Effectiveness of revitalization in treating apical periodontitis: A systematic review and meta-analysis.

BACKGROUND: Revitalization procedures primarily aim to eliminate clinical symptoms and heal periapical lesions. OBJECTIVES: The objective of the study was to elucidate the effectiveness of revitalization in treating apical periodontitis in necrotic mature and immature permanent teeth based on the following PICO question: In patients with permanent immature or mature teeth and pulp necrosis with or without signs of apical periodontitis (P) what is the effectiveness of revitalization (I) in comparison with calcium hydroxide apexification, apical plug and root canal treatment (C) in terms of tooth survival, pain, tenderness, swelling, need for medication (analgesics and antibiotics), radiographic evidence of reduction of apical lesion size, radiographic evidence of normal periodontal ligament space, radiographic evidence of increased root thickness and length (not for mature teeth), tooth function (fracture and restoration longevity), need for further intervention, adverse effects (including exacerbation, restoration integrity, allergy and discolouration), oral health-related quality of life (OHRQoL), presence of sinus tract and response to sensibility testing (O). (T) = Defined as a minimum of 1 year and maximum of as long as possible for all outcome measures, except 'pain, tenderness, swelling, need for medication (analgesics)', which is a minimum of 7 days and maximum of 3 months and OHRQoL which is minimum of 6 months and a maximum of as long as possible. METHODS: Three databases (PubMed, Embase and Cochrane Library) were searched for human, experimental and observational studies in English, complemented with hand search, until 31/10/2021. Studies recruiting teeth with pulp necrosis (with/without apical periodontitis), with minimum 10 teeth/arm at the end of the study and with a follow-up of at least 1 year, were included. Records without an abstract and a full text were excluded. The qualitative analysis of the included (non-) randomized controlled clinical trials was performed with the Revised Cochrane risk-of-bias tools (RoB 2 and ROBINS-I). Meta-analysis for survival and success (including a subgroup analysis for mature/immature permanent teeth) was performed using the Mantel-Haenszel method. The certainty of evidence was assessed using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). RESULTS: From the 365 identified records, five met the inclusion criteria. The 12 months survival rate was 100% for all (im)mature permanent teeth in all groups (3 studies). The success rate at 12 months was 100% for immature permanent teeth for I and C (1 study), however, reduced to 92% and 80% for mature teeth in I and C respectively (1 study, p > .05). The risk of bias for the most critical outcome (survival) was high for two studies and low for one. For the critical outcome success, all assessed studies were highly biased. Meta-analyses provided pooled relative risk with no statistically significant difference between I and C for both survival (RR = 1.00, 95%CI = 0.96-1.04, p = 1.00) and success (RR = 1.06; 95%CI = 0.83-1.35, p = .66). The evidence level for survival was kept 'low' and for success was downgraded to 'very low' due to inconsistency and imprecision. DISCUSSION: The survival and success rates were favourable in all included studies and for all groups; however, these outcomes are not reliable due to the low certainty level. Clinically, the most reported adverse event was tooth discolouration, hence the application of bismuth oxide containing calcium silicate cements should be avoided in revitalization. Radiographically, caution is needed when assessing periapical bone healing and further root development with periapical radiographs, due to multifactorial inaccuracies of this imaging technique. Methodological and assessment concerns need to be addressed in future clinical trials. Long-term results are necessary for studies reporting revitalization of mature permanent teeth, as they seem to be experimental so far. CONCLUSIONS: No robust evidence was discovered to support that revitalization is effective to treat apical periodontitis in (im)mature permanent teeth. The success and survival rates of revitalized and fully pulpectomized (im)mature permanent teeth did not differ significantly. REGISTRATION: Prospero: CRD42021262466.

Effectiveness of endodontic tissue engineering in treatment of apical periodontitis: A systematic review.

