time. Methods QADM and NAg were incorporated into Scotchbond Multi-Purpose adhesive and primer. Microtensile dentin bond strength was measured. Streptococcus mutans (S. mutans) biofilm on resin surface (contact-inhibition) as well as S. mutans in culture medium away from the resin surface (long-distance inhibition) were tested for metabolic activity, colony-forming units (CFU), lactic acid production, and gtf gene expressions. Eluents from cured primer/adhesive samples were used to examine cytotoxicity against human gingival fibroblasts. Results Bonding agent with QADM greatly reduced CFU and lactic acid of biofilms on the resin surface (p < 0.05), while having no effect on S. mutans in culture medium away from the resin surface. In contrast, bonding agent with NAg inhibited not only S. mutans on the resin surface, but also S. mutans in culture medium away from the resin surface. Bonding agent with QADM suppressed gtfB, gtfC and gtfD gene expressions of S. mutans on its surface, but not away from its surface. Bonding agent with NAg suppressed S. mutans gene expressions both on its surface and away from its surface. Bonding agents with QADM and NAg did not adversely affect microtensile bond strength or fibroblast cytotoxicity, compared to control (p > 0.1). Significance QADM-containing adhesive had contact-inhibition and inhibited bacteria on its surface, but not away from its surface. NAg-containing adhesive had long-distance killing capability and inhibited bacteria on its surface and away from its surface. The novel antibacterial adhesives are promising for caries-inhibition restorations, and QADM and NAg could be complimentary agents in inhibiting bacteria on resin surface as well as away from resin surface.
Objectives In tissue regeneration research, the term “bioactivity” was initially used to describe the resistance to removal of a biomaterial from host tissues after intraosseous implantation. Hydraulic calcium silicate cements (HCSCs) are putatively accepted as bioactive materials, as exemplified by the increasing number of publications reporting that these cements produce an apatite-rich surface layer after they contact simulated body fluids. Methods In this review, the same definitions employed for establishing in vitro and in vivo bioactivity in glass–ceramics, and the proposed mechanisms involved in these phenomena are used as blueprints for investigating whether HCSCs are bioactive. Results The literature abounds with evidence that HCSCs exhibit in vitro bioactivity; however, there is a general lack of stringent methodologies for characterizing the calcium phosphate phases precipitated on HCSCs. Although in vivo bioactivity has been demonstrated for some HCSCs, a fibrous connective tissue layer is frequently identified along the bone–cement interface that is reminiscent of the responses observed in bioinert materials, without accompanying clarifications to account for such observations. Conclusions As bone-bonding is not predictably achieved, there is insufficient scientific evidence to substantiate that HCSCs are indeed bioactive. Objective appraisal criteria should be developed for more accurately defining the bioactivity profiles of HCSCs designed for clinical use.
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