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Tissue repair is an essential process that reestablishes tissue integrity and regular function. Nevertheless, different therapeutic factors and clinical conditions may interfere in this process of periapical healing. This review aims to discuss the important therapeutic factors associated with the clinical protocol used during root canal treatment and to highlight the systemic conditions associated with the periapical healing process of endodontically treated teeth. The antibacterial strategies indicated in the conventional treatment of an inflamed and infected pulp and the modulation of the host's immune response may assist in tissue repair, if wound healing has been hindered by infection. Systemic conditions, such as diabetes mellitus and hypertension, can also inhibit wound healing. The success of root canal treatment is affected by the correct choice of clinical protocol. These factors are dependent on the sanitization process (instrumentation, irrigant solution, irrigating strategies, and intracanal dressing), the apical limit of the root canal preparation and obturation, and the quality of the sealer. The challenges affecting the healing process of endodontically treated teeth include control of the inflammation of pulp or infectious processes and simultaneous neutralization of unpredictable provocations to the periapical tissue. Along with these factors, one must understand the local and general clinical conditions (systemic health of the patient) that affect the outcome of root canal treatment prediction.

Introduction: The purpose of this study was to ascertain the regenerative characteristics of apical papilla-derived cells (APDCs) from immature teeth with pulpal and periapical pathosis and thus to provide proof-of-principle evidence for further regenerative endodontic research., Methods: Pulpal and periapical pathosis was induced in immature permanent double-rooted premolars of beagles, which were randomly assigned to experimental treatment groups: group AO (n = 14), pulp disruption and access left open; group PS (n = 14), supragingival plaque suspension-soaked cotton pellet was introduced, and access was sealed; and control (n = 7), untreated. The teeth were extracted at 2- and 4-week periods after experimental treatments. APDCs were cultured from the extracted teeth, and their cellular proliferation, differentiation characteristics, and stemness were assessed. The data were statistically analyzed., Results: After 4 weeks of intentional pulpal and periapical pathosis induction period, all teeth in group PS showed features of apical periodontitis with necrotic pulp, and their APDCs showed significantly increased proliferation rate and osteogenic/odontogenic differentiation capabilities (P < .05). The stemness was maintained in all APDCs, although the stem cell population was smaller in group PS at 2-week period when the inflammatory responses were most fulminant (P < .05)., Conclusions: The APDCs from immature teeth retained the regenerative characteristics with the differences according to their pulpal and periapical pathosis. The results of this study partly provide the evidence for regenerative endodontic research., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study evaluated the pulpal and periapical responses of dogs' teeth after pulpotomy and pulp capping with a new tricalcium silicate-based cement (Biodentine) when compared with mineral trioxide aggregate (MTA) by radiographic, histopathologic, and histomicrobiological analyses., Methods: Sixty roots (30 teeth) of dogs were divided into 2 groups, Biodentine (n = 36 roots) and ProRoot MTA (control, n = 24 roots). Animals were killed after 120 days, and the teeth were subjected to histotechnical processing (hematoxylin-eosin and Brown and Brenn staining). Qualitative and quantitative histopathologic data were analyzed by Fisher exact and Mann-Whitney tests (α = 0.05)., Results: Radiographically, mineralized tissue bridge formation was observed in more specimens treated with Biodentine (96.8%) than with MTA (72.2%) (P = .02). Integrity of the lamina dura and absence of periapical bone rarefaction and root resorption (external and internal) were observed in all specimens. Histopathologic and histomicrobiological analyses revealed mineralized tissue bridge formation, pulpal vitality, odontoblast layer integrity, preserved periodontal ligament, and absence of bone or root resorption and microorganisms in both groups. Although the bridges formed at the amputation site had similar morphology, they were significantly thicker in the Biodentine group (P < .0001). Comparison between the radiographic and histopathologic results showed that radiographic visualization of more bridges in the Biodentine group was related to bridge thickness because radiographic diagnosis was flawed for bridges with thickness less than 0.5 mm. Fluorescence microscopy improved the visualization of bridge structure., Conclusions: Biodentine presented tissue compatibility and allowed for mineralized tissue bridge formation after pulpotomy in all specimens with similar morphology and integrity to those formed with use of MTA. Periapical radiographs failed in detecting mineralized