BACKGROUND: Regenerative endodontics has evolved in recent years with tissue engineering concepts in particular appearing promising. Endodontic tissue engineering (ETE) describes the various approaches based on the orthograde introduction of scaffolds or biomaterials (with or without cells) into the root canal to achieve pulp tissue regeneration. There are currently no systematic reviews investigating whether ETE is a suitable method for the treatment of endodontic disease in both mature and immature permanent teeth. OBJECTIVES: The purpose of this systematic review was to determine the effectiveness of ETE in permanent teeth with pulp necrosis in comparison with conventional endodontic treatment. METHODS: We searched MEDLINE, Embase and the Cochrane Library for published reports as well as Google Scholar for grey literature up to November 2021. Included were studies of patients with permanent immature or mature teeth and pulp necrosis with or without signs of apical periodontitis (P) comparing ETE (I) with calcium hydroxide apexification, apical plug and root canal treatment (C) in terms of tooth survival, pain, tenderness, swelling, need for medication (analgesics and antibiotics), radiographic evidence of reduction in apical lesion size, radiographic evidence of normal periodontal ligament space, function (fracture and restoration longevity), the need for further intervention, adverse effects (including exacerbation, restoration integrity, allergy and discolouration), oral health-related quality of life (OHRQoL), presence of sinus tract and response to sensibility testing (O). An observation period of at least 12 months was mandatory (T) and the number of patients in human experimental studies or longitudinal observational studies had to be at least 20 (10 in each arm) at the end (S). Risk of bias was appraised using the Cochrane risk-of-bias (RoB 2) tool. Two authors independently screened the records, assessed full texts for eligibility and evaluated risk of bias. Heterogeneity of outcomes and limited body of evidence did not allow for meta-analysis. RESULTS: Two randomized clinical trials investigating cell transplantation approaches with a total of 76 participants (40 treated immature teeth and 36 treated mature teeth) were included for qualitative analysis. Both studies had moderate concerns in terms of risk of bias. Due to the lack of homogeneity a meta-analysis was not possible. Tooth survival for ETE, root canal treatment and apexification was 100% after 12 months. Teeth treated with ETE showed a higher number of cases with positive pulpal responses to sensitivity tests and with blood perfusion compared with root canal treatment or apexification. DISCUSSION: This systematic review highlights that there is limited evidence for ETE approaches. Even though the results of this review suggest a high survival with ETE in mature and immature teeth, there is a moderate risk of bias due to methodological limitations in the included studies, so the overall results should be interpreted with caution. Lack of a robust control group was a common problem during literature screening, and outcomes besides dental survival were reported inconsistently. Future clinical trials need to address methodical as well as assessment concerns and report long-term results. CONCLUSION: The benefits and high survival rates reported for ETE techniques suggest that this procedure might be an alternative to conventional procedures for permanent teeth with pulpal necrosis. However, more appropriate studies are needed to derive clinical recommendations. REGISTRATION: PROSPERO (CRD42021266350).

Present status and future directions: Hydraulic materials for endodontic use.

BACKGROUND: Hydraulic materials are used in Endodontics due to their hydration characteristics namely the formation of calcium hydroxide when mixing with water and also because of their hydraulic properties. These materials are presented in various consistencies and delivery methods. They are composed primarily of tricalcium and dicalcium silicate, and also include a radiopacifier, additives and an aqueous or a non-aqueous vehicle. Only materials whose primary reaction is with water can be classified as hydraulic. OBJECTIVES: Review of the classification of hydraulic materials by Camilleri and the literature pertaining to specific uses of hydraulic cements in endodontics namely intra-coronal, intra-radicular and extra-radicular. Review of the literature on the material properties linked to specific uses providing the current status of these materials after which future trends and gaps in knowledge could be identified. METHODS: The literature was reviewed using PUBMED, and for each clinical use, the in vitro properties such as physical, chemical, biological and antimicrobial characteristics and clinical data were extracted and evaluated. RESULTS: A large number of publications were retrieved for each clinical use and these were grouped depending on the property type being investigated. CONCLUSIONS: The hydraulic cements have made a difference in clinical outcomes. The main shortcoming is the poor testing methodologies employed which provide very limited information and also inhibits adequate clinical translation. Furthermore, the clinical protocols need to be updated to enable the materials to be employed effectively.

Multi-modular bone healing assessment in a randomized controlled clinical trial of root-end surgery with the use of leukocyte- and platelet-rich fibrin and an occlusive membrane.

