A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review.

Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.

Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/ß-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

Retrospective Evaluation of Treatment Planning for Dental Implant.

This retrospective study investigates the diagnostic rationale for the extraction of teeth and their replacement with implants in a dental school setting. Most of the teeth were extracted for restorative reasons (62.7%). The other reasons for extraction were periodontal (35.1%) and endodontic (1.3%). A panel of endodontists disagreed with the treatment-planning dentists' decisions in 40.3% of the cases. Slightly more than half, 52.9%, of the disagreements were for restorative reasons. Most of the decisions in disagreement were made by general dentists (60.6%), far fewer by prosthodontists (25.5%), periodontists (12.2%), and oral surgeons (1.6%). An extensive review of the literature is provided.

Cpne7 deficiency induces cellular senescence and premature aging of dental pulp.

Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.

Engineering of a periodontal ligament construct: cell and fibre alignment induced by shear stress.

AIM: We report an in vitro technique to establish alignment of collagen fibres and cells within a three-dimensional tissue equivalent that mimics the natural periodontal ligament (PDL) using a novel custom-designed bioreactor. MATERIAL AND METHODS: Shear stress was applied to the tissue equivalent prepared with collagen solution and seeded with human PDL cells. Stress-strain dynamics and the alignment of collagen fibres and PDL cells in tissue equivalents were analysed. RESULTS: Shear stress aligned collagen fibres and PDL cells in a direction parallel to the principle strain vector. PDL cells and Collagen fibres aligned in strained tissue equivalents with higher uniformity than in unstrained tissue equivalents. CONCLUSIONS: The cell and fibre alignment of the engineered PDL was precisely guided by mechanical shear stress along the direction of principal strain vector using a custom-designed bioreactor, suggesting that the enhanced functional property of engineered PDL constructs could be achieved with this technique.

Regenerative Endodontic Therapy in Mature Teeth Using Human-Derived Composite Amnion-Chorion Membrane as a Bioactive Scaffold: A Pilot Animal Investigation.

INTRODUCTION: Human-derived composite amnion-chorion membrane (ACM) has been used for various regenerative treatments. The aim of this pilot study was to investigate the effectiveness of the ACM as a scaffold for pulp regeneration in mature canine teeth. METHODS: A total of 24 roots from mature premolars in dogs were included for regenerative procedures using blood clots (BC) (group 1, n = 8), collagen membrane (CM) (group 2, n = 8), and ACM (group 3, n = 8). Each tooth was left open through a buccal access to induce root canal infection and inflammation. The root canals were disinfected with 1.5% NaOCl and calcium hydroxide intracanal medicament. After 2 weeks, bleeding was evoked to induce blood clot formation (group 1) or before the placement of the membranes (groups 2 and 3). After 12 weeks, the animals were euthanized for histologic assessment. The histologic data including intracanal fibrous connective tissue, odontoblast-like cell lining, intracanal mineralized tissue, periapical inflammation, and apical closure were qualitatively and quantitively analyzed. RESULTS: Histologic analysis revealed that intracanal fibrous connective tissue was identified in all groups, but a higher volume of the fibrous tissues was formed in the ACM group. Odontoblast-like cells were only observed in the ACM group. The intracanal mineralized tissue was observed only in the BC and CM groups. The BC group showed more periapical inflammation than the ACM group (P < .05). Apical closure was more often found in the CM group than the BC group (P < .05). CONCLUSIONS: More intracanal fibrous tissue and odontoblast-like cell lining, and less periapical inflammation were observed after regenerative endodontic treatment in mature teeth using the ACM than blood clot alone or blood clot with collagen membrane. The use of the ACM may be useful for a cell-homing-based pulp regeneration in mature teeth.

The Disease Process, Diagnosis and Treatment of Invasive Cervical Resorption: A Review.

Invasive cervical resorption (ICR) is a localized, subepithelial, supra-osseous resorptive process of the tooth. Although there are several predisposing factors associated with ICR, its etiology and pathogenesis are poorly understood. The damage to the protective layer on the external root surface appears to allow for the attachment of clastic cells and initiate the resorptive process, which is confined by the inner protective pericanalar resorption-resistant sheet surrounding the root canal space. The use of cone-beam computed tomography (CBCT) is recommended for the diagnosis and assessment of a resorptive lesion. Based on the thorough evaluation of the size and location of the ICR lesion using CBCT, surgical or nonsurgical treatment can be chosen to address the source of the resorption. This review discusses the current status of knowledge regarding the biology of ICR lesions as well as their external or internal treatment using hydraulic calcium silicate-based materials. Future clinical outcome studies are necessary to evaluate the impact of hydraulic calcium silicate-based materials on the healing of ICR lesions.

A Novel Approach to Fracture Resistance Using Horizontal Posts after Endodontic Therapy: A Case Report and Review of Literature.

