[The efficacy of iRoot BP plus in the treatment of adult carious pulp exposure and its impact on pulp blood flow].

PURPOSE: To explore the efficacy of iRoot BP plus in the treatment of adult carious pulp exposure and its impact on pulp blood flow. METHODS: A total of 126 cases of 156 permanent teeth from adult patients with carious pulp exposure who were treated from January 2020 to January 2022 were selected, the patients were divided into experimental group(63 cases with 79 permanent teeth) and control group(63 cases with 77 permanent teeth) by the envelope method. The experimental group was treated with iRoot BP plus, while the control group was treated with mineral trioxide polymer. The differences in treatment effectiveness, operation time, and tooth discoloration between the two groups were observed. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: There was no significant difference in treatment success rates between the experimental group and the control group at 3, 6, and 12 months after surgery(P＞0.05). The operating time for each capsule in the experimental group was (2.53±0.41) min, which was significantly shorter than that in the control group(P＜0.05). The incidence of tooth discoloration in the experimental group at 12 months after surgery was 3.80%, which was significantly lower than that in the control group (P＜0.05). The bite force quotient and masticatory efficiency of the experimental group 12 months after operation were (16.65±1.14) Ibs and (94.45±5.65)%, which were significantly higher than those of the control group(P＜0.05). CONCLUSIONS: IRoot BP plus has good efficacy in the treatment of adult carious pulp exposure, with advantages such as convenient operation, less tooth discoloration, less inflammatory reactions and stable pulp blood flow after decline.

Neovascularization by DPSC-ECs in a Tube Model for Pulp Regeneration Study.

The process of neovascularization during cell-based pulp regeneration is difficult to study. Here we developed a tube model that simulates root canal space and allows direct visualization of the vascularization process in vitro. Endothelial-like cells (ECs) derived from guiding human dental pulp stem cells (DPSCs) into expressing endothelial cell markers CD144, vWF, VEGFR1, and VEGFR2 were used. Human microvascular endothelial cells (hMVECs) were used as a positive control. DPSC-ECs formed tubules on Matrigel similar to hMVECs. Cells were mixed in fibrinogen/thrombin or mouse blood and seeded into wells of 96-well plates or injected into a tapered plastic tube (14 mm in length and 1 or 2 mm diameter of the apex opening) with the larger end sealed with MTA to simulate root canal space. Cells/gels in wells or tubes were incubated for various times in vitro and observed under the microscope for morphological changes. Samples were then fixed and processed for histological analysis to determine vessel formation. Vessel-like networks were observed in culture from 1 to 3 d after cell seeding. Cells/gels in 96-well plates were maintained up to 25 d. Histologically, both hMVECs and DPSC-ECs in 96-well plates or tubes showed intracellular vacuole formation. Some cells showed merged large vacuoles indicating the lumenization. Tubular structures were also observed resembling blood vessels. Cells appeared healthy throughout the tube except some samples (1 mm apical diameter) in the coronal third. Histological analysis also showed pulp-like soft tissue throughout the tube samples with vascular-like structures. hMVECs formed larger vascular lumen size than DPSC-ECs while the latter tended to have more lumen and tubular structure counts. We conclude that DPSC-ECs can form vascular structures and sustained in the 3-dimensional fibrin gel system in vitro. The tube model appears to be a proper and simple system simulating the root canal space for vascular formation and pulp regeneration studies.

Effect of Orthognathic Surgery On Pulp Blood Flow and Pulp Sensibility: A Prospective Control Trial.

