Effect of access cavities on the biomechanics of mandibular molars: a finite element analysis.

INTRODUCTION: This study aimed to predict the fracture resistance of a mandibular first molar (MFM) with diverse endodontic cavities using finite element analysis (FEA). METHODS: Five experimental finite element models representing a natural tooth (NT) and 4 endodontically treated MFMs were generated. Treated MFM models were with a traditional endodontic cavity (TEC) and minimally invasive endodontic (MIE) cavities, including guided endodontic cavity (GEC), contracted endodontic cavity (CEC) and truss endodontic cavity (TREC). Three loads were applied, simulating a maximum bite force of 600 N (N) vertically and a normal masticatory force of 225 N vertically and laterally. The distributions of von Mises (VM) stress and maximum VM stress were calculated. RESULTS: The maximum VM stresses of the NT model were the lowest under normal masticatory forces. In endodontically treated models, the distribution of VM stress in GEC model was the most similar to NT model. The maximum VM stresses of the GEC and CEC models under different forces were lower than those of TREC and TEC models. Under vertical loads, the maximum VM stresses of the TREC model were the highest, while under the lateral load, the maximum VM stress of the TEC model was the highest. CONCLUSION: The stress distribution of tooth with GEC was most like NT. Compared with TECs, GECs and CECs may better maintain fracture resistance, TRECs, however, may have a limited effect on maintenance of the tooth resistance.

Clinical effect of a manual toothbrush with tapered filaments on dental plaque and gingivitis reduction.

PURPOSE: To evaluate the anti-plaque efficacy (Study 1) and the anti-gingivitis efficacy (Study 2) of a manual toothbrush with tapered bristles compared to marketed control manual toothbrushes. METHODS: Studies 1 and 2 were independent, randomized and controlled, single-center, examiner-blind clinical trials in generally healthy adults. Study 1 included a 2-day acclimation period, followed by a 5-day twice daily toothbrushing test phase with the assigned brush. Baseline and Day 5 pre- and post-brushing plaque levels were assessed via Turesky Modified Quigley-Hein Plaque Index (TMQHPI). In Study 2, subjects with existing gingivitis brushed with their assigned toothbrush twice daily for 4 weeks. Gingivitis was measured using the Mazza Modification of the Papillary Bleeding Index at Baseline and Weeks 2 and 4. In both trials, subjects were randomly assigned to either the manual toothbrush with tapered bristles (Oral-B Super Thin Indicator toothbrush, OM159) or the marketed control (Study 1: Oral-B Complete Clean & Sensitive toothbrush; Study 2: Crest Pro-Health Complete 7 Brush 35 toothbrush) for use with a regular fluoridated dentifrice. RESULTS: 40 (Study 1) and 63 (Study 2) subjects were randomized in each trial. In Study 1, both the tapered bristle and marketed control brushes provided significant (P< 0.0001) mean whole mouth plaque reductions at Day 1 and Day 5 post-brushing relative to pre-brushing as measured via TMQPHI, with no between-brush significant differences. Both groups showed a significant reduction in Day 5 post-brushing mean plaque scores versus Day 1 pre- brushing mean plaque scores (P< 0.0001), but the reductions were not significantly different between groups (P= 0.4274). In Study 2, both the tapered bristle brush and the marketed control brush produced significant (P< 0.0001) reductions in both gingivitis and number of gingival bleeding sites at both Weeks 2 and 4 versus baseline. At Week 4, the tapered filament toothbrush group showed 8.6% less gingivitis (P= 0.0017) and 33.4% fewer bleeding sites (P= 0.0030) versus the control brush. All toothbrushes were well-tolerated. CLINICAL SIGNIFICANCE: Twice daily customary use of a manual toothbrush with tapered bristles provided clinically meaningful plaque and gingivitis reduction benefits.

Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts.