OBJECTIVES: The aim of this study was to assess in a multi-modular manner the bone healing 1 year post root-end surgery (RES) with leukocyte- and platelet-rich fibrin (LPRF) and Bio-Gide® (BG; Geistlich Pharma North America, Inc., Princeton, USA) as an occlusive membrane. MATERIALS AND METHODS: A randomized controlled clinical trial (RCT) of RES +/- LPRF and +/- BG was performed. The follow-up until 1 year post RES was performed by means of ultrasound imaging (UI), periapical radiographs (PR), and cone-beam computed tomography (CBCT). RESULTS: From the 50 included patients, 6 dropped-out during follow-up. For the 44 assessed patients (34 with UI and 42 with PR and CBCT), there was no evidence (p > 0.05) for an effect of LRPF, neither on UI measurements nor on CBCT assessments. On the contrary, there was an indication for a better outcome with BG. UI presented significant shorter healing time for the bony crypt surface (p = 0.014) and cortical opening (p = 0.006) for the groups with BG. The qualitative CBCT assessment for the combined scores of the apical area and cortical plane was significantly higher for BG (p = 0.01 and 0.02). The quantitative CBCT measurement for bone healing after 1 year was lower with BG (p = 0.019), as well as the percentage of non-zero values (p = 0.026), irrespective of the preoperative lesion size and type. Furthermore, UI seemed to be safer for frequent follow-up during the early postoperative stage (0-3 months), whereas CBCT gave more accurate results 1 year post RES. Amongst the assessors, the qualitative PR analysis was inconsistent for a favorable outcome 1 year post RES with LPRF (p = 0.11 and p = 0.023), but consistent for BG (p = 0.024 and p = 0.023). CONCLUSIONS: There was no evidence for improvement of bone healing when RES was applied with LPRF in comparison with RES without LPRF. However, RES with BG gave evidence for a better outcome than RES without BG. CLINICAL RELEVANCE: The addition of an occlusive membrane rather than an autologous platelet concentrate improved bone regeneration 1 year post RES significantly, irrespective of the assessment device applied. The accuracy of PR assessment is questionable.

Root-end surgery with leucocyte- and platelet-rich fibrin and an occlusive membrane: a randomized controlled clinical trial on patients' quality of life.

OBJECTIVES: The aim of this study was to investigate the impact of the adjunct of leukocyte- and platelet-rich fibrin (LPRF) to root-end surgery (RES) on the patients' quality of life during the first week post RES. MATERIALS AND METHODS: Patients in need of RES were recruited for an open randomized controlled clinical trial (RCT) with a 2 × 2 factorial design. They were randomly allocated to the test (+LPRF) and control (-LPRF) group. Each group was subsequently divided into two strata: with or without an occlusive membrane (Bio-Gide®, Geistlich Biomaterials, Switzerland; BG). After RES, the patients completed daily for 1 week a visual analog pain scale (VAS) and a 5-point Likert-type scale questionnaire concerning activity impairment, occurrence of symptoms, and medication use. RESULTS: Fifty patients were included, equally divided between the test and control group. Only one patient in the "-LPRF+BG-group" had to take additional antibiotics due to a persistent jaw swelling. There was no evidence (p ≤ 0.05) for a difference between the test and control group in VAS, occurrence of pain symptoms, impairment of daily activities, and medication use, over the 7 days and daily during the 7 days post RES. CONCLUSIONS: There was no statistical significant evidence for improvement of patients' quality of life during the first week post RES with LPRF in comparison with RES without LPRF. CLINICAL RELEVANCE: Although LPRF seems to be an inexpensive and autologous agent to reduce pain and swelling post RES, this RCT does not provide a statistical significant evidence for that.

Regenerative potential of leucocyte- and platelet-rich fibrin. Part A: intra-bony defects, furcation defects and periodontal plastic surgery. A systematic review and meta-analysis.

AIM: To analyse the regenerative potential of leucocyte- and platelet-rich fibrin (L-PRF) during periodontal surgery. MATERIALS AND METHODS: An electronic and hand search were conducted in three databases. Only randomized clinical trials were selected and no follow-up limitation was applied. Pocket depth (PD), clinical attachment level (CAL), bone fill, keratinized tissue width (KTW), recession reduction and root coverage (%) were considered as outcome. When possible, meta-analysis was performed. RESULTS: Twenty-four articles fulfilled the inclusion and exclusion criteria. Three subgroups were created: intra-bony defects (IBDs), furcation defects and periodontal plastic surgery. Meta-analysis was performed in all the subgroups. Significant PD reduction (1.1 ± 0.5 mm, p < 0.001), CAL gain (1.2 ± 0.6 mm, p < 0.001) and bone fill (1.7 ± 0.7 mm, p < 0.001) were found when comparing L-PRF to open flap debridement (OFD) in IBDs. For furcation defects, significant PD reduction (1.9 ± 1.5 mm, p = 0.01), CAL gain (1.3 ± 0.4 mm, p < 0.001) and bone fill (1.5 ± 0.3 mm, p < 0.001) were reported when comparing L-PRF to OFD. When L-PRF was compared to a connective tissue graft, similar outcomes were recorded for PD reduction (0.2 ± 0.3 mm, p > 0.05), CAL gain (0.2 ± 0.5 mm, p > 0.05), KTW (0.3 ± 0.4 mm, p > 0.05) and recession reduction (0.2 ± 0.3 mm, p > 0.05). CONCLUSIONS: L-PRF enhances periodontal wound healing.

