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.

Modified minimally invasive surgical technique with clindamycin-augmented or non-augmented platelet-rich fibrin in periodontal regeneration: A randomized clinical trial.

AIM: Injectable platelet-rich fibrin (I-PRF), a second-generation platelet concentrate, is widely used to enhance soft and hard tissue healing alone or in combination with biomaterials, relying on its harboring of various pivotal growth/differentiation factors. This randomized trial assessed the effect of clindamycin (CLN) augmented injectable platelet-rich fibrin (I-PRF) with modified minimally invasive surgical technique (M-MIST) versus I-PRF alone with M-MIST on the clinical and radiographic parameters in the management of periodontal intra-bony defects in patients with stage-III grade B periodontitis. METHODS: This is a 9-month parallel-grouped, two arm, double-blinded, randomized controlled trial (RCT) that included 28 patients (n = 28) with stage-III grade B periodontitis, who were allocated randomly to test- (CLN/I-PRF + M-MIST, 50 µL of CLN per 1 mL of I-PRF; n = 14) or control-group (I-PRF + M-MIST; n = 14). Clinical attachment level (CAL; primary outcome), probing depth (PD), gingival margin level (GML), plaque index (PI), and gingival index (GI) were recorded at baseline, 3, 6, and 9 months, whereas radiographic parameters radiographic linear defect depth (RLDD), and radiographic defect area (RDA) were recorded at baseline, 6, and 9 months. The CLN release kinetics from the I-PRF were further characterized. RESULTS: Compared to baseline, both groups independently demonstrated significant improvements in CAL, PD, GML, GI, PI, RLDD and BDA at 3, 6 and 9 months (p < .05). A significant reduction in CAL measurements was noticeable in the CLN/I-PRF + M-MIST and I-PRF + M-MIST group independently over time (p < .05). CLN/I-PRF + M-MIST showed significantly lower CAL than PRF + M-MIST group at baseline, after three as well as 9 months (p < .05). Intergroup comparisons at 9 months demonstrated that CAL-gain was non-significant between groups (p > .05), GI significantly lower in CLN/I-PRF + M-MIST, whereas PD-reduction significantly higher I-PRF + M-MIST group (p < .05). CLN was steadily released for the I-PRF for up to 48 h, with a peak concentration at 24 h, which then gradually declined till the seventh day. CONCLUSIONS: I-PRF with M-MIST provided significant clinical and radiographic improvement up to 9 months postoperatively in stage-III grade B periodontitis. CLN, at the applied concentration and release duration, does not appear to further positively impact these observed I-PRF effects.

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.

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.

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 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.

Alvogyl and absorbable gelatin sponge as palatal wound dressings following epithelialized free gingival graft harvest: a randomized clinical trial.

OBJECTIVES: This randomized controlled trial compares for the first time effects of Alvogyl versus absorbable gelatin sponge as palatal wound dressings on postoperative pain, amount of analgesic consumption, post-surgical bleeding, and wound re-epithelization. MATERIALS AND METHODS: Following sample size calculation, 36 systemically healthy patients requiring palatal mucosal graft harvesting were randomized to receive Alvogyl (intervention group, 18 patients) or absorbable gelatin sponge (control group, 18 patients) palatal dressings. Patient-reported VAS pain scores over 2 weeks were defined as primary outcome. Post-surgical bleeding, number of analgesics consumed, and complete re-epithelialization of the palatal wound for up to 5 weeks were defined as secondary outcomes. RESULTS: Although significantly higher VAS pain scores were reported in the control as compared with the intervention group up to 12 days post-surgically (from (median [range]) 8.5 [2-10] to 1 [0-2] and from 6 [0-10] to 0 [0-2] respectively), with higher analgesics consumption (from 2 [1-3] to 1 [0-3] and from 1 [0-3] to 0 [0-2] tablets respectively), a multivariate regression analysis considering age, gender, graft width/length, tissue thickness, analgesics intake, and dressing type demonstrated no statistically significant effect of any factor, including dressing type on VAS pain scores. At 4 weeks, 22.2% of patients in the intervention group versus 11.1% in the control group demonstrated complete re-epithelization of their palatal engraftment site, before complete re-epithelization in both groups at 5 weeks. No post-surgical bleeding was reported with both dressings. CONCLUSIONS: Within the study's limitations, results suggest Alvogyl as a practical palatal surgical dressing, comparable with absorbable gelatin sponge in cost, pain reduction, hemostasis, and re-epithelization properties. TRIAL REGISTRATION: www.ClinicalTrials.gov Identifier: NCT03402321 CLINICAL RELEVANCE: Alvogyl could present a novel palatal wound dressing material, comparable with gelatin sponge.

Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/ß-catenin.

BACKGROUND AND OBJECTIVE: Inflammatory cytokines impact the course of periodontal disease, repair, and regeneration. Vitamin A and its metabolites are inflammation-modulatory biomolecules, affecting cellular pluripotency. The aim of this study was to investigate the effect of retinol and periodontal inflammatory cytokines (IL-1ß/TNF-α/IFN-γ) on pluripotency and proliferative properties of gingival mesenchymal stem/progenitor cells (G-MSCs), for the first time. MATERIAL AND METHODS: Human G-MSCs (n = 5) were STRO-1 immuno-magnetically sorted, characterized and expanded 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 group), in basic medium with retinol (20 µmol/L) (retinol group) and with retinol added to the inflammatory group (inflammatory/retinol group). ß-catenin levels at 1 hour, cellular proliferation over 14 days, and colony-forming units (CFUs) at 14 days were investigated. Pluripotency gene expressions were examined at 1, 3, and 5 days via reverse transcription-polymerase chain reaction (RT-PCR). Multilineage differentiation potential was evaluated, following 5 days priming, using qualitative and quantitative histochemistry and RT-PCR. RESULTS: G-MSCs were CD14- , CD34- , CD45- , CD73+ , CD90+ , CD105+ , and showed mesenchymal stem/progenitor cells' hallmarks, CFUs, and multilineage differentiation potential. Intracellular ß-catenin significantly declined in the stimulated groups (P < 0.001, Friedman test). Cellular proliferation at 72 hours was most prominent in the control and inflammatory group [Median cell numbers (Q25/Q75); 6806 (4983/7312) and 5414 (4457/7230), respectively], followed by an upsurge in the retinol group. At 14 days, the retinol group exhibited the highest CFUs [Median CFUs (Q25/Q75); 35 (20/58), P = 0.043, Wilcoxon signed-rank]. Nanog was most expressed in the inflammatory and retinol group [Median gene expression/PGK1 (Q25/Q75); 0.0006 (0.0002/0.0014) and 0.0005 (0.0003/0.0008)]. Inflammation significantly upregulated Sox2 expression [0.0002 (0.0008/0.0005)], while its expression was diminished in the retinol and inflammatory/retinol group (P < 0.001, Friedman test). Inflammatory/retinol group exhibited the highest multilineage differentiation potential. CONCLUSION: Controlled short-term inflammatory/retinol stimuli activate the Wnt/ß-catenin pathway, affecting G-MSCs' pluripotency, proliferation, and differentiation. The present findings provide further insights into the inflammatory-regenerative interactions and their modulation potential for G-MSCs-mediated periodontal repair/regeneration.

The periodontal stem/progenitor cell inflammatory-regenerative cross talk: A new perspective.

Adult multipotent stem/progenitor cells, with remarkable regenerative potential, have been isolated from various components of the human periodontium. These multipotent stem/progenitor cells include the periodontal ligament stem/progenitor cells (PDLSCs), stem cells from the apical papilla (SCAP), the gingival mesenchymal stem/progenitor cells (G-MSCs), and the alveolar bone proper stem/progenitor cells (AB-MSCs). Whereas inflammation is regarded as the reason for tissue damage, it also remains a fundamental step of any early healing process. In performing their periodontal tissue regenerative/reparative activity, periodontal stem/progenitor cells interact with their surrounding inflammatory micro-environmental, through their expressed receptors, which could influence their fate and the outcome of any periodontal stem/progenitor cell-mediated reparative/regenerative activity. The present review discusses the current understanding about the interaction of periodontal stem/progenitor cells with their surrounding inflammatory micro-environment, elaborates on the inflammatory factors influencing their stemness, proliferation, migration/homing, differentiation, and immunomodulatory attributes, the possible underlying intracellular mechanisms, as well as their proposed relationship to the canonical and noncanonical Wnt pathways.

