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.

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.

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.

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.

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.

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.

Hydrogels and Dentin-Pulp Complex Regeneration: From the Benchtop to Clinical Translation.

Dentin-pulp complex is a term which refers to the dental pulp (DP) surrounded by dentin along its peripheries. Dentin and dental pulp are highly specialized tissues, which can be affected by various insults, primarily by dental caries. Regeneration of the dentin-pulp complex is of paramount importance to regain tooth vitality. The regenerative endodontic procedure (REP) is a relatively current approach, which aims to regenerate the dentin-pulp complex through stimulating the differentiation of resident or transplanted stem/progenitor cells. Hydrogel-based scaffolds are a unique category of three dimensional polymeric networks with high water content. They are hydrophilic, biocompatible, with tunable degradation patterns and mechanical properties, in addition to the ability to be loaded with various bioactive molecules. Furthermore, hydrogels have a considerable degree of flexibility and elasticity, mimicking the cell extracellular matrix (ECM), particularly that of the DP. The current review presents how for dentin-pulp complex regeneration, the application of injectable hydrogels combined with stem/progenitor cells could represent a promising approach. According to the source of the polymeric chain forming the hydrogel, they can be classified into natural, synthetic or hybrid hydrogels, combining natural and synthetic ones. Natural polymers are bioactive, highly biocompatible, and biodegradable by naturally occurring enzymes or via hydrolysis. On the other hand, synthetic polymers offer tunable mechanical properties, thermostability and durability as compared to natural hydrogels. Hybrid hydrogels combine the benefits of synthetic and natural polymers. Hydrogels can be biofunctionalized with cell-binding sequences as arginine-glycine-aspartic acid (RGD), can be used for local delivery of bioactive molecules and cellularized with stem cells for dentin-pulp regeneration. Formulating a hydrogel scaffold material fulfilling the required criteria in regenerative endodontics is still an area of active research, which shows promising potential for replacing conventional endodontic treatments in the near future.

Ascorbic Acid, Inflammatory Cytokines (IL-1ß/TNF-α/IFN-γ), or Their Combination's Effect on Stemness, Proliferation, and Differentiation of Gingival Mesenchymal Stem/Progenitor Cells.

OBJECTIVE: Ascorbic acid (AA) and controlled inflammatory stimuli are postulated to possess the ability to independently exert positive effects on a variety of proliferative, pluripotency, and differentiation attributes of gingival mesenchymal stem/progenitor cells (G-MSCs). The current study's objective was to explore and compare for the first time the impact of the major inflammatory cytokines (IL-1ß/TNF-α/IFN-γ), AA, or their combination on multipotency/pluripotency, proliferative, and differentiation characteristics of G-MSCs. DESIGN: Human G-MSCs (n = 5) were isolated and cultured in basic medium (control group), in basic medium with major inflammatory cytokines; 1 ng/ml IL-1ß, 10 ng/ml TNF-α, and 100 ng/ml IFN-γ (inflammatory group), in basic medium with 250 µmol/l AA (AA group) and in inflammatory medium supplemented by AA (inflammatory/AA group). All media were renewed three times per week. In stimulated G-MSCs intracellular ß-catenin at 1 hour, pluripotency gene expression at 1, 3, and 5 days, as well as colony-forming units (CFUs) ability and cellular proliferation over 14 days were examined. Following a five-days stimulation in the designated groups, multilineage differentiation was assessed via qualitative and quantitative histochemistry as well as mRNA expression. RESULTS: ß-Catenin significantly decreased intracellularly in all experimental groups (p = 0.002, Friedman). AA group exhibited significantly higher cellular counts on days 3, 6, 7, and 13 (p < 0.05) and the highest CFUs at 14 days [median-CFUs (Q25/Q75); 40 (15/50), p = 0.043]. Significantly higher Nanog expression was noted in AA group [median gene-copies/PGK1 (Q25/Q75); 0.0006 (0.0002/0.0007), p < 0.01, Wilcoxon-signed-rank]. Significant multilineage differentiation abilities, especially into osteogenic and chondrogenic directions, were further evident in the AA group. CONCLUSIONS: AA stimulation enhances G-MSCs' stemness, proliferation, and differentiation properties, effects which are associated with a Wnt/ß-catenin signaling pathway activation. Apart from initially boosting cellular metabolism as well as Sox2 and Oct4A pluripotency marker expression, inflammation appeared to attenuate these AA-induced positive effects. Current results reveal that for AA to exert its beneficial effects on G-MSCs' cellular attributes, it requires to act in an inflammation-free microenvironment.

