Karim Mohamed Fawzy El-Sayed

Background: Tobacco smoking remains a major global health burden. Although electronic cigarettes (EC) are considered less harmful than conventional cigarette, their effects on oral health are not fully defined. Cannabis use is increasing worldwide, yet its impact on oral tissues is poorly understood. This investigation evaluated the effects of EC aerosol, conventional cigarettes smoke and cannabis smoke on cellular viability, mitochondrial integrity and gene expression in osteogenically induced gingival fibroblast/gingival mesenchymal stem cells (GF/GMSCs). Methods: Isolation and characterization of human GF/GMSCs ( n = 32) were performed, followed by osteogenic induction using (BMP-2) and aerosol/smoke application. Osteogenically induced GF/GMSCs were assessed via MTT-assay, mitochondrial depolarization assessed using JC-1 dye, ATM, p21, Oct4 and Nanog gene expression, and osteogenic differentiation. Results: Viability (OD450nm) was significantly reduced in the cannabis/BMP- (mean ± SD: 1.02 ± 0.24) and cigarettes/BMP-(1.05 ± 0.39; p < 0.05), with no reduction in viability in the EC/BMP-(1.78 ± 0.47) and BMP-group (1.74 ± 0.59; p > 0.05). Upregulated expression of ATM, Oct4, and Nanog (gene copies/GAPDH) was significant with cannabis/BMP-(2.23 ± 0.34, 1.73 ± 0.53 and 2.04 ± 0.33 respectively), cigarettes/BMP-(2.58 ± 0.69, 1.91 ± 1.03 and 2.26 ± 0.6; p < 0.05 respectively), with no significant upregulation in EC/BMP-(0.72 ± 0.37; 0.91 ± 0.56; 1.11 ± 0.49) compared to BMP-group (0.51 ± 0.17, 0.64 ± 0.2, and 1.01 ± 0.58; p > 0.05 respectively). p21 expression was significantly downregulated in EC/BMP-(1.97 ± 0.52), cannabis/BMP-(1.26 ± 0.29) and cigarettes/BMP-(1.38 ± 0.74) compared to BMP-group (4.24 ± 0.69; p < 0.05). Osteogenic differentiation was impeded with reduced Alizarin-red straining and significant downregulation of osteopontin expression in EC/BMP-(2.12 ± 0.47), cannabis/BMP-(1.48 ± 0.99), and cigarettes/BMP- -(1.36 ± 0.38) compared to BMP-group (3.95 ± 0.88;p˂0.05). Conclusion: Cannabis smoke and cigarette smoke negatively influence the viability, gene expression, and cause DNA damage in osteogenically induced GF/GMSCs, with a lesser effect of EC-aerosol on these findings. Still, all tested exposures negatively affected the differentiation of osteogenically induced GF/GMSCs.

Background: Vitamins A and C (VitA+C) are pivotal biomolecules, with synergistic effects, especially in conjoint presence, on cellular pluripotency and regenerative capabilities. This randomized trial aimed to evaluate (VitA+C)‐augmented injectable platelet‐rich fibrin (i‐PRF) versus i‐PRF alone with a modified minimally invasive surgical technique (M‐MIST) in periodontal intraosseous defects in patients with stage III periodontitis. Methods: This parallel group, two‐arm, triple‐blinded, randomized controlled trial included patients with stage III grade B periodontitis ( n = 28) randomly allocated to the test (VitA+C/i‐PRF+M‐MIST; n = 14) or the control (i‐PRF+M‐MIST; n = 14) group. The changes in radiographic linear defect depth (RLDD) (primary outcome), radiographic bone fill (RBF), and radiographic bone density (RBD) were recorded at baseline, 6, and 9 months. Clinical attachment level (CAL), probing depth (PD), gingival margin level (GML), plaque index (PI), and gingival index (GI; secondary outcomes) were recorded at baseline, 3 6, and 9 months. The in vitro release kinetics of VitA and VitC from the i‐PRF were characterized over 7 days using high‐performance liquid chromatography (HLPC). Results: VitA+C/i‐PRF+M‐MIST demonstrated a significantly higher RLDD‐reduction at 6 months and a higher RBF percentage at 6 and 9 months compared with i‐PRF+M‐MIST ( p < 0.05), with no intergroup differences regarding RBD. Both groups independently demonstrated significant improvements in CAL, PD, GML, RLDD, and BDA over time ( p < 0.05). Significantly higher CAL‐gain and PD‐reduction were evident in the VitA+C/i‐PRF+M‐MIST group at 9 months ( p < 0.05). Conclusions: I‐PRF with M‐MIST significantly enhance periodontal clinical and radiographic parameters over time. Conjoint vitamin A/C augmentation of i‐PRF at the described concentration results in significantly greater improvement in radiographic and clinical parameters of intraosseous defects compared with i‐PRF alone. Clinical trial registration: This study was registered in the US National Institutes of Health Clinical Trials Registry (NCT05499598; https://www.clinicaltrials.gov/ ).

