Evaluation of minimally invasive esthetic crown lengthening using an open flap versus flapless surgical approach: A randomized controlled clinical trial.

OBJECTIVES: Esthetic crown lengthening (ECL) is commonly advocated to treat patients with altered passive eruption (APE). Since the introduction of the minimally invasive surgical concept, a limited number of studies have investigated this technique in a standardized manner, with further studies required to verify the validity and predictability of the minimally invasive FL-technique. The current randomized trial compares a minimally invasive (ECL), using piezosurgery with flapless-approach (FL), versus an open-flap (OF) approach in the management of patients with APE Type 1B. MATERIALS AND METHODS: Twenty-four patients diagnosed with APE Type 1B were randomly assigned into test (FL) with tunneling approach or control (OF) group with minimally invasive flap reflection (n = 12/group). Postoperative pain was assessed during the first 48 h. Gingival margin (GM) level relative to a custom-made stent (rGM) and patient satisfaction were assessed preoperative, immediately after surgery, at 3 and 6 months postsurgically. Postoperative swelling was reported for the first week postsurgically. Plaque index (PI), bleeding on probing (BoP), clinical attachment level (CAL), pocket depth (PD) and pink esthetic score (PES), were evaluated at baseline and 6 months. Linear regression analysis was conducted for pain. RESULTS: OF-group reported significantly higher pain and swelling scores than FL-group during the first 48 h (p < 0.05). FL-group showed no significant differences regarding rGM between 3 and 6 months, in contrast to OF-group, where a significant decrease in rGM was notable (p < 0.05). No significant differences in PI, BoP, CAL, PD, PES, and patient satisfaction scores were evident between groups (p > 0.05). Regression analysis demonstrated that treatment and gender were significant predictors for pain (p < 0.05). CONCLUSIONS: Within the current study's limitations, piezo-surgical ECL with FL-approach presented significantly lower postoperative pain, swelling, and early GM stability compared to OF-approach. CLINICAL SIGNIFICANCE: Piezosurgical ECL with a FL-approach can be considered a predictable technique with advantages over the OF-approach in the management of patients with APE Type1B.

Micro-needling versus acellular dermal matrix in RT1 gingival recession coverage: A randomized clinical trial.

AIMS: This randomized trial assessed for the first time the efficacy of coronally advanced flap (CAF) followed by micro-needling (MN) in contrast to CAF with acellular dermal matrix (ADM) on gingival thickness (GT, primary outcome), keratinized tissue width (KTW), clinical attachment level (CAL), probing depth (PD), recession depth (RD), recession width (RW), recession reduction (Rec-Red), complete root coverage (CRC) and percentage of root coverage (all secondary outcomes) in management of RT1 gingival recession in patients with thin gingival phenotype. METHODS: A total of 24 patients (n = 24) with a thin gingival phenotype and single RT1 gingival recession in the aesthetic zone were randomly allocated to test- (CAF + MN; n = 12) or control group (CAF + ADM; n = 12). All clinical parameters were evaluated at baseline, 3 and 6 months. RESULTS: Both groups independently demonstrated significant gain in GT, RW, RD, CAL, PD, Rec-Red, CRC and percentage of root coverage, with reduced PI and BOP (p < .05) at 3 and 6 months, without intergroup differences (p > .05). At 6 months, KTW gain was significantly higher in CAF + MN (5.08 ± 0.9 mm) than in CAF + ADM-group (4.25 ± 1.06 mm; p < .05). Stepwise linear regression model with GT as dependent variable showed that base-line GT was the only statistically significant predictor for GT with a direct correlation between base-line GT and GT after 6 months. CONCLUSION: CAF followed by MN could represent a promising graft-less approach for increasing gingival thickness, comparable to CAF with ADM, with superior keratinized tissue width improvement, in the treatment of RT1 recession defects in patients with thin gingival phenotype.

Effect of Hyperbaric Oxygen and Inflammation on Human Gingival Mesenchymal Stem/Progenitor Cells.