Regenerative potential of leucocyte- and platelet-rich fibrin. Part B: sinus floor elevation, alveolar ridge preservation and implant therapy. A systematic review.

AIM: To analyse the effect of leucocyte- and platelet-rich fibrin (L-PRF) on bone regeneration procedures and osseointegration. MATERIALS AND METHODS: An electronic and hand search was conducted in three databases (MEDLINE, EMBASE and Cochrane). Only randomized clinical trials, written in English where L-PRF was applied in bone regeneration and implant procedures, were selected. No follow-up restrictions were applied. RESULTS: A total of 14 articles were included and processed. Three subgroups were created depending on the application: sinus floor elevation (SFE), alveolar ridge preservation and implant therapy. In SFE, for a lateral window as well as for the trans-alveolar technique, histologically faster bone healing was reported when L-PRF was added to most common xenografts. L-PRF alone improved the preservation of the alveolar width, resulting in less buccal bone resorption compared to natural healing. In implant therapy, better implant stability over time and less marginal bone loss were observed when L-PRF was applied. Meta-analyses could not be performed due to the heterogeneity of the data. CONCLUSIONS: Despite the lack of strong evidence found in this systematic review, L-PRF might have a positive effect on bone regeneration and osseointegration.

The impact of autologous platelet concentrates on endodontic healing: a systematic review.

The current literature was reviewed to determine the impact of autologous platelet concentrates (APCs) on endodontic healing. All types of clinical study designs concerning any kind of endodontic treatment involving the application of APCs were included. Two independent reviewers searched three databases (PubMed, Embase, and Cochrane Library) for studies, complemented by hand search, until 16/1/2016. From the 423 identified records, 48 articles met the inclusion criteria. Selected randomized controlled clinical trials (RCTs) underwent Cochrane Collaboration's risk-of-bias assessment and data extraction. Only two RCTs showed low risk of bias. There was considerable heterogeneity between the RCTs with regard to the type of therapy, type of APCs, assessment method, and study quality, and therefore the data could not be analyzed quantitatively. The included case reports/series and non-randomized comparative studies underwent qualitative analysis with the revised Methodological Index for Non-Randomized Studies (MINORS) and data extraction. The two comparative non-randomized studies scored qualitatively high, though the MINORS-scores of the case series and reports were dispersed. APCs were involved in five endodontic treatment modalities, namely apexification, regenerative endodontic procedures, pulpotomy, apical surgery, and treatment of endo-perio/perio-endo lesions. APCs seem to accelerate postoperative bone healing, augment the patients' postoperative quality of life, aid further root development, and support maintenance/regaining of pulp vitality. No adverse events were reported. APCs in endodontic treatments seem to contribute to the healing of soft and hard tissues, though there is a lack of long-term high quality clinical trials and standardized treatment protocols.

Regenerative endodontic procedure of an infected immature permanent human tooth: an immunohistological study.

OBJECTIVES: An immunohistological study of an infected immature permanent human tooth after a regenerative endodontic procedure (REP) was conducted in order to determine the histologic outcome of this procedure. Besides observed signs of angiogenesis and neurogenesis, repair and/or regeneration of the pulp-dentin complex was also investigated. MATERIALS AND METHODS: A REP was performed on tooth 45 of a 10-year-old girl. Eleven months post-treatment, the tooth had to be removed for orthodontic reasons. The following investigations were performed: immunohistology and radiographic quantification of root development. After hematoxylin-eosin (HE) staining, the following immunomarkers were selected: neurofilament (NF), pan cytokeratin (PK), osteocalcin (OC), and CD34. RESULTS: The REP resulted in clinical and radiographic healing of the periradicular lesion and quantifiable root development. The HE staining matches with the medical imaging post-REP: underneath the mineral trioxide aggregate a calcified bridge with cell inclusions, connective pulp-like tissue (PLT) with blood vessels, osteodentin against the root canal walls, on the root surface cementum (Ce), and periodontal ligament (PDL). The PDL was PK(+). The blood vessels in the PLT and PDL were CD34(+). The Ce, osteodentin, and stromal cells in the PLT were OC(+). The neurovascular bundles in the PLT were NF(+). CONCLUSIONS: Immunohistologically, REP of this infected immature permanent tooth resulted in an intracanalar connective tissue with a regulated physiology, but not pulp tissue. CLINICAL RELEVANCE: REP of an immature permanent infected tooth may heal the periapical infection and may result in a combination of regeneration and repair of the pulp-dentin complex.