Aim: This retrospective cohort study evaluate tooth loss and predictors during exceptionally long term supportive periodontal care (SPC), focusing on residual disease severity at SPC initiation. Materials and Methods: Seventy patients maintained under SPC for > 30 years were analysed using negative binomial regression (log[SPC‐duration] offset) and Cox proportional hazards models (clustered by patient). Results: Over a mean SPC duration of 36.1 ± 3.0 [30–43] years, 63 patients lost 322 teeth (4.6 ± 4.2 per patient; 0.13 ± 0.12 per patient‐year). Despite advanced baseline disease (stage III/IV: 97%), 35‐year molar survival was 77% for FI 0 versus 51% for FI II–III. Tooth loss rate was significantly associated with PPD ≥ 6 mm (IRR 1.012; 95% CI 1.003–1.021; p = 0.009) and molar FI II–III (IRR 1.178; 95% CI 1.050–1.321; p = 0.005). A tooth‐level Cox model confirmed elevated hazard for PPD ≥ 6 mm (HR 4.02; 95% CI 2.10–7.69) and FI II–III (HR 2.87; 95% CI 1.61–5.11). However, predictive accuracy was modest (PPV 36%–55%), indicating these markers reflect population‐level risk rather than individual prognosis. Conclusion: Tooth loss remained low over > 30 years of SPC even for molars with advanced FI, while residual disease severity modulated this risk. Given strong survivorship bias (3.3% of eligible patients), generalisability beyond university‐based specialist care is limited.

The present review article explores the emerging evidence on the use of autologous platelet concentrates (APCs) as sustained release vehicles for a variety of drugs, including antibiotics, antifungals, antidiabetic drugs, exosomes, and vitamins for localized delivery approaches. The incorporation of such bioactive agents into APCs could enhance their therapeutic efficacy, support antimicrobial effects, wound healing and regeneration, and potentially reduce the need for systemic therapy. Although platelet‐rich plasma (PRP) has also been studied as a carrier of bioactive agents, the rapid degranulation of platelets and lack of a cohesive fibrin network in PRP lead to a short‐lived burst‐type release profile. On the other hand, platelet‐rich fibrin (PRF) has a three‐dimensional scaffold of fibrin in which the growth factors and drug agents are retained, characteristics which make PRF‐based APCs advantageous over PRP in the field of drug‐delivery systems. However, a major challenge remains to be the absence of standardized drug‐loaded APCs preparation protocols, with variations in centrifugation parameters, tube composition, and biomolecules' loading techniques, thereby influencing the APCs' structural integrity and release kinetics. The present review further highlights key findings on optimal loading strategies and the interactions between incorporated agents and the carrying APCs. It further highlights the level of current evidence for each of these drug‐loaded APCs under investigation, their strength of recommendation, and possible knowledge gaps. Future work should focus on further developing and standardizing preparation protocols, advancing controlled release technologies, and validating efficacy through large scale clinical trials. Overall, bioactive drug‐loaded APCs could represent a promising platform for targeted antimicrobial, antifungal, and regenerative therapies, bridging infection management with precision‐guided tissue healing.