INTRODUCTION: Orthognathic surgery has the potential to compromise the vitality of the teeth. This paper aims to assess changes in pulp blood flow (PBF) and pulp sensibility (PS) of the anterior dentition following orthognathic surgery and to assess the influence of the proximity of the surgical osteotomy on the PBF and/or PS. METHODS: Twenty-six patients undergoing orthognathic surgery (Le Fort I or bilateral sagittal split osteotomy [BSSO]) were compared to sixteen control patients treated by fixed appliances only using Laser Doppler flowmeter (LDF) and thermal testing (CO2 snow). Surgery patients were tested at T1 (presurgery), T2 (4-5 weeks postsurgery), T3 (3 months postsurgery), and T4 (6 months postsurgery). Control patients were tested at T1 (pretreatment), T2 (6 months posttreatment), T3 (12 months posttreatment), and T4 (18 months posttreatment). Differences between the maxilla and mandible were assessed. RESULTS: No differences in PBF or PS were recorded in the control group. In the surgery group, both jaws followed the same pattern after surgery, an initial decrease at T2 followed by a gradual recovery to pretreatment PBF levels with no significant difference between T1 versus T4 in both jaws. No difference in PBF was observed between the maxilla and mandible at any testing time interval. CONCLUSIONS AND CLINICAL IMPLICATIONS: PBF and PS of the anterior dentition was severely affected immediately postsurgery, followed by a gradual increase to full recovery. This pattern of recovery was exhibited in both jaws. A negative sensibility response or discoloration should not be seen as an indication of irreversible ischemic pulp changes. Monitoring for at least 6 months or using LDF as a confirmatory test is required before any irreversible endodontic treatment is to be considered.

Extraction of high inverted mesiodentes via the labial, palatal and subperiostal intranasal approach：A clinical prospective study.

The aim of this study is to provide criteria for the choice of the surgical approach for extraction of high inverted mesiodens. The operation statistics, life quality of postoperative patients, and the operative injury/recovery were compared and analysed. The laser Doppler blood flowmetry, laser speckle contrast imaging, and electric pulp testing were explored to detect the postoperative pulp and gingiva blood supply of adjacent teeth. For the clinician's primary concerns, the surgical time, the volume of osteotomy, and the amount of bleeding in the labial approach group (The p values are 0.0001, <0.0001, and 0.0131, respectively.) and intranasal approach group (All p values were <0.0001.) were significantly less than that in the palatal approach group. However, from the patient's perspective, the postoperative swelling in the labial approach was far more than that in the intranasal approach group (p =0.0044), with unsurprisingly lower satisfaction (p <0.0001). There were no significant differences in pulp and gingival blood supply of adjacent teeth and jaw development. Trauma was manageable in all patients. Within the limitations of the study it seems that extraction of mesiodens by the intranasal approach achieves a delicate balance between reducing surgical trauma and optimizing postoperative recovery.

Assesment of radiotherapy effects on the blood flow in gingiva and dental pulp - a laser Doppler flowmetry study.

OBJECTIVE: This study aims to determine and compare the dental pulp and gingival blood flow in patients referred for oropharyngeal radiotherapy (RT) at three different time points: before the start, immediately after, and six months following the completion of RT. The aim is also to evaluate the dependence of the pulp and gingival blood flow on the radiation dose. METHODOLOGY: A prospective study included 10 patients referred for intensity-modulated RT (IMRT) in the oropharyngeal region, with at least one intact tooth surrounded by a healthy gingiva. The dose received by each selected tooth and adjacent gingiva was determined according to the map of treatment planning and computer systems. The blood flow measurements were performed using the laser Doppler flowmetry (LDF) method. RESULTS: Comparing vascular flows at three different time points, the median blood flow in the dental pulp showed no statistically significant difference (p=0.325), contrary to gingiva (p=0.011). Immediately after RT completion, the gingival flow significantly increased compared to its starting point (p=0.012). The pulp flow correlated negatively with the radiation dose, whereas a strong correlation was noted 6 months following the RT completion. CONCLUSIONS: RT caused a significant acute gingival blood flow increase, followed by a long-term (over six months) tendency to return to the starting levels. The dental pulp blood flow is differently affected by higher radiation doses (over 50Gy) in comparison to lower doses (below 50Gy). During RT planning, considering the possibility of protecting the teeth localized near the Gross Tumor Volume as a sensitive organ is recommended.

