Tooth Regeneration Research Articles

STEM CELL APPROACHES IN ORGAN REGENERATION AND REPAIR

Recent advances in stem cell research have provided new hope for treating a variety of diseases and conditions that currently have no effective cure. Stem cells have the unique ability to differentiate into various cell types, enabling them to support tissue growth and replace damaged or specialized cells throughout the lifespan. Among the most promising types of stem cells are mesenchymal stem cells (MSCs), which are easily harvested from adipose tissue and can be cultured and expanded in the lab. Due to their versatility, MSCs have become a focal point in tissue regeneration and have been widely used in animal studies and clinical trials involving humans. This review aims to summarize the current understanding of MSCs, focusing on the various types of stem cells isolated from different animal models such as horses, pigs, goats, dogs, rabbits, cats, rats, and mice. Given the growing interest in MSCs, we will also discuss their applications in veterinary and regenerative medicine. Current research highlights the potential of MSCs in treating conditions like heart failure, wound healing, and tooth regeneration, demonstrating their broad therapeutic potential. KEYWORDS: Mesenchymal stem cells (MSCs), animal models, cell-based therapy, regenerative medicine

Papillary Coronal Anchorage Technique for Periodontal Reconstruction of Infrabony Defect and Interdental Papilla: A Case Report.

Esthetic issues and phonetic disturbances frequently occur after periodontal regeneration of the anterior teeth, even if treatment is supposed to be successful. Conventional regenerative techniques are predominantly targeted at infrabony defects and often inadequately address the loss of the interdental papilla. This study introduces the papillary coronal anchorage technique, a novel modified tunnel surgical procedure, to facilitate the reconstruction of the interdental papilla. This method allows for coronal movement of the entire interdental papilla without incisions at the papilla to facilitate primary wound healing. Using a combination of bone grafts and recombinant human fibroblast growth factor 2 and anchoring the tunnel-like flap coronally using sutures, we successfully achieved a reconstruction of the infrabony defects as well as the interdental papilla. The papillary coronal anchorage technique is effective as it enables the simultaneous reconstruction of both the infrabony defect and the interdental papilla.

Induction of human stem cells into ameloblasts by reaggregation strategy

BackgroundHuman epithelium-derived stem cells and induced pluripotent stem cells (hiPSCs) possess the capability to support tooth formation and differentiate into functional enamel-secreting ameloblasts, making them promising epithelial-component substitutes for future human tooth regeneration. However, current tissue recombination approaches are not only technically challenging, requiring precise induction procedures and sophisticated microsurgery, but also exhibit low success rates in achieving tooth formation and ameloblastic differentiation.MethodsSuspended human keratinocyte stem cells (hKSCs) or cells from three hiPSC lines were directly mixed with dissociated embryonic mouse dental mesenchymal cells (mDMCs) that possess odontogenic potential in different proportions and reaggregated them to construct bioengineered tooth germs. The success rates of tooth formation and ameloblastic differentiation were confirmed after subrenal culture. The sorting capability, sequential development, and ameloblastic differentiation of stem cells were examined via GFP tracing, RT-PCR, and histological analysis, respectively.ResultsOur reaggregation approach achieved an impressive success rate of more than 90% in tooth formation and 100% in ameloblastic differentiation when the chimeric tooth germs contained 1%~10% hKSCs or 5% hiPSCs. In addition, we observed that hiPSCs, upon exposure to mDMCs, initially transformed into epidermal cells, as indicated by KRT14 and CD29 expression, before progressing into dental epithelial cells, as indicated by SP6 and SHH expression. We also found that epithelial-derived hiPSCs, when reaggregated with mDMCs, were more favorable for tooth formation than their mesenchymal-derived counterparts.ConclusionsThis study establishes a simplified yet highly effective cell-cell reaggregation strategy for inducing stem cells to support tooth formation and differentiate into functional ameloblasts, paving the way for novel approaches for the development of stem cell-based tooth organoids and bioengineered tooth germs in vitro.

