The effect of smoking on clinical and biochemical early healing outcomes of coronally advanced flap with connective tissue graft: Prospective cohort study.

BACKGROUND: This study aimed to determine the effects of smoking on early (≤3 months) clinical outcomes and relevant molecular biomarkers following root coverage surgery. METHODS: Eighteen smokers and 18 nonsmokers, status biochemically verified, with RT1 gingival recession defects were recruited and completed study procedures. All patients received coronally advanced flap plus connective tissue graft. Baseline and 3 month recession depth (RD), recession width (RW), keratinized tissue width (KTW), clinical attachment level (CAL), and gingival phenotype (GP) were recorded. Root coverage (RC) percentage and complete root coverage (CRC) were calculated. Recipient (gingival crevicular fluid) and donor (wound fluid) site VEGF-A, HIF-1α, 8-OHdG, and ANG levels were determined. RESULTS: There were no significant intergroup differences for any baseline or postoperative clinical parameters (P > 0.05), except for whole mouth gingival index (increased in nonsmokers at 3 months; P < 0.05). Compared to baseline, RD, RW, CAL, KTW, and GP significantly improved postoperatively, without significant intergroup differences. There were no significant intergroup differences for RC (smokers = 83%, nonsmokers = 91%, P = 0.069), CRC (smokers = 50%, nonsmokers = 72%, P = 0.177), and CAL gain (P = 0.193). The four biomarker levels significantly increased postoperatively (day 7; P ≤ 0.042) in both groups and returned to baseline (day 28) without significant intergroup differences (P > 0.05). Similarly, donor site parameters were not different between groups. Strong correlations, consistent over time, were found between biomarkers implicated in angiogenesis (VEGF-A, HIF-1α, and ANG). CONCLUSIONS: The early (3 month) clinical and molecular changes after root coverage surgery utilizing a coronally advanced flap plus connective tissue graft are similar between smokers and nonsmokers.

Contemporary treatment techniques for excessive gingival display caused by altered passive eruption or lip hypermobility.

OBJECTIVES: Excessive gingival display (EGD), also known as gummy smile, has various causes, including altered passive eruption (APE) and hypermobile upper lip (HUL). This state-of-the art narrative review explores current concepts regarding soft tissue EGD etiologies and the contemporary modalities available for APE or HUL treatment. DATA, SOURCES, STUDY SELECTION: Literature search was conducted for a narrative review on the etiology, diagnosis, and treatment of EGD caused by APE and HUL. Searching for articles was carried out in PubMed and Google Scholar. Published articles, including case reports, case series, observational and interventional clinical trials, and critical appraisals of the literature (e.g., systematic reviews) on the etiology, diagnosis, and treatment of EGD caused by APE and HUL were retrieved and reviewed. Particular focus was placed on novel treatment modalities introduced in the last five years. CONCLUSIONS: Recent research evidence indicates that APE and HUL are the two major soft tissue-based EGD etiologies. Aesthetic crown lengthening (ACL) and lip repositioning surgery (LRS) are the established surgical treatment modalities for APE and HUL, respectively. The last few years have seen the introduction of new techniques for APE and HUL management, an expansion of the available ACL and LRS technique variations, and additional evidence further supporting the effectiveness of these two procedures. Several of the recently introduced approaches offer unique, innovative, and potentially impactful concepts. However, for many of these newly described treatments the available evidence is limited to case reports and the exact indications remain to be adequately defined. CLINICAL SIGNIFICANCE: Altered passive eruption and hypermobile upper lip are the common soft tissue causes of gummy smile and can be successfully managed through aesthetic crown lengthening and lip repositioning surgery, respectively. A wide range of newly introduced approaches promises to further facilitate gummy smile treatment and improve outcomes.

Patient-reported outcomes following guided bone regeneration: Correlation with clinical parameters.

