CELL PROLIFERATION
·
2020
·Vol. 53
·期 8
·e12871
·
IF 5.753
Hongping Yu,Pei Liu,Daoyu Zhu,Junhui Yin,Qianhao Yang,Yigang Huang,Yixuan Chen,Changqing Zhang,Youshui Gao
Objectives Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. Materials and Methods The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. Results In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. Conclusions We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.
研究领域:
药理学
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骨科
·
干细胞研究
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Zhi Zheng,Jian Sun,Jun Wang,Suisui He,Yun Huang,Xu Yang,Yuqi Zhao,Cui-Yun Yu,Hua Wei
The compromised microenvironment after cartilage injury generally leads to low survival or abnormal differentiation of implanted stem cells for fibrocartilage formation with weak mechanical properties. Suitable and safe bionic materials can provide mechanical properties for cartilage repair while promoting cartilage regeneration effects. However, to our knowledge, mechanical strength modulation of therapeutic peptide-based bionic hydrogels remains relatively unexplored, and further application of peptide-based bionic hydrogels in a negative feedback manner for defective cartilage repair has been seldom reported so far. In this study, we reported the first sophisticated design and fabrication of a dual cross-linked peptide-based hydrogel for promoted cartilage regeneration in a feedback-regulated manner. The integration of multiple supramolecular forces including host–guest interactions and extensive hydrogen bonding endow the resulting hydrogels with excellent self-healing and mechanical strength for highly synergistic lubrication properties and compressive performance. More importantly, the unique integrative peptide VPM-pmTGF-β1 can realize on-demand pmTGF-β1 release that is triggered by the MMP-3-responsive cleavage of a VPM sequence. When the VPM-pmTGF-β1-modified hydrogel system is implanted into the cartilage defect sites in a model of SD rats, MMP-3-triggered on-demand pmTGF-β1 release suppresses IκBα/NF-κB signaling pathway-induced cartilage inflammation in a negative feedback manner while promoting the targeted cartilage differentiation of BMSCs for efficient cartilage regeneration. The novel strategy developed herein contributes to a more comprehensive and in-depth understanding of the biological properties of peptide-based hydrogels for cartilage defect repair and provides a simple yet powerful means for clinical translations.
研究领域:
生物材料
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组织工程
·
再生医学
·
生物力学
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分子生物学
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产品关联
DOI
高影响因子
Lipids in Health and Disease
·
2024
·Vol. 23
·期 1
·1-11
·
IF 3.9
Li Jinying,Chen Yongshao,Zha Dingsheng,Wu Chunhui,Li Xiaofen,Yang Li,Cao Hui,Cai Shexing,Cai Yuebo
The accumulation of reactive oxygen species (ROS) within the bone marrow microenvironment leads to diminished osteogenic differentiation and heightened lipogenic differentiation of mesenchymal stem cells residing in the bone marrow, ultimately playing a role in the development of osteoporosis (OP). Mitigating ROS levels is a promising approach to counteracting OP. In this study, a nanozyme composed of magnesium-based zeolitic imidazolate frameworks (Mg-ZIF) was engineered to effectively scavenge ROS and alleviate OP. The results of this study indicate that Mg-ZIF exhibits significant potential in scavenging ROS and effectively promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Additionally, Mg-ZIF was found to inhibit the differentiation of BMSCs into adipose cells. In vivo experiments further confirmed the ability of Mg-ZIF to mitigate OP by reducing ROS levels. Mechanistically, Mg-ZIF enhances the differentiation of BMSCs into osteoblasts by upregulating lipid metabolic pathways through ROS scavenging. The results indicate that Mg-ZIF has potential as an effective therapeutic approach for the treatment of osteoporosis.