The present study explores for the first time the effect of hyperbaric oxygen (HBO) on gingival mesenchymal stem cells' (G-MSCs) gene expression profile, intracellular pathway activation, pluripotency, and differentiation potential under an experimental inflammatory setup. G-MSCs were isolated from five healthy individuals (n = 5) and characterized. Single (24 h) or double (72 h) HBO stimulation (100% O2, 3 bar, 90 min) was performed under experimental inflammatory [IL-1ß (1 ng/mL)/TNF-α (10 ng/mL)/IFN-γ (100 ng/mL)] and non-inflammatory micro-environment. Next Generation Sequencing and KEGG pathway enrichment analysis, G-MSCs' pluripotency gene expression, Wnt-/ß-catenin pathway activation, proliferation, colony formation, and differentiation were investigated. G-MSCs demonstrated all mesenchymal stem/progenitor cells' characteristics. The beneficial effect of a single HBO stimulation was evident, with anti-inflammatory effects and induction of differentiation (TLL1, ID3, BHLHE40), proliferation/cell survival (BMF, ID3, TXNIP, PDK4, ABL2), migration (ABL2) and osteogenic differentiation (p < 0.05). A second HBO stimulation at 72 h had a detrimental effect, significantly increasing the inflammation-induced cellular stress and ROS accumulation through HMOX1, BHLHE40, and ARL4C amplification and pathway enrichment (p < 0.05). Results outline a positive short-term single HBO anti-inflammatory, regenerative, and differentiation stimulatory effect on G-MSCs. A second (72 h) stimulation is detrimental to the same properties. The current results could open new perspectives in the clinical application of short-termed HBO induction in G-MSCs-mediated periodontal reparative/regenerative mechanisms.

Can vitamins improve periodontal wound healing/regeneration?

Periodontitis is a complex inflammatory disorder of the tooth supporting structures, associated with microbial dysbiosis, and linked to a number if systemic conditions. Untreated it can result in an irreversible damage to the periodontal structures and eventually teeth loss. Regeneration of the lost periodontium requires an orchestration of a number of biological events on cellular and molecular level. In this context, a set of vitamins have been advocated, relying their beneficial physiological effects, to endorse the biological regenerative events of the periodontium on cellular and molecular levels. The aim of the present article is to elaborate on the question whether or not vitamins improve wound healing/regeneration, summarizing the current evidence from in vitro, animal and clinical studies, thereby shedding light on the knowledge gap in this field and highlighting future research needs. Although the present review demonstrates the current heterogeneity in the available evidence and knowledge gaps, findings suggest that vitamins, especially A, B, E, and CoQ10 , as well as vitamin combinations, could exert positive attributes on the periodontal outcomes in adjunct to surgical or nonsurgical periodontal therapy.

Toll-like receptor expression profile of stem/progenitor cells from human exfoliated deciduous teeth.

BACKGROUND: Stem/progenitor cells from human exfoliated deciduous teeth (SHED) show remarkable pluripotent, regenerative, and immunological capacities. During in vivo regenerative processes, there could be the presence of SHED in the surrounding inflammatory microenvironment, through toll-like receptors (TLRs). AIM: The aim of this paper was to present a characteristic TLR expression profile on SHED for the first time. DESIGN: Cells were harvested from extracted primary teeth (n = 10), anti-STRO-1 immunomagnetically sorted and cultivated, through colony-forming units (CFUs). SHED were examined for mesenchymal stem/progenitor cell traits, including the expression of clusters of differentiation (CDs) 14, 34, 45, 73, 90, 105, and 146, and their multilineage differentiation aptitude. TLRs 1-10 expression was investigated for SHED in uninflamed and inflamed (25 ng/mL IL-1ß, 103 U/mL IFN-γ, 50 ng/mL TNF-α, and 3 × 103 U/mL IFN-α; SHED-i) microenvironmental conditions. RESULTS: SHED were negative for CDs 14, 34, and 45, but were positive for CDs 73, 90, 105, and 146, and demonstrated characteristic multilineage differentiation. In an uninflamed microenvironment, SHED expressed TLRs 1, 2, 3, 4, 6, 8, 9, and 10. The inflammatory microenvironment downregulated TLR7 significantly on gene level and upregulated TLR8 on gene and protein levels (p < .05; Wilcoxon signed-rank test). CONCLUSION: There appears to be a unique TLR expression profile on SHED, which could modulate their immunological and regenerative abilities in oral tissue engineering approaches.

Effect of operators' proficiency level and patients' related factors on possible complications, using a high frequency polyamide sonic intracanal irrigation device: A prospective clinical cohort study.