The NLRP3/caspase-1 inflammasome pathway plays an important role in cellular immune defence against bacterial infection; however, its function in human dental pulp tissue and human dental pulp fibroblasts remains poorly understood. We demonstrate that NLRP3 protein expression occurs to a greater extent in pulp tissue with irreversible pulpitis than in normal pulp tissue and in tissue with reversible pulpitis. Caspase-1 is present in its active (cleaved) form only in pulp tissue with irreversible pulpitis. NLRP3 and caspase-1 are expressed in the odontoblast layers in normal human dental pulp tissue, whereas in inflamed pulp tissue, the odontoblast layers are disrupted and dental pulp cells are positive for NLRP3 and caspase-1. Additionally, we investigate the role of the NLRP3/caspase-1 inflammasome pathway in human dental pulp fibroblasts and show that ATP activates the P2X7 receptor on the cell membrane triggering K(+) efflux and inducing the gradual recruitment of the membrane pore pannexin-1. Extracellular lipopolysaccharide is able to penetrate the cytosol and activate NLRP3. Furthermore, the low intracellular K(+) concentration in the cytosol triggers reactive oxygen species generation, which also induces the NLRP3 inflammasome. Thus, the NLRP3/caspase-1 pathway has a biological role in the innate immune response mounted by human dental pulp fibroblasts.

Nemotic human dental pulp fibroblasts promote human dental pulp stem cells migration.

Dental pulp inflammation has long been perceived as a negative factor leading to pulp disruption. Previous studies have suggested that the inflammatory reaction might be a prerequisite for the burst of progenitors implicated in pulp repair. To investigate the migration of human dental pulp stem cells (hDPSCs) in response to human dental pulp fibroblasts (HDPFs) nemosis, an in vitro model of nemosis-induced inflammation in three-dimensional culture was used in this study. We observed HDPF spheroid formation and that cell-cell adhesion between HDPFs leads to necrosis. Cell death detection and cell counting kit-8 assays showed reduced live cell numbers and increased levels of cell membrane leakage in HDPF spheroids. HDPFs spheroids expressed cyclooxygenase-2 and released an increasing amount of prostaglandin E2 and interleukin-8, indicating inflammation in response to nemosis. The Transwell assays showed that the conditioned medium from HDPFs spheroids significantly induced hDPSCs migration more than the medium from the monolayer. Taken together, these results indicate that HDPFs spheroids induce nemosis and contribute to the migration of hDPSCs. This model might provide a potential research tool for studying interactions between fibroblasts and stem cells, and studies concerning nemosis-targeted stem cells might help treat pulp inflammation.

The role of pyroptosis in inflammatory diseases.

Programmed cell death has crucial roles in the physiological maturation of an organism, the maintenance of metabolism, and disease progression. Pyroptosis, a form of programmed cell death which has recently received much attention, is closely related to inflammation and occurs via canonical, non-canonical, caspase-3-dependent, and unclassified pathways. The pore-forming gasdermin proteins mediate pyroptosis by promoting cell lysis, contributing to the outflow of large amounts of inflammatory cytokines and cellular contents. Although the inflammatory response is critical for the body's defense against pathogens, uncontrolled inflammation can cause tissue damage and is a vital factor in the occurrence and progression of various diseases. In this review, we briefly summarize the major signaling pathways of pyroptosis and discuss current research on the pathological function of pyroptosis in autoinflammatory diseases and sterile inflammatory diseases.

Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells.

Mitogen-activated protein kinase (MAPK) pathways are involved in stem cell differentiation. However, the odontoblastic differentiation-inducing effects by mineral trioxide aggregate (MTA) via MAPK pathways have not been clarified in human dental pulp stem cells (DPSCs). In this study we investigated the effects of MTA on cell viability and production of differentiation markers, and the involvement of MAPK signaling pathways in cultured human DPSCs. Cells were cultured with MTA, and the viability and differentiation productions of the cells were determined using the MTT assay and real-time PCR analysis, respectively. MAPK activation was measured by western blotting. MTA at concentrations of 20 and 10 mg/ml was toxic for human DPSCs. MTA significantly increased the expression of alkaline phosphatase (ALP), dentin sialophosphoprotein (DSPP), type I collagen (COLI), osteocalcin (OCN) and bone sialoprotein (BSP) mRNAs and induced the phosphorylation of p42 and p44 (p42/44), p38 and c-Jun N-terminal kinases 1 and 2 (JNK1/2) MAPK. Furthermore, the inhibitor of p42/44 MAPK attenuated the MTA-induced odontoblastic differentiation. These data indicated that MTA-induced odontoblastic differentiation of human DPSCs was via MAPK pathways, which may play a key role in the repair responses of dentin-pulp-like complexes.