tissue bridges with thickness less than 0.5 mm., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Regenerative endodontics is a promising alternative treatment for immature teeth with necrotic pulps. The present study was performed to assess the regenerative potential of young permanent immature teeth with necrotic pulp after the following treatment protocols: (1) a mineral trioxide aggregate (MTA) apical plug, (2) the regenerative endodontic protocol (blood clot scaffold), and (3) the regenerative endodontic protocol with a blood clot and an injectable scaffold impregnated with basic fibroblast growth factor., Methods: Immature necrotic permanent maxillary central incisors (n = 36) of patients 9-13 years old were divided into 3 groups according to the treatment protocol: the MTA group (MTA apical plug), the REG group (regenerative endodontic protocol [blood clot]), and the FGF group (regenerative endodontic protocol [blood clot + injectable scaffold]). Follow-up was done up to 18 months. Standardized radiographs were digitally evaluated for an increase in root length and thickness, a decrease in the apical diameter, and a change in periapical bone density., Results: After a follow-up period of 18 months, most of the cases showed radiographic evidence of periapical healing. Groups 2 and 3 showed a progressive increase in root length and width and a decrease in apical diameter., Conclusions: The regenerative endodontic procedure allowed the continued development of roots in teeth with necrotic pulps. The use of artificial hydrogel scaffold and basic fibroblast growth factor was not essential for repair., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Of 3,216 root canals treated endodontically at the Creighton University School of Dentistry from September 1, 2005, to August 31, 2007, with LightSpeedLSX instruments (LightSpeed Technology, Inc, San Antonio, TX), there were 12 cases of irretrievable instrument separation. More than 5 years after the separations, an attempt was made to contact the patients and assess for healing and tooth retention., Methods: Third- and fourth-year dental students performed root canal procedures according to protocol from September 1, 2005, to August 31, 2007. A database was collected during the 24-month period recording cases with irretrievable LightspeedLSX separation. Efforts were made from July 2011 to December 2011 to contact the 12 patients for endodontic follow-up. Clinical and radiographic evaluations of healing were performed., Results: Of the 12 patients with irretrievable separations, 8 patients were contacted and 5 returned to Creighton University School of Dentistry for follow-up. All 8 contacted patients confirmed the presence of the root canal-treated tooth in question, and the teeth of the 5 evaluated patients were determined to be asymptomatic and functional. Radiographic analysis resulted in 2 teeth being classified as complete healing, 2 as uncertain healing, and 1 as no healing., Conclusions: The 100% tooth retention rate and the lack of symptoms in 8 contacted (5 evaluated) patients 5 years after treatment suggests that long-term retention and functionality can occur after irretrievable instrument separation. Although tooth retention and functionality are desirable outcomes, radiographic findings may be indicative of inadequate periapical healing, thus requiring the clinician to evaluate whether additional treatment is necessary., (Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Clinical experience has shown that most avulsed teeth are replanted after a long extra-alveolar time and dry or inadequate wet storage, causing necrosis of periodontal ligament cells. This condition invariably leads to development of external root resorption, leaving the filling material in contact with the periapical connective tissues. In this study, the periapical tissue reactions to calcium hydroxide (CH) and mineral trioxide aggregate (MTA) were evaluated after occurrence of external root resorption as an expected sequela of delayed tooth replantation. Twenty male Wistar rats (Rattus norvegicus, albinus) had their right upper incisor extracted and maintained in dry storage for 60 min. Then, the dental papilla, enamel organ, pulp tissue, and periodontal ligament were removed, and the teeth were immersed in a 2% acidulated phosphate sodium fluoride solution, pH 5.5, for 10 min. The teeth were randomly assigned into two groups (n = 10), in which the canals were filled with either a CH and saline paste (CH group) or MTA (MTA group). The sockets were irrigated with saline, and the teeth were replanted. After 80 days, it was possible to observe large areas of replacement root resorption and some areas of inflammatory root resorption in both groups. More severe inflammatory tissue reaction was observed in contact with calcium hydroxide compared with the mineral trioxide aggregate. New bone formation was more intense at the bottom of the socket in the MTA group. In conclusion, as far as periapical tissue compatibility is concerned, intracanal MTA can be considered as a viable option for root canal filling in delayed tooth replantation, in which external root resorption is an expected sequela., (© 2011 John Wiley & Sons A/S.)