OBJECTIVES: Sonic/ultrasonic devices are essential tools in today's endodontics. This prospective trial evaluated for the first time the impact of practitioners' proficiency levels and patient-related factors on complications associated with a high frequency polyamide sonic irrigant activation device. METHODS: In total 334 patients (females:158, males:176; age:18-95 years) received in the course of their endodontic therapy an intracanal irrigation, using a high frequency polyamide sonic irrigant activation device, by practitioners of different proficiency levels (undergraduate students, general practitioners or endodontists). Intracanal bleeding (yes/no), postoperative pain (0-10 scale), emphysema (yes/no) and polyamide tip fractures (yes/no) were recorded and related to proficiency levels, age, gender, tooth type, smoking-status, systemic conditions affecting healing ability, baseline pain, swelling, fistula, sensitivity to percussion and diagnosis. RESULTS: Intracanal bleeding was associated with patients' age (p<0.05), baseline pain level (OR = 1.14, 95%CI = 0.91-1.22) and baseline swelling (OR = 2.73, 95%CI = 0.14-0.99; p<0.05) but not proficiency level, gender, tooth type, smoking, systemic conditions, baseline fistula or sensitivity to percussion (p>0.05). Postoperative pain development was related to proficiency level (p<0.05) and baseline pain level (p<0.001), with no influence of age, gender, tooth type, smoking, systemic conditions, baseline fistula, swelling or sensitivity to percussion (p>0.05). Emphysema and polyamide tip fractures were not reported. CONCLUSIONS: Within the current study's limitations, younger patients with higher baseline pain and swelling, were associated with higher intracanal bleeding. Apart from higher postoperative pain observed with less experienced practitioners, proficiency level had no influence on bleeding, polyamide tip fracture or emphysema, endorsing the high frequency polyamide sonic irrigation device as a safe therapeutic device.

Injectable platelet-rich fibrin with demineralized freeze-dried bone allograft compared to demineralized freeze-dried bone allograft in intrabony defects of patients with stage-III periodontitis: a randomized controlled clinical trial.

AIM: The current randomized controlled clinical trial assessed the effect of injectable platelet-rich fibrin (I-PRF) combined with demineralized freeze-dried bone allograft (DFDBA) compared to DFDBA alone in the management of intrabony defects of stage-III periodontitis patients. METHODOLOGY: Following sample size calculation, twenty stage-III periodontitis patients with ≥ 5 mm clinical attachment level (CAL)-loss and ≥ 3 mm intrabony defects were randomized into test (I-PRF + DFDBA; n = 10) and control (DFDBA; n = 10) groups. CAL (primary outcome), periodontal probing depth (PPD), gingival recession depth (GRD), full-mouth plaque scores (FMPS), full-mouth bleeding scores (FMBS), radiographic linear defect depth (RLDD), and bone fill (secondary outcomes) were examined at baseline, 3, 6, and 9 months post-surgically. RESULTS: I-PRF + DFDBA and DFDBA independently demonstrated significant intragroup CAL-gain, PPD-, and RLDD-reduction at 3, 6, and 9 months (p < 0.05), with no significant intergroup differences observed (p > 0.05). CAL-gain (mean ± SD) of 2.40 ± 0.70 mm and 2.50 ± 0.85 mm and PPD-reduction of 3.50 ± 1.18 mm and 2.80 ± 0.42 mm were demonstrated for I-PRF + DFDBA and DFDBA at 9 months respectively. Both groups showed significant intragroup RLDD improvement, with a RLDD of 3.58 ± 0.66 mm and 3.89 ± 1.57 mm for I-PRF + DFDBA and DFDBA at 9 months respectively. Stepwise linear regression analysis revealed that baseline RLDD and bone fill at 9 months were significant predictors of CAL (p < 0.05). CONCLUSION: Within the present study's limitations, DFDBA with or without I-PRF resulted in significant improvement in clinical and radiographic periodontal parameters in the surgical treatment of periodontal intrabony defects of stage-III periodontitis patients. Addition of I-PRF to DFDBA does not appear to significantly enhance the DFDBA's reparative/regenerative outcomes. CLINICAL RELEVANCE: Within the current study's limitations, routinely adding I-PRF to DFDBA cannot be recommended to significantly improve DFDBA's treatment outcomes in intrabony defects.

Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review.