Association between Orthodontic Force and Dental Pulp Changes: A Systematic Review of Clinical and Radiographic Outcomes.

INTRODUCTION: Orthodontic force triggers a sequence of biological responses that can affect dental pulp. The aim of this study was to systematically evaluate the clinical and radiographic findings of orthodontic force application on dental pulp. METHODS: Two reviewers comprehensively and systematically searched 6 electronic databases (Latin American and Caribbean Health Sciences [LILACS], Embase, Cochrane Library, MEDLINE/PubMed, Scopus, and Web of Science) and the gray literature (Google Scholar, OpenGrey, and ProQuest) until April 2021. According to the PICOS criteria, randomized clinical trials and observational studies that evaluated clinical or radiographic findings compatible with dental pulp changes due to orthodontic force were included. Studies in open apex or traumatized teeth, case series or reports, and laboratory-based or animal studies were excluded. The Newcastle-Ottawa Scale and Cochrane Risk of Bias 2.0 tool were used to determine the risk of bias assessment. The overall certainty level was evaluated with the Grading of Recommendations, Assessment, Development and Evaluations tool. RESULTS: Twenty-six studies were included. Among the clinical findings, orthodontic force promoted an increased pulp sensibility response and decreased pulp blood flow. Changes in pulp cavity volume and increased incidence of pulp stones were the radiographic findings observed. The studies presented a moderate risk of bias for most of the domains. The certainty of the evidence was considered very low. CONCLUSIONS: Orthodontic force promoted changes in the dental pulp, generating clinical and radiographic findings. It is crucial to know these changes so that orthodontic mechanics can be safely performed. The clinician has effective noninvasive methods to assess the health and possible pulp changes during orthodontic treatment.

Which experimental models and explorations to use in regenerative endodontics? A comprehensive review on standard practices.

Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.

Treatment outcomes of pulp revascularization in traumatized immature teeth using calcium hydroxide and 2% chlorhexidine gel as intracanal medication

Abstract Objective Pulp revascularization is an effective treatment for immature necrotic teeth. Calcium hydroxide has been used in pulp revascularization as an intracanal medication due to its antimicrobial action and the non-exhibition of crown discoloration and cytotoxicity for stem cells from the apical papilla. Our study aimed to investigate the clinical success and quantitative radiographic changes of root development in immature traumatized teeth using calcium hydroxide plus 2% chlorhexidine gel as intracanal medication. Methodology In this retrospective study, 16 patients were treated with a standardized pulp revascularization protocol. Calcium hydroxide and 2% chlorhexidine gel were manipulated in a 1:1 (v/v) ratio and inserted into root canals with Lentulo spirals (Dentsply Maillefer, Baillaigues, Switzerland). Patients were followed up for a period from 9 to 36 months for the evaluation of clinical and radiological data. Radiographic measurements of root length, root width, apical diameter, and MTA placement from the apex were quantified using software ImageJ. Wilcoxon test and t-test were used, according to nonparametric or parametric data, respectively, for changes over time in root length, root width, and apical diameter. Results Fifteen teeth survived during the follow-up period (93.75%) and met the criteria for clinical success. Although the changes seem to be very small in many cases, significant increases in the average root length (14.28%, p<0.0001), root width (8.12%, p=0.0196), and decrease in apical diameter (48.37%, p=0.0007) were observed. MTA placement from the apex and age at the time of treatment was not significantly associated with the quantitative radiographic outcomes. Conclusions Pulp revascularization in traumatized immature teeth treated with calcium hydroxide plus 2% chlorhexidine gel as intracanal medication had high success and survival rates, showing periodontal healing and resolution of signs and symptoms. However, concerning the continued root development, the outcomes can still be considered unpredictable.

Changes in pulp blood flow and pulp sensibility resulting from surgically assisted rapid maxillary expansion: A clinical study.

