ACS Applied Materials & Interfaces
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2024
·
IF 8.3
Danle Lin,Ziyu Zhou,Mengdan Zhang,Songyou Yao,Lingling Yuan,Meng Xu,Xiaoyue Zhang,Xiaoli Hu
Biophysical and biochemical cues of biomaterials can regulate cell behaviors. Dental pulp stem cells (DPSCs) in pulp tissues can differentiate to odontoblast-like cells and secrete reparative dentin to form a barrier to protect the underlying pulp tissues and enable complete pulp healing. Promotion of the odontogenic differentiation of DPSCs is essential for dentin regeneration. The effects of the surface potentials of biomaterials on the adhesion and odontogenic differentiation of DPSCs remain unclear. Here, poly(vinylidene fluoride-trifluoro ethylene) (P(VDF-TrFE)) films with different surface potentials were prepared by the spin-coating technique and the contact poling method. The cytoskeletal organization of DPSCs grown on P(VDF-TrFE) films was studied by immunofluorescence staining. Using atomic force microscopy (AFM), the lateral detachment forces of DPSCs from P(VDF-TrFE) films were quantified. The effects of electrical stimulation generated from P(VDF-TrFE) films on odontogenic differentiation of DPSCs were evaluated in vitro and in vivo. The unpolarized, positively polarized, and negatively polarized films had surface potentials of −52.9, +902.4, and −502.2 mV, respectively. DPSCs on both negatively and positively polarized P(VDF-TrFE) films had larger cell areas and length-to-width ratios than those on the unpolarized films (P < 0.05). During the detachment of DPSCs from P(VDF-TrFE) films, the average magnitudes of the maximum detachment forces were 29.4, 72.1, and 53.9 nN for unpolarized, positively polarized, and negatively polarized groups, respectively (P < 0.05). The polarized films enhanced the mineralization activities and increased the expression levels of the odontogenic-related proteins of DPSCs compared to the unpolarized films (P < 0.05). The extracellular signal-regulated kinase (ERK) signaling pathway was involved in the odontogenic differentiation of DPSCs as induced by surface charge. In vivo, the polarized P(VDF-TrFE) films enhanced adhesion of DPSCs and promoted the odontogenic differentiation of DPSCs by electrical stimulation, demonstrating a potential application of electroactive biomaterials for reparative dentin formation in direct pulp capping.
研究领域:
生物材料
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干细胞生物学
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组织工程
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牙科材料
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细胞粘附
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分化
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信号转导
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DOI
PubMed
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-12
·
IF 4.38
Ma Lan,Yu Yijun,Liu Hanxiao,Sun Weibin,Lin Zitong,Liu Chao,Miao Leiying
The repair of skeletal defects in maxillofacial region remains an intractable problem, the rising technology of bone tissue engineering provides a new strategy to solve it. Scaffolds, a crucial element of tissue engineering, must have favorable biocompatibility as well as osteoinductivity. In this study, we prepared berberine/polycaprolactone/collagen (BBR/PCL/COL) scaffolds with different concentrations of berberine (BBR) (25, 50, 75 and 100 μg/mL) through electrospinning. The influence of dosage on scaffold morphology, cell behavior and in vivo bone defect repair were systematically studied. The results indicated that scaffolds could release BBR stably for up to 27 days. Experiments in vitro showed that BBR/PCL/COL scaffolds had appropriate biocompatibility in the concentration of 25–75 μg/mL, and 50 and 75 μg/mL scaffolds could significantly promote osteogenic differentiation of dental pulp stem cells. Scaffold with 50 μg/mL BBR was implanted into the critical bone defect of rats to evaluate the ability of bone repair in vivo. It was found that BBR/PCL/COL scaffold performed more favorable than polycaprolactone/collagen (PCL/COL) scaffold. Overall, our study is the first to evaluate the capability of in vivo bone repair of BBR/PCL/COL electrospun scaffold. The results indicate that BBR/PCL/COL scaffold has prospective potential for tissue engineering applications in bone regeneration therapy.
