The purpose of this study was to develop robust class II organic–inorganic films as antibacterial coatings on titanium alloy (Ti6Al4V) implants. Coating materials were prepared from organic chitosan (20–80 wt.%) coupled by 3-glycydoxytrimethoxysilane (GPTMS) with inorganic tetraethoxysilane (TEOS). These hybrid networks were imbedded with antimicrobial silver nanoparticles (AgNPs) and coated onto polished and acid-etched Ti6Al4V substrates. Magic-angle spinning nuclear magnetic resonance (13CMAS-NMR), attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) and the ninhydrin assay, confirmed the presence and degree of covalent crosslinking (91%) between chitosan and GPTMS. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) identified surface roughness and microtopography on thin films and confirmed homogeneous distribution of elements throughout the coating. Cross-hatch and tensile adhesion testing demonstrated the robustness and adherence (15–20 MPa) of hybrid coatings to acid-etched titanium substrates. Staphylococcus aureus and Escherichia coli cultures and their biofilm formation were inhibited by all hybrid coatings. Antibacterial effects increased markedly for coatings loaded with AgNPs and appeared to increase with chitosan content in biofilm assays. These results are promising in the development of class II hybrid materials as robust and highly adherent antibacterial films on Ti6Al4V implants.

Diseases and disorders of dental, oral, and craniofacial (DOC) tissues represent a significant global health burden and have been found to have the greatest age‐standardized prevalence and incidence of all reported diseases worldwide. While the application of novel therapies has been suggested to address the different types of oral health diseases, only a limited number of interventional regenerative therapies have been reported to improve clinical therapeutic outcomes. The lack of novel therapies in DOC tissue regeneration may be in part attributed to the highly resource‐intensive translational path from preclinical models to clinical trials. Recently, stakeholders and regulatory agencies have begun to encourage the use of alternative preclinical models using human tissues for testing therapeutic interventions in place of animal models. This advocacy may provide an opportunity to reduce or eliminate animal testing, ultimately limiting resource expenditure and providing a more efficient regulatory pathway for the approval of novel DOC therapies. While the complexity of DOC physiology, defects, and diseases is not effectively recapitulated in traditional 2D or 3D in vitro culture models, the emergence of more sophisticated in vitro models (or so‐called microphysiological systems that include spheroid, organoid and organ on‐chip (OoC) systems) has enabled effective modeling of clinically simulated disease states in several DOC tissue and organ systems. Here, we aim to provide an overview and collective comparison of these microphysiological systems, outline their current uses in DOC research, and identify important gaps in both their utilization and abilities to recapitulate essential features of native oral‐craniofacial physiology, towards enabling the therapeutic performance of de novo interventions targeted at regeneration outcomes in vivo.

Bacterial-derived secondary caries is a primary cause of dental treatment failure at the artificial material-tissue interface. We previously developed ultra-long-term antimicrobial/antidegradative drug-silica particles (DSPs) to counter this interfacial failure. The aim of the current study was to evaluate a novel DSP-filled-adhesive system via in vitro and in vivo (rat) anti-secondary-caries studies. DSPs were incorporated into commercial total-etch dental adhesive at 10 % wt. to make DSP-SBMP. Interfacial specimens of DSP-SBMP-dentin and control SBMP-dentin were incubated 0- or 6-months in simulated salivary esterase, and subsequently with S. mutans/L. rhamnosus co-culture. Interfacial biomarkers were assessed via confocal microscopy and micro-computed-tomography. DSP-SBMP and SBMP were used to restore teeth in 16 SD rats in a 7-week split-mouth secondary caries study followed by clinical and µCT caries analysis and organ histology to assess biocompatibility. In vitro, interfacial biofilm viability (-23.1 ± 4.3 %) and biomass (-19.2 ± 4.9) were reduced by DSP-SBMP, as was cavitated (-78.6 ± 13.8 %) and demineralized (-33.4 ± 8 %) volume (ANOVA, Tukey HSD, p < 0.05). In vivo clinically observed primary and secondary caries counts were reduced on DSP-SBMP-restored teeth (χ² p < 0.05). No significant toxic effects were observed. This comprehensive in vitro and in vivo antimicrobial/antidegradative analysis of a new dental biomaterial, accurately modeling the chemical and biological environment these materials must perform in, provided comprehensive understanding of potential material performance that strongly supports continued development and clinical evaluation. The clinical relevance of the in vitro model used in this study was validated by the in vivo animal model and could be used to assess new dental biomaterials.

To assess the antiproteolytic effect of EGCG-methacrylate monomers and its inhibitory effect on gelatinolytic activity in the hybrid layer. Also, to investigate the effect of an adhesive material functionalized with EGCG-methacrylate monomers on immediate and long-term dentin-resin bond strength. Neat EGCG (E0) was reacted with three different ratios of methacryloyl ester and dissolved in ethyl acetate to obtain EGCG-methacrylates with hydroxyl functionalization at 33 % (M-E33), 67 % (M-E67) and 100 % (M-E100) levels. Resin composite blocks were built on human dentin surfaces using self-etching adhesive containing E0, M-E33, M-E67, and M-E100 at 1 wt%. Demineralized human dentin disks were immersed in deionized water (DW) or lactic acid (LA) and subsequently treated with DW, acetone (as controls), E0, M-E33, M-E67 and M-E100 diluted in acetone. Concentrations of solubilized type I collagen C-terminal (CTX and ICTP) and N-terminal (NTX) telopeptides were determined from 7-day extracts of dentin matrix specimens by ELISA assays. In situ zymography of adhesive-dentin interface slices from restored teeth was performed by confocal microscope after 24 h dentin treatment. Microtensile bond strength (µTBS) and failure pattern were evaluated after 24 h and 6 months. Data were analyzed using two-way ANOVA and Tukey post hoc test (p < 0.05). All experimental groups statistically reduced the release of solubilized telopeptides from dentin samples in DW and LA. E0 and M-E100 incorporated into the adhesive system reduced the gelatinolytic activity within the hybrid layer. The lowest µTBS values for restored teeth were observed for E0 and M-E100 groups, after 24 h and 6 months, respectively. The most prevalent failure observed was classified as type 4, except for M-E100. EGCG-methacrylate monomers effectively protected collagen from degradation. When incorporated into adhesive systems, EGCG-methacrylates reduced gelatinolytic activity within the hybrid layer, and did not affect immediate and long-term bond strength values of restorations.