Secreted frizzled-related protein 5 serum levels in human periodontitis-A nested case-control study.

AIM: Recombinant secreted frizzled-related protein 5 (sFRP5) improved periodontal status in mice. Thus, this study aimed to investigate this finding in human periodontitis using an epidemiological approach. MATERIALS AND METHODS: sFRP5 and wnt5a concentrations were determined in human serum from the Food Chain Plus cohort using ELISAs. A total of 128 patients with periodontitis and tooth loss and 245 patients with periodontitis without tooth loss were compared to 373 sex-, smoker-, age- and BMI-matched individuals in a nested case-control design. RESULTS: Systemic sFRP5 serum levels were significantly lower in patients with periodontitis and tooth loss (2.5 [0.0-10.4] ng/ml, median [IQR]) compared to patients with periodontitis without tooth loss (6.0 [2.5-15.8] ng/ml, median [IQR], p = 0.04] and matched controls (7.0 [2.5-18.3] ng/ml, median [IQR], p = 0.02). No significant differences in sFRP5 serum levels were found among patients with periodontitis without tooth loss (6.0 [2.5-15.8] ng/ml, median [IQR]) and controls (3.1 [0.0-10.6] ng/ml, median [IQR], p = 0.06). CONCLUSIONS: sFRP5 might serve as a novel biomarker for periodontitis severity. Modulating the inflammatory background of severe forms of periodontitis, in the time of precision medicine, needs to be revealed in further studies.

TLR-induced immunomodulatory cytokine expression by human gingival stem/progenitor cells.

During therapeutic application, mesenchymal stem cells (MSCs) may interact with their environment via their expressed toll-like-receptors (TLRs) leading to pro- or anti-inflammatory immune responses. The present study aimed to describe the gingival margin-derived stem/progenitor cells' (G-MSCs) TLR-induced immune regulatory response to specific TLR agonists. Gingival cells were obtained, immunomagnetically sorted via anti-STRO-1 antibodies and seeded out to achieve colony forming units (CFUs). G-MSCs were investigated for stem cell characteristics and TLR expression. Specific TLR agonists were applied and m-RNA expression of pro- and anti-inflammatory factors was analyzed via real-time polymerase chain reaction. G-MSCs showed all characteristics of stem/progenitor cells. All TLR agonists induced pro-inflammatory cytokines, except for the TLR3 agonist, which significantly promoted the anti-inflammatory response. (p⩽0.05, Wilcoxon-Signed-Ranks-Test). TLR-induced immunomodulation by G-MSCs could impact their therapeutic potential in vivo. Two distinctive pro-inflammatory and an anti-inflammatory TLR-induced phenotypes of G-MSCs become noticeable in this study.

Porphyromonas gingivalis lipopolysaccharides affect gingival stem/progenitor cells attributes through NF-κB, but not Wnt/ß-catenin, pathway.