研究领域:
生物医学工程
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组织工程
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再生医学
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DOI
PubMed
高影响因子
Regenerative Therapy
·
2026
·
IF 4
Ke Zheng,Jingwen Xiao,Jiacheng Qian,Guijuan Feng,Xinyue Zhang,Dan Huang,Shiyu Shi,Ke Xu
Introduction Bone tissue defects frequently occur following trauma, bone tumor resection, and orthopedic surgery. The complex local microenvironment serves as a critical factor impeding bone tissue repair. Cell-based scaffolds typically exhibit stable physicochemical properties, provide a favorable growth microenvironment. Hydrogels and electret membranes have been widely applied in bone tissue engineering. Methods In this study, we fabricated polyvinylidene fluoride (PVDF) electret membranes and sodium alginate/sodium hyaluronate (SA/HA) double-network hydrogels separately, and systematically characterized their physicochemical and biological properties. Results Following verification of their favorable biocompatibility, we found that the combined application of SA/HA@PVDF composites significantly enhances calcium nodule formation in human dental pulp stem cells (DPSCs) in vitro. In addition, the expression levels of osteogenic marker proteins were elevated in the SA/HA@PVDF group and were significantly higher than those in the single-agent application groups, indicating that SA/HA@PVDF exhibits a stronger capacity to promote the osteogenic differentiation of DPSCs in vitro. Subsequently, rat mandibular defect models were established, and PVDF electret membranes, SA/HA hydrogels, and SA/HA@PVDF composites were transplanted into the defect sites. The results of micro-computed tomography, hematoxylin-eosin staining, Masson staining, and immunohistochemical staining demonstrated that the composite scaffold significantly accelerated the repair of mandibular bone defects. Conclusions Our findings may provide novel insights into the combined application of electret membranes and hydrogels in bone regeneration.
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高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Shengnan Zhang,Hongxian Zhou,Xin Liu,Yantong Wu,Shuran Yang,Jia Yin,Mohammad H. Shubair,Mingzhu Zhang
Periodontitis, a chronic inflammatory disease, leads to the progressive destruction of tooth-supporting tissues, and current treatments fall short of fully restoring periodontal regeneration. Dental pulp stem cells (DPSCs) have shown great promise for periodontal regeneration due to their ability to differentiate into multiple cell types and modulate immune responses. However, clinical use of DPSCs remains challenging due to poor cell retention, dependence on scaffolds, and high costs. Additionally, excessive reactive oxygen species (ROS) in the periodontal microenvironment hinder stem cell proliferation and differentiation, further limiting their regenerative potential. To address these challenges, we developed ultrafine cerium oxide nanoparticles (CeO2NPs) and engineered DPSCs (E-DPSCs) by incorporating these antioxidant nanozymes via endocytosis. The modified E-DPSCs exhibited enhanced proliferation, migration, and osteogenic differentiation under normal conditions. Crucially, under oxidative stress, E-DPSCs effectively neutralized ROS, reduced apoptosis, and maintained their osteogenic capacity. In vivo studies further demonstrated that E-DPSCs significantly enhanced periodontal regeneration compared to unmodified DPSCs. These findings highlight E-DPSCs as a promising solution to overcome current limitations in stem cell therapy, offering a more effective strategy for periodontal repair and regeneration.
研究领域:
牙科学
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纳米医学
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干细胞研究
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再生医学
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DOI
高影响因子
CELLULAR & MOLECULAR BIOLOGY LETTERS
·
2024
·
IF 9.2
Zeying Zhang,Di Yang,Xiaoyuan Yan,Qiujing Qiu,Jiajie Guo,Lihong Qiu
Background Differentiating dental pulp stem cells (DPSCs) into odontoblasts is a critical process for tooth self-repair and dentine‒pulp engineering strategies in the clinic. However, the mechanism underlying the regulation of DPSC odontoblastic differentiation remains largely unknown. Here, we demonstrated that BCL-2 interacting protein 3 (BNIP3)-dependent mitophagy is associated with importin subunit beta-1 (KPNB1)-activating transcription factor 4 (ATF4), which promotes DPSC odontoblastic differentiation. Methods The key genes involved in DPSC odontogenic differentiation were identified via bioinformatics. Stable silencing or overexpression of BNIP3 was performed to investigate its impact on DPSC differentiation in vitro ( n ≥ 3). To explore the role of BNIP3 in vivo, tooth root fragments loaded with the hydrogel-transfected DPSC complex were implanted into nude mice ( n ≥ 6). Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) polymerase chain reaction (PCR) were conducted to explore the binding site of ATF4 to the BNIP3 promoter ( n ≥ 3). Mitochondrial function experiments were performed to investigate the impact of ATF4-BNIP3 on mitochondria ( n ≥ 3). Immunoprecipitation (IP) mass spectrometry (MS) was used to investigate the interaction between ATF4 and its binding protein, KPNB1. Plasmids containing wild-type (WT)/mutant (MUT)-nuclear localization signal (NLS) forms of ATF4 were constructed to determine the specific amino acid residues recognized by KPNB1 and their effects on DPSC odontoblastic differentiation ( n ≥ 3). Results Compared with those in the control group, the levels of autophagy and mitophagy, especially BNIP3-dependent mitophagy, were greater in the DPSC odontoblastic differentiation group ( P < 0.05). Genetic silencing or overexpression of BNIP3 demonstrated that BNIP3 expression was positively correlated with the transition of DPSCs into odontoblasts both in vitro and in vivo ( P < 0.05). ATF4 regulates the expression of BNIP3 by directly binding to approximately −1292 to −1279 bp and approximately −1185 to −1172 bp within the BNIP3 promoter region, which is associated with mitophagy and mitochondrial reactive oxygen species (mtROS) levels ( P < 0.05). Moreover, ATF4 increased mitophagy, mitochondrial function, and cell differentiation potential via BNIP3 ( P < 0.05). Mechanistically, KPNB1 is a novel interacting protein of ATF4 that specifically recognizes amino acids (aa) 280–299 within ATF4 to control its translocation into the nucleus and subsequent transcription and differentiation processes ( P < 0.05). Conclusions We reported that the critical role of KPNB1/ATF4/BNIP3 axis-dependent mitophagy could provide new cues for the regeneration of the dental pulp‒dentin complex in DPSCs. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s11658-024-00664-9.