Multimodal Imaging of Dental Pulp Healing Patterns Following Tooth Autotransplantation and Regenerative Endodontic Treatment.

INTRODUCTION: Understanding the healing process of dental pulp after tooth autotransplantation (TAT) and regenerative endodontic treatment (RET) of immature teeth is important both clinically and scientifically. This study aimed to characterize the pattern of dental pulp healing in human teeth that underwent TAT and RET using state-of-the-art imaging techniques. MATERIALS AND METHODS: This study examined 4 human teeth, 2 premolars that underwent TAT, and 2 central incisors that received RET. The premolars were extracted after 1 year (case 1) and 2 years (case 2) due to ankylosis, while the central incisors were extracted after 3 years (cases 3 and 4) for orthodontic reasons. Nanofocus x-ray computed tomography was used to image the samples before being processed for histological and immunohistochemical analysis. Laser scanning confocal second harmonic generation imaging (SHG) was used to examine the patterns of collagen deposition. A maturity-matched premolar was included as a negative control for the histological and SHG analysis. RESULTS: Analysis of the 4 cases revealed different patterns of dental pulp healing. Similarities were observed in the progressive obliteration of the root canal space. However, a striking loss of typical pulpal architecture was observed in the TAT cases, while a pulp-like tissue was observed in one of the RET cases. Odontoblast-like cells were observed in cases 1 and 3. CONCLUSIONS: This study provided insights into the patterns of dental pulp healing after TAT and RET. The SHG imaging sheds light on the patterns of collagen deposition during reparative dentin formation.

Regenerative Endodontic Procedure of Immature Permanent Teeth with Leukocyte and Platelet-rich Fibrin: A Multicenter Controlled Clinical Trial.

INTRODUCTION: The aim of this nonrandomized, multicenter controlled clinical trial was to evaluate the impact of leukocyte-platelet-rich fibrin (LPRF) on regenerative endodontic procedures (REPs) of immature permanent teeth in terms of periapical bone healing (PBH) and further root development (RD). METHODS: Healthy patients between 6-25 years with an inflamed or necrotic immature permanent tooth were included and divided between the test (= REP + LPRF) and control (= REP-LPRF) group depending on their compliance and the clinical setting (university hospital or private practice). After receiving REP ± LPRF, the patients were recalled after 3, 6, 12, 24, and 36 months. At each recall session, the teeth were clinically and radiographically (by means of a periapical radiograph [PR]) evaluated. A cone-beam computed tomographic (CBCT) imaging was taken preoperatively and 2 and 3 years postoperatively. PBH and RD were quantitatively and qualitatively assessed. RESULTS: Twenty-nine teeth with a necrotic pulp were included, from which 23 (9 test and 14 control) were analyzed. Three teeth in the test group had a flare-up reaction in the first year after REP. Except for 2 no shows, all the analyzed teeth survived up to 3 years after REP, and, in case of failure, apexification preserved them. Complete PBH was obtained in 91.3% and 87% of the cases based on PR qualitative and quantitative evaluation, respectively, with no significant difference between the groups with respect to the baseline. The PR quantitative change in RD at the last recall session with respect to the baseline was not significant (all P values > .05) in both groups. The qualitative assessment of the type of REP root healing was nonuniform. In the test group, 55.6% of the teeth presented no RD and no apical closure. Only 50% of the 14 teeth assessed with CBCT imaging presented complete PBH. Regarding volumetric measurements on RD 3 years after REP for the change with respect to the baseline in root hard tissue volume, mean root hard tissue thickness, and apical area, the control group performed significantly in favor of RD than the test group (P = .03, .003, and 0.05 respectively). For the volumetric change 3 years after REP with respect to the baseline in root length and maximum root hard tissue thickness, no significant difference (P = .72 and .4, respectively) was found between the groups. The correlation between the PR and CBCT variables assessing RD was weak (root lengthening) to very weak (root thickening). CONCLUSIONS: REP-LPRF seems to be a viable treatment option to obtain PBH and aid further RD of necrotic immature permanent teeth. Caution is needed when evaluating REP with PR.