INTRODUCTION: The aim of this work was to assess and compare changes in pulp blood flow (PBF) and pulp sensibility (PS) after surgically assisted rapid maxillary expansion (SARME) and rapid orthopedic maxillary expansion (OME). METHODS: Ten patients requiring SARME and 10 requiring OME had the pulp status of their maxillary incisors and canines assessed with the use of laser Doppler flowmetry, electric pulp testing (EPT), and CO2 snow. The SARME group was assessed at T1-S (before surgery), T2-S (after surgery, before expansion), T3-S (after surgery, at completion of expansion), and T4-S (3 months after surgery). The OME group was assessed at T1-O (before expansion), T2-O (after rapid expansion), and T3-O (3 months after expansion commencement). Relationships between PBF/PS and the procedures, assessment times, and tooth types were evaluated. RESULTS: In the SARME group, surgery did not cause significant (P ≥0.05) reduction in PBF, maxillary expansion did cause significant (P ≤0.05) reduction in PBF, pretreatment PBF was reestablished by T4-S, and nonresponses to both EPT and CO2 peaked at T2-S. In the OME group, rapid expansion caused significant (P ≤0.05) reduction in PBF, pretreatment PBF was reestablished by T3-O, and all teeth responded to at least 1 of EPT or CO2 at each assessment time. CONCLUSIONS AND CLINICAL IMPLICATIONS: Within the study's limitations, it can be concluded that both SARME and OME induce reduction but not elimination of PBF to maxillary anterior teeth and therefore do not cause loss of pulp vitality; surgery for SARME does not significantly reduce PBF to maxillary anterior teeth, rather it is the process of maxillary expansion that significantly reduces PBF in SARME patients; and caution when using CO2 and EPT tests alone to assess pulp status after SARME is warranted because the capacity for CO2 or EPT to provide negative sensibility responses despite the presence of PBF was observed.

Changes in the Periodontium and Pulp in ISIAH Rats Caused by Stress Exposures in Different Modes.

It was shown that the intensity of morphological changes in the dental system tissues (periodontium and pulp) of ISIAH rats depends on the mode of stress exposure. Acute stress was associated with a significant increase in the area of periodontal and pulp vessels, a decrease in the area of connective tissue of these components, and an increase in the thickness of the vascular endothelium. Chronic stress in these animals induced an increase in the thickness of the endothelial layer of the periodontal and pulp vessels, fibromatosis (increase in the number of fibroblasts), and a sharp decrease in the level of odontoblasts.

Prolonged release of iloprost enhances pulpal blood flow and dentin bridge formation in a rat model of mechanical tooth pulp exposure.

The aim of this study was to investigate the effect of prolonged release of iloprost, a prostacyclin analog, on angiogenesis and dental pulp healing in a rat model of mechanical pulp exposure. The profile of iloprost release from poly (lactic-co-glycolic) acid (PLGA) microspheres was evaluated, and expression of vascular endothelial growth factor (VEGF) mRNA was determined. The molars of rats were subjected to mechanical pulp exposure and 5 different forms of treatment: Ca(OH)2, PLGA (blank), iloprost, and iloprost/PLGA. Blood flow was determined at 0, 3, and 7 days using laser Doppler flowmetry. After 30 days, the tooth specimens were collected, and subjected to micro-CT and immunohistological analysis. The results showed that iloprost release from the microspheres was prolonged for 4 days, and that the treatment increased tooth blood flow for up to 7 days. At 30 days, an increase of mineralized tissue formation and dentin bridge formation was observed in the iloprost and iloprost/PLGA microsphere groups. VEGF expression was significantly increased in the iloprost/PLGA microsphere group relative to the other groups. In conclusion, this PLGA microsphere iloprost delivery system significantly increased dental pulp blood flow in a prolonged manner and increased tertiary dentin formation in this rat pulp injury model. Prolonged prostacyclin release could be a potentially useful approach for regeneration of dental pulp.