Periodontitis is the sixth most common chronic inflammatory disease, destroying the tissues supporting the teeth. There are three distinct stages in periodontitis: infection, inflammation, and tissue destruction, where each stage has its own characteristics and hence its line of treatment. Illuminating the underlying mechanisms of alveolar bone loss is vital in the treatment of periodontitis to allow for subsequent reconstruction of the periodontium. Bone cells, including osteoclasts, osteoblasts, and bone marrow stromal cells, classically were thought to control bone destruction in periodontitis. Lately, osteocytes were found to assist in inflammation-related bone remodeling besides being able to initiate physiological bone remodeling. Furthermore, mesenchymal stem cells (MSCs) either transplanted or homed exhibit highly immunosuppressive properties, such as preventing monocytes/hematopoietic precursor differentiation and downregulating excessive release of inflammatory cytokines. In the early stages of bone regeneration, an acute inflammatory response is critical for the recruitment of MSCs, controlling their migration, and their differentiation. Later during bone remodeling, the interaction and balance between proinflammatory and anti-inflammatory cytokines could regulate MSC properties, resulting in either bone formation or bone resorption. This narrative review elaborates on the important interactions between inflammatory stimuli during periodontal diseases, bone cells, MSCs, and subsequent bone regeneration or bone resorption. Understanding these concepts will open up new possibilities for promoting bone regeneration and hindering bone loss caused by periodontal diseases.

Polymeric Nanocomposite Hydrogel Scaffolds in Craniofacial Bone Regeneration: A Comprehensive Review.

Nanocomposite biomaterials combine a biopolymeric matrix structure with nanoscale fillers. These bioactive and easily resorbable nanocomposites have been broadly divided into three groups, namely natural, synthetic or composite, based on the polymeric origin. Preparing such nanocomposite structures in the form of hydrogels can create a three-dimensional natural hydrophilic atmosphere pivotal for cell survival and new tissue formation. Thus, hydrogel-based cell distribution and drug administration have evolved as possible options for bone tissue engineering and regeneration. In this context, nanogels or nanohydrogels, created by cross-linking three-dimensional polymer networks, either physically or chemically, with high biocompatibility and mechanical properties were introduced as promising drug delivery systems. The present review highlights the potential of hydrogels and nanopolymers in the field of craniofacial tissue engineering and bone regeneration.

Clinical and radiographic evaluation of low-speed platelet-rich fibrin (PRF) for the treatment of intra-osseous defects of stage-III periodontitis patients: a randomized controlled clinical trial.

AIM: The current randomized controlled trial assessed for the first time the effect of a low-speed platelet-rich fibrin (PRF) with open flap debridement (OFD) versus OFD alone in the treatment of periodontal intra-osseous defects of stage-III periodontitis patients. METHODS: Twenty-two periodontitis patients with ≥ 6 mm probing depth (PD) and ≥ 3 mm intra-osseous defects were randomized into test (PRF + OFD; n = 11) and control (OFD; n = 11) groups. Clinical attachment level (CAL)-gain (primary outcome), PD-reduction, gingival recession depth (GRD), full-mouth bleeding scores (FMBS), full-mouth plaque scores (FMPS), radiographic linear defect depth (RLDD), and radiographic bone fill (secondary-outcomes) were examined over 9 months post-surgically. RESULTS: Low-speed PRF + OFD and OFD demonstrated significant intra-group CAL-gain and PD- and RLDD-reduction at 3, 6, and 9 months (p < 0.01). Low-speed PRF + OFD exhibited a significant CAL-gain of 3.36 ± 1.12 mm at 6 months (2.36 ± 0.81 mm for the control group; p < 0.05), and a significantly greater PD-reduction of 3.36 ± 1.12 mm at 3 months, of 3.64 ± 1.12 mm at 6 months and of 3.73 ± 1.19 mm at 9 months (2.00 ± 0.89 mm, 2.09 ± 1.04 mm, and 2.18 ± 1.17 mm in the control group respectively; p < 0.05). No significant differences were notable regarding GRD, FMPS, FMBS, RLDD, or bone fill between both groups (p > 0.05). CONCLUSIONS: Within the current clinical trial's limitations, the use of low-speed PRF in conjunction with OFD improved CAL and PD post-surgically, and could provide a cost-effective modality to augment surgical periodontal therapy of intra-osseous defects of stage-III periodontitis patients. CLINICAL RELEVANCE: Low-speed PRF could provide a cost-effective modality to improve clinical attachment gain and periodontal probing depth reduction with open flap debridement approaches.

Immediate implant placement utilizing vestibular socket therapy versus early implant placement with contour augmentation for rehabilitation of compromised extraction sockets in the esthetic zone: A randomized controlled clinical trial.