Aim: This pilot randomized controlled trial evaluated the efficacy of demineralized dentin graft (DDG) combined with injectable platelet‐rich fibrin (I‐PRF) and metronidazole (MTZ) versus DDG with I‐PRF and DDG alone in alveolar ridge preservation (ARP) of chronically infected extraction sockets. Methods: Patients with non‐restorable teeth and chronic periapical infection in the maxillary anterior and premolar regions were randomly assigned to three groups ( n = 18/group): DDG alone, DDG + I‐PRF, and DDG + I‐PRF/MTZ. After extraction, graft materials were placed into sockets. Cone‐beam CT scans at baseline and 6 months assessed vertical and horizontal ridge dimensions. Virtual implant planning evaluated the need for further augmentation. Pain was recorded daily for 7 days using a visual analogue scale (VAS). Bone biopsies at 6 months were harvested during implant placement for histomorphometric analysis. Results: Fifty‐four patients were analyzed. No significant differences were found in vertical and horizontal ridge dimensional changes ( p > 0.05). Minimal additional augmentation was needed. The DDG + I‐PRF/MTZ group showed significantly the highest mineralized bone percentage (55.02% ± 3.65%), followed by DDG + I‐PRF (41.14% ± 7.00%) and DDG alone (30.21% ± 3.72%) ( p < 0.05). Soft tissue proportion histologically was significantly lowest in the DDG + I‐PRF/MTZ group ( p < 0.05). Conclusion: All protocols were effective for ARP. Addition of I‐PRF with MTZ enhanced bone mineralization. Trial Registration: www.clinicaltrials.gov : NCT06374784

Human gingival mesenchymal stem/progenitor cells (hGMSCs) exert remarkable tissue regeneration properties. A combination of vitamins C and A at specified concentrations enhanced cellular dedifferentiation and multipotency of hGMSCs. To our knowledge, vitamins A/C-primed hGMSCs in the prevention of medication-related osteonecrosis of the jaw (MRONJ) have not been investigated. Thus, this study evaluated the impact of vitamins A/C in pluripotency-inductive concentrations on the regenerative/reparative potential of hGMSCs in preventing MRONJ development in rats. Thirty albino rats ( n = 10/group) were administered zoledronic acid and dexamethasone three times a week for 4 weeks. The upper first molar was extracted 2 weeks following the first administration. Immediately after extraction, rats received normal saline (group Ι), hGMSCs (group ΙΙ), and hGMSCs primed with vitamins A/C (group ΙΙΙ). Rats were euthanized 2 and 4 weeks after extraction. The maxillae were analyzed using dual-energy X-ray absorptiometry, histologically, histomorphometrically, and by quantitative real-time polymerase chain reaction analysis. Groups II and III displayed elevated bone mineral density, with a significant rise in group ΙΙΙ relative to group ΙΙ at 4 weeks. Histomorphometrically, groups II and III revealed an elevation in area percentage of newly generated bone, with a significant rise in group ΙΙΙ at both time intervals. Gene expression of transforming growth factor-β1 (TGF-β1) and runt-related transcription factor 2 (Runx2) presented a significant elevation in groups II and III, with a significant rise in group ΙΙΙ at both time intervals. In conclusion, vitamins A/C-primed hGMSCs at the tested pluripotency-inductive concentrations prevented MRONJ development, primarily through encouraging wound healing and bone repair in the extraction sockets of rats.

Objective: The current trial assessed for the first time radiographic and histological alterations, following alveolar ridge preservation (ARP), using autogenous demineralized dentin graft carried in 0.2% high molecular weight sodium hyaluronate (ADDG+HA; test group) versus autogenous demineralized dentin graft (ADDG, control group) alone. Material and Methods: Thirty patients ( n = 30) with non‐restorable single‐rooted teeth were randomly assigned into two groups ( n = 15/group). Following extraction, ARP was performed using either ADDG solely or ADDG+HA. Bucco‐lingual alveolar ridge width (BLRW; primary outcome), buccal (BRH) and lingual ridge height (LRH), percentage of newly formed bone, soft tissue and residual graft in human biopsies histologically, as well as patients' pain and discomfort (all secondary outcomes) were assessed after 6 months at the time of implant placement. Sample bone core biopsies were further collected, processed, and histomorphometrically and SEM analyzed. Results: For the ADDG and ADDG+HA groups, the alveolar ridge dimensional changes were comparable, being −1.21 ± 0.77 mm and −1.18 ± 0.86 mm in BLRW, −0.89 ± 0.74 and −0.83 ± 0.85 mm in BRH, and −0.9 ± 0.76 mm and −1.05 ± 1.18 mm in LRH respectively ( p > 0.05). Clinically, no complications, pain, or inflammatory responses were reported. Histologically, all samples demonstrated bone growth and socket bone fill, while the ADDG+HA group showed a significantly greater presence of mineralized mature bone, which accounted for 33% ± 8.1% of the specimen after 6 months. Conclusions: Both ADDG and ADDG+HA demonstrated comparable outcomes in terms of ARP. HA amalgamation with ADDG appears to enhance bone mineralization and maturation, yet without a significant impact on dimensional changes during ARP procedures. Trial Registration: NCT05613075

