Human dental pulp stem/stromal cells in clinical practice.

Dental pulp stem/stromal cells (DPSCs) are fibroblast-like, neural crest-derived, and multipotent cells that can differentiate into several lineages. They are relatively easy to isolate from healthy and inflamed pulps, with little ethical concerns and can be successfully cryopreserved and thawed. The therapeutic effects of DPSCs derived from animal or human sources have been extensively studied through in-vitro and in-vivo animal experiments and the findings indicated that DPSCs are effective not only for dental diseases but also for systemic diseases. Understanding that translational research is a critical step through which the fundamental scientific discoveries could be translated into applicable diagnostics and therapeutics that directly benefit humans, several clinical studies were carried out to generate evidence for the efficacy and safety of autogenous or allogeneic human DPSCs (hDPSCs) as a treatment modality for use in cell-based therapy, regenerative medicine/dentistry and tissue engineering. In clinical medicine, hDPSCs were effective for treating acute ischemic stroke and human exfoliated deciduous teeth-conditioned medium (SHED-CM) repaired vascular damage of the corpus cavernous, which is the main cause of erectile dysfunction. Whereas in clinical dentistry, autologous SHED was able to regenerate necrotic dental pulp after implantation into injured teeth, and micrografts enriched with autologous hDPSCs and collagen sponge were considered a treatment option for human intrabony defects. In contrast, hDPSCs did not add a significant regenerative effect when they were used for the treatment of post-extraction sockets. Large-scale clinical studies across diverse populations are still lacking to provide robust evidence on the safety and efficacy of hDPSCs as a new treatment option for various human diseases including dental-related problems.

Stem cell-derived exosomes for dentin-pulp complex regeneration: a mini-review.

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

Impact of corticosteroid administration on the response of exposed dental pulp to capping with bioactive cements-experimental study on mongrel dogs.

BACKGROUND: Corticosteroids are commonly used as a treatment for a variety of pathological conditions, however, systemic corticosteroid administration has adverse effects including impaired immune response and wound healing. Such complications may affect pulp healing after direct pulp capping. The current study evaluated the influence of corticosteroids on the healing ability of exposed dogs' dental pulps after direct pulp capping (DPC) with bioactive materials. METHODS: Ten healthy male dogs were assigned randomly into two groups, 5 dogs each: group I represent the control group which did not receive any medication, and group II was given corticosteroid for 45 days before DPC and till the dogs were euthanized (n = 75 teeth for each group). Following mechanical exposure, the pulps were randomly capped with either Ca(OH)2, MTA, or Biodentine. The pulpal tissues' reaction to the capping materials was evaluated 65 days postoperatively according to the following parameters: calcific bridge formation, pulpal inflammation, pulp necrosis, and bacterial infiltration. RESULTS: The corticosteroid-treated group revealed no significant difference compared to the control group concerning the pulp healing response (P > 0.05). Both Biodentine and MTA-treated specimens revealed significant differences with Ca(OH)2-treated specimens (P < 0.05) which displayed a superior positive effect of both MTA and Biodentine to Ca(OH)2 regarding all the parameters. CONCLUSIONS: Direct pulp capping technique whenever indicated in subjects treated with corticosteroid immunosuppressive drugs like prednisone performed well in aseptic conditions especially when capped with bioactive materials.

Use of Melatonin/Decorticotomy and Autogenous Bone Graft in Induced 1-Wall Defect.

PURPOSE: This study was designed to investigate the effect of intramarrow penetration (IMP) and 1% melatonin (MLN) gel on the remodelling process of autogenous bone graft (ABG) in an induced 1-osseous wall defect model. METHODS: Sixty-four intrabony induced mandibular defects were created on the distal side of premolars-P1, P2, P3, and P4 (on each side)-in 8 beagle dogs. A ligature-induced periodontitis was initiated in each defect. Defects were then divided into 4 equal groups. Group I was treated with open-flap debridement (OFD) alone, group II was treated with OFD/ABG, group III was treated with OFD/IMP/ABG, and group IV was treated with OFD/ABG/IMP/1% MLN gel. The study parameters were bone fill, histologic analysis, and immunohistochemical evaluation of endothelial nitric oxide synthase (eNOS) expression at 2-week (2W) and 8-week (8W) time intervals. RESULTS: At 8W, significant differences were revealed amongst all groups regarding the amount of bone fill and eNOS expressions (P < .001). Bone fill percentages were 55.5%, 22.3%, 16.8%, and 0% in groups IV, III, II, and I, respectively. eNOS expressions were 1.68 ± 0.06, 8.43 ± 0.04, 16.80 ± 0.17, and 1.97 ± 0.07 in groups IV, III, II, and I, respectively. The favourable results were in line with group IV. CONCLUSIONS: According to these preliminary results, defects treated by ABG augmented with IMP and 1% MLN gel revealed a greater amount of bone fill and reduced eNOS expression. This combination is therefore highly suggested as an adjunct to ABG.