Overexpression of ephrinB2 in stem cells from apical papilla accelerates angiogenesis.

OBJECTIVES: We aimed to accelerate angiogenesis in pulp regeneration by modulating ephrinB2 expression in stem cells from apical papilla (SCAPs). MATERIALS AND METHODS: Stem cells from apical papilla were transducted with ephrinB2-lentiviral expression vector (ephrinB2-SCAPs) in experimental group and green fluorescent protein (GFP-SCAPs) in control group. The transduction efficiency was confirmed by real-time PCR and Western blot assays. MTT assay was performed to detect the proliferative capacity of SCAPs after transduction. In vitro Matrigel assay and in vivo Matrigel plug assay were carried out to evaluate the angiogenic capacity. RESULTS: Results showed that ephrinB2-SCAPs had significantly higher ephrinB2 expression than GFP-SCAPs. EphrinB2-SCAPs upregulated vascular endothelial growth factor (VEGF) secretion under hypoxia. In vitro Matrigel assay demonstrated that human umbilical vein endothelial cells (HUVECs) cocultured with ephrinB2-SCAPs under hypoxia formed vascular-like structures earlier than GFP-SCAPs. Animal experiments confirmed that SCAPs co-transplanted with HUVECs enabled to generate greater amount of blood vessels than SCAPs alone. EphrinB2-SCAPs produced increased number of blood vessels with references to GFP-SCAPs, and those co-transplanted with HUVECs generated vessels with larger and functional tubule volumes. CONCLUSIONS: Regulating ephrinB2 expression in SCAPs may act as a new avenue for enhancing angiogenesis in dental pulp regeneration.

Clinical antibacterial effectiveness and biocompatibility of gaseous ozone after incomplete caries removal.

OBJECTIVES: To evaluate local effect of gaseous ozone on bacteria in deep carious lesions after incomplete caries removal, using chlorhexidine as control, and to investigate its effect on pulp vascular endothelial growth factor (VEGF), neuronal nitric oxide synthase (nNOS), and superoxide dismutase (SOD). MATERIALS AND METHODS: Antibacterial effect was evaluated in 48 teeth with diagnosed deep carious lesion. After incomplete caries removal, teeth were randomly allocated into two groups regarding the cavity disinfectant used: ozone (open system) or 2% chlorhexidine. Dentin samples were analyzed for the presence of total bacteria and Lactobacillus spp. by real-time quantitative polymerase chain reaction. For evaluation of ozone effect on dental pulp, 38 intact permanent teeth indicated for pulp removal/tooth extraction were included. After cavity preparation, teeth were randomly allocated into two groups: ozone group and control group. VEGF/nNOS level and SOD activity in dental pulp were determined by enzyme-linked immunosorbent assay and spectrophotometric method, respectively. RESULTS: Ozone application decreased number of total bacteria (p = 0.001) and Lactobacillus spp. (p < 0.001), similarly to chlorhexidine. The VEGF (p < 0.001) and nNOS (p = 0.012) levels in dental pulp after ozone application were higher, while SOD activity was lower (p = 0.001) comparing to those in control pulp. CONCLUSIONS: Antibacterial effect of ozone on residual bacteria after incomplete caries removal was similar to that of 2% chlorhexidine. Effect of ozone on pulp VEGF, nNOS, and SOD indicated its biocompatibility. CLINICAL RELEVANCE: Ozone appears as effective and biocompatible cavity disinfectant in treatment of deep carious lesions by incomplete caries removal technique.

Quantitative assessment of morphological changes of dental pulp components of teeth affected by occlusal trauma.

