Materials Today Bio
·
2025
·
IF 10.2
Yue Fei,Xiao Wang,Zhichen Ling,Yuran Jiang,Ting Jiang,Lingyan Cao,Jun Wang
Angiogenesis remains a key challenge in pulp regeneration due to the ischemic and hypoxic root canal environment. Apoptotic vesicles (ApoVs) offer unique advantages as a breakthrough strategy due to their stability in hypoxic environments, resistance to immune clearance, and high yield. However, a critical gap persists in biomaterials capable of spatiotemporal ApoVs delivery for pulp regeneration. To address this, an ApoVs-laden silk fibroin/sodium alginate (SF/SA/ApoVs) hydrogel with tunable release kinetics was fabricated. This hydrogel exhibited superior shapeability, injectability, and self-healing properties. SF/SA/ApoVs hydrogel improved angiogenesis by enhancing paracrine functions of dental pulp stem cells (DPSCs), and promoting capillary lumen formation of human umbilical vein endothelial cells via the focal adhesion signaling pathway. It also effectively created an odontogenic and neurogenic inductive micro-environment for pulp-dentin complex formation. Furthermore, in-vivo studies showed that semi-orthotopic transplantation of SF/SA/ApoVs hydrogel accelerated micro-vessels formation, and orthotopic transplantation further confirmed its capacity in generating full-length vascularized pulp tissue with aligned odontoblast-like cells and neuronal extension. Our study pioneers an ApoVs-functionalized hydrogel system with advanced angiogenic potential for promoting pulp regeneration.
研究领域:
生物材料学
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组织工程
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再生医学
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牙体牙髓病学
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生物医学工程
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DOI
PubMed
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
·
2020
·Vol. 41
·期 24
·2000102
·
IF 4.886
Yanan Liu,Ying Qiu,Shilei Ni,Xuewei Zhang,Hongchen Sun,Wenlong Song,Xiangwei Li
Dental pulp engineering possesses a promising perspective to replacing lost pulp in the root canal and restoring its functions. Stable adhesion of dental pulp stem cells (DPSCs) on the root canal dentin wall is a key element required for reconstruction of a functional odontoblast layer in dental pulp regeneration. To address this challenge, dopamine-modified hyaluronic acid (DA-HA) is coated on dentin to obtain a stable adhesion of DPSCs. The dopamine segment provides adhesion ability to the coating, and the hyaluronic acid increases the biocompatibility. The results show that DPSCs can adhere on the DA-HA coated dentin slice better than those without coating. Simultaneously, DPSCs proliferation can be further promoted on the prepared coating. Therefore, the DA-HA coating may provide a possible way to immobilize odontoblast cell onto dentin surface for pulp regeneration.
研究领域:
口腔医学
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组织工程
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生物材料学
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DOI
PubMed
高影响因子
INTERNATIONAL DENTAL JOURNAL
·
2025
·Vol. 76
·期 1
·109304
·
IF 3.7
Zhaoxia Yu,Shihui Jiang,Xinxin Li,Xingjiao Li,Guanhua Wang,Xiaohua Dai,Xiaoli Lian,Yan Yan,Yue Wang,Zhimou Yang,Huiru Zou
Objectives Enamel matrix derivative (EMD) is widely recognized for its ability to induce osteogenic and odontogenic differentiation. However, the complex composition of EMD frequently results to inconsistent experimental and clinical outcomes. Amelogenin, a key component of EMD, plays crucial roles in tooth germ development as well as in the repair and regeneration of dental tissue. In this study, an amelogenin peptide was investigated on the proliferation and odontogenic differentiation of human dental pulp cells (HDPCs). Methods The amelogenin peptide with the amino acid sequence KWYQNMIR was synthesized using solid-phase techniques. HDPCs were stimulated with various concentrations of the peptide. CCK-8 assays, alkaline phosphatase (ALP) activity measurements, quantitative reverse transcription-polymerase chain reaction, Western blot analysis, Alizarin red staining, and scanning electron microscopy were used to assess the effects. Results The amelogenin peptide concentrations of 100 nM and 1 μM significantly enhanced HDPC proliferation at 5 and 7 days ( P < .01), with 1 μM exhibiting the most pronounced effect. Treatment with 1 μM amelogenin peptide enhanced ALP activity in HDPCs at 7 and 14 days ( P < .01) and markedly upregulated the mRNA expression of DSPP, DMP-1 , and RUNX-2 . Western blot analysis revealed that 1 μM amelogenin peptide enhanced the protein expression of DSPP, DMP-1, and ALP in HDPCs at 7 and 14 days. Additionally, it promoted calcium deposition and mineralized nodule formation at 28 days. Importantly, the amelogenin peptide upregulated the phosphorylation level of ERK1/2 (p-ERK1/2), and the application of an ERK1/2 inhibitor suppressed HDPC differentiation. Conclusions The amelogenin peptide stimulates both the proliferation and odontogenic differentiation of HDPCs via the ERK1/2 pathway. These findings suggest that the amelogenin peptide may have significant implications for regenerative dentistry, particularly in the context of dentine-pulp complex regeneration.