The effect of submucosal injection of platelet-rich fibrin vs. platelet-rich plasma on orthodontic tooth movement in rabbits; 28 days follow-up.

OBJECTIVE: This study aimed to compare between the effects of submucosal injection of platelet rich fibrin (i-PRF) versus platelet rich plasma (PRP) on orthodontic tooth movement (OTM) in a rabbit model over a 28-day follow-up period. MATERIALS AND METHODS: Sixty-three rabbits were assigned into 3 equal groups. Group I animals were subjected to the OTM without any treatments and considered as the control. Whereas groups II and III were handled as group I and instead i-PRF and PRP were injected submucosally in the buccal vestibular mucosa next to the mandibular 1st premolar, respectively. The distance of OTM was consecutively measured clinically after 7, 14 and 28 days. Seven rabbits from each group were euthanized after 7, 14 and 28 days for histological evaluation. Two-way ANOVA followed by LSD post-hoc statistical tests were used for comparison. RESULTS: After 28 days, the mean tooth movements were 4.36±0.04mm in the control group, 6.30±0.06mm in the group receiving PRP and, 6.85±0.09mm in the group receiving i-PRF. Statistical analysis for the values of teeth movements revealed highly significant differences between different groups (P=0.001) and between different time periods (P=0.001). Histological analysis showed that submucosal injection of PRP and i-PRF yielded significant differences in periodontal ligament width in compression and tension sides between different groups (P=0.001) and between different time periods (P=0.001). CONCLUSION: Submucosal injection of either PRP or i-PRF is a minimally invasive and safe approach for accelerating OTM. In this rabbit model, the effect of i-PRF is significantly more pronounced than the effect of PRP.

Impact of bone marrow mesenchymal stem cells on the submandibular gland structure of adult male albino rats exposed to cadmium chloride toxicity.

OBJECTIVE: This study was carried out in submandibular salivary glands of rats to demonstrate the changes induced by cadmium intoxication and the possible prophylactic and therapeutic effects of bone marrow mesenchymal stem cells (BMSCs). DESIGN: Sixty-five rats were divided into five groups. Rats in Group I were controls while those of Group II received daily dose of 10 mg/kg cadmium for 24 days. Rats in Group III received single prophylactic dose of 1 × 106 BMSCs one week before cadmium administration. Rats of Group IV were concomitantly administered cadmium and BMSCs, while those of Group V received cadmium for 24 days and were then treated with single dose of 1 × 106 BMSCs. Rats of Groups I, II, III, and IV were euthanized at the end of the experiment while those of Group V were euthanized one week later. Salivary gland specimens were processed and stained with H&E and inducible nitric oxide synthase; other specimens were used to demonstrate metallothionein gene expression using RT-PCR, malondialdehyde and catalase enzymes were detected by ELISA. RESULTS: Groups III and IV had nearly comparable findings to Group I regarding histological pattern with normal gland features. Group III recorded a lower fold of change for metallothionein gene (1.14 ± 0.20), a lower malondialdehyde enzyme (21.67 ± 1.63 nmol/mg), and a higher catalase enzyme (66.33 ± 2.16 mmol/mg). Regarding all variables, significant differences were found between the different groups (P < 0.001). CONCLUSION: BMSCs have prophylactic and therapeutic effects against cadmium-induced cytotoxicity in rat salivary glands.

Socket-shield Technique vs Conventional Immediate Implant Placement for Esthetic Rehabilitation: A Systematic Review and Meta-analysis.