AIM: In the general economy of the stomatognathic system functionality, the occlusal function has an important role, meaning both the dental-dental reports and the dynamic reports interarch-interarch. Because of the interrelationships and inter-dependency that govern the functioning of the biological systems, a pathological change affecting a component of the stomatognathic system produces impaired functioning of the others. The aim of the present study is to assess the morphological changes occurred in the dental pulp components of teeth affected by occlusal trauma. MATERIALS AND METHODS: Fragments of dental pulp coming from 45 patients with occlusal trauma were processed using classical histological techniques (formalin fixation and paraffin embedment) and stained with Hematoxylin-Eosin (HE), Masson's trichrome and anti-CD34 antibody immunostaining, in order to highlight the peripheral zone and central connective tissue of dental pulp morphological changes. A set of parameters namely thickness of peripheral zone components, calcifications, fibrosis and vascular density in the dental pulp were assessed individually and based on three topographical criteria namely the affected tooth, the position on the dental arches and the position according to sagittal plane. RESULTS: There was no correlation between morphological changes of dental pulp and the topography of teeth with occlusal trauma. The size of the peripheral area of the dental pulp and that of its components evolved in the same sense, whether it was growth or decrease. Decrease of the peripheral area was associated with the increase of collagen fibers density, calcium deposits and density of the capillary network. The direct correlation between the amount of collagen fibers and vascular density seems somewhat paradoxical but it can be explained by the reemergence of chronic inflammatory events located in the dental pulp. CONCLUSIONS: It seems that dental pulp morphological changes are not influenced by the teeth with occlusal trauma topography. With one exception (the components of peripheral zone), most of the correlations between the dental pulp morphological changes were only suggested but not validated statistically, which requires further studies on larger groups together with the introduction of inflammatory cell population studies.

[Vascular endothelial growth factor-loaded microspheres promote dental pulp regeneration and vascularization].

Objective: To evaluate the effect of vascular endothelial growth factor (VEGF)-loaded microspheres on dental pulp tissue regeneration and vascularization in vivo. Methods:In vitro release experiment and human umbilical vein endothelial cell migration experiment were conducted with VEGF loaded microspheres. The dental pulp stem cells (DPSC) were co-cultured with VEGF microspheres to observe the compatibility between the cells and the microspheres. DPSC and VEGF loaded microspheres were injected into the root lumen through the apical foramen, which were then transplanted subcutaneously into nude mice. Histological and immunohistochemical features were observed after nine weeks. Results: DPSCs attached and spread on the surface of the microspheres. HE staining showed that the regenerated pulp-like tissue fulfilled the whole apex and middle third of the root. Differentiated odontoblast-like cells aligned with the existing tubular root dentin. Conclusions: VEGF-loaded microspheres promoted the regeneration of pulp-like tissues and formation of blood vessels.

[An in vitro study of the angiogenic effects of concentrate growth factor on human umbilical vein endothelial cells].

OBJECTIVE: This study aimed to explore the effects of concentrate growth factor extracts (CGFe) on human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: Concentrate growth factor (CGF) were prepared from the peripheral blood of healthy donors, followed by CGFe. Four groups were designed based on cell culture medium, as follows: 2%CGFe, 5%CGFe, 10%CGFe, and control. The proliferation activity of HUVECs was detected by cell cycle and CCK-8 assays. The migration of HUVECs was detected by scratch assay. The mRNA expression levels of vascular endothelial growth factor (VEGF), chemokine receptor 4 (CXCR4), and platelet derived growth factor (PDGF) were examined by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: Results of CCK-8 and cell cycle assays showed that CGFe promoted the proliferation capability of HUVECs in a dose-dependent manner, and the data had statistical significance among four groups (P<
0.05). The cell migration assay indicated that CGF accelerated wound closure in a dose-dependent manner after 12 h of culture (P<0.05). The results of qRT-PCR showed that CGF upregulated the expression levels of VEGF, CXCR4, and PDGF in HUVECs. CONCLUSIONS: CGFe can promote the proliferation, migration, and angiogenic differentiation of HUVECs. Thus, CGF might be an appropriate cure for dental pulp revascularization.

[State of the art and perspective of pulp regeneration].