Identification and Characterization of Key Genes Associated with Amelogenesis

Abstract Objectives The identification of key genes associated with amelogenesis would be helpful in finding solutions to genetic disorders in oral biology. The study aimed to use in silico analysis to identify the key genes involved in tooth development associated with preameloblasts (PABs) and secretory ameloblasts (SABs). Material and Methods The data was subjected to quality analysis and uniform manifold approximation and projection analysis. To examine the distribution of the genes and identify important upregulated loci, a p-value histogram, a quantile plot, a mean difference and mean-variance plot, and a volcano plot were generated. Finally, protein-protein interaction and gene enrichment analyses were performed to determine the ontology, relevant biological processes, and molecular functions of selected genes. Results A total of 157 genes were found to be significant in the PAB versus SAB comparison. HIST1H31 revealed strong interaction with HIST1H2BM, and EXO1, ASPM, SPC25, and TTK showed strong interactions with one other. The STRING database revealed that NCAPG, CENPU, NUSAP1, HIST1H2BM, and HIST1H31 are involved in biological processes. NCAPG, CENPU, SPC25, ETV5, TTK, ETV1, FAM9A, NUSAP1, HIST1H2BM, and HIST1H31 are involved in cellular components. Conclusion The TTK, NUSAP1, CENPU, NCAPG, FAM9A, ASPM, SPC25, and HIST1H31 genes demonstrate functions in cell division. These genes might play a role in ameloblast development. These results will be useful in developing new methods to stimulate ameloblast development, which is essential for tooth regeneration and tissue engineering. However, more research is required to validate the functions of these genes and the genes with which they interact. A wide variety of genetic, epigenetic, and exogenous signaling factors regulate these genes and pathways throughout development and differentiation, cell fate, and behavior.

Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation

BackgroundThe molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge.ResultsHere, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar.ConclusionsOur results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside–stimulated dental pulp stem cells-derived exosomes for wound healing and bone regeneration

Background/purpose-2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is a bioactive component in the Chinese herb Polygonum multiflorum, recognized for its anti-inflammatory and lipid-lowering properties. Human dental pulp stem cells (hDPSCs) have excellent capabilities in tooth regeneration, wound healing, and neural repair. The exosomes (Exo) released by hDPSCs contain bioactive molecules that influence cell proliferation, differentiation, and immune responses. Therefore, we aimed to unveil the potential of THSG-Exo and evaluate its regenerative capabilities through the in vitro experiment and rat bone defect model. Materials and methodsThe effects of hDPSC-derived exosomes, with or without THSG treatment, on repair and bone regeneration were evaluated through in vitro and in vivo studies. Finally, we conducted a proteomic analysis to meticulously compare the compositional contents of the two types of exosomes. ResultsIn vitro data showed that 10 and 100 μM THSG-Exo enhanced cell proliferation and osteogenic differentiation, reducing wound size to 40 % of its original size. In our maxillary bone defect rat model, THSG-Exo significantly increased bone volume, trabecular thickness, and bone density in the bone defect area. In addition, proteomic analysis of THSG-Exo revealed diverse proteins linked to bone differentiation and tissue repair, including bone morphogenetic protein-1 (BMP-1) and tumor necrosis factor (TNF)-α-stimulated gene 6 (TNFAIP6). Our searches in functional databases revealed that THSG-Exo is involved in numerous biological pathways. ConclusionTHSG-Exo enhanced cell proliferation, wound healing, and osteogenesis in vitro, while also expediting tissue repair and bone regeneration in vivo. The protein diversity of THSG-Exo contributes significant value in both basic and regenerative medicine.

Engineered pre-dentin with well-aligned hierarchical mineralized collagen fibril bundles promote bio-root regeneration

Stem cell-mediated bio-root regeneration is an alternative tooth replacement strategy; however, physiologically functional bio-root regeneration with distinctive dentin structure remains challenging. In this study, the distinct arrangements of collagen fibril bundles were identified that account for hierarchical structural differences between dentin, cementum, and alveolar bone. Thus, an “engineered pre-dentin” was fabricated, which was a dentin hierarchical structure mimicking collagen (MC) scaffold, with well-aligned hierarchical mineralized collagen fibril bundles. The results revealed that it has a stronger effect on promoting biological root regeneration in nude mice and miniature pigs with dental pulp stem cell (DPSC) and periodontal ligament stem cell (PDLSC) sheets compared to hydroxyapatite tricalcium phosphate (HA/TCP). The success rate in the MC group was also higher than that in the HA/TCP group (67% and 33%, respectively). In conclusion, the hierarchical dentin-mimicking scaffold can enhance the regeneration of bio-roots, which provides a promising strategy for tooth regeneration.

Indomethacin Delivery from PCL Nanofibrous Scaffolds Enhances Biomineralization and Cell Adhesion: Biocompatible Scaffold Model for Teeth Regeneration

Indomethacin Delivery from PCL Nanofibrous Scaffolds Enhances Biomineralization and Cell Adhesion: Biocompatible Scaffold Model for Teeth Regeneration

Derivation of dental epithelial-like cells from murine embryonic stem cells for tooth regeneration.

