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γδ T cells are a unique T cell subpopulation that are rare in secondary lymphoid organs but enriched in many peripheral tissues, such as the skin, intestines and lungs. By rapidly producing large amounts of cytokines, γδ T cells make key contributions to immune responses in these tissues. In addition to their immune surveillance activities, recent reports have unravelled exciting new roles for γδ T cells in steady-state tissue physiology, with functions ranging from the regulation of thermogenesis in adipose tissue to the control of neuronal synaptic plasticity in the central nervous system. Here, we review the roles of γδ T cells in tissue homeostasis and in surveillance of infection, aiming to illustrate their major impact on tissue integrity, tissue repair and immune protection.This Review focuses on the roles of γδ T cells in tissue homeostasis and immune surveillance. The authors discuss exciting new studies showing how γδ T cells can regulate diverse physiological responses in tissues, ranging from thermogenesis in adipose tissue to remodelling at neuronal synapses.

Human oral cavity (mouth) hosts a complex microbiome consisting of bacteria, archaea, protozoa, fungi and viruses. These bacteria are responsible for two common diseases of the human mouth including periodontal (gum) and dental caries (tooth decay). Dental caries is caused by plaques, which are a community of microorganisms in biofilm format. Genetic and peripheral factors lead to variations in the oral microbiome. It has known that, in commensalism and coexistence between microorganisms and the host, homeostasis in the oral microbiome is preserved. Nonetheless, under some conditions, a parasitic relationship dominates the existing situation and the rise of cariogenic microorganisms results in dental caries. Utilizing advanced molecular biology techniques, new cariogenic microorganisms species have been discovered. The oral microbiome of each person is quite distinct. Consequently, commonly taken measures for disease prevention cannot be exactly the same for other individuals. The chance for developing tooth decay in individuals is dependent on factors such as immune system and oral microbiome which itself is affected by the environmental and genetic determinants. Early detection of dental caries, assessment of risk factors and designing personalized measure let dentists control the disease and obtain desired results. It is necessary for a dentist to consider dental caries as a result of a biological process to be targeted than treating the consequences of decay cavities. In this research, we critically review the literature and discuss the role of microbial biofilms in dental caries.

Oral mechanoreception is implicated in fundamental functions including speech, food intake and swallowing; yet, the neuroanatomical substrates that encode mechanical stimuli are not well understood. Tactile perception is initiated by intricate mechanosensitive machinery involving dedicated cells and neurons. This signal transduction setup is coupled with the topology and mechanical properties of surrounding epithelium, thereby providing a sensitive and accurate system to detect stress fluctuations from the external environment. We mapped the distribution of anatomically distinct neuronal endings in mouse oral cavity using transgenic reporters, molecular markers and quantitative histomorphometry. We found that the tongue is equipped with an array of putative mechanoreceptors that express the principal mechanosensory channel Piezo2, including end bulbs of Krause innervating individual filiform papillae and a novel class of neuronal fibers innervating the epithelium surrounding taste buds. The hard palate and gums are densely populated with three classes of sensory afferents organized in discrete patterns including Merkel cell-neurite complexes, Meissner’s corpuscles and glomerular corpuscles. In aged mice, we find that palatal Merkel cells reduce in number at key time-points that correlate with impaired oral abilities, such as swallowing and mastication. Collectively, this work identifies the mechanosensory architecture of oral tissues involved in feeding.

Orthodontic forces deform the extracellular matrix and activate cells of the paradental tissues, facilitating tooth movement. Discoveries in mechanobiology have illuminated sequential cellular and molecular events, such as signal generation and transduction, cytoskeletal re-organization, gene expression, differentiation, proliferation, synthesis and secretion of specific products, and apoptosis. Orthodontists work in a unique biological environment, wherein applied forces engender remodeling of both mineralized and non-mineralized paradental tissues, including the associated blood vessels and neural elements. This review aims at identifying events that affect the sequence, timing, and significance of factors that determine the nature of the biological response of each paradental tissue to orthodontic force. The results of this literature review emphasize the fact that mechanoresponses and inflammation are both essential for achieving tooth movement clinically. If both are working in concert, orthodontists might be able to accelerate or decelerate tooth movement by adding adjuvant methods, whether physical, chemical, or surgical.