Material Pulp Cells and Tissue Interactions.

Two increasingly common endodontic procedures, vital pulp therapy (VPT) and regenerative endodontic procedures, rely on dental tissue regeneration/repair mechanisms with the aid of biomaterials. These materials are applied in close contact to the pulpal tissue and are required to be biocompatible, form an antimicrobial seal, not induce staining, and be easy to manipulate. Historically, calcium hydroxide played an important role in VPT. However, over the last 3 decades, significant efforts in research and industry have been made to develop various biomaterials, including hydraulic tricalcium silicate cements. The present review summarized various hydraulic tricalcium silicate cements and their biological properties in clinical procedures, namely VPT and regenerative endodontic procedures.

Bioactivity potential of Portland cement in regenerative endodontic procedures: From clinic to lab.

OBJECTIVE: The aim of this study was to evaluate the bioactivity potential of an hydraulic calcium-silicate cement, Pure Portland Cement Med-PZ (Medcem, Weinfelden, Switzerland: 'MPC'), applied in a tooth extracted because of failed regenerative endodontic procedures (REP) and by means of ex vivo (EV) specimens. METHODS: Ten EV cylindrical dentin cavities were prepared and filled with MPC and stored for 1 month in distilled water (DW), Hank's balanced salt solution (HBSS), Dulbecco's phosphate-buffered saline (DPBS), simulated body fluid (SBF), versus no media (NM) serving as control. Six additional EV specimens were filled with MPC and exposed for 2 weeks to leucocyte-and-platelet-rich fibrin (LPRF)-clot (C), LPRF-membrane (M) and LPRF-exudate (E). MPC in the EV specimens and in the coronal part of the REP tooth was analyzed by means of micro-Raman spectroscopy (MR), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). RESULTS: SEM showed rough crystallite surfaces for the EV samples and a porous surface for the REP tooth. EDS of the EV samples revealed prominent peaks for Ca, Si and O. Storage in HBSS, DPBS, SBF, exposure to LPRF and the REP tooth showed considerable amounts of P as well. MR exhibited vibrations of phosphate (DPBS, SBF), carbonated hydroxyapatite (DPBS, SBF), calcium carbonate (DW, HBSS, NM, REP-tooth, LPRF-E), oxidized (ferric) proteins (LPRF-E/C/M) and the amide III band (all samples). Hence, only storage of MPC in DPBS and SBF for 1 month revealed bioactivity. SIGNIFICANCE: The environmental conditions, namely the laboratory and clinical settings, affect the bioactivity potential of MPC.

Regenerative Endodontic Procedures Posttrauma: Immunohistologic Analysis of a Retrospective Series of Failed Cases.

INTRODUCTION: Regenerative endodontic procedures (REP) are a novel treatment modality to restore the function of necrotic pulp tissue via stimulation or transplantation of stem cells into the root canal. This study aimed to investigate the immunohistologic outcome of 3 extracted teeth because of sequelae of trauma and unsatisfactory REP outcomes. METHODS: Three immature permanent maxillary central incisors of 3 female patients (6-9 years) were extracted 5.5-22 months after REP. Additionally, 1 sound permanent immature central maxillary incisor of 1 of the included patients was extracted for orthodontic reasons. The teeth were immunohistologically stained with Masson's trichrome, neurofilament (NF), pan cytokeratin, dentin sialophosphoprotein, and Gram+/-. RESULTS: The REP-teeth presented intracanalar vascularized connective/mineralized reparative tissue (RT), which was less organized than the pulp tissue of the sound tooth. Moderate to considerable calcification was observed below the Portland cement used during REP. In 1 case, the RT was NF+; in the 2 other cases, the periodontal ligament and apical granuloma/papilla were NF+. All teeth were Gram+/- negative; nevertheless, inflammatory cells were present in 2 cases. The pan cytokeratin and dentin sialophosphoprotein stainings were not specific enough for 2 cases. CONCLUSIONS: This immunohistologic study of failed REP cases resulted in bacteria-free intracanalar RT and biomaterial-induced calcification. Nevertheless, the presence of inflammatory cells revealed a persistent inflammation. Hence, the clinical and radiographic signs were decisive for tooth survival and multidisciplinary outcome determination.