OBJECTIVES: Postoperative oral health-related quality of life is procedure-dependent and may vary during early healing. There is scarce evidence on patient-reported outcome measures (PROMs) after extraction and guided bone regeneration (GBR) or on the clinical parameters influencing PROMs. This prospective observational study aimed to evaluate PROMs during the first 2 weeks following extraction and GBR and correlate them with clinical parameters. METHODS: Patients undergoing extraction and GBR (bone graft and resorbable membrane) at a single tooth-bound site were recruited. PROMs (pain, swelling, difficulty of mouth opening, and OHIP-14) were recorded immediately preoperatively, and at 2, 7, and 14 days postoperatively. Flap advancement, gingival and mucosal thickness, duration of surgery, and wound opening were the clinical parameters assessed. RESULTS: Twenty-seven patients were included. All PROMs peaked on postoperative day 2, decreased subsequently and were significantly correlated with each other. Although 41-56% of patients reported moderate to severe pain, swelling, or mouth opening difficulty on day 2, most patients experienced mild or no symptoms throughout the postoperative period. Pain, swelling and difficulty of mouth opening were determinants of OHIP-14 and were correlated with all OHIP-14 domains during different time points. Wound opening peaked on day 7. Flap advancement, soft tissue thickness, wound opening, duration of surgery and preoperative PROMs affected postoperative PROMs. CONCLUSIONS: Within the limitations of the present study, postoperative symptoms after guided bone regeneration are worst on day 2 and oral health-related quality of life is significantly impacted by pain, swelling, difficulty of mouth opening, surgery duration and flap advancement. CLINICAL SIGNIFICANCE: This is the first study to report PROMs following extraction and GBR with particulate bone graft and resorbable membrane in preparation for implant placement. It will help guide both practitioners and patients on what should be the anticipated experiences following such a routinely performed surgery.

Intra-marrow penetrations and root coverage outcomes: a systematic review.

BACKGROUND: Intra-marrow penetrations (IMPs) have been performed during guided tissue regeneration (GTR) procedures with reported clinical benefits. The aim of this systematic review was to investigate the use and effect of IMPs during root coverage procedures. METHOD: A broad search for human and animal studies was performed on PubMed, Cochrane Database of Systematic Reviews and Cochrane Central Registry of Controlled Trials and Web of Science, following a registered review protocol (PROSPERO). All prospective study designs, case series and case reports on gingival recession treatment (follow-up ≥ 6 months) that employed IMPs were included. Root coverage, complete root coverage prevalence, and adverse effects were recorded, and risk of bias was assessed. RESULTS: Of 16,181 screened titles, 5 articles (all of them human studies) met inclusion criteria. All studies (including two randomized clinical trials) treated Miller class I and II recession defects, using coronally advanced flap with IMPs alone or in conjunction with GTR protocols. Therefore, all treated defects received IMPs and no studies compared protocols with and without IMPs. Outcomes were indirectly compared with existing root coverage literature. Mean root coverage was 2.7 mm and 68.5% at 6.8 months (median: 6 months, range 6-15 months) for sites treated with IMPs. CONCLUSION: IMPs are rarely used during root coverage procedures, have not been associated with intra-surgical or wound healing adverse effects and have not been investigated as independent factor. Future clinical studies are needed to directly compare treatment protocols with and without IMPs and investigate the potential benefits of IMPs for root coverage.

Comparison of maxillary tuberosity and palatal donor sites for soft tissue augmentation at implant placement: A pilot controlled clinical study.