Two-week extrinsic stain removal efficacy of a sodium fluoride dentifrice with high cleaning silica: results from two randomized, controlled clinical trials.

PURPOSE: To evaluate a stannous-containing sodium fluoride dentifrice with high cleaning silica and polychelation technology (test dentifrice) compared to a currently marketed whitening dentifrice, which carries the ADA Seal of Acceptance for whitening, for its efficacy in removing existing natural stain over a 2-week period. METHODS: Two independent, randomized, positive-controlled, 2-treatment, parallel group, double-blind, 2-week studies with identical protocols were conducted in China. At baseline, subjects received an oral soft tissue (OST) examination followed by a Lobene stain examination. In each study, approximately 60 subjects having a Lobene stain composite score above 1 were randomized to one of two dentifrice products: the test dentifrice or the positive control. Subjects were instructed to brush twice daily for at least 1 minute with their assigned product. Lobene stain and OST examinations were conducted again after 2 weeks of use. RESULTS: In both studies, the test dentifrice and the positive control dentifrice demonstrated statistically significant reductions in Lobene composite (P<0.0001), area (P<0.0001) and intensity (P<0.0001) stain scores after 2 weeks of use versus baseline. At Week 2, there were no statistically significant differences in stain scores between treatment groups in either study (P>0.12).

Detection of vertical root fractures in non-endodontically treated molars using cone-beam computed tomography: a report of four representative cases.

Vertical root fractures (VRFs) in teeth without endodontic treatment are relatively uncommon. The diagnosis is based on clinical and radiographic presentations. It might be difficult to detect VRFs in non-endodontically treated molars by conventional radiographs in certain situations because of the limitations of 2D images and many others factors such as the VRFs being in their early stages. Root morphology variation and the orientation of VRFs can influence conventional radiographic detection and the interpretation of a radiolucent fracture line. The four case reports presented here describe and discuss the use of cone-beam computed tomography (CBCT) in successfully diagnosing VRFs based on direct visualization of radiolucent lines, especially those suspected from routine conventional radiographs, as well as their symptoms and clinical findings. CBCT also provides more information on the presence of VRFs.

Corrigendum to "Nav1.7 via Promotion of ERK in the Trigeminal Ganglion Plays an Important Role in the Induction of Pulpitis Inflammatory Pain".

[This corrects the article DOI: 10.1155/2019/6973932.].

The role of runt-related transcription factor 2 (Runx2) in the late stage of odontoblast differentiation and dentin formation.

Runx2, of the Runx family, is an essential transcription factor that controls bone and tooth development by regulating osteoblast and odontoblast differentiation. However, the function of Runx2 in late stage odontoblast differentiation is not clear. We studied the function of Runx2 in dentinogenesis by generating transgenic mice expressing Runx2 specifically in odontoblasts. We observed dentin formation in postnatal day 3 (P3), P7 and P28 mice and measured the expression levels of Runx2 and matrix proteins in dentin. The odontoblasts in transgenic mice (Tg) lost their tall columnar shape and polarization and dentinal tubules were absent. The dental pulp chamber was dramatically enlarged and the dentin in Tg mice was thinner. Osteoblast-like cells were seen instead of normal odontoblasts and were embedded in a bone-like matrix, indicating that dentin formation was replaced with bone. Predentin was disorganized possessing lacunae that contained odontoblasts. The mandibular molars of Tg mice showed noticeable defects by Micro-CT. Using quantitative real-time PCR, the expression of dentin matrix proteins, particularly dentin sialophosphoprotein (DSPP), was found to be upregulated in 3-day-old Tg mice and downregulated at 1 month of age. These findings indicate that Runx2 inhibited odontoblast terminal differentiation and induced transdifferentiation of odontoblasts to osteoblasts at the late cell differentiation stage. Therefore, Runx2 should be inhibited in odontoblasts to encourage normal cell maturation, differentiation and dentinogenesis.

Evaluation of horizontal/oblique root fractures in the palatal roots of maxillary first molars using cone-beam computed tomography: a report of three cases.