Introduction: The purpose of this study was to evaluate the influence of anorganic bovine bone as a grafted biomaterial on newly formed bone and cementum in periapical regions after surgical endodontic treatment in cats., Methods: After inducing apical periodontitis in 9 cats, root canal and surgical endodontic treatment were performed on 72 roots of first and second maxillary premolars. Bone defects were treated with biomaterial particles + a membrane, biomaterial only, a membrane only, or left unfilled (control). Histomorphometry on nondecalcified sections were performed at 3 and 6 months after surgery. Analysis of variance with repeated measures was used within 2 and 3 subject factors to analyze newly formed bone, cementum, biomaterial conduction, and resorption., Results: At each time period, bone formation was greater at the grafted membrane-protected sites than in the grafted-unprotected sites. At 6 months, the bone area fraction at membrane nongrafted sites was greater than in the grafted-protected sites. The new cementum was significantly greater at 6 months than at 3 months and greater at the grafted membrane-protected sites over the unprotected ones at 6 months. Statistically, the grafted biomaterial, the membrane, and the time contributed significantly to the amount of new bone (P<.05) with no significant interaction. Biomaterial osteoconduction was significantly affected by the time. All 3 variables showed a significant interaction on new cementum., Conclusions: There was significantly more bone formation after surgical endodontic treatment when membrane and bone grafts were used as compared with bone grafts only or unfilled control sites. However, it appears that the key factor to the enhanced tissue regeneration is the membrane and not the grafted biomaterial., (Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to determine the bone regeneration potential to different root-end filling materials by evaluating the distance between the materials and newly regenerated bone after root-end surgery., Material and Methods: Periapical lesions were induced in premolars and molars of five female beagle dogs. The teeth were treated endodontically after the development of the lesions. After 1 week, the teeth underwent root-end surgery using modern microsurgical techniques. Three different root-end filing materials were used: amalgam (Tytin; Kerr Mfg Co, Romulus, MI), SuperEBA (Bosworth, Skokie, IL), and mineral trioxide aggregates (MTA; Dentsply, York, PA). After 4 months, the dogs were sacrificed, and the jaws were prepared for histological sectioning. The distances from the root-end filling materials to the regenerated bone were determined by the evaluation of microradiographic images of the sections with imaging software (Sigma Scan/Image; Jandel Scientific Software, San Rafael, CA). The results were statistically analyzed with analysis of variance using Sigma Stat software (Jandel Scientific Software, San Rafael, CA)., Results: The mean distances from the newly regenerated bone were 0.397 +/- 0.278 mm in the MTA group, 0.756 +/- 0.581 mm in the SuperEBA group, and 1.290 +/- 0.386 mm in the amalgam group. There was a statistically significant difference between the amalgam and MTA groups (p < 0.05). No significant differences existed for amalgam versus SuperEBA and SuperEBA versus MTA., Conclusion: MTA showed the most favorable periapical tissue response. The distance from MTA to the regenerated bone was similar to the normal average periodontal ligament thickness in dogs., (Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The purpose of this report was to present the case of a patient wherein revascularization of the necrotic infected pulp space of an immature permanent maxillary central incisor tooth was induced in vivo by stimulation of a blood clot from the periapical tissues into the canal space. This was achieved after disinfection of the canal space with a topical antibiotic paste followed by a blood clot scaffold induced from the periapical tissues. This treatment approach offers clinicians great potential to avoid the need for traditional apexification with calcium hydroxide or the need to achieve an artificial apical barrier with mineral trioxide aggregate. Furthermore, this treatment approach can help rescue infected immature teeth by physiologically strengthening the root walls.

