Journal of Materials Chemistry B
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2015
·Vol. 4
·期 2
·245-256
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IF 4.726
Surakshya Shrestha,Pengfei Jiang,Marcelo Henrique Sousa,Paulo Cesar Morais,Zhengwei Mao,Changyou Gao
Surface modification of iron oxide nanoparticles may cause unexpected impact upon interaction with cells, such as cytotoxicity and change in the differentiation potential of stem cells. In this study, two kinds of iron oxide nanoparticles with different surface chemistries, i.e. one in its pristine form (P-NPs) without extra capping molecules and the other coated with citrate (C-NPs), and with similar sizes, ∼10 nm, as measured by transmission electron microscopy and X-ray diffractometry, were prepared. Both P-NPs and C-NPs aggregated to some extent in water, with hydrodynamic diameters of 211.4 ± 29 and 128.6 ± 6.3 nm, and surface zeta potential values of +23.5 ± 0.3 and −49.6 ± 0.5 mV, respectively. However, both NPs further aggregated to a similar extent with hydrodynamic diameters of 260 ± 5.5 and 214 ± 6.4 nm and with a slightly negative surface charge (∼−10 mV) in cell differentiation media. After being incubated with rat mesenchymal stem cells (MSCs) for 14 d, both types of NPs showed similar cell uptake kinetics and final intracellular iron content, i.e. 53.3 pg per cell for P-NPs and 59.9 pg per cell for C-NPs, and minimal cytotoxicity at a concentration below 100 μg mL−1. The adipogenic differentiation potential of MSCs was unaltered regardless of the NP types, and the P-NPs did not have an obvious impact on the osteogenic differentiation potential of MSCs. The osteogenic differentiation potential of the MSCs, however, was significantly impaired by incubation with the C-NPs, as evidenced by significantly reduced expression of osteogenic markers, namely collagen type I (COL) and osteocalcin (OCN) and calcium deposition. The uptake of C-NPs and surface-anchored citrate molecules were found to have a synergistic effect.
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RSC Advances
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2017
·Vol. 7
·期 25
·15284-15292
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IF 3.108
Xiao Liu,Naru Zhao,Haibo Duan,Yijuan Ma,Xiaoheng Guo,Jingjing Diao,Xuetao Shi,Yingjun Wang
Material properties and cellular behaviours seemed to be coupled, implying the existence of reciprocities between cells and materials. Understanding cellular behaviours and material structure is indispensable for materials synthesis and design but has mostly focused on shape, neglecting the status of the sub-structure. Hence we utilized a similar route to regulate the different morphology of HAp particles and then investigated reciprocities between particles and bone marrow mesenchymal stem cells (BMSCs). Based on our cell experiment, we revealed the side effects of dissociated micro-rods on cellular behaviours. Despite the facts that both particles showed modestly cytotoxicity, the multi-structure HAp sphere could positively-regulate the proliferation, viability and differentiation of bone marrow mesenchymal stem cells (BMSCs) which indicated that the dissociated micro-rods may deteriorate the biological properties in vitro.
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CONNECTIVE TISSUE RESEARCH
·
2025
·
IF 2.1
Lin Liu,Zhuangzhuang Chu,Xiao Han,Jin Wu,Kunzhan Cai,Jiaohong Wang,Zixiang Guo,Shan Gao,Guoqing Li,Chunbo Tang
Objective We aimed to demonstrate the effects of creatine (Cr) on osteogenic differentiation (OD) in HDPSCs.Materials and methods HDPSCs were treated with Cr and an inhibitor of Cr transporter. The OD capacity was evaluated by detecting ALP staining and activity, alizarin red staining (ARS), as well as osteogenesis-related protein levels. Transcriptomic sequencing, western blotting, transmission electron microscopy, immunofluorescence staining, and autophagy-related protein marker detection were applied to illustrate the underlying mechanism. Furthermore, the impact of Cr on bone regeneration was investigated in vivo.Results We found that 1 mm of Cr effectively enhanced the OD of HDPSCs. The creatine group displayed significantly increased AMPK phosphorylation, overexpressed autophagy-related proteins, enhanced OD, and mineralization capabilities. We also found that ULK1 is the downstream molecule through which AMPK induces cellular autophagy. In vivo results demonstrated that Cr could increase the new bone formation of periodontitis.Conclusion Our research discovered a new AMPK-ULK1-autophagy pathway through which Cr enhances OD in HDPSCs. Cr enhanced HDPSCs-mediated periodontal tissue regeneration in a periodontitis mouse model, providing a theoretical foundation for the study of bone repair in periodontitis.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Li Jinxin,Wu Honghui,Yu Zebin,Wang Qiwei,Zeng Xin,Qian Wenchang,Lu Siqi,Jiang Lingli,Li Jingyi,Zhu Meng,Han Yingli,Gao Jianqing,Qian Pengxu
Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin β2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.