OBJECTIVE: The present randomized controlled trial compares for the first time the vestibular socket therapy (VST) to the contour augmentation technique in the management of compromised fresh extraction sockets in the maxillary esthetic zone, regarding mid-facial soft tissue changes (primary outcome), mesial and distal papillae dimensions, horizontal soft tissue changes and labial bone plate thickness at apical, middle and coronal levels (secondary outcomes) over 1-year. MATERIALS AND METHODS: Forty participants with single nonrestorable maxillary teeth in the esthetic zone were randomized into two groups; VST (test; n = 20) utilizing vestibular access for guided bone regeneration (GBR) with immediate implant placement, or contour augmentation (control; n = 20) undergoing an initial healing period followed by implant placement with GBR through a conventional access flap. RESULTS: All implants were successfully osseo-integrated, except for one implant in the test group. VST showed significantly less mid-facial soft tissue changes of -0.53 ± 1.17 mm versus -1.87 ± 0.69 mm in the control group (p < 0.001). Similarly, changes in mesial papilla (test = -0.64 ± 0.95 mm, control = -1.20 ± 0.81 mm), distal papilla (test = -0.56 ± 1.17 mm, control = -1.26 ± 0.63 mm), horizontal soft-tissue (test = -0.82 ± 0.95 mm, control = -1.84 ± 0.88 mm; p < 0.05) were significantly less in VST. Intra-group comparisons demonstrated a significant increase in labial bone thickness, with no differences between groups. Regression analysis revealed a significant correlation between VST as well as increased coronal bone thickness with the reduction in mid-facial soft-tissue changes. CONCLUSION: The VST showed less soft-tissue changes and could represent an innovative technique for implant placement in the maxillary esthetic zone. Both techniques showed a high implant survival rate and increased bone thickness after 12 months.

Vitamin C and Omega-3 Fatty Acid Intake Is Associated with Human Periodontitis-A Nested Case-Control Study.

Vitamins and omega-3 fatty acids (Ω3FA) modulate periodontitis-associated inflammatory processes. The aim of the current investigation was to evaluate associations of oral nutrient intake and corresponding serum metabolites with clinical severity of human periodontitis. Within the Food Chain Plus cohort, 373 periodontitis patients­245 without (POL) and 128 with tooth loss (PWL)­were matched to 373 controls based on sex, smoking habit, age and body mass index in a nested case-control design. The amount of oral intake of vitamins and Ω3FAs was assessed from nutritional data using a Food Frequency Questionnaire. Oral intake and circulatory bioavailability of vitamins and Ω3FA serum metabolomics were compared, using ultra-high-resolution mass spectrometry. Periodontitis patients exhibited a significantly higher oral intake of vitamin C and Ω3FA Docosapentaenoic acid (p < 0.05) compared to controls. Nutritional intake of vitamin C was higher in PWL, while the intake of Docosapentaenoic acid was increased in POL (p < 0.05) compared to controls. In accordance, serum levels of Docosapentaenoic acid were also increased in POL (p < 0.01) compared to controls. Vitamin C and the Ω3FA Docosapentaenoic acid might play a role in the pathophysiology of human periodontitis. Further studies on individualized nutritional intake and periodontitis progression and therapy are necessary.

Cellular properties of human gingival fibroblasts on novel and conventional implant-abutment materials.

