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Are Regenerative Endodontic Procedures Working?

By Avina K. Paranjpe, BDS, M.S., MSD, Ph.D.

There has been an ongoing debate about Regenerative Endodontic (RegEndo) procedures and if they actually work. This ongoing debate stems from the success rates for this procedure, which varies. However, the question always remains: do we know everything about this procedure? The answer is “no”.

The success of Tissue Engineering is based on a triad of stem cells, a scaffold and growth factors (1). However, one main difference in regenerating tissue within the tooth versus other parts of the body is the presence of various species of bacteria within the canal space. When performing non-surgical root canal treatments the canals are chemomechanically debrided with the help of endodontic files and various irrigants. However, when a tooth has an immature, open apex and the clinician plans to perform a RegEndo procedure, the main considerations should be adequate disinfection. This could prove challenging as the canal walls are thin and cannot be instrumented. Hence, the clinician needs to rely on irrigation, irrigation techniques and intracanal medicaments for disinfection. However, is this enough? This procedure additionally requires stem cells for tissue formation. These stem cells are present in the apical portion of the tooth and are the Stem Cells of the Apical Papilla (SCAP). SCAP are expected to survive the various procedures and then differentiate in the root canal space into a different cell type. Can they do this effectively and efficiently?

Current research has focused heavily on various aspects of RegEndo procedures. The research various from systematic reviews to bench-top studies. However, the literature still reports a high number of failures to about 39%, two years after initiation of treatment (2). The failures ranged from tooth discoloration to fracture to signs of periapical pathosis and presence of symptoms.  Other studies have demonstrated success rates of up to 91% in these cases (3). These numbers are varied and depend on the type study conducted (systematic reviews, cohort studies etc.) and the factors that were considered (success, failure, outcomes etc.) (2-6)

The varied success and failures rates could be attributed to various reasons some of which include 1) no standardized technique 2) inadequate disinfection, 3) insufficient knowledge about the SCAP and 4) scaffolds used (2, 7).

A recent web-based survey demonstrated clinicians use various irrigants and intracanal medicaments for disinfection during these procedures. Clinicians used various irrigants like Chlorhexidine (CHX- concentrations ranging from 0.12% -0.2%), NaOCl (concentrations ranging from 1%-5.25%) and not all clinicians used EDTA at the second appointment (2, 7). CHX is cytotoxic to SCAP (8, 9). EDTA is essential to release the growth factors from the dentin, which in turn would help the SCAP to differentiate (8, 10, 11). However, a recent study demonstrated that a final rinse with EDTA prior to inducing bleeding causes a decrease in clot formation and recommended the use of saline after EDTA (12).

Clinicians use various intracanal medicaments during the procedure, which include calcium hydroxide, or antibiotics are varied concentrations (7). However, is this enough to disinfect the root canal space? Persistent infection has been attributed to 79% of failed RegEndo cases (2). Other studies have demonstrated that residual bacteria in the canal could affect treatment outcomes significantly by either affecting the release of growth factors from the dentin, the differentiation of the SCAP and the survival of the SCAP once they are introduced into the root canal space (13-16). Bacteria can activate the immune system present in the blood clot and this activated immune system could be cytotoxic to the SCAP. Hence, disinfection of the canal space is imperative to the success of these procedures (15).

The cellular properties of SCAP play an important role in RegEndo procedures. A recent study demonstrated that SCAP are less resistant to cell death and have a lower differentiation potential as compared to some other oral stem cells, which could make them more vulnerable to the immune cells (17). It is a possibility that the SCAP do not survive due to these reasons, thereby contributing to the failure of some RegEndo procedures.

The traditional blood clot has been the scaffold of choice until date. However, some studies have demonstrated that the blood clot may not be necessary or may not be the ideal scaffold for these procedures (2, 18, 19). Research studies related to various scaffolds and their effectiveness during RegEndo procedures have been published and are ongoing (20-22).

“Life isn’t black or white, it’s a million gray areas.”- Ridley Scott

Although RegEndo is an important treatment alternative when treating permanent teeth with open apices, it should be noted that there are many gray areas that need to be investigated. Research is ongoing and it is possible that developments in the near future will enable the clinician to perform these procedures with more desirable and predictable outcomes.

Dr. Avina Paranjpe, Diplomate, American Board of Endodontics, is associate professor, Department of Endodontics, University of Washington, School of Dentistry. She can be reached at



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