Shi Qiang Gong

Quaternary ammonium silane-functionalized, methacrylate resin composition with antimicrobial activities and self-repair potential.

The design of antimicrobial polymers to address healthcare issues and minimize environmental problems is an important endeavor with both fundamental and practical implications. Quaternary ammonium silane-functionalized methacrylate (QAMS) represents an example of antimicrobial macromonomers synthesized by a sol-gel chemical route; these compounds possess flexible Si-O-Si bonds. In present work, a partially hydrolyzed QAMS co-polymerized with 2,2-[4(2-hydroxy 3-methacryloxypropoxy)-phenyl]propane is introduced. This methacrylate resin was shown to possess desirable mechanical properties with both a high degree of conversion and minimal polymerization shrinkage. The kill-on-contact microbiocidal activities of this resin were demonstrated using single-species biofilms of Streptococcus mutans (ATCC 36558), Actinomyces naeslundii (ATCC 12104) and Candida albicans (ATCC 90028). Improved mechanical properties after hydration provided the proof-of-concept that QAMS-incorporated resin exhibits self-repair potential via water-induced condensation of organic modified silicate (ormosil) phases within the polymerized resin matrix.

Intrafibrillar silicification of collagen scaffolds for sustained release of stem cell homing chemokine in hard tissue regeneration

Traditional bone regeneration strategies relied on supplementation of biomaterials constructs with stem or progenitor cells or growth factors. By contrast, cell homing strategies employ chemokines to mobilize stem or progenitor cells from host bone marrow and tissue niches to injured sites. Although silica‐based biomaterials exhibit osteogenic and angiogenic potentials, they lack cell homing capability. Stromal cell‐derived factor‐1 (SDF‐1) plays a pivotal role in mobilization and homing of stem cells to injured tissues. In this work, we demonstrated that 3‐dimensional collagen scaffolds infiltrated with intrafibrillar silica are biodegradable and highly biocompatible. They exhibit improved compressive stress‐strain responses and toughness over nonsilicified collagen scaffolds. They are osteoconductive and up‐regulate expressions of osteogenesis‐ and angiogenesis‐related genes more significantly than nonsilicified collagen scaffolds. In addition, these scaffolds reversibly bind SDF‐1α for sustained release of this chemokine, which exhibits in vitro cell homing characteristics. When implanted subcutaneously in an in vivo mouse model, SDF‐1α‐loaded silicified collagen scaffolds stimulate the formation of ectopic bone and blood capillaries within the scaffold and abrogate the need for cell seeding or supplementation of osteogenic and angiogenic growth factors. Intrafibrillar‐silicified collagen scaffolds with sustained SDF‐1α release represent a less costly and complex alternative to contemporary cell seeding approaches and provide new therapeutic options for in situ hard tissue regeneration.—Niu, L.‐N., Jiao, K., Qi, Y.‐P., Nikonov, S., Yiu, C. K. Y., Arola, D. D., Gong, S.‐Q., El‐Marakby, A., Carrilho, M. R. O., Hamrick, M. W., Hargreaves, K. M., Diogenes, A., Chen, J.‐H., Pashley, D. H., Tay, F. R. Intrafibrillar silicification of collagen scaffolds for sustained release of stem cell homing chemokine in hard tissue regeneration. FASEB J. 26, 4517–4529 (2012). www.fasebj.org

An ORMOSIL-containing orthodontic acrylic resin with concomitant improvements in antimicrobial and fracture toughness properties

Global increase in patients seeking orthodontic treatment creates a demand for the use of acrylic resins in removable appliances and retainers. Orthodontic removable appliance wearers have a higher risk of oral infections that are caused by the formation of bacterial and fungal biofilms on the appliance surface. Here, we present the synthetic route for an antibacterial and antifungal organically-modified silicate (ORMOSIL) that has multiple methacryloloxy functionalities attached to a siloxane backbone (quaternary ammonium methacryloxy silicate, or QAMS). By dissolving the water-insoluble, rubbery ORMOSIL in methyl methacrylate, QAMS may be copolymerized with polymethyl methacrylate, and covalently incorporated in the pressure-processed acrylic resin. The latter demonstrated a predominantly contact-killing effect on Streptococcus mutans ATCC 36558 and Actinomyces naselundii ATCC 12104 biofilms, while inhibiting adhesion of Candida albicans ATCC 90028 on the acrylic surface. Apart from its favorable antimicrobial activities, QAMS-containing acrylic resins exhibited decreased water wettability and improved toughness, without adversely affecting the flexural strength and modulus, water sorption and solubility, when compared with QAMS-free acrylic resin. The covalently bound, antimicrobial orthodontic acrylic resin with improved toughness represents advancement over other experimental antimicrobial acrylic resin formulations, in its potential to simultaneously prevent oral infections during appliance wear, and improve the fracture resistance of those appliances.