PURPOSE: To compare the outcomes of soft tissue augmentation during one-stage implant placement using grafts harvested from the hard palate or the maxillary tuberosity. MATERIALS AND METHODS: In this pilot controlled clinical study, non-smoking adults with a single missing tooth in the anterior or premolar region and adequate ridge dimensions for implant placement were enrolled. Each received a single implant and connective tissue graft harvested either from the hard palate (n = 10) or the maxillary tuberosity (n = 10). Digital impressions were taken prior to treatment (T0) and then 2 and 12 months postoperatively (T1 and T2, respectively). The primary study outcome was changes in horizontal ridge dimension. Secondary outcomes included marginal bone level changes over time, pain levels in the first 2 postoperative weeks (W1 and W2) and pink aesthetic score and patient-reported outcome measures at T2. Data analysis included repeated measures analysis of variance for intergroup comparisons. RESULTS: The horizontal ridge dimension increased significantly in both groups (P ≤ 0.002) at all apico-coronal levels examined, with no significant intergroup differences. There was also no significant intergroup difference in marginal bone level changes (P = 0.376). The hard palate group experienced higher pain levels in the donor site compared to the tuberosity group at W1 (P = 0.023). The pink aesthetic score and patient-reported outcome measures were similar between groups at T2. CONCLUSIONS: Soft tissue augmentation during one-stage implant placement results in significant increases in the horizontal ridge dimension.

Lip Repositioning Techniques and Modifications.

A common etiology of excessive gingival display is hypermobile upper lip, which can be managed by non-surgical and surgical approaches. Among the surgical options, lip repositioning surgery is a relatively simple procedure with minimal complications. Since the original description of the technique almost 50 years ago, several minor and major modifications have been introduced. The available evidence indicates that, when applied to properly diagnosed cases, the technique is effective in reducing gingival display and results in improved smile esthetics and high patient satisfaction. This article reviews the various techniques and modifications and summarizes the reported outcomes of the procedure.

Smile Management: A Discussion with the Masters.

Smile design is an ongoing challenge in both dentistry and facial cosmetics surgery. Herein, some very common smile design scenarios are shared with six world known masters. Each case will be reviewed by 2 cosmetic dentists, 2 periodontists, and 2 oral and maxillofacial surgeons. At the end, contributors will describe current advances and future prospects of this evolving field.

Titanium as a Possible Modifier of Inflammation Around Dental Implants.

PURPOSE: The exact etiopathogenesis of peri-implant diseases remains unclear. While significant information on molecular markers is available, studies on biomarkers related to possible biocorrosion are sparse. This study aimed to evaluate periimplant crevicular fluid (PICF) for possible titanium (Ti) contamination and explore associations between clinical findings, inflammatory mediators, and Ti levels. MATERIALS AND METHODS: Patients with implant-supported restoration (≥ 1 year in function) were recruited for this cross-sectional study. Demographics, systemic, and periodontal health history were recorded. Clinical evaluations were conducted to reach peri-implant/periodontal diagnoses and grade severity of peri-implant soft tissue inflammation. Crevicular fluid (CF) was collected from both implants and adjacent teeth (PICF, gingival crevicular fluid [GCF]) and analyzed for Ti (inductively coupled plasma mass spectrometry) and inflammatory mediators (V-plex assays). Multiple regression analysis with a linear mixed effect model was used to analyze possible associations between clinical diagnosis, PICF/GCF cytokine, and Ti concentrations. RESULTS: Seventy-seven patients (aged 62 ± 2 years; 39 male) with 117 implants (9 ± 1 years in function) were recruited. Diabetes, positive periodontitis history, and current/former smoking were reported by 8%, 39%, and 39% of subjects, respectively. Seventy-nine implant sites (63 patients) were included in CF cytokine analysis, and 45 of these sites (42 patients) were paired with Ti analysis. Statistically significant increases from health to disease were noted in log-transformed PICF concentrations of IL-1ß, IL-6, IL-10, and INF-γ (P ≤ .05). Also, statistically significant increases from health to severe clinical inflammation were detected in log-transformed PICF concentrations of IL-8, IL-13, and TNF-α (P ≤ .05). Ti was detected in the majority (82%) of PICF and GCF samples. There was no statistically significant difference in log-transformed Ti concentration based on disease status. However, log-transformed Ti concentration was positively correlated to IL-1ß, IL-2, IL-4, IL-8, IL-13, and INF-γ concentrations when data were adjusted for site-specific health (P ≤ .05). CONCLUSION: Ti was detectable in PICF and adjacent GCF, even in health. Specific inflammatory mediator concentrations were increased in peri-implant disease and significantly associated with Ti concentrations, even when data were adjusted for peri-implant health status. Increased GCF inflammatory mediator concentrations were also associated with increased Ti concentrations. Ti effects on peri-implant as well as periodontal tissues require additional longitudinal investigations.