In order to advance models of human oral mucosa towards routine use, these models must faithfully mimic the native tissue structure while also being scalable and cost efficient. The goal of this study was to develop a low-cost, keratinized human gingival model with high fidelity to human attached gingiva and demonstrate its utility for studying the implant-tissue interface. Primary human gingival fibroblasts (HGF) and keratinocytes (HGK) were isolated from clinically healthy gingival biopsies. Four matrices, electrospun collagen (ES), decellularized dermis (DD), type I collagen gels (Gel) and released type I collagen gels (Gel-R)) were tested to engineer lamina propria and gingiva. HGF viability was similar in all matrices except for Gel-R, which was significantly decreased. Cell penetration was largely limited to the top layers of all matrices. Histomorphometrically, engineered human gingiva was found to have similar appearance to the native normal human gingiva except absence of rete pegs. Immunohistochemical staining for cell phenotype, differentiation and extracellular matrix composition and organization within 3D engineered gingiva made with electrospun collagen was mostly in agreement with normal gingival tissue staining. Additionally, five types of dental material posts (5-mm diameter x 3-mm height) with different surface characteristics were used [machined titanium, SLA (sandblasted-acid etched) titanium, TiN-coated (titanium nitride-coated) titanium, ceramic, and PEEK (Polyetheretherketone) to investigate peri-implant soft tissue attachment studied by histology and SEM. Engineered epithelial and stromal tissue migration to the implant-gingival tissue interface was observed in machined, SLA, ceramic, and PEEK groups, while TiN was lacking attachment. Taken together, the results suggest that electrospun collagen scaffolds provide a scalable, reproducible and cost-effective lamina propria and 3D engineered gingiva that can be used to explore biomaterial-soft tissue interface.

Human gingival fibroblasts (HGnFs) maintain periodontal tissue homeostasis through active proliferation and migration. Clinically, it is considered that the wound-healing ability of the gingival tissue is maintained even in environments with insufficient supply of nutrients, such as glucose, immediately after periodontal surgery. However, the effects of such glucose-deficient environments on HGnFs remain unclear. This study aimed to investigate the effects of low-glucose environment on HGnFs homeostasis. We evaluated gingival wound healing by examining cell proliferation and migration and collagen synthesis in HGnFs cultured in 100, 50, 25, and 0 mg/dL glucose in vitro. The cellular stress levels were determined by measuring the lactate dehydrogenase (LDH) and reactive oxygen species (ROS) levels. The glucose metabolism of HGnFs in the low-glucose concentrations was studied by measuring glucose transporter type 1 (GLUT1) mRNA expression, glucose uptake assays, lactate and ATP productions. Molecular effects were examined with a focus on the LKB1-AMPK signaling pathway. Autophagy activity in glucose-deprived HGnFs was evaluated by measuring the levels of autophagy-related proteins. Low glucose levels increased cellular stress levels, autophagy activity, and enhanced glucose metabolism through the LKB1-AMPK signaling pathway, providing more ATPs to promote wound healing. Our results regarding glucose transfer suggest the rapid healing of gingival wounds.

The clinical benefits of simultaneous implant placement and soft tissue augmentation using different treatment modalities are unclear. The current meta-analysis aimed to compare the effect of simultaneous soft tissue augmentation using subepithelial connective tissue graft (SCTG) around immediate or delayed dental implant placement with other treatment modalities on the peri-implant tissue health and esthetic. Up to May 2021, four databases (PubMed, EMBASE, Cochrane Central, and Google Scholar) were searched. Randomized control trials with follow-up >3 months, evaluating simultaneous implant placement (immediate or delayed) and soft tissue augmentation using SCTG compared with other treatment modalities were included. The predictor variables were SCTG versus no augmentation with/without guided bone regeneration (GBR) or other augmentation techniques (Acellular dermal matrix (ADM), Xenogeneic collagen matrix (XCM). The outcome variables were buccal tissue thickness (BTT), mid-buccal gingival level (MGL), marginal bone loss (MBL), and pink esthetic scores (PES). Cumulative mean differences (MD) and 95% confidence interval (CI) were estimated. Twelve studies were included. SCTG along with immediate implant placement (IIP) or delayed implant placement (DIP) showed a statistically significant improvement in BTT (Fixed; MD, 0.74; 95% CI, 0.51; 0.97), MGL (Fixed; MD, 0.5; 95% CI, 0.21; 0.80), PES (Fixed; MD, 0.79; 95% CI, 0.29; 1.29), and less MBL (Fixed; MD, -0.11; 95% CI, -0.14; -0.08) compared to no graft (P<0.05). A statistically insignificant differences in BTT (Random; MD, 0.62; 95% CI, -0.41; 1.65), MGL (Fixed; MD, -0.06; 95% CI, -0.23; 0.11), MBL (Fixed; MD, 0.36; 95% CI, -0.05; 0.77) and PES (Fixed; MD, 0.28; 95% CI, -0.10; 0.67) was observed when SCTG along with DIP was compared with no augmentation plus GBR. Similarly, no statistically significant difference was observed when comparing SCTG along with DIP with acellular dermal matrix (ADM) concerning BTT (MD:0.71, P = 0.18) and KMW (MD: 0.6, P = 0.19). There is a very low quality of evidence to provide recommendations on whether simultaneous dental implant placement (IIP or DIP) and soft tissue augmentation using SCTG is superior to no augmentation or is comparable to the other tissue augmentation materials in improving the quality and quantity of peri-implant tissues. Therefore, further, well-designed RCTs with larger sample sizes and long follow-up times are still needed.