Toll-like Receptor Expression Profile of Human Stem/Progenitor Cells Form the Apical Papilla.

INTRODUCTION: Stem/progenitor cells from the apical papilla (SCAPs) demonstrate remarkable regenerative and immunomodulatory properties. During their regenerative events, SCAPs, similar to other stem/progenitor cells, could interact with their local inflammatory microenvironment via their expressed toll-like receptors (TLRs). The present study aimed to describe for the first time the unique TLR expression profile of SCAPs. METHODS: Cells were isolated from the apical papilla of extracted wisdom teeth (n = 8), STRO-1 immunomagnetically sorted, and cultured to obtain single colony-forming units. The expression of CD14, 34, 45, 73, 90, and 105 were characterized on the SCAPs, and their multilineage differentiation potential was examined to prove their multipotent aptitude. After their incubation in basic or inflammatory medium (25 ng/mL interleukin 1 beta, 103 U/mL interferon gamma, 50 ng/mL tumor necrosis factor alpha, and 3 × 103 U/mL interferon alpha), a TLR expression profile for SCAPs under uninflamed as well as inflamed conditions was respectively generated. RESULTS: SCAPs demonstrated all predefined stem/progenitor cell characteristics. In basic medium, SCAPs expressed TLRs 1-10. The inflammatory microenvironment up-regulated the expression of TLR1, TLR2, TLR4, TLR5, TLR6, and TLR9 and down-regulated the expression of TLR3, TLR7, TLR8, and TLR10 in SCAPs under the inflamed condition. CONCLUSIONS: The present study defines for the first time a distinctive TLR expression profile for SCAPs under uninflamed and inflamed conditions. This profile could greatly impact SCAP responsiveness to their inflammatory microenvironmental agents under regenerative conditions in vivo.

Induced Pluripotent Stem Cells in Dental and Nondental Tissue Regeneration: A Review of an Unexploited Potential.

Cell-based therapies currently represent the state of art for tissue regenerative treatment approaches for various diseases and disorders. Induced pluripotent stem cells (iPSCs), reprogrammed from adult somatic cells, using vectors carrying definite transcription factors, have manifested a breakthrough in regenerative medicine, relying on their pluripotent nature and ease of generation in large amounts from various dental and nondental tissues. In addition to their potential applications in regenerative medicine and dentistry, iPSCs can also be used in disease modeling and drug testing for personalized medicine. The current review discusses various techniques for the production of iPSC-derived osteogenic and odontogenic progenitors, the therapeutic applications of iPSCs, and their regenerative potential in vivo and in vitro. Through the present review, we aim to explore the potential applications of iPSCs in dental and nondental tissue regeneration and to highlight different protocols used for the generation of different tissues and cell lines from iPSCs.

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.

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications.

Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue' diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs' secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.

Mesenchymal Stem/Progenitor Cells: The Prospect of Human Clinical Translation.

Mesenchymal stem/progenitor cells (MSCs) are key players in regenerative medicine, relying principally on their differentiation/regeneration potential, immunomodulatory properties, paracrine effects, and potent homing ability with minimal if any ethical concerns. Even though multiple preclinical and clinical studies have demonstrated remarkable properties for MSCs, the clinical applicability of MSC-based therapies is still questionable. Several challenges exist that critically hinder a successful clinical translation of MSC-based therapies, including but not limited to heterogeneity of their populations, variability in their quality and quantity, donor-related factors, discrepancies in protocols for isolation, in vitro expansion and premodification, and variability in methods of cell delivery, dosing, and cell homing. Alterations of MSC viability, proliferation, properties, and/or function are also affected by various drugs and chemicals. Moreover, significant safety concerns exist due to possible teratogenic/neoplastic potential and transmission of infectious diseases. Through the current review, we aim to highlight the major challenges facing MSCs' human clinical translation and shed light on the undergoing strategies to overcome them.