Gingival crevicular fluid lipocalin-2 and semaphorin3A in stage III periodontitis: Non-surgical periodontal treatment effects.

BACKGROUND AND OBJECTIVE: Identification of biomarkers to assess individual risk and monitor periodontal health status is important. Research on lipocalin-2 (LCN2) and semaphorin3A (Sema3A) is lacking. This study aimed to evaluate gingival crevicular fluid (GCF) LCN2, Sema3A, and tumor necrosis factor-α (TNF-α) levels in periodontally healthy (H), gingivitis (G), and periodontitis (P) patients, and their changes following non-surgical periodontal therapy. METHODS: Sixty systemically healthy and non-smoker participants, diagnosed as periodontally healthy, gingivitis, and stage III grade C periodontitis, were recruited (n = 20/group). Clinical periodontal parameters were recorded and GCF samples were obtained at baseline from all groups; for group P, these were repeated one and three months following non-surgical periodontal treatment. GCF LCN2, Sema3A, and TNF-α levels were evaluated with enzyme-linked immunosorbent assay. RESULTS: GCF LCN2, Sema3A, and TNF-α total amounts were significantly higher in disease groups than group H (p < .001). Between P and G groups, only TNF-α levels were significantly different (p < .001). Non-surgical periodontal therapy resulted in significant improvement of all clinical parameters and significant decreases of GCF LCN2 and TNF-α levels, at both time points, compared with baseline (p < .001). Sema3A levels remained unchanged following treatment (p > .05). LCN2 and TNF-α levels were significantly positively correlated with clinical parameters. LCN2 (AUC [area under the curve] = 0.94) and TNF-α (AUC = 0.98) levels were similarly accurate in differentiating between periodontal disease (whether G or P) and healthy controls. CONCLUSIONS: LCN2 and TNF-α levels in GCF are correlated with clinical parameters and could prove useful as non-invasive screening tools for periodontitis.

Post-surgical emergency after-hours calls: Prevalence, concerns, and management.

OBJECTIVE: The purpose of this study was to investigate the prevalence, nature, and management of post-surgical emergency after-hours calls in a dental school setting with predoctoral students, graduate students/residents, and faculty providers. METHODS: A patient chart review (March 2018-February 2020) for post-surgical calls through the emergency after-hours pager system was conducted at the Marquette University School of Dentistry. The total number of surgical procedures, procedure type, the timing of call, operator experience, concern, and recommendation given during the call were documented. RESULTS: During the review period, 83 calls (from 75 patients) were recorded after 8,487 surgical procedures (1% of procedures). Patients called 5.4 ± 0.8 days postoperatively. Procedure type affected call prevalence (p = 0.04), with most calls made after extractions (69.9% of all calls; 1% of extractions; 58/5,725), implant placement (6%; 0.9% of implant placements; 5/530) and periodontal plastic surgery (6%; 3.1% of all plastic surgeries; 5/161). The most common concern was pain (72.3%), then swelling (36.1%), bleeding (12%), and infection (9.6%). Operator experience did not affect call prevalence. Recommendations given were next business day follow-up (79.5%), reinforcement of already given postoperative instructions (51.8%), prescription (15.7%), and hospital emergency department (ED) visit (7.2%). CONCLUSIONS: Post-surgical emergency after-hours calls in a dental school setting occur within the first postoperative week and are rare, unrelated to operator experience, typically prompted by pain, and rarely resulting in referral to hospital ED. The use of a pager system is adequate for the management of after-hours emergencies and may reduce self-referrals to the hospital ED.