Diagnosis of root fractures is generally based on clinical and radiographic presentations. This case report aims to detect horizontal/oblique root fractures in posterior teeth using a combination of conventional radiographs and cone-beam computed tomography (CBCT). Three maxillary first molars with horizontal/oblique root fractures in the palatal roots are presented. More detailed information on root fractures can be obtained using CBCT compared with conventional radiography. As such, CBCT might be a useful complementary diagnostic method to conventional radiography in cases of suspected horizontal/oblique root fractures.

A randomized, controlled clinical trial of one-step self-etching adhesive systems in non-carious cervical lesions.

PURPOSE: To evaluate the clinical effectiveness of two different one-step self-etching adhesives. METHODS: Two single-step self-etching adhesive systems, Clearfil Tri-S Bond and G-Bond, were evaluated. As a control, a two-step self-etching adhesive system, Clearfil SE Bond, was used. The teeth to be restored were randomly assigned. The resin composite used to restore the teeth was Clearfil AP-X. The three adhesive systems were evaluated by Modified USPHS at baseline, 3 months, 6 months, and 12 months. The evaluation consisted of retention rate, color match, marginal discoloration (interfacial staining), marginal adaptation (integrity), wear, post-operative sensitivity, caries recurrence, and other failures. Changes over time and across groups were evaluated statistically using generalized estimating equations. RESULTS: During the 12-month study period, no statistical differences were observed among the three groups (P > 0.05) in retention rate, color match, marginal discoloration (interfacial staining), marginal adaptation (integrity). No wear, post-operative sensitivity, caries recurrence, or other failures were detected in any groups. The two one-step self-etching adhesives tested showed good clinical performance at the end of 12 months.

Nav1.7 via Promotion of ERK in the Trigeminal Ganglion Plays an Important Role in the Induction of Pulpitis Inflammatory Pain.

The trigeminal ganglion (TG) refers to sensory neurons bodies that innervate the spinal cord and peripheral axons that innervate teeth. The tetrodotoxin-sensitive sodium (NA) channels (Nav1.7) play important roles in the pathophysiology of pain. In this study, we investigated the TG expression of Nav1.7 and extracellular signal-regulated kinase (ERK) in a rat model of pulpitis to explore the correlation between these channels and inflammatory pain. Pulpitis was confirmed by hematoxylin-eosin staining. In this study, we demonstrated that the reflex of rats to mechanical stimulation increases after pulp exposure and that the exposed rat molar pulp can upregulate the expression of Nav1.7 and ERK in the rat TG. Three days after rat pulp exposure, the expression levels of the two ion channels in the TG increased. TG target injection of PF04856264, a Nav1.7 inhibitor, dose-dependently increased the mechanical pain threshold and was able to inhibit ERK expression. TG target injection of PD98059, an ERK inhibitor, dose-dependently increased the mechanical pain threshold. These factors simultaneously resulted in the highest production. In this study, with the established link to inflammatory pain, we found that Nav1.7 and ERK both play important roles in the induction of inflammatory pain caused by pulpitis. We also found a correlation between the expression levels of Nav1.7 and ERK and the degree of inflammatory pain. Furthermore, ERK signaling pathways were promoted by the Nav1.7 in TG after pulpitis.

Wnt-GSK3ß/ß-Catenin Regulates the Differentiation of Dental Pulp Stem Cells into Bladder Smooth Muscle Cells.

Smooth muscle cell- (SMC-) based tissue engineering provides a promising therapeutic strategy for SMC-related disorders. It has been demonstrated that human dental pulp stem cells (DPSCs) possess the potential to differentiate into mature bladder SMCs by induction with condition medium (CM) from bladder SMC culture, in combination with the transforming growth factor-ß1 (TGF-ß1). However, the molecular mechanism of SMC differentiation from DPSCs has not been fully uncovered. The canonical Wnt signaling (also known as Wnt/ß-catenin) pathway plays an essential role in stem cell fate decision. The aim of this study is to explore the regulation via GSK3ß and associated downstream effectors for SMC differentiation from DPSCs. We characterized one of our DPSC clones with the best proliferation and differentiation abilities. This stem cell clone has shown the capacity to generate a smooth muscle layer-like phenotype after an extended differentiation duration using the SMC induction protocol we established before. We further found that Wnt-GSK3ß/ß-catenin signaling is involved in the process of SMC differentiation from DPSCs, as well as a serial of growth factors, including TGF-ß1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor-homodimer polypeptide of B chain (BB) (PDGF-BB), and vascular endothelial growth factor (VEGF). Pharmacological inhibition on the canonical Wnt-GSK3ß/ß-catenin pathway significantly downregulated GSK3ß phosphorylation and ß-catenin activation, which in consequence reduced the augmented expression of the growth factors (including TGF-ß1, HGF, PDGF-BB, and VEGF) as well as SMC markers (especially myosin) at a late stage of SMC differentiation. These results suggest that the canonical Wnt-GSK3ß/ß-catenin pathway contributes to DPSC differentiation into mature SMCs through the coordination of different growth factors.