Effect of water-aging on the antimicrobial activities of an ORMOSIL-containing orthodontic acrylic resin.

Quaternary ammonium methacryloxy silicate (QAMS), an organically modified silicate (ORMOSIL) functionalized with polymerizable methacrylate groups and an antimicrobial agent with a long lipophilic alkyl chain quaternary ammonium group, was synthesized through a silane-based sol-gel route. By dissolving QAMS in methyl methacrylate monomer, this ORMOSIL molecule was incorporated into an auto-polymerizing, powder/liquid orthodontic acrylic resin system, yielding QAMS-containing poly(methyl methacrylate). The QAMS-containing acrylic resin showed a predominant contact-killing effect on Streptococcus mutans (ATCC 35668) and Actinomyces naeslundii (ATCC 12104) biofilms, while inhibiting adhesion of Candida albicans (ATCC 90028) on the acrylic surface. The antimicrobial activities of QAMS-containing acrylic resin were maintained after a 3month water-aging period. Bromophenol blue assay showed minimal leaching of quaternary ammonium species when an appropriate amount of QAMS (<4wt.%) was incorporated into the acrylic resin. The results suggest that QAMS is predominantly co-polymerized with the poly(methyl methacrylate) network, and only a minuscule amount of free QAMS molecules is present within the polymer network after water-aging. Acrylic resin with persistent antimicrobial activities represents a promising method for preventing bacteria- and fungus-induced stomatitis, an infectious disease commonly associated with the wearing of removable orthodontic appliances.

Peptide aptamers against titanium-based implants identified through phage display

Commercially pure titanium (cp-Ti) is widely used in the field of long-term clinical oral implantology owing to its ability to allow close bone-implant apposition. The optimization of its function based on artificial proteins has become a key issue in the development of improved cp-Ti implants. Here, we set out to identify peptide aptamers with preferential adsorption towards titanium-based implants through the phage display methodology. Fifteen sequences were selected in the third round of biopanning. One sequence, ATWVSPY (named TBP1), had a 40% repetition rate and exhibited the strongest binding affinity to cp-Ti disks. Ten sequences were selected in the fourth round, among which the repetition rate is 80% for TBP1 and 20% for TBP2 (GVGLPHT). The peptide aptamers against cp-Ti disks can provide an alternative method of functional coating for biomaterial surfaces.

Using rigidly fixed autogenous tooth graft to repair bone defect: an animal model.

OBJECTIVE This study describes a new approach to regenerate bone defect using autogenous tooth. MATERIALS AND METHODS Freshly extracted teeth were used as autogenous grafts. Teeth were sectioned, cut into desired shape, and disinfected. The grafts were rigidly fixed to the mandibular defects in eighteen rabbits using titanium screws to achieve good stability. Every six rabbits were stochastically sacrificed at 1, 3, and 6 months after implantation, respectively. For all specimens, clinical, radiographical, and histological measurements were performed. RESULTS The boundaries of the grafts were distinctly visible in the implanted area during the first and third month. However, the teeth grafts were fully covered by new bone by the sixth month. The radiograph demonstrated the progressive change in the bone and grafted tooth interface from radiolucency to radiopacity during different time periods. Histologically, vascularization led to a temporary fibrous integration in the graft-bone interface. The bone contact rate of 1 and 3 months was significantly lower than that of the 6 months. During this period, grafts were gradually resorbed and replaced by new bone. CONCLUSION Rigid fixation of autogenous tooth could serve as a novel approach for the repair of bone defect.

In Vitro Evaluation of Antibacterial Effect of AH Plus Incorporated with Quaternary Ammonium Epoxy Silicate against Enterococcus faecalis

INTRODUCTION The purpose of this study was to evaluate the in vitro antibacterial effect of AH Plus (Dentsply, DeTrey, Konstanz, Germany) incorporated with quaternary ammonium epoxy silicate (QAES) against Enterococcus faecalis. METHODS QAES particles were synthesized by the cocondensation of tetraethoxysilane with 2 trialkoxysilanes (3-[trimethoxysilyl]propyldimethyloctadecyl ammonium chloride and 3-glycidyloxypropyltrimethoxysilane) through a 1-pot sol-gel route. Dried QAES particles were then characterized by attenuated total reflection Fourier transform infrared spectroscopy and scanning electron microscopy. AH Plus sealers incorporated with 0-8 wt% QAES were tested after 4 weeks of water aging to assess the in vitro antibacterial activity against E. faecalis by the direct contact test (DCT) and 3-dimensional image analysis of live/dead-stained E. faecalis biofilms using confocal laser scanning microscopy. RESULTS The Fourier transform infrared spectroscopy spectrum of QAES particles revealed the coexistence of the characteristic absorbance band of the siloxane backbone (Si-O-Si) from 1,000-1,100 cm(-1), epoxide band peaking at ∼916 cm(-1), and C-N stretching vibration peaking at 1,373 cm(-1). The scanning electron microscopic image showed the spherical morphology of QAES particles with ∼120 nm in diameter and a rough surface. DCT results revealed that AH Plus alone (0 wt% QAES) after 4 weeks of water aging had no inhibitory effect on E. faecalis growth (P = .569). AH Plus incorporated with QAES (2-8 wt%) showed antibacterial activity against E. faecalis as shown in DCT and biofilm viability results (P < .001). CONCLUSIONS The incorporation of QAES into epoxy resin-based AH Plus may be a promising approach for controlling endodontic infection at the time of canal filling and preventing subsequent reinfection.