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PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Jianmao Zheng,Jiyuan Zuo,Cairong Xiao,Qining Guo,Xiaobin Fu,Chengyun Ning,Peng Yu
The induction of dental pulp stem cells (DPSCs) into odontogenic differentiation is a cutting-edge method of dental pulp regeneration treatment. However, it remains a challenge to develop biomaterials and therapies that can induce odontogenic differentiation. Here, we propose a wireless electrical stimulation strategy to induce DPSCs odontogenic differentiation via K 0.5 Na 0.5 NbO 3 piezoelectric nanoparticles (KNN) and polarized KNN (PKNN), which can be endocytosed by DPSCs. In vitro, several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN, and the increase was more obvious in the PKNN group. Intracellular wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter (MCU), increased the production of adenosine triphosphate (ATP), and induced odontogenic differentiation through the activation of the cAMP-PKA signaling pathway. In vivo, dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN, which was more clinically friendly compared with the wired device, and the induction was more obvious in the PKNN group consistent with in vitro experiments. In conclusion, this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.
研究领域:
牙科学
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生物材料
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干细胞生物学
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纳米技术
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再生医学
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DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Zhang Yingjuan,Huang Xianxian,Luo Yicai,Ma Xiangyu,Luo Ling,Liang Ling,Deng Tingting,Qiao Yang,Ye Fanggui,Liao Hongbing
Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment.
研究领域:
牙科
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材料科学
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纳米技术
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再生医学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Zhuo Xie,Peimeng Zhan,Xinfang Zhang,Shuheng Huang,Xuetao Shi,Zhengmei Lin,Xianling Gao
Regenerative endodontic therapy is a promising approach to restore the vitality of necrotic teeth, however, pulp regeneration in mature permanent teeth remains a substantial challenge due to insufficient developmental signals. The dentin is embryologically and histologically similar to the pulp, which contains a cocktail of pulp-specific structural proteins and growth factors, thus we proposed an optimizing strategy to obtain dentin matrix extracted proteins (DMEP) and engineered a DMEP functionalized double network hydrogel, whose physicochemical property was tunable by adjusting polymer concentrations to synchronize with regenerated tissues. In vitro models showed that the biomimetic hydrogel with sustained release of DMEP provided a beneficial microenvironment for the encapsulation, propagation and migration of human dental pulp stem cells (hDPSCs). The odontogenic and angiogenic differentiation of hDPSCs were enhanced as well. To elicit the mechanism hidden in the microenvironment to guide cell fate, RNA sequencing was performed and 109 differential expression of genes were identified, the majority of which enriched in cell metabolism, cell differentiation and intercellular communications. The involvement of ERK, p38 and JNK MAPK signaling pathways in the process was confirmed. Of note, in vivo models showed that the injectable and in situ photo-crosslinkable hydrogel was user-friendly for root canal systems and was capable of inducing the regeneration of highly organized and vascularized pulp-like tissues in root segments that subcutaneously implanted into nude mice. Taken together, this study reported a facile and efficient way to fabricate a cell delivery hydrogel with pulp-specific developmental cues, which exhibited promising application and translation potential in future regenerative endodontic fields.