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International Journal of Nanomedicine
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2024
·
IF 6.6
Xiaoyuan Yan,Na An,Zeying Zhang,Qiujing Qiu,Di Yang,Penggong Wei,Xiyue Zhang,Lihong Qiu,Jiajie Guo
Background In bone tissue engineering (BTE), cell-laden scaffolds offer a promising strategy for repairing bone defects, particularly when host cell regeneration is insufficient due to age or disease. Exogenous stem cell-based BTE requires bioactive factors to activate these cells. Graphene oxide quantum dots (GOQDs), zero-dimensional derivatives of graphene oxide, have emerged as potential osteogenic nanomedicines. However, constructing biological scaffolds with GOQDs and elucidating their biological mechanisms remain critical challenges.Methods We utilized GOQDs with a particle size of 10 nm, characterized by a surface rich in C–O–H and C–O–C functional groups. We developed a gelatin methacryloyl (GelMA) hydrogel incorporated with GOQDs-treated dental pulp stem cells (DPSCs). These constructs were transplanted into rat calvarial bone defects to estimate the effectiveness of GOQDs-induced DPSCs in repairing bone defects while also investigating the molecular mechanism underlying GOQDs-induced osteogenesis in DPSCs.Results GOQDs at 5 μg/mL significantly enhanced the osteogenic differentiation of DPSCs without toxicity. The GOQDs-induced DPSCs showed active osteogenic potential in three-dimensional cell culture system. In vivo, transplantation of GOQDs-preactivated DPSCs/GelMA composite effectively facilitated calvarial bone regeneration. Mechanistically, GOQDs stimulated mitophagy flux through the phosphatase-and-tensin homolog-induced putative kinase 1 (PINK1)/Parkin E3 ubiquitin ligase (PRKN) pathway. Notably, inhibiting mitophagy with cyclosporin A prevented the osteogenic activity of GOQDs.Conclusion This research presents a well-designed bionic GOQDs/DPSCs/GelMA composite scaffold and demonstrated its ability to promote bone regeneration by enhancing mitophagy. These findings highlight the significant potential of this composite for application in BTE and underscore the crucial role of mitophagy in promoting the osteogenic differentiation of GOQDs-induced stem cells.
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Advanced Healthcare Materials
·
2025
·
IF 9.6
Xinxiao Chen,Weijia Wang,Yuhan Hu,Jiao Sun,Liguo Zhang,Yi Chen,Jin Liu,Yang Yu,Jianhua Li,Shaohua Ge
The hyperglycemic microenvironment of diabetes inevitably leads to the accumulated reactive oxygen species (ROS) and impairs the function of stem cells, thereby impeding the process of osseointegration after implant placement. In this study, a self-assembled metal-phenolic nanozyme coating is presented for alleviating diabetic oxidative stress and improving osseointegration at implant interfaces. The antioxidant-like enzyme activity is induced by phenolic ligand−metal charge transfer (LMCT) during the coordination of epigallocatechin-3-gallate (EGCG) with copper phosphate nanosheets (Cu NS). The metal-phenolic nanozyme biointerfaces exhibits scavenging activity against a range of free radicals and facilitated the adhesion, migration, and osteogenic differentiation of stem cells, thereby enhancing the osseointegration of implants in diabetic rats. Additionally, the nanozyme coating strategy inhibits bacterial invasion and supports the adhesion of soft tissue cells. This study provides a prospective approach for surface modification to safeguard and enhance the osseointegration of implants in diabetic subjects.