Teeth are comprised of epithelial and mesenchymal cells, and regenerative teeth rely on the regeneration of both cell types. Transcription factors play a pivotal role in cell fate determination. In this study, we establish fluorescence models based on transcription factors to monitor and analyze dental epithelial cells. Using Pitx2-P2A-copGFP mice, we observe that Pitx2+ epithelial cells, when combined with E14.5 dental mesenchymal cells, are sufficient for the reconstitution of teeth. Induced-Pitx2+ cells, directly isolated from the embryoid body that employs the Pitx2-GFP embryonic stem cell line, exhibit the capacity to differentiate into ameloblasts and develop into teeth when combined with dental mesenchymal cells. The regenerated teeth exhibit a complete structure, including dental pulp, dentin, enamel, and periodontal ligaments. Subsequent exploration via RNA-seq reveals that induced-Pitx2+ cells exhibit enrichment in genes associated with FGF receptors and WNT ligands compared with induced-Pitx2- cells. Our results indicate that both primary Pitx2+ and induced Pitx2+ cells possess the capability to differentiate into enamel-secreting ameloblasts and grow into teeth when combined with dental mesenchymal cells.

Spatial and temporal gene expression patterns during early human odontogenesis process.

Studies on odontogenesis are of great importance to treat dental abnormalities and tooth loss. However, the odontogenesis process was poorly studied in humans, especially at the early developmental stages. Here, we combined RNA sequencing (RNA-seq) with Laser-capture microdissection (LCM) to establish a spatiotemporal transcriptomic investigation for human deciduous tooth germs at the crucial developmental stage to offer new perspectives to understand tooth development and instruct tooth regeneration. Several hallmark events, including angiogenesis, ossification, axonogenesis, and extracellular matrix (ECM) organization, were identified during odontogenesis in human dental epithelium and mesenchyme from the cap stage to the early bell stage. ECM played an essential role in the shift of tooth-inductive capability. Species comparisons demonstrated these hallmark events both in humans and mice. This study reveals the hallmark events during odontogenesis, enriching the transcriptomic research on human tooth development at the early stage.

Induced pluripotent stem cells: A game-changer in dentistry’s regenerative landscape

In recent years, induced pluripotent stem cells (iPSCs) have emerged as a transformative force in regenerative medicine, offering unprecedented opportunities for advancements in various fields. This review explores the revolutionary impact of iPSCs specifically within the realm of dentistry, where regenerative strategies are increasingly sought to address oral and craniofacial tissue defects. iPSCs, derived from somatic cells through reprogramming, exhibit pluripotency and can differentiate into various cell types, including dental-specific lineages such as odontoblasts, ameloblasts, and osteoblasts. The application of iPSCs in dentistry holds immense promise for tissue repair, regeneration, and disease modelling. This review delves into the key aspects of iPSC-based approaches in dental research, covering topics such as tooth regeneration, periodontal tissue engineering, and craniofacial defect repair. We discuss the challenges and advancements in iPSC technology, emphasizing the potential for personalized regenerative therapies tailored to individual patients.

Odontogenesis-Empowered Extracellular Vesicles Safeguard Donor-Recipient Stem Cell Interplay to Support Tooth Regeneration.

Harnessing the developmental events of mesenchymal condensation to direct postnatal dental stem cell aggregation represents a cutting-edge and promising approach to tooth regeneration. Tooth avulsion is among the most prevalent and serious dental injuries, and odontogenic aggregates assembled by stem cells from human exfoliated deciduous teeth (SHED) have proven effective in revitalizing avulsed teeth after replantation in the clinical trial. However, whether and how SHED aggregates (SA) communicate with recipient components and promote synergistic tissue regeneration to support replanted teeth remains elusive. Here, it is shown that SA-mediated avulsed tooth regeneration involves periodontal restoration and recovery of recipient Gli1+ stem cells, which are mobilized and necessarily contribute to the reestablishment of the tooth-periodontal ligament-bone interface. Mechanistically, the release of extracellular vesicles (EVs) is revealed indispensable for the implanted SA to mobilize recipient Gli1+ cells and regenerate avulsed teeth. Furthermore, SHED aggregates-released EVs (SA-EVs) are featured with odontogenic properties linked to tissue regeneration, which enhance migration, proliferation, and differentiation of Gli1+ cells. Importantly, local application of SA-EVs per se empowers recipient Gli1+ cells and safeguards regeneration of avulsed teeth. Collectively, the findings establish a paradigm in which odontogenesis-featured EVs govern donor-recipient stem cell interplay to achieve tooth regeneration, inspiring cell-free translational regenerative strategies.

Effect of Curcumin-containing Nanofibrous Gelatin-hydroxyapatite Scaffold on Proliferation and Early Osteogenic Differentiation of Dental Pulp Stem Cells.