Hey1 functions as a positive regulator of odontogenic differentiation in odontoblast­lineage cells.

Substantial evidence has indicated that Notch and bone morphogenetic protein (BMP) signaling may regulate odontoblastic differentiation. Hairy/enhancer­of­split related with YRPW motif 1 (Hey1), a downstream target gene of Notch and BMP signaling, is expressed in dental pulp tissues and has been demonstrated to be responsible for osteoblast mineralization. The aim of this study was to investigate the effects of Hey1 on odontoblast differentiation. The results of the study demonstrated that Hey1 expression in odontoblast­lineage cells (OLCs) was upregulated by stimulation of osteoblastic/odontoblastic differentiation medium containing ascorbic acid, ß­glycerol phosphate and dexamethasone. Furthermore, stable Hey1­overexpressing cells expressed higher levels of dentin sialophosphoprotein (DSPP) and exhibited higher mineralization capabilities following stimulation by differentiation medium. Furthermore, RNA interference­mediated knockdown of Hey1 downregulated the expression levels of DSPP in OLCs stimulated by differentiation medium. Taken together, the findings indicate that Hey1 may be a positive regulator of odontoblastic differentiation. The present study broadens the understanding of odontoblast differentiation and biomineralization.

The Regulatory Effects of Long Noncoding RNA-ANCR on Dental Tissue-Derived Stem Cells.

Long noncoding RNAs (lncRNA) have been recognized as important regulators in diverse biological processes, such as transcriptional regulation, stem cell proliferation, and differentiation. Previous study has demonstrated that lncRNA-ANCR (antidifferentiation ncRNA) plays a key role in regulating the proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). However, little is known about the role of ANCR in regulating other types of dental tissue-derived stem cells (DTSCs) behaviours (including proliferation and multiple-potential of differentiation). In this study, we investigated the regulatory effects of lncRNA-ANCR on the proliferation and differentiation (including osteogenic, adipogenic, and neurogenic differentiation) of DTSCs, including dental pulp stem cells (DPSCs), PDLSCs, and stem cells from the apical papilla (SCAP) by downregulation of lncRNA-ANCR. We found that downregulation of ANCR exerted little effect on proliferation of DPSCs and SCAP but promoted the osteogenic, adipogenic, and neurogenic differentiation of DTSCs. These data provide an insight into the regulatory effects of long noncoding RNA-ANCR on DTSCs and indicate that ANCR is a very important regulatory factor in stem cell differentiation.

Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp.

Dental pulp infection and necrosis are widespread diseases. Conventional endodontic treatments result in a devitalized and weakened tooth. In this work, we synthesized novel star-shaped polymer to self-assemble into unique nanofibrous spongy microspheres (NF-SMS), which were used to carry human dental pulp stem cells (hDPSCs) into the pulp cavity to regenerate living dental pulp tissues. It was found that NF-SMS significantly enhanced hDPSCs attachment, proliferation, odontogenic differentiation and angiogenesis, as compared to control cell carriers. Additionally, NF-SMS promoted vascular endothelial growth factor (VEGF) expression of hDPSCs in a 3D hypoxic culture. Hypoxia-primed hDPSCs/NF-SMS complexes were injected into the cleaned pulp cavities of rabbit molars for subcutaneous implantation in mice. After 4 weeks, the hypoxia group significantly enhanced angiogenesis inside the pulp chamber and promoted the formation of ondontoblast-like cells lining along the dentin-pulp interface, as compared to the control groups (hDPSCs alone group, NF-SMS alone group, and hDPSCs/NF-SMS group pre-cultured under normoxic conditions). Furthermore, in an in situ dental pulp repair model in rats, hypoxia-primed hDPSCs/NF-SMS were injected to fully fill the pulp cavity and regenerate pulp-like tissues with a rich vasculature and a histological structure similar to the native pulp. STATEMENT OF SIGNIFICANCE: Vascularization is key to the regeneration of many vital tissues. However, it is challenging to create a suitable microenvironment for stem cells to regenerate vascularized tissue structure. This manuscript reports a novel star-shaped block copolymer that self-assembles into unique nanofibrous spongy microspheres, which as an injectable scaffold recapitulate the cell-cell and cell-matrix interactions in development. Using a clinically-relevant surgical procedure and a hypoxic treatment, the nanofibrous spongy microspheres were used to deliver stem cells and successfully regenerate dental pulp with a rich vasculature and a complex histologic structure similar to that of the native dental pulp. The novel microspheres can likely be used to regenerate many other vascularized tissues.

