Biogeographical Impacts of Dental, Oral, and Craniofacial Microbial Reservoirs.

The human mouth, or oral cavity, is at the crossroads of our external and internal environments, and it is increasingly evident that local colonization of dental, oral, and craniofacial (DOC) tissues and cells by bacteria and viruses may also have systemic effects across myriad diseases and disorders. Better understanding of this phenomenon will require a holistic understanding of host-microbial interactions in both spatiotemporal and biogeographical contexts while also considering person-, organ-, tissue-, cell-, and molecular-level variation. After the acute phase interaction with microbes, the establishment of site-specific reservoirs constitutes an important relationship to understand within the human body; however, despite a preliminary understanding of how viral reservoirs originate and persist across the human body, the landscape of single-cell and spatial multiomic tools has challenged our current understanding of what cells and niches can support microbial reservoirs. The lack of complete understanding impacts research into these relevant topics and implementing precision care for microbial-induced or microbial-influenced diseases. Here, via the lens of acute and chronic microbial infections of the DOC tissues, the goal of this review is to highlight and link the emerging spatiotemporal biogeography of host-viral interactomics at 3 levels: (1) DOC cell types in distinct tissues, (2) DOC-associated microbes, and (3) niche-specific DOC pathologies. Further, we will focus on the impact of postacute infectious syndromes such as long COVID, neurodegenerative disorders, and other underappreciated postviral conditions. We will provide hypotheses about how DOC tissues may play roles systemically in these conditions. Throughout, we will underscore how COVID-19 has catalyzed a new understanding of these biological questions, discuss future directions to study these phenomena, and highlight the utility of noninvasive oral biofluids in screening, monitoring, and intervening to prevent and/or ameliorate human infectious diseases.

A Roadmap for the Human Oral and Craniofacial Cell Atlas.

Oral and craniofacial tissues are uniquely adapted for continuous and intricate functioning, including breathing, feeding, and communication. To achieve these vital processes, this complex is supported by incredible tissue diversity, variously composed of epithelia, vessels, cartilage, bone, teeth, ligaments, and muscles, as well as mesenchymal, adipose, and peripheral nervous tissue. Recent single cell and spatial multiomics assays-specifically, genomics, epigenomics, transcriptomics, proteomics, and metabolomics-have annotated known and new cell types and cell states in human tissues and animal models, but these concepts remain limitedly explored in the human postnatal oral and craniofacial complex. Here, we highlight the collaborative and coordinated efforts of the newly established Oral and Craniofacial Bionetwork as part of the Human Cell Atlas, which aims to leverage single cell and spatial multiomics approaches to first understand the cellular and molecular makeup of human oral and craniofacial tissues in health and to then address common and rare diseases. These powerful assays have already revealed the cell types that support oral tissues, and they will unravel cell types and molecular networks utilized across development, maintenance, and aging as well as those affected in diseases of the craniofacial complex. This level of integration and cell annotation with partner laboratories across the globe will be critical for understanding how multiple variables, such as age, sex, race, and ancestry, influence these oral and craniofacial niches. Here, we 1) highlight these recent collaborative efforts to employ new single cell and spatial approaches to resolve our collective biology at a higher resolution in health and disease, 2) discuss the vision behind the Oral and Craniofacial Bionetwork, 3) outline the stakeholders who contribute to and will benefit from this network, and 4) outline directions for creating the first Human Oral and Craniofacial Cell Atlas.

Flossing Is Associated with Improved Oral Health in Older Adults.

The effect of preventive oral habits is largely unexplored in older individuals. The purpose of this study was to evaluate the associations between home use of flossing and prevalence of periodontal disease and caries in older adults. Five-year incident tooth loss was also evaluated. Data on 686 individuals ≥65 y-old from the Piedmont 65+ Dental Study were examined including: 1) interproximal clinical attachment level (iCAL), 2) interproximal probing depth (iPD), 3) numbers of caries, and 4) missing teeth. Flossing behavior was evaluated according to the Periodontal Profile Class (PPC) system. Five-year follow-up data (n = 375) was evaluated for incident tooth loss. Dichotomous and categorical variables were analyzed using Pearson chi-square tests as well as covariate-adjusted Cochran-Mantel-Haenszel tests. Multiple linear regression compared clinical parameters based on flossing behavior. Elderly flossers had lower (mean, SE) %iCAL≥3 mm (38.2, 2.38 vs. 48.8, 1.56) and %iPD≥4 mm (8.70, 1.41 vs. 14.4, 0.93) compared to nonflossers (P ≤ 0.005). Flossers showed less coronal caries compared to nonflossers (P = 0.02). Baseline number of missing teeth (mean, SE) was 11.5 (0.35) in nonflossers compared to 8.6 (0.53) in flossers (P < 0.0001). Regular dental visitors had lower oral disease levels compared to episodic dental users. The majority of flossers classified into PPC-Stage I (health) whereas nonflossers classified as PPC-Stages V, VI, and VII (disease). At the 5-y follow-up visit, the average tooth loss for flossers was ~1 tooth compared to ~4 teeth lost for nonflossers (P < 0.0001). Among all teeth, molars showed the highest benefit (>40%) for flossing behavior (P = 0.0005). In conclusion, the extent of oral disease for older individuals was significantly less in flossers than in nonflossers. Flossers showed less periodontal disease, fewer dental caries, and loss of fewer teeth over a 5-y period. These findings further support flossing as an important oral hygiene behavior to prevent oral disease progression in older adults.

Transcriptomic profiling of tantalum metal implant osseointegration in osteopenic patients.

OBJECTIVES: The 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 METHODS: Implant 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. RESULTS: Compared 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. CONCLUSIONS: Our 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.

Closing the Gap: Mouse Models to Study Adhesion in Secondary Palatogenesis.

Secondary palatogenesis occurs when the bilateral palatal shelves (PS), arising from maxillary prominences, fuse at the midline, forming the hard and soft palate. This embryonic phenomenon involves a complex array of morphogenetic events that require coordinated proliferation, apoptosis, migration, and adhesion in the PS epithelia and underlying mesenchyme. When the delicate process of craniofacial morphogenesis is disrupted, the result is orofacial clefting, including cleft lip and cleft palate (CL/P). Through human genetic and animal studies, there are now hundreds of known genetic alternations associated with orofacial clefts; so, it is not surprising that CL/P is among the most common of all birth defects. In recent years, in vitro cell-based assays, ex vivo palate cultures, and genetically engineered animal models have advanced our understanding of the developmental and cell biological pathways that contribute to palate closure. This is particularly true for the areas of PS patterning and growth as well as medial epithelial seam dissolution during palatal fusion. Here, we focus on epithelial cell-cell adhesion, a critical but understudied process in secondary palatogenesis, and provide a review of the available tools and mouse models to better understand this phenomenon.