Enamel matrix derivative effects on palatal mucosa wound healing: Randomized clinical trial.

BACKGROUND: This study was conducted to evaluate the clinical, immunologic, and patient-centered outcomes of enamel matrix protein derivative (EMD) on excisional wounds in palatal mucosa. MATERIALS: Forty-four patients in need of ridge preservation were randomly allocated into two groups: control group (n = 22): open palatal wound after free gingival graft (FGG) harvest and EMD group (n = 22): open palatal wound after FGG harvest that received 0.3 ml of EMD. Clinical and patient-centered parameters were analyzed for 3 months post-treatment. Wound fluid levels of inflammatory markers were assessed 3 and 7 days postoperatively. RESULTS: No significant inter-group difference was observed in remaining wound area and re-epithelialization. EMD and control groups achieved wound closure and re-epithelialization 30 days postoperatively (p < .001), without inter-group differences. Similarly, number of analgesics and Oral Health Impact Profile scores did not present significant inter-group differences (p > .05). EMD appeared to selectively modulate wound fluid levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, matrix metallopeptidase 9, and tissue inhibitor of metalloproteinases-2. CONCLUSION: Within the limits of the present study, it can be concluded that EMD application to excisional palatal wounds using the investigated protocol does not provide clinical healing benefits, despite an apparent modulation of selected inflammatory markers.

Lip repositioning surgery for gummy smile: 6-month clinical and radiographic lip dimensional changes.

OBJECTIVES: The present case series aimed to examine lip repositioning surgery (LRS) outcomes related to changes in external and internal upper lip (UL) dimensions, utilizing both conventional clinical and novel radiographic approaches. MATERIALS AND METHODS: Patients (n = 13) diagnosed with hypermobile UL (>8-mm mobility during smile) and excessive gingival display (≥4-mm) were included and assessed at baseline and 6 months postoperatively. Clinical parameters at rest included total lip and internal lip length (vestibular depth). At maximum smile included total lip, philtrum (ergotrid), and vermilion lengths. Cephalometric parameters included anterior maxillary height; lip length; nasolabial angle; anteroposterior lip thickness; internal lip length (vestibular depth); and vestibular fornix position (using novel approach employing radiopaque marker). Linear mixed-effect models, Pearson's correlation, and linear regression were used for statistical analyses. RESULTS: LRS did not affect total UL length at rest (p = 0.418). It resulted in significant internal UL length decrease (-3.8 ± 2.1 mm, p < 0.001) and significant increases of vermilion length (1.9 ± 1.0 mm, p < 0.001) and anteroposterior lip thickness (0.7 ± 0.7 mm, p = 0.002). The clinical and radiographic measurements of total UL length at rest (r ≥ 0.734) and of internal UL length (r ≥ 0.737), and the two radiographic assessments of vestibular depth (r = 0.842), were strongly correlated. CONCLUSIONS: LRS resulted in significant decrease of vestibular depth/internal UL length and in significant increases of UL vertical vermilion length and UL anteroposterior thickness, without affecting total UL length at rest. CLINICAL RELEVANCE: The documented lip dimensional outcomes should help practitioners when treatment-planning LRS and counseling patients seeking treatment for hypermobile UL.

Selective outcome reporting in root coverage randomized clinical trials.