The purpose of this study was twofold: first, to determine the influence on the healing of the periapical tissues when selected bacterial strains and combinations thereof remain after root canal treatment; and, second, the relationship to healing of the quality of the root filling. In eight monkeys, 175 root canals, previously infected with combinations of four or five bacterial strains and with radiographically verified apical periodontitis, were endodontically treated, bacteriologically controlled, and permanently obturated. After 2-2.5 yr, the periapical regions were radiographically and histologically examined. Of these teeth, 48 root canals were also examined for bacteria remaining after removal of the root fillings. When bacteria remained after the endodontic treatment, 79% of the root canals showed non-healed periapical lesions, compared with 28% where no bacteria were found. Combinations of residual bacterial species were more frequently related to non-healed lesions than were single strains. When no bacteria remained, healing occurred independently of the quality of the root filling. In contrast, when bacteria remained, there was a greater correlation with non-healing in poor-quality root fillings than in technically well-performed fillings. In root canals where bacteria were found after removal of the root filling, 97% had not healed, compared with 18% for those root canals with no bacteria detected. The present study demonstrates the importance of obtaining a bacteria-free root canal system before permanent root filling in order to achieve optimal healing conditions for the periapical tissues.

The ultimate aim of endodontic treatment is to encourage the healing of apical periodontitis, or to prevent it from occurring if it was not present prior to treatment. Apical periodontitis is a general term used to describe an inflammatory response to irritation caused by the contents of a root canal system and it has several distinct forms. The most common is a granuloma but this can develop into other disease entities such as an abscess, a periapical pocket cyst or a true cyst, all of which present as radiolucencies. However, periapical radiolucencies may also be caused by extra-radicular infections, foreign body reactions and periapical scars, or they may be due to other tumours and cysts that have not originated from pulp disease. Practitioners must recognise and understand the different pathological entities and the dynamic interactions that occur in the periapical tissues in order to correctly diagnose and treat these conditions.

Periradicular surgery has become an established treatment option in endodontic surgery. The major objective of this surgery is to obtain periradicular tissue regeneration, including the formation of a new attachment apparatus, by exclusion of any potentially noxious agent within the physical confines of the affected root. However, in a substantial number of cases, the endodontic lesion has a concomitant marginal periodontal lesion that may complicate the healing success. In periodontology, the guided tissue regeneration (GTR) principle using a barrier membrane has been extensively studied and successfully used, and thus may become an adjunct in endodontic surgery. This article presents a classification system of endodontic and periodontal lesions with respect to the application of the membrane technique and reviews the pertinent literature based upon this classification system.

Aim: To radiographically compare periapical repair of roots with infected root canals obturated in one-step or with calcium hydroxide (Ca(OH)2) intracanal medication in two steps., Methodology: Standardized preoperative periapical radiographs were taken of 72 roots of vital dogs' teeth. All roots were then aseptically instrumented to ISO size 45. As negative controls, 12 roots were aseptically obturated. The remaining roots were infected with dental plaque and closed. Six weeks later, apical periodontitis was radiographically confirmed in the infected roots. The roots were divided into the following groups: group 1, one-step (n = 24); roots were irrigated with 10 cc saline, obturated, and permanently restored. Group 2, Ca(OH)2 (n = 24); roots were treated as in group 1, except that after saline irrigation Ca(OH)2 medicament was placed in the canal 1 week before obturation. Group 3, positive control (n = 12); the roots were irrigated with saline, access permanently closed but canals not obturated. Group 4, negative control (n = 12); previously aseptically obturated roots were permanently restored. After 6 months, standardized postoperative radiographs were obtained. Three independent evaluators blinded to the treatment groups evaluated the preoperative and postoperative radiographs. The evaluators were instructed to rate each root, based on changes on the radiographs, as failed, improved or healed., Results: Radiographically, the percentage of cases that completely healed were similar for the one-step and Ca(OH)2 groups (35.3% vs. 36.8%). However, the Ca(OH)2 group had fewer failed cases (15.8% vs. 41.2%) and more improved cases (47.4% vs. 23.5%) than the one-step group., Conclusion: Power statistics demonstrated that at 43 cases per group, Ca(OH)2 treatment would be statistically superior to one-step treatment. We consider this number to be clinically important.

