Clinical Considerations for Regenerative Endodontic Procedures

The management of a tooth with incomplete root maturation and a necrotic pulp is an endodontic and a restorative challenge. Apexification procedures alone leave the tooth in a weakened state and at risk for reinfection. Regenerative endodontic procedures potentially offer advantages, including the possibility of hard tissue deposition and continued root development. Case studies have reported regeneration of human pulplike tissues in vivo, but there is no protocol that reliably regenerates pulplike tissue. This article summarizes historical, current, and future regenerative treatment approaches.

  • Case reports have indicated that biologically based endodontic therapies can result in the elimination of apical periodontitis. There is no question that regenerative endodontics procedures can be successful. The present issue is how to develop safe, effective and consistent methods for regenerating a functional pulp-dentin complex in patients.

  • There are obvious benefits of regenerative endodontic procedures for the immature root; however, mature teeth may also benefit from the regeneration of a vital pulp-dentin complex. If the treatment plan of a tooth with extensive caries could be altered from certain extraction to being properly restored as a result of the regeneration of dentinal tooth structure, endodontists would have engineered a more desirable outcome.

  • The reestablishment of vitality and a functional immune response may allow the body to better fight the presence of any remaining bacteria within the canal system. Thus, future efforts must focus on a more biologic and scientific approach to these endodontic procedures.

  • Randomized prospective multicenter trials offer the potential to develop evidenced-based methodologies for these pioneering regenerative endodontic procedures.

Key Points

Introduction

Regenerative endodontic procedures (REPs) can be defined as biologically based procedures designed to replace damaged structures including dentin and cells of the pulp-dentin complex. Case studies have presented clinically successful regenerative endodontic procedures in vivo ( Table 1 ), but the present information remains inadequate to define a single regenerative protocol. Despite published outcomes, clinicians continue to question the predictability of the procedure. Anecdotal evidence suggests moderate success rates and a need for more reliable protocols.