BACKGROUND: Outcome discrepancies between protocols and respective publications represent a concerning bias. The purpose of this study was to assess the prevalence of selective outcome reporting (SOR) in root coverage randomized clinical trials (RCTs). METHODS: Published root coverage RCTs (July 2005 to March 2020) were included if a corresponding protocol could be identified in a public registry. Discrepancies between protocol and its correspondent publication(s) were compared regarding primary and secondary outcomes and other study characteristics. Associations between trial characteristics and SOR were evaluated. RESULTS: Forty four studies (54 publications) were included. The majority of studies (77.3%) were retrospectively registered. SOR was frequent (40.9% of trials) and consisted of primary outcome downgrade (22.7%); secondary outcome upgrade (11.4%); new primary outcome introduced in publication (25%); protocol primary outcome omitted from publication (13.6%) and discrepancy in primary outcome timing (18.2%). SOR was unclear in 20.5% of studies and favoured statistical significance in 12 studies (27.3%). SOR was significantly associated with study significance (p < 0.001) and unclear outcome definition in the publication (p < 0.001). Only a third (32.8%) of primary outcomes were completely defined. CONCLUSIONS: The present study identified high prevalence of SOR in root coverage RCTs.

Aesthetic crown lengthening and lip repositioning surgery: Pre- and post-operative assessment of smile attractiveness.

AIM: To assess the effect of aesthetic crown lengthening (ACL) and lip repositioning surgery (LRS) on perception of smile attractiveness. MATERIALS AND METHODS: Preoperative and 6-month postoperative smile photographs of ACL- or LRS-treated patients were evaluated by 100 raters (five gender-balanced groups of ten per procedure) of diverse background (dental students, general dentists, periodontists and laypersons with and without any aesthetic concerns about their own smile). Smile attractiveness was rated by visual analogue scale (VAS). Multivariate mixed-effect models were applied to determine the effect of procedure, rater (age, gender and group) and case (gingival display and GD) on smile attractiveness rating. RESULTS: Average preoperative and postoperative VAS scores for ACL patients were 3.8 ± 2.0 and 6.2 ± 1.9, respectively. Corresponding LRS patient values were 4.8 ± 2.0 and 6.4 ± 1.9. Treatment, baseline GD and rater age were significant determinants (p < .001) of smile attractiveness for both procedures. Rater gender was not significant. Rater group was significant (p < .032) only for ACL. Procedure (p < .001), baseline VAS (p < .001), change in GD (p ≤ .002) and rater age (p ≤ .017) were significant determinants of smile attractiveness change from preoperative to postoperative. CONCLUSIONS: ACL and LRS are two periodontal plastic surgery procedures that deliver significant smile attractiveness improvements, in the eyes of both laypersons and dental professionals.

Multiple Epithelial Origin Complications Following Subepithelial Connective Tissue Graft for Root Coverage.

INTRODUCTION: The subepithelial connective tissue graft (SCTG) and flap combination is a highly predictable root coverage procedure, with low complication rates. To our knowledge, this article reports the first case of two late SCTG complications, epithelial cell discharge, and subsequent epidermal inclusion cyst (EIC) formation. CASE PRESENTATION: A 35-year-old male presented with a 3-mm deep Miller Class II recession defect on the mandibular right canine and mesial root of mandibular right first molar. A mild discomfort was reported at 8 weeks after envelope flap+SCTG in #27. At 4 months after the procedure, the patient presented with persistent discomfort and minimally compressible recipient site diffuse swelling with discharge, which was cytologically diagnosed as normal epithelial cells. One year postoperatively, enlargement of the lesion was seen, and excisional biopsy was performed simultaneously with SCTG in #30. The lesion was diagnosed as EIC. At 8 months follow-up, the site healed uneventfully, the patient remained asymptomatic, and the site exhibited scar formation and no recurrence of the lesion. CONCLUSION: This report highlights epithelial cell discharge and EIC formation as a rare yet possible SCTG complication and emphasizes the importance of an excisional biopsy as the means to obtain a definitive diagnosis and manage this complication.

Microcurrent electrotherapy improves palatal wound healing: Randomized clinical trial.