OBJECTIVES: To characterize human-gingival-fibroblast-(HGFs) viability, proliferation and adhesion on polymer-infiltrated-ceramic-network-(PICN), polyetheretherketone-(PEEK), hydroxyapatite-reinforced-polyetheretherketone-(HA-PEEK), polyetherketoneketone-(PEKK), as well as conventional titanium-(Ti) and zirconia ceramic-(Zr) implant materials in-vitro. METHODS: Six materials (n = 40/group, 240 specimens) were standardized for surface roughness, assessed employing water contact angle measurements (WCA) and loaded with HGFs. HGF viability and proliferation were assessed at 24 and 72 h. Cell adhesion strength was evaluated after 24 h exposure to lateral shear forces using a shaking-device at 320 and 560-rpm.and qualitatively tested by scanning-electron-microscopy-(SEM) at 3, 24 and 72 h. RESULTS: PICN demonstrated the lowest mean WCA (48.2 ± 6.3º), followed by Zr (73.8 ± 5.1º), while HA-PEEK showed the highest WCA (87.2 ± 1.5º; p ≤ 0.05). After 24 h, Zr showed the highest mean HGFs-viability rate (88 ± 14%), while PEKK showed the lowest one (78 ± 7%). At 72 h, Zr continued to show the highest HGF-viability (80 ± 6%) compared to PEKK (67.5 ± 6%) and PEEK (67%±5). SEM did not reveal differences between different materials with respect to cell attachment at 3, 24 or 72 h. At 320 rpm shaking, HGFs showed to be best attached to PICN (mean%-of-detached-cells ± SD; 26 ± 11%) and worst to PEEK (54 ± 18%). At 560 rpm shaking, Zr showed the least detached cells (32 ± 4%), while HA-PEEK revealed the highest number of detached cells (58 ± 3%; ANOVA/Tukey-post-hoc-test, differences not statistically significant). SIGNIFICANCE: Dental implant abutment materials and their wettability strongly affect HGF proliferation and adhesion properties. Although, PICN showed the best wettability properties, Zr exhibited the strongest adhesion strength at high shaking. Within the current study's limitations, Zr remains the most biocompatible abutment material.

Effects of Periodontal Endoscopy-Assisted Nonsurgical Treatment of Periodontitis: Four-Month Results of a Randomized Controlled Split-Mouth Pilot Study.

OBJECTIVE: Although the therapeutic effects of nonsurgical periodontal therapy (NSPT) are well established, the clinical benefits of the additional use of periodontal endoscopy (PE) remain controversial. Therefore, this randomized controlled split-mouth pilot study evaluated the effect of NSPT using PE versus NSPT without nPE on bleeding on probing (BOP) in sites with probing depth (PD)≥4 mm (primary outcome), PD, clinical attachment level (CAL), number of hard deposits (HDs), and treatment time per tooth (TrT). METHODS: Two calibrated operators performed NSPT in twenty periodontitis patients, randomized into two quadrants for PE or nPE treatment. BOP, PD, and CAL were recorded at the first visit for NSPT (T0) and during reevaluation (T1: mean (SD) 119.7 (24.6) days after T0). The average TrT and the number of sites with HDs were documented at T0. RESULTS: For BOP, no significant differences were found at the patient's level (10/10 (male/female); aged 54.3 (10.9) years) neither within or between the groups. At tooth surface level, a lower number of surfaces with BOP (p=0.026) was observed in nPE. CAL and PD improved significantly during NSPT in both groups (p ≤ 0.001), with higher PD reduction (p < 0.001) and CAL gain (p < 0.001) in nPE. There are significantly longer TrT (p < 0.001) and more surfaces with subgingival HDs evident in PE at T0 (p=0.001). CONCLUSION: Whereas subgingival HDs can be visually detected with PE during NSPT, no additional clinical benefits regarding BOP, PD, or CAL were notable compared to conventional systematic periodontal instrumentation. Additionally, PE-assisted NSPT required a longer treatment time.

2D radiographs, cone-beam computed tomography and 3D CBCT-based planning software in access cavity preparation: A single blinded randomised controlled in vitro study.

This study compared endodontic access cavities prepared by operators of different experience levels (students, general-practitioners and specialists), guided by periapical radiographs, cone-beam computed tomography (CBCT) or 3D CBCT-based planning software, with regards to tooth substance loss and preparation errors. Operators (n = 34) prepared endodontic access cavities in 306 three-dimensionally printed copies of human teeth with standardised anatomies. Access cavities were volumetrically assessed post-operative using digital scans, while preparation errors were evaluated with CBCT. Tooth substance loss was significantly influenced by the operator's experience, being highest with students', followed by general-practitioners and specialists (P < 0.05), with no significant association with the employed imaging/planning modality. Pulp chamber floor, iatrogenic perforations and incomplete pulpal roof removal were insignificant between operator groups or imaging/planning modalities. It can be concluded that irrespective of advancement in imaging/planning modalities the practitioner's experience level remains to be the decisive factor significantly influencing tooth substance loss during endodontic access cavity preparations.

In vitro evaluation of the effect of the electronic cigarette aerosol, Cannabis smoke, and conventional cigarette smoke on the properties of gingival fibroblasts/gingival mesenchymal stem cells.