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ADVANCED FUNCTIONAL MATERIALS
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2024
·
IF 18.5
Yinqiu Yan,Liling Chen,Liwen Zheng,Gen Wang,Hongmei Zhang,Xing Feng,Yaxian Liu,Lan Li,Yu Shrike Zhang,Ping Ji,Ximu Zhang
Wound repair is a complex and dynamic process, involving stages of hemostasis, inflammation, proliferation, and remodeling. Standard methods currently used for clinical treatment of skin defects remain unsatisfying and alternative treatments have emerged including acupuncture mostly relying on the conventional needle method. It is applied sustained acupuncture therapy with bioengineered stem cell-loaded hydrogel microspheres (A-SGC), where the data gathered through transcriptomics, metabolomics, and single-cell omics analyses are used to construct a comprehensive multi-omics map underlying the wound regeneration process with such a therapy. Under the treatment of A-SGC, the interactions and Yin-Yang balance among fibroblasts, macrophages, endothelial cells, and keratinocytes facilitated skin regeneration instead of scarred healing. The genes related to the promotion of matrix synthesis and re-epithelialization played important roles in the transition from the inflammatory granulation phase to the stromal remodeling phase. This convergence use of hydrogel microspheres, stem cells, and sustained acupuncture therapy could have previously unattainable therapeutic implications for improved wound treatment.
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JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
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2024
·Vol. 50
·期 12
·2338-2345
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IF 1.6
Yang Wang,Wenxin Liu,Hui Xu,Liyuan Dong,Yalou Jiao,Zhe Qiao
Objective Thin endometrium caused by various factors affects the conception rate of females worldwide; however, current medications are still insufficient. Therefore, a novel approach is needed. We previously reported the effect of menstrual blood-derived mesenchymal stem cells (MenSCs) in ameliorating ethanol-induced endometrial injuries. In the present study, we aimed to investigate whether the effect of MenSCs is enhanced by a combination of platelet-rich plasma (PRP) infusion. Methods An endometrial injury mouse model was established by infiltrating 95% ethanol for 15 s into the uterus, followed by MenSCs, PRP, or MenSCs + PRP treatment. Pathological changes were observed by HE staining. The expression of CK18, vimentin, ItgαVβ3, and VEGF was determined using IHC staining and WB blotting. Results Compared with the model, MenSCs, PRP, and MenSCs + PRP treatments significantly improved endometrial damage and thickness, with the combined therapy displaying the most pronounced efficacy. The density of CK18-, vimentin-, and ItgαVβ3 positive cells increased most significantly in the MenSCs + PRP group of mice. In addition, the protein expression of CK18, vimentin, and VEGF was significantly upregulated after MenSCs + PRP, MenSCs, and PRP treatment, with MenSCs + PRP therapy showing the best efficacy. Conclusion MenSCs + PRP therapy is more beneficial for ameliorating ethanol-induced endometrial damage than MenSCs or PRP alone, providing a basis for the investigation of novel approaches for treating thin endometria.
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Small Structures
·
2024
·
IF 13.9
Han Zhao,Fangyu Zhu,Yusi Guo,Xuliang Deng,Wenwen Liu
Conventional methods to stimulate the metabolism of bone marrow mesenchymal stem cells (BMSCs) for osteogenic differentiation typically involve systemic mobilization, which faces challenges including limited in vivo half-life, lack of selectivity, and potential side-effects. Therefore, localized modulation of BMSCs represents a more efficient and safer alternative. However, few studies have explored the regulation of a localized stimuli-responsive microenvironment to activate osteogenic differentiation via mitochondrial pathways and clarified its underlying mechanisms. Herein, a novel strategy to accelerate the metabolic switch of BMSCs in tissue defects through targeted modulation using built-in magnetoelectric biomaterials is proposed. BMSCs cultured in the magnetoelectric microenvironment exhibited an increased mitochondrial membrane potential, the highest oxygen consumption rate and enhanced adenosine triphosphate production. Furthermore, BMSCs in the magnetoelectric microenvironment demonstrated a successful metabolic switch of energy resource from glycolysis to oxidative phosphorylation, indicating a strong tendency toward osteogenic differentiation. The highest multiclass metabolite profile, indicating the most active metabolic state, was shown in rats cranial defect model treated with magnetoelectric microenvironment. This research introduces a novel approach to accelerate bone defect repair by targeted modulation of BMSC mitochondria with magnetoelectric microenvironment and provides a promising direction for exploring the intrinsic mechanisms through which the magnetoelectric microenvironment promotes bone regeneration.