AIM: This study investigates for the first time the effect of Porphyromonas gingivalis lipopolysaccharides (Pg-LPS) on proliferative/regenerative aptitudes of gingival stem/progenitor cells (G-MSCs). MATERIAL AND METHODS: G-MSCs (n = 5) were treated by 0, 10 ng/ml, 100 ng/ml, 1 µg/ml or 10 µg/ml Pg-LPS. At 1 hour, Toll-like receptor 4 (TLR-4) expression and NF-κB and Wnt/ß-catenin signalling pathways were examined. Colony-forming unit assay was conducted at day 12. At 24 and 48 hours, MTT test, ALP activity, mRNA for tumour necrosis factor-α (TNF-α), interleukin-6, collagen-I (Col-I), collagen-III, RUNX-2, alkaline phosphatase (ALP), osteonectin and protein expression of interleukin-6 and TNF-α were analysed. RESULTS: With increasing Pg-LPS, TLR-4 was upregulated, pNF-κB-p65 rose from median (Q25/Q75) 6.56% (4.19/7.90) to 13.02% (8.90/16.50; p = 0.002) and pNF-κB-p65/tNF-κB-p65 from 0.14(0.10/0.17) to 0.30(0.21/0.42; p = 0.002). pß-Catenin, tß-catenin and pß-catenin/tß-catenin showed no differences. Increasing Pg-LPS concentration increased cell numbers from 288.00(72.98/484.32) to 861.39 (540.41/1599.94; p = 0.002), ALP mRNA from 0.00(0.00/0.01) to 0.56(0.00/1.90; p = 0.004) and TNF-α from 32.47(12.11/38.57) to 45.32(28.68/48.65; p = 0.036). Over time, ALP activity increased from 0.89(0.78/0.95) to 1.90(1.83/2.09; p < 0.001), mRNA for TNF-α from 0.00(0.00/0.12) to 0.01(0.00/0.06; p = 0.007), mRNA for Col-I from 82.70(0.03/171.50) to 124.00(52.85/232.50; p = 0.019), while mRNA for RUNX-2 decreased from 1.73(0.92/3.20) to 0.84(0.48/1.47; p = 0.005). CONCLUSIONS: Pg-LPS upregulated G-MSCs' proliferation, without attenuation of their regenerative potential. The effects were NF-κB, but not Wnt/ß-catenin, pathway dependent.

Periodontal regeneration employing gingival margin-derived stem/progenitor cells in conjunction with IL-1ra-hydrogel synthetic extracellular matrix.

AIM: This study investigated the periodontal regenerative potential of gingival margin-derived stem/progenitor cells (G-MSCs) in conjunction with IL-1ra-releasing hyaluronic acid synthetic extracellular matrix (HA-sECM). MATERIALS AND METHODS: Periodontal defects were induced at four sites in eight miniature pigs in the premolar/molar area (-4 weeks). Autologus G-MSCs were isolated from the free gingival margin and magnetically sorted, using anti-STRO-1 antibodies. Colony formation and multilineage differentiation potential were tested. The G-MSCs were expanded and incorporated into IL-1ra-loaded/unloaded HA-sECM. Within every miniature pig, four periodontal defects were randomly treated with IL-1ra/G-MSCs/HA-sECM (test group), G-MSCs/HA-sECM (positive-control), scaling and root planing (SRP; negative control-1) or left untreated (no-treatment group; negative control 2). Differences in clinical attachment level (ΔCAL), probing depth (ΔPD), gingival recession (ΔGR), radiographic defect volume (ΔRDV), and changes in bleeding on probing (BOP) between baseline and 16 weeks post-transplantation, as well as periodontal attachment level (PAL), junctional epithelium length (JE), connective tissue adhesion (CTA), cementum regeneration (CR) and bone regeneration (BR) at 16 weeks post-transplantation were evaluated. RESULTS: Isolated G-MSCs showed stem/progenitor cell characteristics. IL-1ra loaded and unloaded G-MSCs/HA-sECM showed higher ΔCAL, ΔPD, ΔGR, PAL, CR and BR as well as a lower JE compared to their negative controls and improved BOP. CONCLUSION: G-MSCs in conjunction with IL-1ra-loaded/unloaded HA-sECM show a significant periodontal regenerative potential.

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.

Periodontal regeneration employing gingival margin-derived stem/progenitor cells: an animal study.

AIM: This study investigated the periodontal regenerative potential of gingival margin-derived multipotent postnatal stem/progenitor cells. MATERIAL AND METHODS: Periodontal defects were induced at six sites in eight miniature pigs in the premolar/molar area (-4 weeks). Autologous cells isolated from the gingival margin were magnetically sorted using STRO-1 antibodies and characterized flow cytometrically for the expression of CD14, CD31, CD34, CD45, CD117 and STRO-1 surface markers. Colony formation and multilineage differentiation potential were tested. The cells were expanded and loaded on deproteinized bovine cancellous bone (DBCB) and Collagen scaffolds. Within every miniature pig, six periodontal defects were randomly treated with loaded-DBCB (test group 1), unloaded-DBCB (control group 1), loaded-Collagen scaffolds (test group 2), unloaded-Collagen scaffolds (control group 1), scaling and root planing (negative control 1) or left untreated (negative control 2). Differences in clinical attachment level (ΔCAL), probing depth (ΔPD), gingival recession (ΔGR) and radiographic defect volume (ΔRDV) between baseline and 12 weeks, as well as histological attachment level (HAL), junctional epithelium length (JE) and connective tissue adhesion (CTA) after 12 weeks were evaluated. RESULTS: Isolated cells showed stem/progenitor cell characteristics. Cell-loaded scaffolds showed higher ΔCAL, ΔPD, ΔGR, HAL and lower JE and CTA compared with unloaded scaffolds and negative controls. The sort of scaffold had no significant influence on the measured outcomes. CONCLUSION: Gingival margin-derived stem/progenitor cells show significant periodontal regenerative potential.