Studies of endodontic outcomes suggest that fracture of the tooth after endodontic therapy may be a greater problem than endodontic reinfection. Immediate full coverage with or without a post and core is the best way to prevent fracture. Unfortunately, in many population areas, due predominantly to cost, this restoration is often delayed, leading to fracture of the tooth. Reviews of several in vitro studies suggest that a composite restoration reinforced with glass fibers, particularly with fiberglass posts laid horizontally in a buccolingual direction, significantly increased the resistance to fracture. This case report describes in detail the placement of horizontal posts in an endodontically treated molar to reinforce the coronal structure. In the discussion, we outlined the agreement of most of the authors on the increase in fracture resistance and the lack of consensus on what constitutes a catastrophic fracture.

Diagnostic Accuracy of 5 Dental Pulp Tests: A Systematic Review and Meta-analysis.

INTRODUCTION: The aim of this systematic review was to investigate and compare the diagnostic accuracy including sensitivity, specificity, adjusted accuracy, adjusted positive predictive value (PPV), and adjusted negative predictive value (NPV) of cold pulp testing (CPT), heat pulp testing (HPT), electric pulp testing (EPT), laser Doppler flowmetry (LDF), and pulse oximetry (PO). METHODS: Three electronic databases were searched from January 1964 to December 2016. True-positive, false-positive, true-negative, and false-negative values were extracted from data in each study. Sensitivity, specificity, adjusted accuracy, adjusted PPV, and adjusted NPV were calculated from those values, if not presented. A random effects model was used to calculate pooled estimates of sensitivity, specificity, adjusted accuracy, adjusted PPV, and adjusted NPV. RESULTS: A total of 125 articles were identified, and 28 studies were included for the final review. The pooled estimates of sensitivity for CPT, EPT, HPT, LDF, and PO were 0.87, 0.72, 0.78, 0.98, and 0.97, respectively. Those of specificity were 0.84, 0.93, 0.67, 0.95, and 0.95, respectively. Those of adjusted accuracy were 0.84, 0.82, 0.72, 0.97, and 0.97, respectively. For adjusted PPV, they were 0.81, 0.89, 0.62, 0.94, and 0.94, respectively, and for adjusted NPV, they were 0.87, 0.80, 0.79, 1.00, and 0.99, respectively. CONCLUSIONS: LDF and PO were the most accurate diagnostic methods, and HPT was the least accurate diagnostic method. EPT showed high accuracy when testing vital teeth (specificity = 0.93) but low accuracy when assessing nonvital teeth (sensitivity = 0.72). CPT had moderate accuracy when evaluating vital (specificity = 0.84) and nonvital (sensitivity = 0.87) teeth.

Continued root maturation despite persistent apical periodontitis of immature permanent teeth after failed regenerative endodontic therapy.

Three immature permanent teeth with pulp necrosis and apical periodontitis were treated with regenerative endodontic therapy (RET), which included root canal disinfection with sodium hypochlorite irrigation, intra-canal medication with calcium hydroxide paste, 17% EDTA rinse, induction of periapical bleeding into the canal, collagen matrix and MTA coronal seal, and composite resin restoration of access cavities. After different periods of follow-up, it was observed that continued root maturation, especially apical closure occurred despite persistent apical periodontitis of immature permanent teeth after failed RET. This finding is of interest as the secondary goal of further root maturation occurred despite failure of the primary goal of elimination of clinical symptom/sign and periapical inflammation. The possible biological mechanisms that could allow for further root maturation to occur in spite of persistent root canal infection of immature permanent teeth are discussed. Based on these observations, the biology of wound healing of immature permanent teeth after injury is not fully understood and should be further investigated. This case report demonstrates that whilst further root maturation is considered a successful outcome for teeth treated with RET, the primary objective must be the resolution of the signs and symptoms of apical periodontitis.

Enhancing Effect of Elastinlike Polypeptide-based Matrix on the Physical Properties of Mineral Trioxide Aggregate.

INTRODUCTION: Elastinlike polypeptide (ELP) is 1 of the genetically engineered, protein-based polypeptides, which offers outstanding advantages such as superior biocompatibility, long-term stability, elasticity, and cost-effectiveness. This study aimed to investigate the effect of an ELP-based matrix on the physical properties and biocompatibility of mineral trioxide aggregate (MTA). METHODS: The 2 types of ELPs were synthesized and mixed with the MTA powder in various liquid-to-powder ratios. The physical properties including compressive strength, microhardness and setting time, washout resistance, and biocompatibility were investigated for the ELP-incorporated MTA. The microstructure of the MTA was also analyzed using scanning electron microscopy and Fourier-transform infrared spectroscopy. RESULTS: The ELP-based matrix enhanced the physical properties of MTA, including the compressive strength, microhardness, and washout resistance of MTA. The ELP incorporation showed no negative effect on biocompatibility. However, ELPs prolonged the setting time of MTA. CONCLUSIONS: These results suggested that the addition of the ELP-based matrix to MTA enhanced the physical properties without negatively affecting the chemical structure and biocompatibility of MTA. Further investigation is warranted to overcome a clinical challenge associated with the extended setting time caused by the addition of ELP.