Dentin is primarily composed of hydroxyapatite crystals within a rich organic matrix. The organic matrix comprises collagenous structural components, within which a variety of bioactive molecules are sequestered. During caries progression, dentin is degraded by acids and enzymes derived from various sources, which can release bioactive molecules with potential reparative activity towards the dentin-pulp complex. While these molecules’ repair activities in other tissues are already known, their biological effects are unclear in relation to degradation events during disease in the dentin-pulp complex. This study was undertaken to investigate the effects of dentin matrix components (DMCs) that are partially digested by matrix metalloproteinases (MMPs) in vitro and in vivo during wound healing of the dentin-pulp complex. DMCs were initially isolated from healthy dentin and treated with recombinant MMPs. Subsequently, their effects on the behaviour of primary pulp cells were investigated in vitro and in vivo. Digested DMCs modulated a range of pulp cell functions in vitro. In addition, DMCs partially digested with MMP-20 stimulated tertiary dentin formation in vivo, which exhibited a more regular tubular structure than that induced by treatment with other MMPs. Our results indicate that MMP-20 may be especially effective in stimulating wound healing of the dentin-pulp complex.

These multifaceted approaches to evaluate pulp capping materials may accelerate review processes, ultimately improving vital pulp therapy.

BackgroundBacterial biofilms that develop on root surfaces outside apical foramens have been found to be associated with refractory periapical periodontitis. However, several other factors cause endodontic failures apart from extraradicular biofilms. The aim of this study was to identify the factors causing endodontic failures in general practices in Japan.MethodsPatients diagnosed as having refractory periapical periodontitis by general practitioners and who requested endodontic treatment at Osaka University Dental Hospital were selected by checking medical records from April 2009 to March 2013. Factors causing endodontic failures were identified.ResultsA total of 103 teeth were selected, and 76 teeth completed root-canal treatment. Tooth extractions were required for 18 teeth after or without endodontic treatment. Six teeth required apicoectomy after endodontic treatment. One tooth needed hemisection. One tooth needed intentional replantation. One tooth needed adhesion and replantation. The main causes of treatment failure were open apices (24 teeth), perforation (18 teeth), and root fracture (13 teeth). In six teeth with open apices that required apicoectomy or extraction, extraradicular biofilms may have been related to endodontic failure.ConclusionsMost endodontic cases diagnosed with refractory periapical periodontitis by general practitioners were compromised by any other factors rather than extraradicular biofilms.Electronic supplementary materialThe online version of this article (10.1186/s12903-018-0530-6) contains supplementary material, which is available to authorized users.

The induction of tissue mineralization and the mechanism by which surface pre-reacted glass-ionomer (S-PRG) cement influences pulpal healing remain unclear. We evaluated S-PRG cement-induced tertiary dentin formation in vivo, and its effect on the pulp cell healing process in vitro. Induced tertiary dentin formation was evaluated with micro-computed tomography (μCT) and scanning electron microscopy (SEM). The distribution of elements from the S-PRG cement in pulpal tissue was confirmed by micro-X-ray fluorescence (μXRF). The effects of S-PRG cement on cytotoxicity, proliferation, formation of mineralized nodules, and gene expression in human dental pulp stem cells (hDPSCs) were assessed in vitro. μCT and SEM revealed that S-PRG induced tertiary dentin formation with similar characteristics to that induced by hydraulic calcium-silicate cement (ProRoot mineral trioxide aggregate (MTA)). μXRF showed Sr and Si ion transfer into pulpal tissue from S-PRG cement. Notably, S-PRG cement and MTA showed similar biocompatibility. A co-culture of hDPSCs and S-PRG discs promoted mineralized nodule formation on surrounding cells. Additionally, S-PRG cement regulated the expression of genes related to osteo/dentinogenic differentiation. MTA and S-PRG regulated gene expression in hDPSCs, but the patterns of regulation differed. S-PRG cement upregulated CXCL-12 and TGF-β1 gene expression. These findings showed that S-PRG and MTA exhibit similar effects on dental pulp through different mechanisms.

This new material can be an alternative pulp capping agent to MTA.

No abstract

Dentin consists of inorganic hard tissue and organic dentin matrix components (DMCs). Various kinds of bioactive molecules are included in DMCs and some of them can be released after digestion by endogenous matrix metalloproteinases (MMPs) in the caries region. Digested DMCs induced by MMP20 have been reported to promote pulpal wound healing processes, but the released critical molecules responsible for this phenomenon are unclear. Here, we identified protein S100-A7 as a critical molecule for pulpal healing in digested DMCs by comprehensive proteomic approaches and following pulp capping experiments in rat molars. In addition, immunohistochemical results indicated the specific distribution of S100-A7 and receptor for advanced glycation end-products (RAGE) as receptor for S100-A7 in the early stage of the pulpal healing process, and following accumulation of CD146-positive stem cells in wounded pulp. Our findings indicate that protein S100-A7 released from dentin by MMP20 might play a key role in dentin pulp regeneration.

Aim To evaluate the dentinogenetic effects of tissue inhibitor of metalloprotease (TIMP1) on human pulp cells in vitro and rat pulp tissue in vivo. Methodology The effect of TIMP1 on pulp cell functions related to hard tissue formation as part of the wound healing process (i.e. biocompatibility, proliferation, differentiation and mineralized nodule formation) was evaluated in vitro and using a direct pulp capping experimental animal model in vivo. The effects of different‐sized cavity preparations on hard tissue formation induced by ProRoot MTA at 2 weeks were evaluated using micro‐computed tomography (micro‐CT). Tertiary dentine formation quality and quantity after pulp capping using TIMP1, ProRoot MTA and phosphate‐buffered saline (PBS) was also evaluated after 4 weeks using micro‐CT in term of dentine volume (DV), dentine mineral density (DVD) and histological analysis. The data were evaluated by Student's t‐test, one‐way ANOVA with Tukey's post hoc test, the Kruskal–Wallis test or the Steel–Dwass test. P values < 0.05 were considered statistically significant. Results TIMP1 significantly stimulated dental pulp stem cell proliferation, differentiation, and mineralization and was more biocompatible compared with the PBS control (P < 0.05). In the pulp capping model, the amount of tertiary dentine that formed was directly proportional to the size of the pulp exposure; greater amounts of tertiary dentine were observed in pulps with larger exposures after 2 weeks. 4‐week samples of TIMP1 and ProRoot MTA had similar characteristics, but both sample significantly induced tertiary dentine formation beneath the cavity compared with PBS (P <  0.05) under standardized cavity preparations. Conclusions TIMP1 has an important role in pulpal wound healing, which makes it a potential biological pulp capping material and candidate molecule for regenerative endodontic therapy.