AIM: The present systematic review and meta-analysis (SR/MA) aimed to test the null hypothesis that there is no difference between socket-shield technique (SST) and conventional immediate implant placement (CIIP) as an esthetic rehabilitation option for permanent human anterior teeth, against the alternative one of a difference. BACKGROUND: Socket-shield technique is considered as a highly promising procedure that has the potential to prevent resorption of anterior alveolar ridges, maintains white and pink esthetics, and provides a solution for esthetically critical cases. Controlled randomized clinical trials (RCT) and nonrandomized ones had been identified by searching the following databases: Google Scholar, Scopus, and PubMed. Literature search was determined from January 2010 up to June 2020. Hand searches were also accomplished for relevant abstracts, books, and reference lists. The eligibility criteria included prospective observational controlled RCTs and non-RCTs. POPULATIONS: patients with endodontically treated/nonrestorable permanent mature anterior teeth indicated for extraction. INTERVENTIONS: the sockets were subjected to immediate implant placement using SST. CONTROLS: implants placed with SST compared with those of CIIP. OUTCOME: the pink esthetic score measured for esthetic rehabilitation. To assess article quality, the Cochrane risk-of-bias tool was used by two independent authors. The data across quantitative studies were analyzed using comprehensive MA software. REVIEW RESULTS: The initial search found out 172 references through the search strategy and three additional ones were recognized through hand searching. After being filtered, 101 references were screened and recorded. After the inclusion and exclusion criteria were applied, only seven unduplicated prospective controlled RCTs and non-RCTs were involved in the quantitative MA. At the 6-month evaluation period, the total standard difference in mean was 1.07 and I 2 test value measuring heterogeneity was 77.182, whereas at the 12-month period, the total standard difference in mean was 1.43 and I 2 test value measuring heterogeneity was 64.914. CONCLUSION: SST had a positive effect on the esthetic rehabilitation for anterior teeth better than CIIP. However, this conclusion was dependent on a very few well-conducted prospective RCT and non-RCT. Further RCTs with longer observational time, proper methodology, and of larger sample size are still required to adequately answer the question of the present SR. CLINICAL SIGNIFICANCE: There is limited knowledge about the appropriateness of SST in the field of implant dentistry, specifically for esthetic consideration. This SR/MA confirmed the positive effect of the SST over CIIP for esthetic rehabilitation for anterior teeth. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020194086.

Demineralized Dentin Matrix for Dental and Alveolar Bone Tissues Regeneration: An Innovative Scope Review.

BACKGROUND: Dentin is a permeable tubular composite and complex structure, and in weight, it is composed of 20% organic matrix, 10% water, and 70% hydroxyapatite crystalline matrix. Demineralization of dentin with gradient concentrations of ethylene diamine tetraacetic acid, 0.6 N hydrochloric acid, or 2% nitric acid removes a major part of the crystalline apatite and maintains a majority of collagen type I and non-collagenous proteins, which creates an osteoinductive scaffold containing numerous matrix elements and growth factors. Therefore, demineralized dentin should be considered as an excellent naturally-derived bioactive material to enhance dental and alveolar bone tissues regeneration. METHOD: The PubMed and Midline databases were searched in October 2021 for the relevant articles on treated dentin matrix (TDM)/demineralized dentin matrix (DDM) and their potential roles in tissue regeneration. RESULTS: Several studies with different study designs evaluating the effect of TDM/DDM on dental and bone tissues regeneration were found. TDM/DDM was obtained from human or animal sources and processed in different forms (particles, liquid extract, hydrogel, and paste) and different shapes (sheets, slices, disc-shaped, root-shaped, and barrier membranes), with variable sizes measured in micrometers or millimeters, demineralized with different protocols regarding the concentration of demineralizing agents and exposure time, and then sterilized and preserved with different techniques. In the act of biomimetic acellular material, TDM/DDM was used for the regeneration of the dentin-pulp complex through direct pulp capping technique, and it was found to possess the ability to activate the odontogenic differentiation of stem cells resident in the pulp tissues and induce reparative dentin formation. TDM/DDM was also considered for alveolar ridge and maxillary sinus floor augmentations, socket preservation, furcation perforation repair, guided bone, and bioroot regenerations as well as bone and cartilage healing. CONCLUSION: To our knowledge, there are no standard procedures to adopt a specific form for a specific purpose; therefore, future studies are required to come up with a well-characterized TDM/DDM for each specific application. Likely as decellularized dermal matrix and prospectively, if the TDM/DDM is supplied in proper consistency, forms, and in different sizes with good biological properties, it can be used efficiently instead of some widely-used regenerative biomaterials.