Local application of hyaluronan gel in conjunction with periodontal surgery: a randomized controlled trial.

Hyaluronic acid application has been proven to be beneficial in a number of medical disciplines. The aim of the current study was to clinically evaluate the effect of local application of hyaluronan gel in conjunction with periodontal surgery. Fourteen patients with chronic periodontitis having four interproximal intrabony defects (≥3 mm) with probing depth values >5 mm were included in this split-mouth study. Following initial nonsurgical periodontal therapy and re-evaluation, defects were randomly assigned to be treated with modified Widman flap (MWF) surgery in conjunction with either 0.8% hyaluronan gel (test) or placebo gel (control) application. Clinical attachment level (CAL), probing depth (PD), gingival recession (GR), plaque index (PI), and bleeding on probing (BOP) values were taken at baseline and 3 and 6 months. Differences between test and control sites were evaluated using a Wilcoxon signed-rank and a McNemar test. A Friedman and a Cochran test were used to test equal ranks over time. Statistically significant differences were noted for CAL and GR (P < 0.05) in favor of the test sites. No significant differences were found regarding PD, BOP, or PI values (P > 0.05). Hyaluronan gel application in conjunction with periodontal surgery appears to result in significant improvement of CAL and in a reduction in GR. Hyaluronan gel application appears to improve the clinical outcome of MWF surgery.

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.

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.

Ultra-short versus standard-length dental implants in conjunction with osteotome-mediated sinus floor elevation: A randomized controlled clinical trial.

BACKGROUND: The ability to restore missing teeth with dental implants is dictated by the available bone and by the presence of anatomical structures. The potential to insert ultrashort implants avoids additional surgical procedures and its inherent complications. The last European Association of Dental Implantologists consensus in 2016 defined ultrashort implants and standard-length dental implants as <6 and >8 mm, respectively. PURPOSE: The present study aimed to investigate whether single standing ultrashort dental implants (US) could provide a viable therapeutic alternative to osteotome mediated sinus floor elevation in combination with standard-length dental implants (SL) 10 mm in posterior maxillary rehabilitation with reduced bone height. MATERIALS AND METHODS: The study was conducted as a prospective parallel group controlled clinical trial with a 12 month follow-up, where 48 implants were randomized into two groups; US-group (5.5 mm) and SL-group (10 mm) implants placed with osteotome-mediated sinus floor elevation. Crestal bone loss (CBL) was defined as the study's primary outcome, while implant survival, buccal bone thickness, implant stability, probing depth, gingival recession, and adverse effects were assessed as secondary outcomes. RESULTS: Mesial CBL was 1.13 ± 0.52 mm in SL- and 0.72 ± 0.52 mm in US-group (P = .021), while distal CBL was 1.44 ± 0.72 mm in SL- and 0.91 ± 0.69 mm in US-group at 12 months (P = .0179). Regarding implant stability, probing depth, and gingival recession there was no statistically significant difference between the two groups. Regarding implants' survival, three implants were lost in the US-while only one implant was lost in the SL-group (P = .6085; Fisher's exact test). Nevertheless, the ultrashort implants were associated with a tripling of the failure rate and uncertainty where the true failure rate is uncertain (relative risk 3.0; confidence interval 0.3-26.8). CONCLUSIONS: Within the current trial's limitations, US-appear appear promising as they are associated less postoperative discomfort, minimal invasiveness and less CBL. However, larger sample size is required to determine whether the ultrashort have an acceptable survival rate.