In recent years, the electrospinning method has received attention because of its usage in producing a mimetic nanocomposite scaffold for tissue regeneration. Hydroxyapatite and gelatin are suitable materials for producing scaffolds, and curcumin has the osteogenesis induction effect. This study aimed to evaluate the toxicity and early osteogenic differentiation stimulation of nanofibrous gelatin-hydroxyapatite scaffold containing curcumin on dental pulp stem cells (DPSCs). The objective of the present investigation was the evaluation of the proliferative effect and primary osteogenic stimulation of DPSCs with a nanofibrous gelatin-hydroxyapatite scaffold containing curcumin. Hydroxyapatite and gelatin were used as suitable and biocompatible materials to make a scaffold suitable for stimulating osteogenesis. Curcumin was added to the scaffold as an osteogenic differentiation- enhancing agent. The effect of nano-scaffold on the proliferation of DPSCs was evaluated. The activity of alkaline phosphatase (ALP) as the early osteogenic marker was considered to assess primary osteogenesis stimulation in DPSCs. The nanofibrous gelatin-hydroxyapatite scaffold containing curcumin significantly increased the proliferation and the ALP activity of DPSCs (P<0.05). The proliferative effect was insignificant in the first 2 days, but the scaffold increased cell proliferation by more than 40% in the fourth and sixth days. The prepared scaffold increased the activity of the ALP of DPSCs by 60% compared with the control after 14 days (p<0.05). The produced nanofibrous gelatin-hydroxyapatite scaffold containing curcumin can be utilized as a potential candidate in tissue engineering and regeneration of bone and tooth. The prepared scaffold in the present study could be a beneficial biomaterial for tissue engineering and the regeneration of bone and tooth soon.

A xenogeneic extracellular matrix-based 3D printing scaffold modified by ceria nanoparticles for craniomaxillofacial hard tissue regeneration via osteo-immunomodulation

Hard tissue engineering scaffolds especially 3D printed scaffolds were considered an excellent strategy for craniomaxillofacial hard tissue regeneration, involving crania and facial bones and teeth. Porcine treated dentin matrix (pTDM) as xenogeneic extracellular matrix has the potential to promote the stem cell differentiation and mineralization as it contains plenty of bioactive factors similar with human-derived dentin tissue. However, its application might be impeded by the foreign body response induced by the damage-associated molecular patterns of pTDM, which would cause strong inflammation and hinder the regeneration. Ceria nanoparticles (CNPs) show a great promise at protecting tissue from oxidative stress and influence the macrophages polarization. Using 3D-bioprinting technology, we fabricated a xenogeneic hard tissue scaffold based on pTDM xenogeneic TDM-polycaprolactone (xTDM/PCL) and we modified the scaffolds by CNPs (xTDM/PCL/CNPs). Through series of in vitro verification, we found xTDM/PCL/CNPs scaffolds held promise at up-regulating the expression of osteogenesis and odontogenesis related genes including collagen type 1, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2, osteoprotegerin, alkaline phosphatase (ALP) and DMP1 and inducing macrophages to polarize to M2 phenotype. Regeneration of bone tissues was further evaluated in rats by conducting the models of mandibular and skull bone defects. The in vivo evaluation showed that xTDM/PCL/CNPs scaffolds could promote the bone tissue regeneration by up-regulating the expression of osteogenic genes involving ALP, RUNX2 and bone sialoprotein 2 and macrophage polarization into M2. Regeneration of teeth evaluated on beagles demonstrated that xTDM/PCL/CNPs scaffolds expedited the calcification inside the scaffolds and helped form periodontal ligament-like tissues surrounding the scaffolds.

Dental pulp stem cells in tooth regeneration: advancement and emerging directions

Regenerating tissues similar to dental structure with normal function are putatively to be the aim in tooth regeneration filed. Currently, researchers preliminarily achieved tooth regeneration by applying dental pulp stem cells (DPSC) and stem cells from human exfoliated deciduous teeth (SHED). However, the regeneration efficiency remains unstable and needs further investigation. The development of single-cell RNA sequencing and organoid culture system provide potential of precise, targeted and controllable functional regeneration. This article reviews the current state of DPSC/SHED on tooth regeneration, and analyzes characteristics and hotspots of them, aiming to shed light on clinical translational application of stable and efficient tooth regeneration.