Calcium Hydroxide Paste, Mineral Trioxide Aggregate, and Formocresol as Direct Pulp Capping Agents in Primary Molars: A Randomized Controlled Clinical Trial.

Purpose: The purpose of this study was to evaluate the clinical and radiographic outcomes of direct pulp capping (DPC) using calcium hydroxide (CH), mineral trioxide aggregate (MTA), and premedicated DPC with formocresol (FC) in primary teeth. Methods: Sixty primary mandibular second molars with pulp exposures in children aged four to eight years old were treated using DPC. The molars were randomly divided into three groups (n equals 20 per group). Pulp exposures in the CH and MTA groups were capped directly using CH and MTA pastes, respectively, while those in the FC group were premedicated with FC and then capped with zinc oxide eugenol (ZOE) cement. All teeth were finally restored with stainless steel crowns, and clinical and radiographic evaluations were carried out at baseline and three, six, and 12 months after restoration. Fisher's exact test was performed to define the significance between the groups and follow-up periods. Results: The clinical and radiographic findings showed no significant difference between the three groups. The overall success in the CH, MTA, and FC groups were 88.2 percent, 100 percent, and 73.3 percent, respectively. However, these differences were not statistically significant (P>0.05). Conclusion: All three materials examined in this study exhibited clinical and radiographical efficacy when used as direct pulp capping materials.

Influence of selective immunosuppressive drug regimens on the healing of exposed dogs' dental pulp capped with a recent calcium silicate-based cement.

OBJECTIVES: In the clinical medicine, immunosuppressive drugs are used for an assortment of disorders, while their effect on the pulp healing is a controversial issue. This study evaluated the effect of different immunosuppressive drugs on the healing capacity of mechanically exposed dogs' dental pulps after direct pulp capping (DPC) with calcium silicate-based cement. MATERIALS AND METHODS: Twelve healthy male dogs were randomly allocated into four equal groups, 3 dogs each: group I allocated as a control group where no drugs were received; group П given prednisone (Pred); group III given a combination of Pred and cyclosporine A (CsA); and group IV given triple dose including Pred, CsA, and mycophenolate mofetil (MMF) for 45 days before the operative procedures and until the dogs were euthanized. In each dog, 16 class V cavities were prepared on the labial surfaces of anterior teeth. Following mechanical exposure, the pulps were capped with Biodentine, calcium silicate-based cement. The pulpal tissues response to Biodentine was assessed 65 days postoperatively. RESULTS: The pulp healing response was inferior in the Pred-CsA- and Pred-CsA-MMF-treated groups compared with the control and Pred-treated groups (P < 0.05). Non-significant difference was found between control and Pred-treated groups (P > 0.05). CONCLUSIONS: Within the limitation of this study, DPC with calcium silicate-based cement performed under strict aseptic condition for traumatically exposed dental pulp can be considered as a successful treatment option for those who receiving Pred immunosuppressive therapy. Meanwhile, DPC with those receiving a combination of Pred, CsA, and/or MMF immunosuppressive drug regimens demonstrated unfavorable results. CLINICAL RELEVANCE: Direct capping of mechanically exposed pulps with calcium silicate-based cement performed with special care for preventing infection considered a suitable strategic measure for preserving pulp vitality in patients receiving corticosteroid immunosuppressive drug.

Efficacy of biocompatible trilayers nanofibrous scaffold with/without allogeneic adipose-derived stem cells on class II furcation defects of dogs' model.