研究领域:
牙科学
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干细胞生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 3
·1-16
·
IF 8.1
Ma Lan,Zhou Xi,Yao Siyue,Zhang Xinyu,Mao Ji,Vona Barbara,Fan Liwen,Lou Shu,Li Dandan,Wang Lin,Pan Yongchu
Craniofacial malformations, often associated with syndromes, are prevalent birth defects. Emerging evidence underscores the importance of m 6 A modifications in various bioprocesses such as stem cell differentiation, tissue development, and tumorigenesis. Here, in vivo, experiments with zebrafish models revealed that mettl3 -knockdown embryos at 144 h postfertilization exhibited aberrant craniofacial features, including altered mouth opening, jaw dimensions, ethmoid plate, tooth formation and hypoactive behavior. Similarly, low METTL3 expression inhibited the proliferation and migration of BMSCs, HEPM cells, and DPSCs. Loss of METTL3 led to reduced mRNA m 6 A methylation and PSEN1 expression, impacting craniofacial phenotypes. Co-injection of mettl3 or psen1 mRNA rescued the level of Sox10 fusion protein, promoted voluntary movement, and mitigated abnormal craniofacial phenotypes induced by mettl3 knockdown in zebrafish. Mechanistically, YTHDF1 enhanced the mRNA stability of m 6 A-modified PSEN1 , while decreased METTL3-mediated m 6 A methylation hindered β-catenin binding to PSEN1, suppressing Wnt/β-catenin signaling. Pharmacological activation of the Wnt/β-catenin pathway partially alleviated the phenotypes of mettl3 morphant and reversed the decreases in cell proliferation and migration induced by METTL3 silencing. This study elucidates the pivotal role of METTL3 in craniofacial development via the METTL3/YTHDF1/PSEN1/β-catenin signaling axis.
研究领域:
发育生物学
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分子生物学
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遗传学
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细胞生物学
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PubMed
高影响因子
Stem Cell Research & Therapy
·
2019
·Vol. 10
·期 1
·1-11
·
IF 4.627
Kong Yuanyuan,Hu Xiaoli,Zhong Yingqun,Xu Ke,Wu Buling,Zheng Jianmao
Background Magnesium (Mg 2+ )-enriched microenvironment promotes odontogenic differentiation in human dental pulp stem cells (DPSCs), but the regulatory mechanisms remain undefined. The aim of this work was to assess magnesium’s function in the above process and to explore the associated signaling pathway. Methods DPSCs underwent culture in odontogenic medium with the addition of 0, 1, 5, or 10 mM MgCl 2 . Intracellular Mg 2+ levels in DPSCs were evaluated flow cytometrically using Mag-Fluo-4-AM. Mg 2+ -entry was inhibited by TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB). RNA-Sequencing was carried out for assessing transcriptome alterations in DPSCs during odontogenic differentiation associated with high extracellular Mg 2+ . KEGG pathway analysis was performed to determine pathways related to the retrieved differentially expressed genes (DEGs). Immunoblot was performed for assessing magnesium’s role and exploring ERK/BMP2/Smads signaling. Results Mg 2+ -enriched microenvironment promoted odontogenic differentiation in DPSCs via intracellular Mg 2+ increase. Consistently, the positive effect of high extracellular Mg 2+ on odontogenic differentiation in DPSCs was blocked by 2-APB, which reduced Mg 2+ entry. RNA-sequencing identified 734 DEGs related to odontogenic differentiation in DPSCs in the presence of high extracellular Mg 2+ . These DEGs participated in many cascades such as MAPK and TGF-β pathways. Consistently, ERK and BMP2/Smads pathways were activated in DPSCs treated with high extracellular Mg 2+ . In agreement, ERK signaling inhibition by U0126 blunted the effect of high extracellular Mg 2+ on mineralization and odontogenic differentiation in DPSCs. Interestingly, BMP2, BMPR1, and phosphorylated Smad1/5/9 were significantly decreased by U0126, indicating that BMP2/Smads acted as downstream of ERK. Conclusions Mg 2+ -enriched microenvironment promotes odontogenic differentiation in DPSCs by activating ERK/BMP2/Smads signaling via intracellular Mg 2+ increase. This study revealed that Mg 2+ -enriched microenvironment could be used as a new strategy for dental pulp regeneration.