Pomegranate (Punica granatum) is a well-established folklore medicine, demonstrating benefits in treating numerous conditions partly due to its antimicrobial and anti-inflammatory properties. Such desirable medicinal capabilities are attributed to a high hydrolysable tannin content, especially punicalagin. However, few studies have evaluated the abilities of pomegranate to promote oral healing, during situations such as periodontal disease or trauma. Therefore, this study evaluated the antioxidant and in vitro gingival wound healing effects of pomegranate rind extract (PRE) and punicalagin, alone and in combination with Zn (II). In vitro antioxidant activities were studied using DPPH and ABTS assays, with total PRE phenolic content measured by Folin–Ciocalteu assay. PRE, punicalagin and Zn (II) combination effects on human gingival fibroblast viability/proliferation and migration were investigated by MTT assay and scratch wounds, respectively. Punicalagin demonstrated superior antioxidant capacities to PRE, although Zn (II) exerted no additional influences. PRE, punicalagin and Zn (II) reduced gingival fibroblast viability and migration at high concentrations, but retained viability at lower concentrations without Zn (II). Fibroblast speed and distance travelled during migration were also enhanced by punicalagin with Zn (II) at low concentrations. Therefore, punicalagin in combination with Zn (II) may promote certain anti-inflammatory and fibroblast responses to aid oral healing.

The biocompatibility of dental implant abutment materials depends on numerous factors including the nature of the material, its chemical composition, roughness, texture, hydrophilicity and surface charge. The aim of the present study was to compare the viability and adhesion strength of human gingival fibroblasts (HGFs) grown on several dental materials used in implant prosthodontics. Surfaces of the tested materials were assessed using an optical imaging profiler. For material toxicity and cellular adhesion evaluation, primary human gingival fibroblast cells were used. To evaluate the strength of cellular adhesion, gingival fibroblasts were cultured on the tested materials and subjected to lateral shear forces by applying 300 and 500 rpm shaking intensities. Focal adhesion kinase (FAK) expression and phosphorylation in cells grown on the specimens were registered by cell-based ELISA. There was a tendency of fibroblast adhesion strength to decrease in the following order: sandblasted titanium, polished titanium, sandblasted zirconium oxide, polished zirconium oxide, gold–alloy, chrome–cobalt alloy. Higher levels of total as well as phospho-FAK protein were registered in HGFs grown on roughened titanium. Material type and surface processing technique have an impact on gingival fibroblast interaction with dental implant abutment materials.

Periodontitis is defined as a chronic inflammatory condition, characterized by destruction of the periodontium, composed of hard (i.e. alveolar bone and cementum) and soft tissues (i.e. gingiva and periodontal ligament) surrounding and supporting the teeth. In severe cases, reduced periodontal support can lead to tooth loss, which requires tissue augmentation or procedures that initiate a repair, yet ideally a regenerative response. However, mimicking the three-dimensional complexity and functional integration of the different tissue components via scaffold- and/or matrix-based guided tissue engineering represents a great challenge. Additive biomanufacturing, a manufacturing method in which objects are designed and fabricated in a layer-by-layer manner, has allowed a paradigm shift in the current manufacturing of medical devices and implants. This shift from design-to-manufacture to manufacture-to-design, seen from a translational research point of view, provides the biomedical engineering and periodontology communities a technology with the potential to achieve tissue regeneration instead of repair. In this review, the focus is put on additively biomanufactured scaffolds for periodontal applications. Besides a general overview of the concept of additive biomanufacturing within this field, different developed scaffold designs are described. To conclude, future directions regarding advanced biomaterials and additive biomanufacturing technologies for applications in regenerative periodontology are highlighted.