OBJECTIVE: This study aimed to evaluate the regenerative capacity of a newly-developed polycaprolactone (PCL)-based nanofibrous composite scaffold either alone or in combination with adipose-derived mesenchymal stem cells (ADSCs) as a treatment modality for class II furcation defects. MATERIALS AND METHODS: After ADSCs isolation and scaffold characterization, the mandibular premolars of adult male mongrel dogs were selected and randomly assigned into three equal groups. In group I, class II furcation defects were surgically induced to the inter-radicular bone. While class II furcation defects of group II were induced as in group I. In addition, the defects were filled with the prefabricated scaffold. Moreover, class II furcation defects of group III were induced as in group II and instead the defects were filled with the prefabricated scaffold seeded with ADSCs. The dogs were sacrificed at 30 days or at 60 days. Periodontal wound healing/regeneration was evaluated by radiological examination using cone beam computed tomography and histologically using ordinary, histochemical, and immunohistochemical staining. RESULTS: In the two examination periods, group II defects compared to group I, and group III compared to the other groups showed a decrease in defect dimensions radiographically. Histologically, histochemically, and immunohistochemically, they significantly demonstrated better periodontal wound healing/regeneration, predominant collagen type I of newly formed bone and periodontal ligament with a significant increase in the immunoreactivity of vascular endothelial growth factor and osteopontin. CONCLUSIONS: The newly fabricated nanofibrous scaffold has enhanced periodontal wound healing/regeneration of class II furcation defects with further enhancement achieved when ADSCs seeded onto the scaffold before implantation. CLINICAL RELEVANCE: The implementation of our newly-developed PCL-based nanofibrous composite scaffolds in class II furcation defect either alone or in conjunction with ADSCs can be considered as a suitable treatment modality to allow periodontal tissues regeneration.

Dental pulp stem cells stimulate neuronal differentiation of PC12 cells.

Dental pulp stem cells (DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium (DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor (NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2 (MAP-2) and cytoskeletal marker ßIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and ßIII-tubulin were analysed by quantitative polymerase chain reaction (qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors (NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and ßIII-tubulin immunostaining. Furthermore, DPSCs-CM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls; however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, anti-GDNF and anti-BDNF antibodies. These findings demonstrated that DPSCs were able to promote PC12 survival and differentiation. DPSCs-derived NGF, BDNF and GDNF were involved in the stimulatory action on neurite outgrowth, whereas GDNF also had a significant role in promoting PC12 survival. DPSCs-derived factors may be harnessed as a cell-free therapy for peripheral nerve repair. All experiments were conducted on dead animals that were not sacrificed for the purpose of the study. All the methods were carried out in accordance with Birmingham University guidelines and regulations and the ethical approval is not needed.

Neurotrophic effects of dental pulp stem cells on trigeminal neuronal cells.

Evidence indicates that dental pulp stem cells (DPSC) secrete neurotrophic factors which play an important role in neurogenesis, neural maintenance and repair. In this study we investigated the trophic potential of DPSC-derived conditioned medium (CM) to protect and regenerate isolated primary trigeminal ganglion neuronal cells (TGNC). DPSC and TGNC were harvested by enzymatic digestion from Wister-Hann rats. CM was collected from 72 h serum-free DPSC cultures and neurotrophic factors; nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial cell line-derived neurotrophic factor (GDNF) were analysed by specific enzyme-linked immunosorbent assays (ELISAs). Primary co-cultures of DPSC and TGNC were established to evaluate the paracrine effects of DPSC. In comparison, NGF was used to evaluate its neurotrophic and neuritogenic effect on TGNC. Immunocytochemistry was performed to detect the neuronal-markers; neuronal nuclei (NeuN), microtubule-associated protein-2 (MAP-2) and ßIII-tubulin. Quantitative real time polymerase chain reaction (qRT-PCR) was used to analyse neuronal-associated gene expression of NeuN, MAP-2, ßIII-tubulin in addition to growth-associated protein-43 (GAP-43), Synapsin-I and thermo-sensitive transient receptor potential vanilloid channel-1 (TRPV1). DPSC-CM contained significant levels of NGF, BDNF, NT-3 and GDNF. DPSC and DPSC-CM significantly enhanced TGNC survival with extensive neurite outgrowth and branching as evaluated by immunocytochemistry of neuronal markers. DPSC-CM was more effective in stimulating TGNC survival than co-cultures or NGF treated culture. In comparison to controls, DPSC-CM significantly upregulated gene expression of several neuronal markers as well as TRPV1. This study demonstrated that DPSC-derived factors promoted survival and regeneration of isolated TGNC and may be considered as cell-free therapy for TG nerve repair.

Emerging therapeutic modality enhancing the efficiency of chemotherapeutic agents against head and neck squamous cell carcinoma cell lines.