Table 1
Human in vivo case reports. The table organizes multiple factors that may be related to specific outcomes such as age, teeth treated, periapical diagnosis (at time of presentation to endodontic clinic), irrigant, depth/technique of irrigation, antimicrobial, antimicrobial placement method, duration of antimicrobial tissue in canal, creation of blood clot scaffold, pulp space barrier/restoration
Age (y) Tooth No. Treated Periapical Diagnosis (at Time of Presentation to Endodontic Clinic) Irrigant(s) Depth/Technique of Irrigation Antimicrobial Antimicrobial Placement Method Duration of Antimicrobial Tissue in Canal? Evoke Blood Clot-Scaffold? Pulp Space Barrier/Restoration
Iwaya et al, 2001 13 29 Chronic apical abscess 5% NaOCl; 3% hydrogen peroxide (weekly for 5 wk) Coronal portion of root Metronidazole; ciprofloxacin (weekly for 5 wk) No indication 4 wk Yes Smooth broach inserted to vital tissue; no report of bleeding Ca(OH) 2 ; glass ionomer; composite resin
Banchs and Trope, 2004 11 29 Chronic apical abscess 5.25% NaOCl; Peridex Within 1 mm of apex Metronidazole; ciprofloxacin; minocycline Lentulo 26 d Yes Endodontic explorer used to create bleeding 3 mm below CEJ MTA; composite resin
Chueh and Huang, 2006 10 20 Chronic apical abscess 2.5% NaOCl Pulp chamber Ca(OH) 2 No indication 3 mo Hard tissue barrier None Ca(OH) 2 ; Cavit; amalgam
10 29 Acute apical abscess 2.5% NaOCl Pulp chamber Ca(OH) 2 No indication 8 wk Hard tissue barrier Hemorrhage observed Ca(OH) 2 ; Cavit; Ketac Silver
10 20 Chronic apical abscess 2.5% NaOCl Canal irrigated Formocresol (before referral) Ca(OH) 2 No indication 1 mo Hard tissue barrier None Ca(OH) 2 ; Cavit; glass ionomer; removed at 18.5 mo and amalgam placed
9 29 Acute apical abscess 2.5% NaOCl Canal irrigated Ca(OH) 2 No indication 5 wk Hard tissue barrier None Ca(OH) 2 ; IRM; removed at 3y and amalgam placed
Petrino 2007 8 8 Chronic apical abscess 5.25% NaOCl; Peridex Within 1 mm of apex Metronidazole; ciprofloxacin; minocycline No indication No indication Yes; vital tissue felt Endodontic explorer used to create bleeding 3 mm below CEJ MTA; composite resin
Thibodeau and Trope, 2007 and 2009 9 8 Acute apical abscess 1.25% NaOCl Canal irrigated Metronidazole; ciprofloxacin; cefaclor Lentulo and tamped down with sterile paper points 11 wk No Endodontic file to create bleeding wMTA; composite resin
Jung et al, 2008 10 29 Chronic apical abscess 5.25% NaOCl Canal irrigated (1) Metronidazole; ciprofloxacin; minocycline. (2) Erythromycin and Ca(OH) 2 . (3) Ca(OH) 2 Lentulo 88 d Hard tissue barrier None Gutta-percha; composite resin
28 Chronic apical abscess 5.25% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Lentulo 67 d Hard tissue barrier None Gutta-percha; composite resin
10 29 Chronic apical abscess 5.25% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Lentulo 11 d Yes None MTA; composite resin
10 20 Asymptomatic apical periodontitis (left open) 5.25% NaOCl Canal irrigated (1) Metronidazole; ciprofloxacin; minocycline (2) Ca(OH) 2 Lentulo (1) 30 d (2) 40 d Yes Hemorrhage observed after 30 d MTA; composite resin
13 20 Symptomatic apical periodontitis 5.25% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Lentulo 2 wk Yes None MTA; IRM
10 20 Asymptomatic apical periodontitis (left open) 2.5% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline No indication 1 wk No Endodontic file to create bleeding MTA; composite resin
9 20 Chronic apical abscess 2.5% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Lentulo 1 wk Yes Endodontic file to create bleeding MTA; composite resin
14 29 Chronic apical abscess 2.5% NaOCl Canal irrigated Ca(OH) 2 (aqueous) No indication 1 wk No Endodontic file to create bleeding MTA; composite resin
10 29 Asymptomatic apical periodontitis (left open) 2.5% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline No indication 3 wk No Endodontic file to create bleeding Collatape; MTA; composite resin
Cotti et al, 2008 9 8 Chronic apical abscess 5% NaOCl; 3% hydrogen peroxide Coronal portion of root Ca(OH) 2 powder Plugger 2 wk Yes Endodontic file to create bleeding MTA; glass ionomer; composite resin
Shah et al, 2008 9–18 14 teeth Chronic apical abscess; asymptomatic apical periodontitis 2.5% NaOCl; 3% hydrogen peroxide Canal irrigated Formocresol Cotton pellet Subsequent appointment No Needle to create bleeding Glass ionomer
Chueh et al, 2009 6–14 23 teeth Chronic apical abscess; asymptomatic apical periodontitis; acute apical abscess 2.5% NaOCl Canal irrigated Ca(OH) 2 Loosely placed 1–25 mo Hard tissue barrier No instrumentation OR Endodontic instrument to create bleeding (1) Gutta-percha/composite or Amal. (2) MTA/gutta-percha/composite or amalgam. (3) Amalgam
Ding et al, 2009 8–11 3 (available for analysis) Chronic apical abscess; acute apical abscess 5.25% NaOCl Gently flushed Metronidazole; ciprofloxacin; minocycline No indication 1 wk No indication Endodontic file to create bleeding MTA; composite
Shin et al, 2009 12 29 Chronic apical abscess 6% NaOCl/Saline/2% chlorhexidine Coronal portion of root None (1-step procedure) N/A N/A Yes Endodontic file to create bleeding wMTA/composite
Reynolds et al, 2009 11 2 teeth Chronic apical abscess 6% NaOCl/Saline/2% chlorhexidine 2 mm from apex Metronidazole; ciprofloxacin; minocycline (composite bonding/no staining) Needle 2 mm short of apex 4 wk No indication Endodontic file to create bleeding gMTA/composite
Kim et al, 2010 7 8 Symptomatic apical periodontitis 3% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline (staining/bleached) Lentulo 6 wk No indication Paper points to create bleeding MTA/glass ionomer/composite
Petrino et al, 2010 6–13 5 teeth Chronic apical abscess; asymptomatic apical periodontitis 5.25% NaOCl/saline/Peridex Canal irrigated Metronidazole; ciprofloxacin; minocycline No indication 3 wk No Endodontic file to create bleeding and CollaPlug (2 teeth) MTA/composite
Thomson and Kahler, 2010 12 20 Chronic apical abscess 1% NaOCl (with ultrasonic activation) 2 mm from apex Metronidazole; ciprofloxacin; minocycline Lentulo 6 wk No indication Endodontic explorer used to create bleeding 3 mm below CEJ wMTA/glass ionomer/composite
Nosrat et al, 2011 9 30 Symptomatic apical periodontitis 5.25% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Placed with K file 3 wk Necrotic tissue Endodontic file to create bleeding CEM cement (calcium-enriched mixture)/glass ionomer/amalgam
8 30 Chronic apical abscess 5.25% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Placed with K file 3 wk No indication Endodontic file to create bleeding CEM cement (calcium-enriched mixture)/glass ionomer/SSC
Lenzi and Trope, 2012 8 8 Inconclusive 2.5% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Lentulo 35 d No indication Endodontic file to create bleeding MTA Angelus/composite
9 Asymptomatic apical periodontitis 2.5% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Lentulo 35 d No indication Endodontic file to create bleeding MTA Angelus/composite
Cehreli et al, 2011 8–11 6 teeth Asymptomatic apical periodontitis 2.5% NaOCl 1–2 mm below orifice Ca(OH) 2 Loosely placed 3 wk No indication Endodontic file to create bleeding MTA; glass ionomer; composite or amalgam
Torabinejad and Turman, 2011 11 4 Symptomatic apical periodontitis 5.25% NaOCl Canal irrigated Metronidazole; ciprofloxacin; minocycline Amalgam carrier and endodontic pluggers 22 d No indication No creation of bleeding; PRP placed MTA/Cavit/amalgam
Iwaya et al, 2011 7 24 Acute apical abscess 5% NaOCl; 3% hydrogen peroxide Coronal portion of root (×5) Ca(OH) 2 6 wk Hard tissue barrier None Gutta-percha/composite resin

