Purpose To evaluate and synthesize the existing evidence on the microbiological and human immune response associated with peri‐implantitis in comparison to healthy implants. Materials and methods Three electronic databases (MEDLINE, Embase, and Cochrane Library) were searched in October 2019 to identify clinical studies evaluating the microbiota and the immune response associated with peri‐implantitis. Two reviewers independently screened the studies and used the full text to extract the data. A qualitative synthesis was performed on the extracted data and summary tables were prepared. Due to clinical and methodological heterogeneity among included studies, no meta‐analysis was performed. Results Forty studies were included in this review. Of these, 20 studies compared the microbiological profile of peri‐implantitis with healthy implants. Nineteen studies focused on the immune response associated with peri‐implantitis in comparison to healthy implants. Three studies focus on gene polymorphism associated with peri‐implantitis. The most commonly reported bacteria associated with peri‐implantitis were obligate anaerobe Gram‐negative bacteria (OAGNB), asaccharolytic anaerobic Gram‐positive rods (AAGPRs), and other Gram‐positive species. In regard to immune response, the most frequently reported pro‐inflammatory mediators associated with peri‐implantitis were IL‐1β, IL‐6, IL‐17, TNF‐α. Osteolytic mediator, e.g., RANK, RANKL, Wnt5a and proteinase enzymes, MMP‐2, MMP‐9, and Cathepsin‐K were also expressed at higher level in peri‐implantitis sites compared to control. Conclusions Peri‐implantitis is associated with complex and different microbiota than healthy implants including bacteria, archaea, fungi, and virus. This difference in the microbiota could provoke higher inflammatory response and osteolytic activity. All of this could contribute to the physiopathology of peri‐implantitis.

Epigenetic factors are heritable genome modifications that potentially impact gene transcription, contributing to disease states. Epigenetic marks play an important role in chronic inflammatory conditions, as observed in periodontal diseases, by allowing microbial persistence or by permitting microbial insult to play a role in the so-called 'hit-and-run' infectious mechanism, leading to lasting pathogen interference with the host genome. Epigenetics also affects the health sciences by providing a dynamic mechanistic framework to explain the way in which environmental and behavioral factors interact with the genome to alter disease risk. In this article we review current knowledge of epigenome regulation in light of the multifactorial nature of periodontal diseases. We discuss epigenetic tagging in identified genes, and consider the potential implications of epigenetic changes on host-microbiome dynamics in chronic inflammatory states and in response to environmental stressors. The most recent advances in genomic technologies have placed us in a position to analyze interaction effects (eg, between periodontal disease and type 2 diabetes mellitus), which can be investigated through epigenome-wide association analysis. Finally, because of the individualized traits of epigenetic biomarkers, pharmacoepigenomic perspectives are also considered as potentially novel therapeutic approaches for improving periodontal disease status.

Oral candidiasis (OC) caused by the fungal pathogen Candida albicans is the most common opportunistic infection in immunocompromised populations. The dramatic increase in resistance to common antifungal agents has emphasized the importance of identifying alternative therapeutic options. Antimicrobial peptides have emerged as promising drug candidates due to their antimicrobial properties; specifically, histatin-5 (Hst-5), a peptide naturally produced and secreted by human salivary glands, has demonstrated potent activity against C. albicans. However, as we previously demonstrated vulnerability for Hst-5 to proteolysis by C. albicans proteolytic enzymes at specific amino acid residues, a new variant (K11R-K17R) was designed with amino acid substitutions at the identified cleavage sites. The new resistant peptide demonstrated no cytotoxicity to erythrocytes or human oral keratinocytes. To evaluate the potential of the new peptide for clinical application, we utilized our FDA-approved polymer-based bioadhesive hydrogel as a delivery system and developed a therapeutic formulation specifically designed for oral topical application. The new formulation was demonstrated to be effective against C. albicans strains resistant to the traditional antifungals, and the in vitro therapeutic efficacy was found to be comparable to that of the common topical antifungal agents in clinical use. Importantly, in addition to its antifungal properties, our findings also demonstrated that the new peptide variant induces cell proliferation and rapid cell migration of human oral keratinocytes, indicative of wound healing properties. The findings from this study support the progression of the novel formulation as a therapeutic agent against oral candidiasis, as well as a therapeutic modality for promoting wound healing.

ObjectivesThe long-term success of dental implants is established by literature. Although clinically well defined, the complex genetic pathways underlying osseointegration have not yet been fully elucidated. Furthermore, patients with osteopenia/osteoporosis are considered to present as higher risk for implant failure. Porous tantalum trabecular metal (PTTM), an open-cell porous biomaterial, is suggested to present enhanced biocompatibility and osteoconductivity. The goal of this study was to evaluate the expression patterns of a panel of genes closely associated with osteogenesis and wound healing in osteopenic patients receiving either traditional titanium (Ti) or PTTM cylinders to assess the pathway of genes activation in the early phases of osseointegration.Material and methodsImplant cylinders made of Ti and PTTM were placed in osteopenic volunteers. At 2- and 4 weeks of healing, one Ti and one PTTM cylinder were removed from each subject for RT-PCR analysis using osteogenesis PCR array.ResultsCompared to Ti, PTTM-associated bone displayed upregulation of bone matrix proteins, BMP/TGF tisuperfamily, soluble ligand and integrin receptors, growth factors, and collagen genes at one or both time points. Histologically, PTTM implants displayed more robust osteogenesis deposition and maturity when compared to Ti implants from the same patient.ConclusionsOur results indicate that PTTM properties could induce an earlier activation of genes associated with osteogenesis in osteopenic patients suggesting that PTTM implants may attenuate the relative risk of placing dental implants in this population.