The current work aimed to evaluate bee venom (BV) cytotoxic effect and its synergistic action when combined with cisplatin (CIS) against four types of head and neck squamous cell carcinoma (HNSCC) cell lines. 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cell viability, reverse transcription-polymerase chain reaction (RT-PCR) for expression of BCL2 associated X (BAX), B-cell lymphoma 2 (BCL2) and epidermal growth factor receptor (EGFR) genes and, flow cytometry for cell cycle analysis were performed. MTT assay revealed that BV caused an approximately 50% cell death for UMSCC12, UMSCC29, UMSCC38 and, UMSCC47 cell lines after 72 hr with 54.809 µg/ml, 61.287 µg/ml, 71.328 µg/ml and, 61.045 µg/ml, respectively. RT-PCR demonstrated a significant up-regulation of BAX gene and a significant down-regulation of BCL2 and EGFR genes among single or combined treatments with CIS and BV as compared to vehicle-treated. The cell lines treated with both BV and CIS showed marked elevation of BAX and a notable drop of BCL2 and EGFR expressions than single-treated groups. Cell cycle analysis via flow cytometry revealed significantly increased cells in the G2/M phase in single or combined-treated cell lines with CIS and BV when compared with vehicle-treated. Moreover, a significant decrease in cells in S phases among all single and combined treatments when matched with vehicle-treated. Briefly, the findings of the present study suggest that BV can exert an anti-cancer effect on HNSCC and may have the potentiality for potentiation of CIS cytotoxic effects and reduction of its adverse effects.

An in-vivo Intraoral Defect Model for Assessing the Use of P11-4 Self-Assembling Peptide in Periodontal Regeneration.

Periodontal disease is one of the most common diseases worldwide. It has a significant impact on oral health and subsequently the individual's quality of life. However, optimal regeneration of periodontal tissues, using current treatments, has yet to be achieved. Peptide self-assembly has provided a step-change in nanobiotechnology and regenerative medicine fields. Our aim was to investigate the effects of a self-assembling peptide (SAP; P11-4) on periodontal regeneration in a preclinical model. Twenty-six bilateral maxillary critical-sized periodontal defects were created surgically in 13 rats. Defects on one side of the mouth were filled with P11-4 hydrogel; the contra-lateral defect was untreated (control). Rats were sacrificed immediately post-surgery (time 0) and after 2 and 4 weeks. Retrieved maxillae were processed for histological, immunohistochemical, and histomorphometric assessments. The results of histological analysis showed greater organization of periodontal fibers in defects treated with P11-4, at both time points, when compared to untreated defects. Histomorphometry showed that treated defects had both a significant increase in functional periodontal ligament length and a reduction in epithelial down growth after 4 weeks. At 2 weeks, treated defects showed a significant increase in expression of osteocalcin and osteoprotegerin as judged by immunohistochemistry. Also, a significantly higher osteoprotegerin/RANKL ratio was shown in treated defects. In conclusion, the results demonstrated enhanced regeneration of periodontal tissues when SAP P11-4 was used to fill periodontal defects in rats. The findings of this study suggest that SAP P11-4 is a promising novel candidate for periodontal regenerative therapy. Further investigations are required for optimization before clinical use.

Challenges of Engineering Biomimetic Dental and Paradental Tissues.

BACKGROUND: Loss of the dental and paradental tissues resulting from trauma, caries or from systemic diseases considered as one of the most significant and frequent clinical problem to the healthcare professionals. Great attempts have been implemented to recreate functionally, healthy dental and paradental tissues in order to substitute dead and diseased tissues resulting from secondary trauma of car accidents, congenital malformations of cleft lip and palate or due to acquired diseases such as cancer and periodontal involvements. METHOD: An extensive literature search has been done on PubMed database from 2010 to 2019 about the challenges of engineering a biomimetic tooth (BioTooth) regarding basic biology of the tooth and its supporting structures, strategies, and different techniques of obtaining biological substitutes for dental tissue engineering. RESULTS: It has been found that great challenges need to be considered before engineering biomimetic individual parts of the tooth such as enamel, dentin-pulp complex and periodontium. In addition, two approaches have been adopted to engineer a BioTooth. The first one was to engineer a BioTooth as an individual unit and the other was to engineer a BioTooth with its supporting structures. CONCLUSION: Engineering of BioTooth with its supporting structures thought to be in the future will replace the traditional and conventional treatment modalities in the field of dentistry. To accomplish this goal, different cell lines and growth factors with a variety of scaffolds at the nano-scale level are now in use. Recent researches in this area of interest are dedicated for this objective, both in vivo and in vitro. Despite progress in this field, there are still many challenges ahead and need to be overcome, many of which related to the basic tooth biology and its supporting structures and some others related to the sophisticated techniques isolating cells, fabricating the needed scaffolds and obtaining the signaling molecules.