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CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Wenjie Zhang,Wenliang Xue,Zhaoli Jia,Rong Yang,Penghui Wang,Yi Hu,Xiaoyan Tan,Qiang Chen,Bo Chi
Regenerating damaged cartilage remains a challenge due to limited cell availability and inefficient chondrogenic differentiation. Here, we present a photo-driven dynamic hydrogel with a double-network structure to meet this challenge. The fabrication strategy involves a combination of a photosensitive host–guest network with a covalent network, providing tunable mechanical cues that effectively regulate bone marrow mesenchymal stem cells (BMSCs) behavior within their microenvironment while maintaining macroscopical stability. Employing a two-step stiffness-tunable process mediated by controlled low-dose light exposure, the hydrogel exerts precise control over BMSCs proliferation and orchestrates chondrogenic differentiation, leading to the upregulation of crucial chondrogenic genes, notably SOX9 and ACAN. Empirical evidence derived from histological analysis substantiates the functional efficacy of the hydrogel, confirming the regenerative potential of cartilage tissues. This study presents an innovative and promising strategy for stem cell culture, in vitro differentiation, and cell delivery, with implications for cartilage defect repair and tissue regeneration.
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Applied Materials Today
·
2024
·
IF 7.2
Zeyi Sun,Tianxiao Mei,Yuanfeng Xin,Tianhao Tan,Muladili Mutailipu,Laihai Zhang,Tieyan Li,Hao Cao,Yihui Hu,Zhongmin Liu,Wenjun Le
Mesenchymal stem cell therapy has emerged as a promising approach for the treatment of myocardial infarction. However, the challenge of low cell survival and retention post injection, particularly under the high levels of reactive oxygen species (ROS) and oxidative stress at the infarct site, has hindered their clinical application. Additionally, traditional drug delivery methods, such as intravenous injection, cannot meet the demand for long-term stem cell residence at the infarct site, which is another critical issue that impedes the therapeutic efficacy of stem cells. Herein, we synthesized indocyanine green-enriched Prussian blue nanozyme, called PB@PEI@ICG, which not only possessed remarkable ROS scavenging capability but also exhibited superior fluorescent tracer property. Subsequently, we engineered mesenchymal stem cells (MSCs) with PB@PEI@ICG by co-culture and found that the introduction of the nanozyme significantly enhanced mitophagy by BNIP3 and PINK1 pathways, which in turn promoted ROS scavenging and protected MSCs from cell death induced by the harsh infarct microenvironment. Furthermore, we employed pericardial injection as an alternative delivery method to prolong the residence time of MSCs at the infarct site, enabling real-time tracking via the fluorescence property of the nanozymes. The results demonstrated that PB@PEI@ICG nanozyme could significantly improve the survival and retention of MSCs at the infarct site, thereby enhancing the therapeutic effect for myocardial infarction. In conclusion, this study presents a novel strategy for stem cell therapy in myocardial infarction by using mitophagy-enhancing nanozyme to scavenge ROS for enhancing the therapeutic potential of stem cells.
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Small
·
2024
·
IF 13
Xuancheng Zhang,Wei Song,Yang Liu,Kang Han,Yuxu Wu,Eunshinae Cho,Zhaoyi Fang,Lianghua Jiang,Yihe Hu,Xuesong Zhu,Jia Jiang,Xiaoqiao Huangfu,Jinzhong Zhao
The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.
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