Recently, various levels of success have been achieved in dental pulp and dentin regeneration using latest techniques such as pulp revascularization, stem cell transplantation and cell homing. These cutting-edge technologies utilize stem cell mobilization, homing and directional differentiation, stem cell sub-population isolation, expansion and transplantation, modification and optimization of biomaterials and/or synergetic effects of biological cues. The objective of this review is to identify approaches for clinical translation and improve the success rates of pulp regeneration. We will focus on either basic and clinical research progress of dental pulp revascularization, or translational challenges and strategies of stem cell transplantation and cell homing in dental pulp regeneration.

Pulp analysis of teeth submitted to different types of forces: a histological study in rats

Abstract Objective: The purpose of this study was to histologically evaluate pulp and dentin under induced tooth movement (ITM) with different types of forces. Material and Methods: The maxillary right first molars of rats were submitted to movement with continuous (CF), continuous interrupted (CIF) and intermittent (IF) forces during 5, 7 and 9 days with nickel-titanium (NiTi) closed-coil springs exerting 50cN force magnitude. The groups were histologically evaluated as for cellularity pattern, presence of dystrophic, hemodynamic alterations in the pulp as well dentin alterations. The main observed alterations were related to hemodynamic pulp characteristics, such as presence of thrombosis, vascular congestion and hemorrhages. The hemodynamic alterations were statistically evaluated by Shapiro-Wilk normality test and analysis of variance by the Kruskall-Wallis test. Results: There was no significant differences observed between groups in the different types of applied forces and duration of ITM (vascular congestion, p=1.000; hemorrhage, p=0.305; thrombosis, p=1.000). Conclusions: Pulp tissue alterations resulting from ITM were limited to hemodynamic events, without progressing to irreversible degeneration, regardless of the type of force applied.

Current challenges in human tooth revitalization.

Tooth vitality and health are related to the presence of a living connective tissue, the dental pulp (DP), in the center of the dental organ. The DP contains the tooth immune defence system that is activated against invading oral cariogenic bacteria during the caries process and the tissue repair/regeneration machinery involved following microorganisms' eradication. However, penetration of oral bacteria into the DP often leads to complete tissue destruction and colonization of the endodontic space by microorganisms. Classical endodontic therapies consist of disinfecting then sealing the endodontic space with a gutta percha-based material. However, re-infections of the endodontic space by oral bacteria can occur, owing to the lack of tightness of the material. Recent findings suggest that regenerating a fully functional pulp tissue may be an ideal therapeutic solution to maintain a tooth defence system that will detect and help manage future injuries. The objective of this paper was to explain the different revascularization and regeneration strategies that have been proposed to reconstitute a living DP tissue and to discuss the main challenges that have to be resolved to improve these therapeutic strategies.

Pulp Vascularization during Tooth Development, Regeneration, and Therapy.

The pulp is a highly vascularized tissue situated in an inextensible environment surrounded by rigid dentin walls, with the apical foramina being the only access. The pulp vascular system is not only responsible for nutrient supply and waste removal but also contributes actively to the pulp inflammatory response and subsequent regeneration. This review discusses the underlying mechanisms of pulp vascularization during tooth development, regeneration, and therapeutic procedures, such as tissue engineering and tooth transplantation. Whereas the pulp vascular system is established by vasculogenesis during embryonic development, sprouting angiogenesis is the predominant process during regeneration and therapeutic processes. Hypoxia can be considered a common driving force. Dental pulp cells under hypoxic stress release proangiogenic factors, with vascular endothelial growth factor being one of the most potent. The benefit of exogenous vascular endothelial growth factor application in tissue engineering has been well demonstrated. Interestingly, dental pulp stem cells have an important role in pulp revascularization. Indeed, recent studies show that dental pulp stem cell secretome possesses angiogenic potential that actively contributes to the angiogenic process by guiding endothelial cells and even by differentiating themselves into the endothelial lineage. Although considerable insight has been obtained in the processes underlying pulp vascularization, many questions remain relating to the signaling pathways, timing, and influence of various stress conditions.