OBJECTIVE: The current study aimed to evaluate the effect of electronic cigarette (EC) aerosol, Cannabis, and conventional cigarettes smoke on gingival fibroblast/gingival mesenchymal stem cells' (GF/G-MSCs) of never smokers. MATERIAL AND METHODS: Human GF/G-MSCs (n = 32) were isolated and characterized using light microscopy, flow cytometry, and multilineage differentiation ability. Following the application of aerosol/smoke extracts, GF/G-MSCs were evaluated for cellular proliferation; colony-forming units (CFU-F) ability; cellular viability (using the MTT assay); mitochondrial depolarization using JC-1 dye; and genes' expression of ATM, p21, Oct4, and Nanog. RESULTS: Colony-forming units and viability (OD 450 nm) were significantly reduced upon exposure to Cannabis (mean ± SD; 5.5 ± 1.5; p < .00001, 0.47 ± 0.21; p < .05) and cigarettes smoke (2.3 ± 1.2 p < .00001, 0.59 ± 0.13, p < .05), while EC aerosol showed no significant reduction (10.8 ± 2.5; p = .05, 1.27 ± 0.47; p > .05) compared to the control group (14.3 ± 3, 1.33 ± 0.12). Significantly upregulated expression of ATM, Oct4, and Nanog (gene copies/GADPH) was noticed with Cannabis (1.5 ± 0.42, 0.82 ± 0.44, and 1.54 ± 0.52, respectively) and cigarettes smoke (1.52 ± 0.75, 0.7 ± 0.14, and 1.48 ± 0.79, respectively; p < .05), whereas EC aerosol caused no statistically significant upregulation of these genes compared to the control group (0.63 ± 0.1, 0.31 ± 0.12, and 0.64 ± 0.46, respectively; p > .05). The p21 gene was not significantly downregulated in EC aerosol (1.22 ± 0.46), Cannabis (0.71 ± 0.24), and cigarettes smokes (0.83 ± 0.54) compared to the control group (p = .053, analysis of variance). CONCLUSION: Cannabis and cigarettes smoke induce DNA damage and cellular dedifferentiation and negatively affect the cellular proliferation and viability of GF/G-MSCs of never smokers, whereas EC aerosol showed a significantly lower impact on these properties.

Ascorbic Acid/Retinol and/or Inflammatory Stimuli's Effect on Proliferation/Differentiation Properties and Transcriptomics of Gingival Stem/Progenitor Cells.

The present study explored the effects of ascorbic-acid (AA)/retinol and timed inflammation on the stemness, the regenerative potential, and the transcriptomics profile of gingival mesenchymal stem/progenitor cells' (G-MSCs). STRO-1 (mesenchymal stem cell marker) immuno-magnetically sorted G-MSCs were cultured in basic medium (control group), in basic medium with IL-1ß (1 ng/mL), TNF-α (10 ng/mL) and IFN-γ (100 ng/mL, inflammatory-medium), in basic medium with AA (250 µmol/L) and retinol (20 µmol/L) (AA/retinol group) or in inflammatory medium with AA/retinol (inflammatory/AA/retinol group; n = 5/group). The intracellular levels of phosphorylated and total ß-Catenin at 1 h, the expression of stemness genes over 7 days, the number of colony-forming units (CFUs) as well as the cellular proliferation aptitude over 14 days, and the G-MSCs' multilineage differentiation potential were assessed. Next-generation sequencing was undertaken to elaborate on up-/downregulated genes and altered intracellular pathways. G-MSCs demonstrated all mesenchymal stem/progenitor cells characteristics. Controlled inflammation with AA/retinol significantly elevated NANOG (p < 0.05). The AA/retinol-mediated reduction in intracellular phosphorylated ß-Catenin was restored through the effect of controlled inflammation (p < 0.05). Cellular proliferation was highest in the AA/retinol group (p < 0.05). AA/retinol counteracted the inflammation-mediated reduction in G-MSCs' clonogenic ability and CFUs. Amplified chondrogenic differentiation was observed in the inflammatory/AA/retinol group. At 1 and 3 days, the differentially expressed genes were associated with development, proliferation, and migration (FOS, EGR1, SGK1, CXCL5, SIPA1L2, TFPI2, KRATP1-5), survival (EGR1, SGK1, TMEM132A), differentiation and mineral absorption (FOS, EGR1, MT1E, KRTAP1-5, ASNS, PSAT1), inflammation and MHC-II antigen processing (PER1, CTSS, CD74) and intracellular pathway activation (FKBP5, ZNF404). Less as well as more genes were activated the longer the G-MSCs remained in the inflammatory medium or AA/retinol, respectively. Combined, current results point at possibly interesting interactions between controlled inflammation or AA/retinol affecting stemness, proliferation, and differentiation attributes of G-MSCs.