研究领域:
再生医学
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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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牙科学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Xi Liang,Li Xie,Qingyuan Zhang,Ge Wang,Siyuan Zhang,Mingyan Jiang,Ruitao Zhang,Ting Yang,Xingyu Hu,Ziyang Yang,Weidong Tian
Combined injectable cell-laden microspheres and angiogenesis approaches are promising for functional vascularized endodontic regeneration. However, advanced microsphere designs and production techniques that benefit practical applications are rarely developed. Herein, gelatin methacryloyl (GelMA)-alginate core-shell microcapsules were fabricated to co-encapsulate human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) based on a coaxial electrostatic microdroplet technique. This technique enables high-throughput production, convenient collection, and minimal material waste. The average diameter of core-shell microcapsules was ∼359 µm, and that of GelMA cores was ∼278 µm. There were higher proliferation rates for hDPSCs and HUVECs co-encapsulated in the GelMA cores than for hDPSCs or HUVECs monoculture group. HUVECs assembled to form 3D capillary-like networks in co-culture microcapsules. Moreover, HUVECs promoted the osteo/odontogenic differentiation of hDPSCs in microcapsules. After 14 days of cultivation, prevascularized microtissues formed in microcapsules that contained abundant deposited extracellular matrix (ECM); no microcapsule aggregation occurred. In vivo studies confirmed that better microvessel formation and pulp-like tissue regeneration occurred in the co-culture group than in hDPSCs group. Thus, an effective platform for prevascularization microtissue preparation was proposed and showed great promise in endodontic regeneration and tissue engineering applications. Statement of significance Cell-laden microspheres combined with the proangiogenesis approach are promising in endodontic regeneration. We proposed GelMA-alginate core-shell microcapsules generated via the coaxial electrostatic microdroplet (CEM) method, which utilizes a double-lumen needle to allow for core-shell structures to form. The microcapsules were used for co-culturing hDPSCs and HUVECs to harvest large amounts of prevascularized microtissues, which further showed improved vascularization and pulp-like tissue regeneration in vivo . This CEM method and the microcapsule system have advantages of high-throughput generation, convenient collection, and avoid aggregation during long-term culturing. We proposed a high-effective platform for mass production of prevascularized microtissues, which exhibit great promise in the clinical transformation of endodontic regeneration and other applications in regenerative medicine.
研究领域:
生物材料
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组织工程
·
再生医学
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牙科科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Yu Qiu,Jun Tian,Siyi Kong,Yanping Feng,Yangyu Lu,Lefeng Su,Yanling Cai,Mengjie Li,Jiang Chang,Chen Yang,Xi Wei
Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries-induced dental pulp infections. However, bacterial contamination negatively affects dentine-pulp complex repair. The common capping materials show limited antimicrobial effects against some microorganisms. To improve the VPT efficacy, capping materials with increased antibacterial properties and enhanced odontogenic and angiogenic activities are needed. Herein, a SrCuSi 4 O 10 /gelatin methacrylate(SC/Gel) composite hydrogel has been proposed for infected dental pulp treatment. SrCuSi 4 O 10 (SC) is a microscale bioceramic composed of assembled multilayered nanosheets that possesses good near-infrared photothermal conversion ability and multiple bioactivities due to sustained Sr 2+ , Cu 2+ , and SiO 3 2− ion release. It is shown that the SC/Gel composite hydrogel efficiently eliminates Streptococcus mutans and Lactobacillus casei and inhibits biofilm formation under photothermal heating, while the ion extract from SC promotes odontogenesis of rat dental pulp stem cells and angiogenesis of human umbilical vein endothelial cells. The as-designed therapeutic effect of SC/Gel composite hydrogel-mediated VPT has been proven in a rat dental pulp infection model and yielded improved dentine-pulp complex repair compared with the commercially used iRoot® BP Plus. This study suggests that the SC/Gel composite hydrogel is a potential pulp-capping material with improved effects on dentine−pulp complex repair in infected pulp.
研究领域:
牙科材料科学
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生物材料
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再生医学
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口腔微生物学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）