Multi-functional nano-adhesive releasing therapeutic ions for MMP-deactivation and remineralization

Abstract

Restoration of hard tissue in conjunction with adhesive is a globally challenging issue in medicine and dentistry. Common clinical therapies involving application of adhesive and substitute material for functional or anatomical recovery are still suboptimal. Biomaterials with bioactivity and inhibitory effects of enzyme-mediated adhesive degradation can render a solution to this. Here, we designed a novel copper-doped bioactive glass nanoparticles (CuBGn) to offer multifunction: metalloproteinases (MMP) deactivation and remineralization and incorporated the CuBGn in resin-dentin adhesive systems, which showed most common failure of MMP mediated adhesive degradation among hard tissue adhesives, to evaluate proposed therapeutic effects. A sol-gel derived bioactive glass nanoparticles doping 10 wt% of Cu (Cu-BGn) for releasing Cu ions, which were well-known MMP deactivator, were successfully created and included in light-curing dental adhesive (DA), a filler-free co-monomer resin blend, at different concentrations (up to 2 wt%). These therapeutic adhesives (CuBGn-DA) showed enhanced (a)cellular bioactivity, cytocompatibility, microtensile bond strength and MMP deactivation-ability. In conclusion, the incorporation of Cu ions releasing nano-bioactive glass demonstrated multifunctional properties at the resin-dentin interface; MMP deactivation and remineralization, representing a suitable strategy to extend the longevity of adhesive-hard tissue (i.e. resin-dentin) interfaces.

The use of bioactive particles and biomimetic analogues for increasing the longevity of resin-dentin interfaces: A literature review

“…Copper-doped glass nanoparticles have been tested as a strategy to increase the inhibitory effect achieved with calcium ions. An experimental adhesive containing 2 wt% of copper-doped nano-scale mesoporous bioactive particles tested in demineralized dentin beams (10% phosphoric acid for 12 h) showed higher MMP inhibition in relation to the adhesive containing nondoped BAG 34) . Differently from the previously described studies, the dentin beams were immersed in a solution containing the non-polymerized adhesive and acetone for 5 min.…”

“…Zinc oxide (ZnO) particles and zinc-loaded polymeric nanoparticles have also been tested as additive in adhesive system due to the protective role of zinc ions against collagen degradation; additionally, it has been shown to induce precipitation of poorly crystalized apatite, in a similar fashion to other metallic oxides [29][30][31][32] . Among the silicabased BAG, the original 45S5 Bioglass, developed by Hench in the late 1960's 33) , is the composition most commonly tested, either unmodified 18,19) , doped with zinc 20,21) , copper 34) , fluoride 22) or treated with polyacrylic acid (PAA) 27) . Other compositions have been tested, including Niobium-based glass 24,25) and a silica-based glass with higher Ca:P molar ratio than 45S5 23) .…”

Bioactivity and Physico-Chemical Properties of Dental Composites Functionalized with Nano- vs. Micro-Sized Bioactive Glass

“…Besides methacrylate-based composites, other material types have also been experimentally functionalized with BG, e.g., epoxy-based root canal sealers [19], calcium silicate cements [20], and root canal dressings [21]. Micro-sized [22,23] and nano-sized [24] BG particles admixed into adhesive systems have demonstrated the potential to improve the stability of the hybrid layer through mineral deposition and possible inhibition of collagenolytic enzymes.…”

Effects of Zn-Doped Mesoporous Bioactive Glass Nanoparticles in Etch-and-Rinse Adhesive on the Microtensile Bond Strength

“…The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT; Sigma, St. louis, MO, USA) colormetric assay was performed in accordance with ISO standards to assess the cytotoxicity of the resin disks constructed with DA-MBN and DA-MBN-Zn [ 39 , 40 ]. DA resin disks that did not contain MBN, DA-1.0% MBN resin disks with the highest MBN content, and DA-1.0% MBN-Zn resin disks with the highest MBN-Zn content, were employed.…”

“…Images of resin disk surfaces were obtained using SEM (MIRA3, Tescan, Brno, Czech Republic) to examine the surface morphology of the resin disks before and after immersion in the SBF. X-ray diffraction (XRD) spectroscopy was performed using an Ultima IV multipurpose XRD system (Rigaku, The Woodland, TX, USA) at 40 kV and 40 mA, with a scanning speed of 0.1°/min, on the disk surfaces [ 40 , 41 ].…”