title: Inhibition of matrix metalloproteinase activity in human dentin via novel antibacterial monomer.
abstract: OBJECTIVE
  Dentin-composite bond failure is caused by factors including hybrid layer degradation, which in turn can be caused by hydrolysis and enzymatic degradation of the exposed collagen in the dentin. The objectives of this study were to investigate a new antibacterial monomer (dimethylaminododecyl methacrylate, DMADDM) as an inhibitor for matrix metalloproteinases (MMPs), and to determine the effects of DMADDM on both soluble recombinant human MMPs (rhMMPs) and dentin matrix-bound endogenous MMPs.
  
  
  METHODS
  Inhibitory effects of DMADDM at six mass% (0.1% to 10%) on soluble rhMMP-8 and rhMMP-9 were measured using a colorimetic assay. Matrix-bound endogenous MMP activity was evaluated in demineralized human dentin. Dentin beams were divided into four groups (n=10) and incubated in calcium- and zinc-containing media (control medium); or control medium+0.2% chlorhexidine (CHX); 5% 12-methacryloyloxydodecylpyridinium bromide (MDPB); or 5% DMADDM. Dissolution of dentin collagen peptides was evaluated by mechanical testing in three-point flexure, loss of dentin mass, and a hydroxyproline assay.
  
  
  RESULTS
  Use of 0.1% to 10% DMADDM exhibited a strong concentration-dependent anti-MMP effect, reaching 90% of inhibition on rhMMP-8 and rhMMP-9 at 5% DMADDM concentration. Dentin beams in medium with 5% DMADDM showed 34% decrease in elastic modulus (vs. 73% decrease for control), 3% loss of dry dentin mass (vs. 28% loss for control), and significantly less solubilized hydroxyproline when compared with control (p<0.05).
  
  
  CONCLUSIONS
  The new antibacterial monomer DMADDM was effective in inhibiting both soluble rhMMPs and matrix-bound human dentin MMPs. These results, together with previous studies showing that adhesives containing DMADDM inhibited biofilms without compromising dentin bond strength, suggest that DMADDM is promising for use in adhesives to prevent collagen degradation in hybrid layer and protect the resin-dentin bond.
authors.affiliation: Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China; Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Mechanical Engineering, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
authors.forename: Hessam
authors.initials: H
authors.lastname: Majd
authors.affiliation: Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weir
authors.affiliation: Department of Mechanical Engineering, University of Maryland, Baltimore County, MD 21250, USA.
authors.forename: Dwayne D
authors.initials: DD
authors.lastname: Arola
authors.affiliation: Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA; Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: hxu@umaryland.edu.
authors.forename: Hockin H K
authors.initials: HH
authors.lastname: Xu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D003124:Colorimetry; D001840:Dental Bonding; D003738:Dental Cements / Q000494:pharmacology; D003804:Dentin / Q000201:enzymology*; D017220:Dentin-Bonding Agents / Q000494:pharmacology; D055119:Elastic Modulus; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008689:Methacrylates / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D003738:Dental Cements; D017220:Dentin-Bonding Agents; D008689:Methacrylates; D000644:Quaternary Ammonium Compounds; C586974:dimethylaminododecyl methacrylate; D003094:Collagen; D020782:Matrix Metalloproteinases
keywords: Antibacterial activity; Dental monomer; Human dentin; Matrix metalloproteinase inhibitor; Quaternary ammonium methacrylate; Tooth restoration