Regeneration processes in periapical tissues were followed up after bone defect repair with hydroxyapatite-based osteoplastic preparations. The terms of regeneration depended on the size of bone defect. The data were evaluated by densitometry.

Dogs' teeth with induced chronic periapical periodontitis were treated endodontically by two different methods, and the results were compared. A total of 40 root canals from the upper and lower premolars of two dogs were prepared chemomechanically. In method 1, a high-concentration (5.25%) hypochlorite solution was used during the instrumentation of the root canal, and an antibacterial dressing was applied between sessions, followed by filling of the root canal. In method 2, a low-concentration (0.5%) sodium hypochlorite solution was used as an adjunct to mechanical debridement, and the root canal was filled during the same session. The histopathological results showed that method 1 led to better periapical repair than method 2.

Following extraction of a symptomatic mandibular premolar which had been subjected to two periradicular surgical procedures, significant apical healing was identified histologically. The implications of these findings are discussed in relation to contemporary advocated treatment regimens, case assessment, and interpretation for success and failure.

Root canal models were implanted in rats in order to investigate histologically the movement of granulation tissue invading apical canals and dead spaces and changes in cell proliferative activity as indicated by 3H-thymidine. The models were prepared to have 1, 2, and 3 mm apical canals, with and without dead spaces, to simulate preparations short of the apex and obturation to several levels. After 12 wks implantation of the models without dead spaces, granulation tissue invading 1 mm apical canals did not degenerate and cell proliferative activity remained high. However, tissue invading the 2 and 3 mm apical canals tended to be necrotic and cell proliferative activity was decreased. In the models with dead spaces, the tissue in the 1 and 2 mm apical canals developed and invaded the dead spaces, and still possessed proliferative activity 12 wks after implantation. In contrast, the tissue in the 3 mm apical canals did not invade the dead spaces, even after 12 wks, and no proliferative activity was observed.

The objective of this study was to determine the effect of demineralization of resected root ends on the temporal and qualitative healing of the dentoalveolar (apical attachment apparatus) and alveolar (osseous) tissues in the excisional wound site created during periradicular surgery. Root end resections to orthograde gutta-percha obturations were performed on the mandibular premolars of six mongrel dogs. Twenty-four experimental root ends were demineralized by citric acid burnishing of the resected surfaces. The remaining 24 standard treatment root ends were not demineralized. Microscopic evaluations at postsurgical intervals from 4 to 45 days revealed that the demineralized root ends were associated with more rapid and complete healing than the nondemineralized root ends. It is proposed that demineralization enhances cementogenesis, the key to dentoalveolar healing, by removing the smear layer barrier and exposing the organic component (collagen fibrils) of resected cementum and dentin.

The roots of two incisors were treated by apicoectomy and a retrograde dentin-bonded composite filling. Periapical healing was observed a few months later by radiography. Later, due to root fracture and marginal bone resorption, the apical parts were removed including adjacent periapical bone. A histological and scanning electron microscopic examination of the tissue showed reformation of periodontium adjacent to the composite, including reformation of a lamina dura, inserting Sharpey's fibers and cementum deposited in intimate contact with the composite. This finding is in agreement with previous observations of tissue surrounding retrograde dentin-bonded composite fillings placed in monkeys, indicating that tissue regeneration including cementogenesis may occur on composite material and consequently form a biological closure of the root canal.

Response of induced periapical lesions in monkeys to a conventional endodontic technique was investigated at varying periods ranging from 15 to 365 days after treatment. The findings indicate that response to treatment is influenced by the extent of the root canal filling, the time lapse between treatment and death, and the presence or absence of bacteria in the apical portion of the canal.