The dental pulp and the periodontal tissues are crucial for maintaining oral health through supporting the structure, function, and integrity of teeth and surrounding tissues. The potential to regenerate these tissues (in case of their damage) represents a significant advancement in dental medicine. A functional regeneration could profoundly impact the quality of life for individuals with dental and periodontal diseases through offering new solutions to tissue loss and dental functional impairment, beyond what conventional dental therapies would provide. Studies on tissue engineering‐based dentin‐pulpal and periodontal regeneration have demonstrated promising results, using mesenchymal stromal cells (MSCs) from sources like bone marrow, adipose tissue, and cord blood. Nevertheless, MSCs derived directly from dental and periodontal tissues exhibit unique biological properties, with the potential to specifically address dental and periodontal regeneration, holding distinctive regenerative and immunomodulatory properties that may allow them to become valuable tools in clinical regenerative procedures. Their use in therapies could greatly benefit patients with oral and periodontal diseases, potentially enhancing life quality. Despite these promising findings, the distinct regenerative capacity of these cells, their mechanisms, and their potential clinical translational applications remain not fully elucidated. This review article aims to consolidate current knowledge about the biological characteristics and regenerative capabilities of dental and periodontal MSCs. By exploring the biology, isolation, and functional capacities of these cells, this work seeks to offer a deeper understanding of their potential and limitations, guiding future research and clinical strategies.

Injectable platelet-rich fibrin (I-PRF) is an autologous fibrin matrix rich in leucocytes, platelets and growth factors, and could serve as a sustained-release vehicle for a variety of active biomolecules. The aim of the current randomized controlled trial was to compare the effect of vitamin C (VitC) with I-PRF as a locally delivered adjunct to professional mechanical plaque removal (PMPR) versus PMPR with local delivery of I-PRF or PMPR alone on non-surgical periodontal treatment (NSPT) outcomes of stage-II periodontitis. Forty-five patients (n = 45) diagnosed with stage-II grade A periodontitis were randomly assigned into test (PMPR + I-PRF/VitC; n = 15) or control groups (PMPR + I-PRF; n = 15 and PMPR; n = 15). Bleeding on probing (BOP; primary outcome), probing depth (PD), clinical attachment level (CAL), gingival margin (GM), plaque index (PI) and radiographic bone gain/loss (horizontal, vertical and total) were assessed at baseline, three- and six-months post-treatment. Post-operative pain was further assessed at second- and third-day post-treatment. Although BOP scores were lower in the PMPR + I-PRF/VitC group, the regression analysis revealed that gender was the only significant predictor for BOP, with females showing a reduced propensity (p < 0.05). Clinical and radiographic parameters significantly improved in all groups independently (p < 0.05). PD-reduction was 1.73 ± 0.59 mm, 1.67 ± 0.49 mm and 1.73 ± 0.59 mm, CAL-change was 1.33 ± 0.49 mm, 1.20 ± 0.56 mm and 0.93 ± 0.59 mm and GM-change was 0.40 ± 0.51 mm, 0.33 ± 0.49 mm and 0.73 ± 0.70 mm in the PMPR + I-PRF/VitC, PMPR + I-PRF and PMPR groups respectively. No intergroup differences were notable regarding BOP or changes in PD, CAL, GM, PI and radiographic bone measurements at three or six months relative to baseline (p > 0.05). Significantly lower pain scores at two and three days were notable in the PMPR + I-PRF/VitC and PMPR + I-PRF groups compared to the PMPR group (p < 0.05). Apart from a positive effect on the patients’ post operative pain perception, I-PRF with or without the addition of vitamin C does not additionally improve the clinical outcomes of PMPR alone in the NSPT of stage-II grade A periodontitis patients. Trial registration. The study was retrospectively registered in the US National Institutes of Health Clinical Trials Registry (NCT05129267) on 2021-11-10.