Pleurocidin congeners demonstrate activity against Streptococcus and low toxicity on gingival fibroblasts.

OBJECTIVES: Fish epidermal antimicrobial peptides, such as pleurocidin, are cathelicidins with broad-spectrum antimicrobial activity against gram negative and gram-positive bacteria, as well as fungi. In the current study, we attempted to optimize peptide bioactivity by sequence modification and assess the antimicrobial activities. METHODS: Fifteen pleurocidin analogues were designed, and the efficacy of pleurocidin congeners against common cariogenic microorganisms was tested; furthermore, we performed a preliminary study of the antimicrobial mechanism. We assayed the minimal inhibitory concentration (MIC), minimal bactericide concentration (MBC) and bactericidal kinetics to determine the cell killing activity. Scanning electron microscopy (SEM) was used to observe the bacterial membrane after treatment with congeners' peptides. Human gingival fibroblasts (HGFs) were also used in toxicity studies. RESULTS: The MIC and MBC results indicated that peptide congeners had different antimicrobial activities against the tested oral strains. Toxicity studies indicated that several congener peptides had little effect on human gingival fibroblasts (HGFs) with 5min of in vitro treatment. CONCLUSION: Our findings suggested that several pleurocidin congeners had the antimicrobial effect against Streptococcus mutans, Streptococcus sanguinis and Streptococcus sobrinus.

Dentin regeneration by stem cells of apical papilla on injectable nanofibrous microspheres and stimulated by controlled BMP-2 release.

UNLABELLED: The aim of this study was to investigate the effects of PLLA nanofibrous microspheres (NF-MS) as a cell delivery carrier in combination with controlled release of BMP-2 from PLGA microspheres on the induction of odontogenic differentiation of human stem cells of apical papilla (SCAP). Injectable NF-MS, which mimic the physical architecture of collagen fibers on the nano scale, were fabricated by combining thermally-induced phase separation techniques with an emulsification process. SCAP cultured in a monolayer or cultured on NF-MS in spinner flasks were treated with 100ng/ml BMP-2 in vitro. Odontogenic differentiation was characterized by measuring alkaline phosphatase activity, odontogenic gene expression levels, calcium content, and dentin sialophosphoprotein accumulation. The results demonstrated that BMP-2 enhanced human SCAP odontogenic differentiation both in monolayer culture and on 3D NF-MS in spinner flask culture in vitro. We also developed and tested a system combining NF-MS with controlled BMP-2 release for dentin regeneration in vivo. The results indicate that controlled release of BMP-2 promoted more mineralization and osteodentin formation compared to a BSA-releasing control in a dose-dependent and time-dependent manner. In summary, the NF-MS combined with controlled release of BMP-2 provides an excellent microenvironment for SCAP to regenerate dentin tissue. STATEMENT OF SIGNIFICANCE: Tooth lesion and loss affect masticatory efficiency, speaking function, facial aesthetics and even psychological health. Current treatments depend on "inert" restorative materials, which do not have the healing capacity and may lead to the failure of the restorations over a long term. The aim of this study was to develop an injectable biomaterial and desired growth factor delivery system to support stem cells for mineralized dental tissue regeneration. The study showed that novel injectable and biodegradable nanofibrous microspheres and controlled release of BMP-2 synergistically induce the odontogenic differentiation of human stem cells from the apical papilla and mineralized tissue regeneration, demonstrating the potential of living dental tissue repair.