Abbreviations: CEJ, cement-enamel junction; gMTA, gray mineral trioxide aggregate; IRM, immediate restorative material; N/A, not available; SSC, stainless steel crown; wMTA, white mineral trioxide aggregate.

Tissue Engineering

The ability to predictably regenerate natural tissues and create new tissues is the objective of the emerging field of tissue engineering. Nakashima described 3 essential components of tissue engineering: stem/progenitor cells, morphogenetic signals and three-dimensional (3D) scaffolds. Stem cells, morphogens/growth factors, and biomimetic scaffolds all play essential roles in the restoration of previously damaged structures. By addressing the 3 elements of tissue engineering in future clinical guidelines, it is hoped to provide a microenvironment that is conducive to regeneration of pulplike tissues in patients.

Commitment to regenerative endodontics

Regenerative endodontics is a high priority for the specialty of endodontics. The number of publications in peer-reviewed journals related to regenerative endodontics has increased greatly in recent years ( Fig. 1 ). Organized endodontics is committed to identifying evidence-based methodologies for these procedures. The next logical phase of regenerative endodontic research will be prospective randomized clinical trials.

Fig. 1
( A ) An OVID/Medline search was performed with the key words revascularization or regenerative or stem cells, and dental pulp or endodontics. Peer-reviewed publication number in each year since 2001 is presented. ( B ) A search was performed on www.jendodon.com with the key words revascu or regen or stem cell. Publication number in each year is presented.
( Courtesy of A. Diogenes.)

The American Association of Endodontists (AAE) and the AAE Foundation recently released a request for proposals for clinical research into regenerative endodontic treatment with up to $2.5 million in funding for the project. Aside from these future high-level studies, the current case studies offer the benefit of being performed in patients and thus provide a higher level of evidence than animal studies or in vitro studies.

