Dissecting dentine–pulp injury and wound healing responses: consequences for regenerative endodontics

Abstract

Summary A thorough understanding of the biology of the dentine–pulp complex is essential to underpin new treatment approaches and maximize clinical impact for regenerative endodontics and minimally invasive vital pulp treatment (VPT) strategies. Following traumatic and carious injury to dentine–pulp, a complex interplay between infection, inflammation and the host defence responses will occur, which is critical to tissue outcomes. Diagnostic procedures aim to inform treatment planning; however, these remain clinically subjective and have considerable limitations. As a consequence, significant effort has focussed on identification of diagnostic biomarkers, although these are also problematic due to difficulties in identifying appropriate diagnostic fluid sources and selecting reproducible biomarkers. This is further compounded by the link between inflammation and repair as many of the molecules involved exhibit significant multifunctionality. The tertiary dentine formed in response to dental injury has been purposefully termed reactionary and reparative dentine to enable focus on associated biological processes. Whilst reactionary dentine produced in response to milder injury is generated from surviving primary odontoblasts, reparative dentine, in response to more intense injury, requires the differentiation of new odontoblast‐like cells derived from progenitor/stem cells recruited to the injury site. These two diverse processes result in very different outcomes in terms of the tertiary dentine produced and reflect the intensity rather than specific nature (nonexposure versus exposure) of the injury. The subsequent identification of the odontoblast‐like cell phenotype remains challenging due to lack of unique molecular or morphological markers. Furthermore, the cells ultimately lining the newly deposited dentine provide only a snapshot of events. The specific source and plasticity of the progenitor cells giving rise to the odontoblast‐like cell phenotype are also of significant debate. It is likely that improved characterization of tertiary dentine may better clarify the influence of cell derivation for odontoblast‐like cells and their diversity. The field of regenerative endodontics offers exciting new treatment opportunities, and to maximize outcomes, we propose that the term regenerative endodontics should embrace the repair, replacement and regeneration of dentine–pulp.

Diagnostic biomarker candidates for pulpitis revealed by bioinformatics analysis of merged microarray gene expression datasets

“…During the treatment of deep caries and traumatic exposure of dental pulp, it is essential to assess whether the pulp inflammation is reversible. It has been reported that inflamed pulp tissue might produce some biomarkers that are secrete to the external environment [13,14], making tests of dental pulp blood and dental fluid in pulpitis possible. Johannes et al [17] used heparinized 10-mL microcapillary tubes to collect pulp blood samples when the dental pulp was exposed during caries removal.…”

“…Dental pulp is not isolated in the oral cavity and releases many biological products to the external environment in response to external harmful stimuli [12][13][14]. At the cellular or molecular level, a wide range of molecules are released during pulpal and periapical inflammation, including cytokines, proteases, inflammatory mediators, growth factors, and antimicrobial peptides [15,16].…”

Pulp Innate Immune Defense: Translational Opportunities

“…The pulp has an innate regenerative and healing capability if a conducive environment is provided, and, therefore, minimally invasive biologically-based dental procedures are being developed 59 . Vital pulp treatments are a component of regenerative endodontic procedures, which aim to maintain and support the pulp tissue that would previously clinically have been removed.…”

Dental Pain: Dentine Sensitivity, Hypersensitivity and Cracked Tooth Syndrome

“…the identification that viable radicular pulp may often be present in cases of severe reversible and irreversible pulpitis has driven an interest in more conservative and biologically considered treatment modalities. [16][17][18][19] paradoxically, the tooth may now appear non-vital, but it has been observed that C fibres (which do not respond readily to ept 20 ) can persist in tissues with low oxygen concentrations and conduct pain until complete pulpal necrosis occurs. 21 this explains the commonly encountered situation where, to all intents and purposes, a tooth considered to be non-vital is exquisitely tender to root canal instrumentation.…”