Design of a hydroxyapatite-binding antimicrobial peptide with improved retention and antibacterial efficacy for oral pathogen control

Controlling and reducing the formation of pathogenic biofilm on tooth surface is the key to the prevention and treatment of the biofilm-associated oral diseases. Antimicrobial peptides (AMPs), considered as possible future alternatives for conventional antibiotics, have been extensively studied for the control of bacterial infection. Due to the rapid dilution and degradation by human saliva, AMP preparations designed for oral use with longer retention and higher efficacy are in urgent need. To this end, a hydroxyapatite (HAp)-binding antimicrobial peptide (HBAMP), which is based on the fusion of a specific HAp-binding heptapeptide (HBP7) domain and a broad-spectrum antimicrobial peptide (KSLW) domain, has been developed in our laboratory. HBAMP was supposed to form a contact-active antibacterial interface on tooth surface to inhibit the formation of biofilms. In this study, we investigated its binding behaviour, antibacterial activity against bacteria in both planktonic and sessile states, enzymatic stability in human saliva, and cytocompatibility to human gingival fibroblasts (HGFs). Our findings suggest that HBAMP could adsorb on tooth surface to provide effective antibacterial activity with improved retention. This study provides a proof-of-concept on using conjugated molecules to promote antibacterial efficacy by synergistically actions of HBAMP free in solution and bound on tooth surface.

Synthesis of antimicrobial silsesquioxane–silica hybrids by hydrolytic co-condensation of alkoxysilanes

Organically modified silicates represent an excellent example of organic–inorganic hybrids in materials science. The routes to achieve incorporation of organic functionalities include grafting and co-condensation (one-pot synthesis). Compared with the grafting method, the advantage of one-pot synthesis manifests as the tunability of both mechanical and biological properties. Herein, we report a silsesquioxane–silica hybrid (SqSH) with dual functional groups (alkylammonium and methacrylate chains) synthesized by the hydrolytic co-condensation of one tetraethoxysilane and two alkoxysilanes. Successful co-condensation is validated by attenuated total reflection-Fourier transform infrared (ATR-FTIR), 29Si nuclear magnetic resonance (29Si NMR), and thermogravimetric analysis (TGA). 3-(Trimethoxysilyl)propyldimethyloctadecyl ammonium chloride (SiQAC), one of the three precursors, simultaneously serves as a structure-directing agent in the modified Stober reaction, resulting in SqSH particles with structural hierarchy of both ordered lamellar structure and spherical morphology, as revealed by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The SqSH particles bear tunable mechanical properties and, when incorporated into bis-GMA/TEGDMA resin, antimicrobial activities against Streptococcus mutans, Actinomyces naeslundii, and Candida albicans.

Antimicrobial activity of a quaternary ammonium methacryloxy silicate-containing acrylic resin: a randomised clinical trial

Quaternary ammonium methacryloxy silicate (QAMS)-containing acrylic resin demonstrated contact-killing antimicrobial ability in vitro after three months of water storage. The objective of the present double-blind randomised clinical trial was to determine the in vivo antimicrobial efficacy of QAMS-containing orthodontic acrylic by using custom-made removable retainers that were worn intraorally by 32 human subjects to create 48-hour multi-species plaque biofilms, using a split-mouth study design. Two control QAMS-free acrylic disks were inserted into the wells on one side of an orthodontic retainer, and two experimental QAMS-containing acrylic disks were inserted into the wells on the other side of the same retainer. After 48 hours, the disks were retrieved and examined for microbial vitality using confocal laser scanning microscopy. No harm to the oral mucosa or systemic health occurred. In the absence of carry-across effect and allocation bias (disks inserted in the left or right side of retainer), significant difference was identified between the percentage kill in the biovolume of QAMS-free control disks (3.73 ± 2.11%) and QAMS-containing experimental disks (33.94 ± 23.88%) retrieved from the subjects (P ≤ 0.001). The results validated that the QAMS-containing acrylic exhibits favourable antimicrobial activity against plaque biofilms in vivo. The QAMS-containing acrylic may also be used for fabricating removable acrylic dentures.