Cell-Based Transplantation versus Cell Homing Approaches for Pulp-Dentin Complex Regeneration.

Regenerative dentistry has paved the way for a new era for the replacement of damaged dental tissues. Whether the causative factor is dental caries, trauma, or chemical insult, the loss of the pulp vitality constitutes one of the major health problems worldwide. Two regenerative therapies were introduced for a fully functional pulp-dentin complex regeneration, namely, cell-based (cell transplantation) and cell homing (through revascularization or homing by injection of stem cells in situ or intravenously) therapies, with each demonstrating advantages as well as drawbacks, especially in clinical application. The present review is aimed at elaborating on these two techniques in the treatment of irreversibly inflamed or necrotic pulp, which is aimed at regenerating a fully functional pulp-dentin complex.

Effect of Polymeric Matrix Stiffness on Osteogenic Differentiation of Mesenchymal Stem/Progenitor Cells: Concise Review.

Mesenchymal stem/progenitor cells (MSCs) have a multi-differentiation potential into specialized cell types, with remarkable regenerative and therapeutic results. Several factors could trigger the differentiation of MSCs into specific lineages, among them the biophysical and chemical characteristics of the extracellular matrix (ECM), including its stiffness, composition, topography, and mechanical properties. MSCs can sense and assess the stiffness of extracellular substrates through the process of mechanotransduction. Through this process, the extracellular matrix can govern and direct MSCs' lineage commitment through complex intracellular pathways. Hence, various biomimetic natural and synthetic polymeric matrices of tunable stiffness were developed and further investigated to mimic the MSCs' native tissues. Customizing scaffold materials to mimic cells' natural environment is of utmost importance during the process of tissue engineering. This review aims to highlight the regulatory role of matrix stiffness in directing the osteogenic differentiation of MSCs, addressing how MSCs sense and respond to their ECM, in addition to listing different polymeric biomaterials and methods used to alter their stiffness to dictate MSCs' differentiation towards the osteogenic lineage.

Effect of locally delivered adjunctive antibiotics during surgical periodontal therapy: a systematic review and meta-analysis.

AIM: The present study aimed to systematically assess current evidence on effects of locally delivered antibiotics during periodontal surgery compared to periodontal surgery alone on clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, recession depth (RD) changes, gingival index (GI), bleeding on probing (BOP), and plaque index (PI). METHODOLOGY: MEDLINE-PubMed, Cochrane-CENTRAL and Scopus databases were searched up to April 2021 for randomized clinical trials (RCT), evaluating effects of locally delivered antibiotics during periodontal surgery. CAL gain served as primary, while PPD reduction, RD changes, GI and PI as secondary outcomes. The Cochrane Risk of Bias Tool was used to assess possible bias. Data were extracted, and meta-analysis was performed where appropriate. RESULT: Screening of 2314 papers resulted in nine eligible studies. No adverse events were reported. Data on outcome variables were pooled and analyzed using generic inverse variance model and presented as weighted mean difference (WMD) and 95% confidence interval (95% CI). Statistically significant improvements in favor of antibiotics' delivery were observed in studies with follow-up of ≤6 months for CAL gain (WMD = 0.61 mm (95% CI [0.07, 1.14]; p = 0.03), PPD reduction (WMD = 0.41 mm (95% CI [0.02, 0.80]; p = 0.04)) and BOP (WMD = -28.47% (95% CI [-33.00, -23.94]); p < 0.001), while for GI improvements were notable for >6 to 12 months (WMD = -0.27 (95% CI [-0.49, -0.06]; p = 0.01)). CONCLUSION: Within the current review's limitations, locally delivered antibiotics during surgical periodontal therapy results in post-surgical improvements for CAL, PPD, and BOP (≤6 months) with a longer-lasting GI improvement. Further randomized controlled trials are needed with true periodontal end-points to assess the ideal antibiotic agent, dosage, and delivery methods. CLINICAL RELEVANCE: Local delivery of antibiotics during periodontal surgery improved clinical parameters for up to 6-month follow-up, with beneficial longer effects on gingival inflammation. Within the current study's limitation, the presented evidence could support the elective usage of locally delivered antibiotics during surgical periodontal therapy.