A Retrospective Case Series in Regenerative Endodontics: Trend Analysis Based on Clinical Evaluation and 2- and 3-dimensional Radiology.

INTRODUCTION: A regenerative endodontic procedure (REP) is a biologically based treatment to functionally replace the pulp of infected immature permanent teeth. The purpose of this retrospective case series was to assess the outcome of REPs of infected immature permanent teeth in terms of periapical bone healing (PBH), root development (RD), and pulp vitality. METHODS: Five patients (1 tooth/patient) who had undergone a REP based on the cell homing concept were recalled 3, 6, 12, 24, and 36 months postoperatively. At each recall session, clinical and periapical radiographic (PR) investigations were performed. Cone-beam computed tomographic (CBCT) imaging was taken before and 36 months after REPs. Qualitative and quantitative PR assessments were performed on the teeth that underwent REPs. Quantitative CBCT analyses were performed on the teeth that underwent REP and contralateral teeth. RESULTS: At each recall session, all teeth were asymptomatic but reacted negatively on carbon dioxide snow and electrical pulp testing. All teeth that underwent a REP showed complete PBH and further RD on PR and CBCT assessments when comparing the baseline with the final recall radiographs. CBCT analyses indicated increases in root hard tissue volume and RL for all teeth that underwent a REP, but they were 5 and 3 times less, respectively, than the contralateral teeth. The postoperative CBCT images presented bone ingrowth inside the root canal, calcification, or nonuniform RD. CONCLUSIONS: Thirty-six months after the REPs (based on the cell homing concept), this RCS resulted radiographically and clinically in functional and asymptomatic teeth with complete PBH and continued reparative RD. CBCT quantitative measurements and qualitative root development observations are more reliable and accurate than PR analysis.

Ultrasound Assessment of Bone Healing after Root-end Surgery: Echoes Back to Patient's Safety.

INTRODUCTION: The aim of this study was to present ultrasound imaging (UI) techniques as promising and safe tools for the follow-up of root-end surgery (RES) in vivo. METHODS: The study included 8 patients who underwent RES. All were followed up using UI at 1 week, 1 month, 2 months, 3 months, and 6 months (if necessary) after RES. The bony crypt was defined on the ultrasound image, and the following observations were made during follow-up: cortical bone interruption and surface area measurement of the residual echoic bony crypt image. RESULTS: In all cases, the hypoechoic image became hyperechoic, indicating gradual bone healing of the crypt. Compared with baseline, at 3 months a remaining cortical opening of 51.2% (±12.6%) and a bony crypt surface area of 24.3% (±10.8%) was detected for all patients. For 50% of the patients, the echographic follow-up ended at 3 months because the ultrasound waves could no longer enter the bony crypt. For 4 patients who attended the 6-month recall, a remaining cortical disruption of 43.2% (±9.9%) and a bony crypt surface area of 17.2% (±7%) compared with the baseline was noted. CONCLUSIONS: UI is a promising follow-up tool for RES. It helps clinicians understand the initial stages of bone healing, allows close healing monitoring, and is radiation free.

Dental Stem Cells in Pulp Regeneration: Near Future or Long Road Ahead?

Although regenerative endodontic procedures have yielded an impressive body of favorable outcomes, the treatment of necrotic immature permanent teeth in particular remains to be a challenge. Recent advances in dental stem cell (DSC) research have gained increasing insight in their regenerative potential and prospective use in the formation of viable dental tissues. Numerous studies have already reported successful dental pulp regeneration following application of dental pulp stem cells, stem cells from the apical papilla, or dental follicle precursor cells in different in vivo models. Next to responsive cells, dental tissue engineering also requires the support of an appropriate scaffold material, ranging from naturally occurring polymers to treated dentin matrix components. However, the routine use and banking of DSCs still holds some major challenges, such as culture-associated differences, patient-related variability, and the effects of culture medium additives. Only in-depth evaluation of these problems and the implementation of standardized models and protocols will effectively lead to better alternatives for patients who no longer benefit from current treatment protocols.