Theory and practice of mesenchymal condensation directing tooth development and regeneration

Mesenchymal stem cells, under spatiotemporal regulation of genes and microenvironment, are capable of spontaneously aggregating into dense regions, a phenomenon known as mesenchymal condensation. Mesenchymal condensation is an evolutionarily conserved developmental event that is critical in initiating morphogenesis of teeth and systemic organs. Mesenchymal stem cells hold the intrinsic ability to self-assemble in culture, and the generation of stem cell aggregates based on this property that mimics developmental mesenchymal condensation has become a potent and promising approach in regenerative medicine. This review discusses the mesenchymal condensation principles and its role as well as mechanism in tooth morphogenesis, as well as the engineering strategies for constructing mesenchymal stem cell aggregates and their application experience in tooth regeneration. It aims to start from the perspective of "development-inspired regeneration" and provide insights into understanding stem cell developmental biology and establishing new organ regenerative strategies.

Investigating the Viability of Human Gingival Fibroblast Cells in a Polyhydroxybutyrate/Chitosan/Bioglass Nanoparticles Scaffold

Background: The primary method for addressing dental problems traditionally involves the removal and replacement of damaged tissue with synthetic substitutes. However, these materials often lack the physical and chemical properties of natural teeth and are prone to mechanical failures. Recent advancements in tissue engineering have highlighted an alternative approach that allows for the regeneration of teeth using scaffolds. Objectives: This study explored the viability of human gingival fibroblast cells in a scaffold composed of polyhydroxybutyrate, chitosan, and bioglass nanoparticles (PHB/chitosan/nBG). Methods: This study is experimental and was conducted in a laboratory setting. Scaffolds of PHB, PHB/chitosan, and PHB/chitosan/nBG were previously prepared from PHB polymer, chitosan, and bioglass using the electrospinning method. Human gingival fibroblast cells (C165) were acquired from the Pasteur Institute and cultured. Twenty thousand cells were seeded onto each scaffold and into the wells of a 24-well plate for periods of 3, 5, and 7 days. Subsequently, cell viability and proliferation were assessed using the MTT assay method, with each experiment repeated three times. Results: Cell viability and proliferation on the PHB/chitosan/nBG scaffold demonstrated a significant increase compared to the other scaffolds (P ≤ 0.01). Conclusions: The PHB/chitosan/nBG scaffold was found to be non-toxic to human gingival fibroblast cells and exhibited good biocompatibility.

Application of Slice Culture System for Successional Dental Lamina in Diphyodont Mammals.

Replacement teeth develop from the successional dental lamina (SDL). Understanding how SDL transitions from quiescence to initiation is crucial for preserving dental lamina stem cells in the jawbone microenvironment and for complete tooth regeneration. Miniature pigs are good models for studying human tooth replacement because of their similarities to humans. However, the molecular mechanisms and cellular composition that initiate SDL development remain unclear. One possible reason for this is the limitations of the current methods for culturing SDL in vitro, such as the inability to directly observe tooth morphological changes during culture and low tissue viability. This study aimed to improve the in vitro culture method for SDL. Using a McIlwain Tissue Chopper, we obtained mandibular slices containing deciduous canine and SDL of permanent canine. The slices were approximately 500 μm thick and were cultured on a Transwell membrane supported with metal grids over medium. The SDL developed into the bud stage on the second day and entered the cap stage on the fifth day in vitro. The expression of proliferation markers, cell death markers, and key odontogenetic genes in vitro was similar to that observed invivo. In conclusion, we successfully applied a slice culture system to the SDL of miniature pigs. This slice culture method allowed us to directly visualize SDL initiation and further elucidate the molecular mechanisms underlying the initiation of permanent tooth development.

KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway

BackgroundDental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs.MethodsDPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins.ResultsThe specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation.ConclusionKAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

Composite or Modified Hydroxyapatite Microspheres as Drug Delivery Carrier for Bone and Tooth Tissue Engineering.

Since hydroxyapatite (HAp) is an important constituent of bone and teeth, it has excellent biocompatibility and bioactivity, good osteoconductive effects and the ability to induce bone formation as a material for bone or tooth repair and replacement. At present, widely used HAp microspheres have some characteristics, such as large specific surface area, light mass, good injection properties, good fluidity, and low aggregation ability, but they are difficult to really meet the biological and clinical needs due to their own mechanical property defects, such as low strength, brittleness, and poor plasticity. Based on the current research status of HAp microspheres, we summarize the research progress of various types of composite microspheres, including inorganic materials, natural polymer materials and synthetic polymer materials, and further analyze the advantages of HAp composite microspheres loaded with drug molecules, proteins and bioactive factors, so as to explore the development prospect of HAp composite microspheres as scaffolds for constructing sustained release systems. It provides a theoretical basis and research direction to prepare HAp composite micro-spheres with superior comprehensive properties so that they can be better applied in bone tissue regeneration and tooth regeneration engineering.