BACKGROUND: This study was conducted to assess the clinical, immunological, and patient-centered outcomes of microcurrent electrotherapy on palatal wound healing. METHODS: This was a parallel, double-masked randomized clinical trial, in which 53 patients with ridge preservation indications were selected and randomly assigned to one of two groups. In the control (sham) group (n = 27), palatal wounds, after free gingival grafts (FGG) harvest, received sham application of electrotherapy. In the test (electrotherapy treatment [EE]) group (n = 26), palatal wounds, after FGG harvest, received application of microcurrent electrotherapy protocol. Clinical parameters, patient-centered outcomes, and inflammatory markers were evaluated, up to 90 days postoperatively. RESULTS: The EE group achieved earlier wound closure (P <0.001) and epithelialization (P <0.05; P = 0.03) at 7 and 14 days after harvest when compared with the sham group. Painful symptomatology was reported less frequently in the EE group than in the sham group at 3-day follow-up (P = 0.008). Likewise, an improvement in Oral Health Impact Profile was reported 2 days after the procedure by the EE group (P = 0.04). In addition, favorable modulation of inflammatory wound healing markers occurred when electrotherapy was applied. CONCLUSION: Within the limits of the present study, it can be concluded that the use of a low-intensity electrotherapy protocol may accelerate palatal wound healing and decrease patient discomfort after FGG harvest.

Bone grafting history affects soft tissue healing following implant placement.

BACKGROUND: This study aimed to determine and compare soft tissue healing outcomes following implant placement in grafted (GG) and non-grafted bone (NGG). METHODS: Patients receiving single implant in a tooth-bound maxillary non-molar site were recruited. Clinical healing was documented. Volume and content of wound fluid (WF; at 3, 6, and 9 days) were compared with adjacent gingival crevicular fluid (GCF; at baseline, 1, and 4 months). Buccal flap blood perfusion recovery and changes in bone thickness were recorded. Linear mixed model regression analysis and generalized estimating equations with Bonferroni adjustments were conducted for repeated measures. RESULTS: Twenty-five patients (49 ± 4 years; 13 males; nine NGG) completed the study. Soft tissue closure was slower in GG (P < 0.01). Differential response in WF/GCF protein concentrations was detected for ACTH (increased in GG only) and insulin, leptin, osteocalcin (decreased in NGG only) at day 6 (P ≤0.04), with no inter-group differences at any time(P > 0.05). Blood perfusion rate decreased immediately postoperatively (P < 0.01, GG) followed by 3-day hyperemia (P > 0.05 both groups). The recovery to baseline values was almost complete for NGG whereas GG stayed ischemic even at 4 months (P = 0.05). Buccal bone thickness changes were significant in GG sites (P ≤ 0.05). CONCLUSION: History of bone grafting alters the clinical, physiological, and molecular healing response of overlying soft tissues after implant placement surgery.

Topical phenytoin effects on palatal wound healing.

BACKGROUND: The clinical benefits of autogenous soft tissue grafts are countered by donor site morbidity. The aim of this prospective split-mouth clinical trial is to assess clinical, histological and patient outcomes following topical phenytoin (PHT) treatment of experimental palatal wounds. METHODS: Systemically healthy adults were recruited. One 6 mm diameter wound (posterior) and one 4 mm diameter wound (anterior), each 1-1.5 mm deep, were created on both sides of the palate. Wounds on one randomly chosen side received 10% phenytoin USP and contralateral wounds received carrier alone. Biopsies were harvested from anterior wounds (Day 1 or Day 5) and were routinely processed for histology. Posterior wounds were left undisturbed to clinically evaluate healing (using photographs and Healing Score Index) on Days 1, 5, 14, and 21. Questionnaires were used to assess patient-centered outcomes. Data analysis was performed using generalized logistic and generalized linear mixed models. RESULTS: Twenty participants completed all visits. 30% of participants reported more pain on control side than the PHT side at Day 1 (P = 0.014). PHT treated sites were more likely to not exhibit swelling (OR = 9.35; P = 0.009) and to not experience pain on palpation (OR = 6.278; P = 0.007). PHT significantly and time-dependently affected granulation tissue appearance (P = 0.004). Histologically, there were no significant differences between control and PHT, at any time point (P ≥ 0.853). CONCLUSIONS: The results of the present study, the first one to report on topical PHT as palatal wound treatment, suggest that PHT application on palatal wounds could result in improved healing outcomes.