研究领域:
牙科研究
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干细胞生物学
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分子生物学
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细胞信号传导
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Guofeng Wang,Yaxin Zhu,Xingjie Zan,Meng Li
There is a substantial global market for orthopedic implants, but these implants still face the problem of a high failure rate in the short and long term after implantation due to the complex physiological conditions in the body. The use of multifunctional coatings on orthopedic implants has been proposed as an effective way to overcome a range of difficulties. Here, a multifunctional (TA@HA/Lys) n coating composed of tannic acid (TA), hydroxyapatite (HA), and lysozyme (Lys) was fabricated in a layer-by-layer (LBL) manner, where TA deposited onto HA firmly stuck Lys and HA together. The deposition of TA onto HA, the growth of (TA@HA/Lys) n , and multiple related biofunctionalities were thoroughly investigated. Our data demonstrated that such a hybrid coating displayed antibacterial and antioxidant effects, and also facilitated the rapid attachment of cells [both mouse embryo osteoblast precursor cells (MC3T3-E1) and dental pulp stem cells (DPSCs)] in the early stage and their proliferation over a long period. This accelerated osteogenesis in vitro and promoted bone formation in vivo . We believe that our findings and the developed strategy here could pave the way for multifunctional coatings not only on orthopedic implants, but also for additional applications in catalysts, sensors, tissue engineering, etc.
研究领域:
生物材料
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骨科
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组织工程
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生物医学工程
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纳米技术
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材料科学
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产品关联
DOI
PubMed
高影响因子
Cellular Reprogramming
·
2014
·Vol. 16
·期 5
·379-391
·
IF 2.345
Chao Yang,Liang Sun,Xinghan Li,Li Xie,Mei Yu,Lian Feng,Zongting Jiang,Weihua Guo,Weidong Tian
Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.
研究领域:
干细胞生物学
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神经科学
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再生医学
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DOI
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 2
·1-15
·
IF 2.2
Hou Huailong,Qiu Zhengjun,Che Jingyi,Li Yanping,Sun Jingxuan,Zhang Weiwei,Ma Jinjie,Zhang Shuang,Li Mengdi,Niu Yumei,He Lina
Dental pulp stem cells (DPSCs), a subset of tooth-derived mesenchymal stem cells (MSCs), demonstrate significant promise in clinical stem cell therapy. However, prolonged in vitro expansion commonly results in compromised stemness, limiting therapeutic efficacy. Thus, maintaining the stemness of DPSCs during expansion and culture is a key challenge for regenerative medicine. In the current study, the impact of simulated microgravity (SMG) on DPSC stemness was investigated using the three-dimensional clinostat Cellspace-3D. After SMG treatment for 3 days, DPSCs demonstrated markedly enhanced replicative activity, proliferation efficiency, self-renewal capacity, and effective inhibition of the senescence process. Under specific differentiation induction conditions, DPSCs in the SMG group exhibited superior osteogenic, adipogenic, chondrogenic, and neural differentiation potentials. Additionally, DPSCs exhibited higher expression levels of the MSC surface markers Stro-1 and CD146 and stemness maintenance-related genes Oct4, Nanog, and Sox2 in the SMG group compared to those from the normal gravity (NG) group. To elucidate the potential molecular mechanisms by which SMG influences the stemness of DPSCs, transcriptome sequencing of total RNA was performed, and identified that differentially expressed genes (DEGs) are closely associated with the MAPK signaling pathway. Further verification experiments demonstrated that the MAPK/ERK signaling pathway was activated in the SMG group. In conclusion, SMG effectively maintains the stemness of DPSCs cultivated in vitro, and its mechanism of action may be associated with the activation of the MAPK/ERK signaling pathway.
研究领域:
干细胞生物学
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再生医学
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细胞生理学
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分子生物学
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转录组学
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产品关联
DOI
PubMed
高影响因子
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