The effect of four materials on direct pulp capping: An animal study.

The aim of this study was to investigate the outcomes of direct pulp capping performed with two types of tricalcium silicate-based materials (mineral trioxide aggregate/MTA and Biodentine/BD); nano-hydroxyapatite (nHAP) crystals or calcium hydroxide (CH) in dogs. Following mechanical exposure, the pulps were randomly capped with one of the four materials. Histological analyses were performed to examine the outcomes after 7 days or 3 months. At 7 days, BD and nHAP showed significantly less inflammatory cell response than MTA and CH. At 3 months, the inflammatory cell response and tissue necrosis were significantly higher in the CH group. There was no significant difference between the tested materials in the calcific bridge formation after 7 days; however, a significant difference was noticed at the 3-month period. Tricalcium silicate-based cements and nHAP are potential alternatives to CH in vital pulp therapy following accidental pulp exposure.

Early therapeutic effect of platelet-rich fibrin combined with allogeneic bone marrow-derived stem cells on rats' critical-sized mandibular defects.

BACKGROUND: Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide. These defects generally result from severe trauma or resection of a whole large tumour. Autologous bone grafts are the current gold standard for the reconstruction of such defects. However, due to increased patient morbidity and the need for a second operative site, other lines of treatment should be introduced. To find alternative unconventional therapies to manage such defects, bone tissue engineering using a combination of suitable bioactive factors, cells, and biocompatible scaffolds offers a promising new approach for bone regeneration. AIM: To evaluate the healing capacity of platelet-rich fibrin (PRF) membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells (BMSCs) on critically sized mandibular defects in a rat model. METHODS: Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur. Rats were allocated to three equal groups of 21 rats each. Group I bone defects were irrigated with normal saline and designed as negative controls. Defects of group II were grafted with PRF membranes and served as positive controls, while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs. Seven rats from each group were killed at 1, 2 and 4 wk. The mandibles were dissected and prepared for routine haematoxylin and eosin (HE) staining, Masson's trichrome staining and CD68 immunohistochemical staining. RESULTS: Four weeks postoperatively, the percentage area of newly formed bone was significantly higher in group III (0.88 ± 0.02) than in groups I (0.02 ± 0.00) and II (0.60 ± 0.02). The amount of granulation tissue formation was lower in group III (0.12 ± 0.02) than in groups I (0.20 ± 0.02) and II (0.40 ± 0.02). The number of inflammatory cells was lower in group III (0.29 ± 0.03) than in groups I (4.82 ± 0.08) and II (3.09 ± 0.07). CONCLUSION: Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.

Characteristics of adhesive bonding with enamel deproteinization.

OBJECTIVE: To evaluate the effect of using sodium hypochlorite (NaOCl) on the bond characteristics of orthodontic metal brackets bonded to enamel surface using three adhesive systems. METHODS: One hundred twenty premolars were selected and randomly divided into two equal groups of 60 teeth/ each (Groups I and II). The teeth of Group I were left untreated while those of Group II were exposed to 5.25% NaOCl for 1 minute. The teeth in either group were randomly subdivided into three equal subgroups of 20 teeth/ each (A, B and C), according to the type of adhesive system used to bond the brackets. In Subgroup A, phosphoric acid + Transbond XT primer and adhesive were used. In subgroup B, Transbond Plus self-etching primer (SEP) + Transbond XT adhesive were utilized. In subgroup C, phosphoric acid + SmartBond LC adhesive were used. The shear bond strength (SBS) and the degree of adhesive penetration to enamel surface were assessed. Data analyses were performed using ANOVA, post-hoc (LSD), t and chi-square test. RESULTS: Transbond XT had significantly higher SBS than SmartBond LC (p< 0.05). Phosphoric acid provided significantly higher SBS and degree of adhesive penetration than SEP (p< 0.05). NaOCl significantly increased SBS and degree of adhesive penetration in Subgroups B and C (p< 0.05). CONCLUSION: Adhesion quality of Transbond XT adhesive is better than SmartBond LC. Phosphoric acid is more effective than SEP. NaOCl enhances the bond characteristics.