Wound Fluid Cytokine Profile Following Bone Regeneration Procedures.

Clinical parameters available to evaluate early healing phases of bone regeneration procedures are limited. This study explores wound fluid (WF) content for molecular markers to differentiate wound healing responses in the early postoperative period after bone graft placement. Fifteen patients (50 ± 5 years old; 8 men) scheduled to receive tooth extraction and bone graft placement at maxillary nonmolar single-tooth sites were recruited. Primary wound closure was not intended at time of surgery. Gingival crevicular fluid from adjacent teeth or WF from surgical wound edges were collected (30 seconds) at baseline, at 3, 6, and 9 days, and at 1 and 4 months. Multiplex protein assay was used to determine concentration of various wound healing mediators. Immediately after surgery, 87% of surgical sites exhibited open wound. At day 9, mean wound exposure was 4.8 ± 0.4 mm. At 1 month, all wounds were clinically closed. The WF tripled in volume at day 3 and day 6 (P ≤ .05), compared with baseline gingival crevicular fluid, and gradually decreased as wounds closed. The WF concentrations of interleukin (IL)-6, placental growth factor, plasminogen activator inhibitor 1, insulin-like growth factor binding protein 1, and soluble cluster determinant 40 ligand were increased during early healing days, generally with peak concentration at day 6 (P ≤ .004). Conversely, WF concentrations of IL-18 and epidermal growth factor were decreased after surgery, generally not reaching baseline values until wound closure (P ≤ .008). In general, WF cytokine expression kinetics were concordant with wound closure dynamics (P ≤ .04). These results suggest that WF molecular markers such as IL-6, and to a lesser extent placental growth factor and IL-18, might help differentiate wound healing responses after bone regeneration procedures.

Whole transcriptome analysis of smoker palatal mucosa identifies multiple downregulated innate immunity genes.

BACKGROUND: Smoking has significant negative impact on periodontal health and treatment outcomes. The molecular effects of smoking on oral immune homeostasis have not been fully elucidated. The present study aimed to provide a comprehensive assessment of smoking-associated gene expression changes in healthy palatal mucosa and to identify potentially implicated immunologic pathways. METHODS: Palatal biopsies, in the form of connective tissue grafts, were obtained from periodontally healthy smokers and non-smokers. Smoking status was biochemically verified (exhaled air CO and serum cotinine). Tissue samples were processed for next generation sequencing, quantitative real-time polymerase chain reaction (qPCR), and immunohistochemistry. Gene set enrichment/pathway analysis and correlation analysis between gene expression and serum cotinine levels were also performed. RESULTS: Analysis of palatal tissues from 12 non-smokers and 10 smokers identified 830 significantly (P <0.05) differentially expressed genes (DEGs), 249 with fold change (FC) >2. Most increased in expression (≥5-FC) were CYP1A1, CYP1B1, and USP17L9P; most decreased (≥6-FC) were IL36A, DEFB4A, DEFB4B, SPRR2F, CCL20, KLK6, and ADH4. 203 DEGs (FC >2) were significantly correlated with serum cotinine levels. Significant enrichment pathways for cotinine-associated genes include antimicrobial humoral response, regulation of humoral response and various metabolic processes. qPCR and immunohistochemistry confirmed gene and protein expression of selected DEGs. CONCLUSIONS: Smoking has a significant effect on the transcriptome of normal human palatal mucosa and seems to target genes important for innate immune defenses, which may prove to be one of the key mechanisms by which tobacco smoking leads to increased periodontitis susceptibility.