Quaternary Ammonium Methacryloxy Silicate-containing Acrylic Resin
Condition: Oral Health
Study type: Interventional
Phase: Phase 2

Summary: 
      One of the major challenges in orthodontic treatment is long-term stability. Because
      removable retainers are worn for at least one year, bacteria and fungi may accumulate on the
      retainers in the form of multi-species plaque biofilms. This may result in increased
      incidence of proximal dental caries or oral candida infection. Thus, incorporation of
      antimicrobial activity in orthodontic acrylic resin to achieve plaque biofilm reduction is
      highly desirable. An antimicrobial and antifungal quaternary ammonium methacryloxy silicate
      molecule (QAMS) has been synthesized by sol-gel reaction and incorporated into orthodontic
      acrylic resin. The QAMS-copolymerized acrylic resin demonstrated contact-killing properties
      against single-species biofilms in previous in vitro studies and has received US FDA 510(K)
      clearance for marketing. The objective of the present randomized clinical trial is to
      determine the in vivo antimicrobial efficacy of the QAMS-containing orthodontic acrylic by
      using removable retainers that are worn by recruited subjects to create 48-hour multi-species
      plaque biofilms. The null hypothesis tested is that there is no difference in the
      antimicrobial activities between QAMS-free and QAMS-containing orthodontic acrylic resin on
      oral biofilms grown in vivo in human subjects.
    

Detailed description: 
      There is increasing demand for orthodontic care worldwide. In the United States,
      approximately one-fifth of the adolescents and teenagers, and up to 1% of young adults are
      receiving some form of the orthodontic treatment. One of the major challenges in orthodontic
      treatment is long-term stability; removable and fixed retainers are required to stabilise the
      aligned dentition and prevent post-treatment relapse. Most removable retainers are
      constructed of polymethyl methacrylates (PMMA), which are held by metal clasps around the
      posterior teeth. Because removable retainers are worn in a moist intraoral environment with
      fluctuating pH for at least one year, bacteria and fungi may accumulate on or within the
      retainers in the form of multi-species plaque biofilms that act as reservoirs of these
      microorganisms. This may result in increased incidence of proximal dental caries or oral
      candidiasis. Moreover, other opportunistic pathogens such as methicillin-resistant
      Staphylococcus aureus have been identified from orthodontic retainers, which may potentially
      lead to local or systemic infection, particularly in orthodontic patients with complicated
      medical disorders. For adult patients, oral microorganisms derived from removable acrylic
      appliances have been implicated in bacteria endocarditis, pneumonia, chronic obstructive
      pulmonary disease and gastrointestinal infection. Production of volatile odoriferous
      compounds by colonized microorganisms also contributes to halitosis, which affects a person's
      communication and psychological well-being.

      Microbial plaque biofilm accumulation on removable orthodontic appliances and retainers is
      usually controlled by mechanical and chemical means. Despite their effectiveness, these
      procedures demand stringent patient compliance, which may not be readily achievable in those
      with restricted dexterity. Hence, incorporation of antimicrobial activity in orthodontic
      acrylic resin to achieve plaque biofilm reduction is highly desirable. Conventional
      PMMA-based antimicrobial approaches are based on leaching of antimicrobial agents of small
      molecular mass (e.g. chlorhexidine) into the intraoral environment, application of an
      antimicrobial coating on the surface of the material or incorporation of antibacterial silver
      nanoparticles into the PMMA resin. Antimicrobial polymers are rapidly becoming a new class of
      biomaterials that can be functionalized and tethered to materials and kill microbes without
      releasing the biocides. For methacrylates, anionic and phosphated PMMA polymers have been
      created that can copolymerize with PMMA to create acrylic resins with permanent, non-leaching
      antimicrobial properties.

      Cationic polymers containing quaternary ammonium and phosphonium groups possess
      contact-killing antimicrobial activities. An antimicrobial and antifungal cationic quaternary
      ammonium methacryloxy silicate molecule (QAMS) has been synthesized by sol-gel reaction
      between a tetraalkoxysilane and two trialkoxysilanes. Containing a methacryloxy functional
      group and a long C-18 carbon chain, the QAMS molecule is soluble in MMA monomer and has been
      incorporated into PMMA orthodontic acrylic resin. The QAMS-copolymerised acrylic resin
      demonstrated improved fracture toughness without adversely affecting flexural modulus and
      strength of the orthodontic acrylic. In previous in vitro studies, orthodontic acrylic resins
      containing 4-6% QAMS were found to possess in vitro immediate diffusional as well as
      contact-killing antimicrobial properties when tested with Streptococcus mutans, Actinomyces
      naeslundii and Candida albicans. To investigate the antimicrobial durability of the
      QAMS-containing acrylic resin, specimens were aged in water for 3 months prior to evaluation
      of their antimicrobial activities. Even after 3 months of water-ageing wherein any residual
      effects of diffusional kill would have been completely eliminated, the QAMS-containing
      orthodontic acrylic resin still possessed antimicrobial activities against single-species
      biofilms generated from the three microbes. Antimicrobial polymers designed for biomedical
      applications should also be minimally cytotoxic to host tissues. In a previous study, the
      viability of an odontoblast-like cell line derived from mouse dental papilla was examined by
      exposing these cells to QAMS-containing orthodontic acrylic resin. Results of the cell
      viability assays indicated that the QAMS-containing orthodontic acrylic resin is relatively
      non-cytotoxic. The QAMS-containing orthodontic acrylic has received 510(K) clearance for
      marketing by the U.S. Food and Drug Administration (FDA). Nevertheless, clinical trials are
      lacking that demonstrate the in vivo antimicrobial potential of QAMS-containing orthodontic
      acrylic on multi-species biofilms.

      Although various multi-species oral biofilm models have been developed and have contributed
      to the understanding of intraoral microbial adhesion and biofilm formation, these models have
      drawbacks in that they are unlikely to replicate the variability and in vivo dynamics of
      plaque biofilms. Apart from differences in structural characteristics between in vitro and in
      vivo biofilms, the presence of host defenses such as antimicrobial peptides derived from
      saliva, is seldom take into account in in vitro multi-species biofilm models. More than 600
      microbial species have been identified in the human oral microflora, of which approximately
      280 species have been isolated in culture. Thus, plaque biofilm profiles are unique among
      individuals, being modulated by different environmental factors as well as variable quorum
      sensing signals derived from adjacent microorganisms. These confounding factors may temper
      the efficacy of antimicrobial polymers in vivo. Accordingly, the objective of the present
      randomised clinical trial was to determine the in vivo antimicrobial efficacy of the
      FDA-approved QAMS-containing orthodontic acrylic by using custom-made removable Hawley
      retainers that were worn intraorally by recruited subjects to create 48-hour multi-species
      plaque biofilms. Because of the anticipated high variability in the microbial composition of
      individual plaque biofilms, a split-mouth design was utilised to reduce inter-subject
      variability, with procedures taken to minimize unwanted carry-across effects. The null
      hypothesis tested was that there is no difference in the antimicrobial activities between
      QAMS-free and QAMS-containing orthodontic acrylic resin on oral biofilms grown in vivo in
      human subjects.
    

Intervention name(s): QAMS-containing PMMA; QAMS-free PMMA
Intervention type(s): Device; Device
Intervention description(s): Wear retainer with QMAS-containing PMMA on one side of retainer; Wear retainer with QMAS-free PMMA on other side of retainer
Intervention MeSH terms: Polymethyl Methacrylate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: antimicrobial; biofilms; acrylic resin; polymethyl methacrylate; confocal laser scanning microscopy; split-mouth design; quaternary ammonium methacryloxy silicate