Commitment to regenerative endodontics

Regenerative endodontics is a high priority for the specialty of endodontics. The number of publications in peer-reviewed journals related to regenerative endodontics has increased greatly in recent years ( Fig. 1 ). Organized endodontics is committed to identifying evidence-based methodologies for these procedures. The next logical phase of regenerative endodontic research will be prospective randomized clinical trials.

Fig. 1
( A ) An OVID/Medline search was performed with the key words revascularization or regenerative or stem cells, and dental pulp or endodontics. Peer-reviewed publication number in each year since 2001 is presented. ( B ) A search was performed on www.jendodon.com with the key words revascu or regen or stem cell. Publication number in each year is presented.
( Courtesy of A. Diogenes.)

The American Association of Endodontists (AAE) and the AAE Foundation recently released a request for proposals for clinical research into regenerative endodontic treatment with up to $2.5 million in funding for the project. Aside from these future high-level studies, the current case studies offer the benefit of being performed in patients and thus provide a higher level of evidence than animal studies or in vitro studies.

Trauma literature

Much of the basis for these case studies has rudiments in the trauma literature. Revascularization can occur but requires a particular set of circumstances that, until recently, were thought to be exclusive to the avulsed immature permanent tooth. First, the exclusion of bacteria is the key factor in the success of this process. Second, the combination of an open apex and a short root allows the ingrowth of well-vascularized tissue. Third, the devitalized uninfected pulp is also thought to act as a scaffold for the ingress of apical tissue. Successful revascularization of the pulp leads to the maturation of the root and deposition of hard tissue within the root, both of which improve the probability of long-term retention of the tooth.

The notion then emerged that, if the pulp could be adequately disinfected, a blood clot matrix induced, and a bacteria-tight seal restored in a necrotic infected immature tooth, then, by extrapolation, revascularization should be expected to occur as in the devitalized, uninfected, avulsed, immature permanent tooth.

Terminology

Revascularization, revitalization, and regeneration have all been used to describe the outcome of these procedures. There remains some disagreement in the terminology. In vivo evidence suggests that it is unlikely that a functional pulp-dentin complex is being regenerating with current protocols. Wang and colleagues noted that the tissue that is responsible for increased root thickness in their study was cementum and not dentin. As more is learned about the tissues that are present through both molecular methods and human histology, it will become possible to better define what it is being accomplished. This article unifies all 3 terms under the broader category of REPs and regenerative endodontic outcomes.

Goals of REPs

The goal of regenerative therapies is to regenerate a fully functional pulp-dentin complex that fosters continued root development for immature teeth, and prevents or resolves apical periodontitis. As in traditional endodontic therapy, outcomes have various criteria for success. The degree of success of REPs is largely measured by the extent to which it is possible to attain primary, secondary, and tertiary goals.

The primary goals are the elimination of symptoms and the evidence of bony healing. Secondary goals (which are desirable but perhaps not essential) include increased root wall thickness and/or increased root length. A tertiary goal (which, if achieved, indicates a high level of success) is a positive response to vitality testing. Histologic confirmation of dental pulp with an intact odontoblastic layer and restoration of a functional pulp is the pinnacle of regenerative treatment goals.

Regardless of this ultimate outcome, it is often beneficial to consider REPs if only to have a tooth act as a space maintainer until a suitable restorative option is available. In some cases, the achievement of the primary goals is all that is necessary to deem the procedure a success. REPs may provide hope for those teeth with unfavorable prognoses ( Fig. 2 ).

Fig. 2
Hope for the hopeless. ( A ) A 10-year-old patient presents with extensive caries, +2 mobility, and sinus tract. ( B ) 1:1 by volume of ciprofloxacin/metronidazole placed in canal. ( C ) At the 3-week visit for finalization of REP. Sinus tract resolved. ( D ) At the 20-month recall. The tooth does not respond to vitality testing but the tooth is asymptomatic with no mobility and there is radiographic evidence of healing.
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Oct 29, 2016 | Posted by in General Dentistry | Comments Off on Clinical Considerations for Regenerative Endodontic Procedures
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