研究领域:
生物材料
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干细胞生物学
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骨代谢
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活性氧
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组织工程
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 25
·14915-14927
·
IF 3.119
Yiqiang Yu,Kai Liu,Zhuo Wen,Weicai Liu,Lei Zhang,Jiansheng Su
Zinc-incorporated biomaterials show promoting effects on osteogenesis; however, excessive zinc ions lead to cytotoxic reactions and also have other adverse effects. Therefore, the double-edged effects of Zn2+ microenvironments on osteogenesis may become critical issues for new material development. This study systematically investigated the bidirectional influences of diverse Zn2+ microenvironments on the cell adhesion, proliferation, osteogenic differentiation and apoptosis of rBMSCs. Furthermore, the mechanisms of zinc-induced osteogenic differentiation of rBMSCs and of cell apoptosis induced by high concentration of Zn2+ were both discussed in detail. The results indicated that the Zn2+ microenvironments of 2 μg mL−1 and 5 μg mL−1 effectively improved the initial adhesion and proliferation of rBMSCs, while that of 15 μg mL−1 had exactly the opposite effect. More importantly, the suitable Zn2+ microenvironments (2 μg mL−1 and 5 μg mL−1) moderately increased the intracellular Zn2+ concentration by regulating zinc transportation, and then activated the MAPK/ERK signaling pathway to induce the osteogenic differentiation of rBMSCs. In contrast, the high Zn2+ concentration (15 μg mL−1) not only inhibited the osteogenic differentiation of rBMSCs by damaging intracellular zinc homeostasis, but also induced rBMSC apoptosis by enhancing intracellular ROS generation. The current study clarified the double-edged effects of Zn2+ microenvironments on the osteogenic properties of rBMSCs and the related mechanisms, and may provide valuable guidance for optimizing the design of zinc-doped biomaterials and zinc-based alloys.
研究领域:
生物材料
·
细胞生物学
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组织工程
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Shengjie Jiang,Hua Jing,Yu Zhuang,Jinjie Cui,Zeyu Fu,Dejian Li,Cancan Zhao,Usman Liaqat,Kaili Lin
Minimally invasive, efficient, and satisfactory treatment for irregular and lacunar bone defects is still a challenge. Alginate hydrogels serve as promising stem cell (SC) delivery systems for bone regeneration but are limited by low cellular viability, poor osteogenic differentiation, and insufficient mechanical support. Herein, we developed a BMSCs-laden mechanically reinforced bioactive sodium alginate composite hydrogel microspheres (BCHMs) system via a microfluidic method that possesses 1) a uniform size and good injectability to meet clinical bone defects with complex shapes, 2) high cellular viability maintenance and further osteogenic induction capacity, and 3) improved mechanical properties. As the main matrix, the sodium alginate hydrogel maintains the high viability of encapsulated BMSCs and efficient substance exchange. Enhanced mechanical properties and osteogenic differentiation of the BCHMs in vitro were observed with xonotlite (Ca 6 Si 6 O 17 (OH) 2 , CSH) nanowires incorporated. Furthermore, BCHMs with 12.5 % CSH were injected into rat femoral bone defects, and satisfactory in situ regeneration outcomes were observed. Overall, it is believed that BCHMs expand the application of polysaccharide science and provide a promising injectable bone substitute for minimally invasive bone repair.
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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材料科学
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骨科
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产品关联
DOI
PubMed
高影响因子
Biofabrication
·
2023
·Vol. 15
·期 2
·025010
·
IF 9
Xin Sun,Jin Yang,Jie Ma,Tianchang Wang,Xue Zhao,Dan Zhu,Wenjie Jin,Kai Zhang,Xuzhou Sun,Yuling Shen,Neng Xie,Fei Yang,Xiushuai Shang,Shuai Li,Xiaojun Zhou,Chuanglong He,Deteng Zhang,Jinwu Wang
The periosteum is a connective tissue membrane adhering to the surface of bone tissue that primarily provides nutrients and regulates osteogenesis during bone development and injury healing. However, building an artificial periosteum with good adhesion properties and satisfactory osteogenesis for bone defect repair remains a challenge, especially using three-dimensional (3D) bioprinting. In this study, dopamine was first grafted onto the molecular chain of gelatin using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (NHS) to activate the carboxyl group and produce modified gelatin-dopamine (GelDA). Next, a methacrylated gelatin, methacrylated silk fibroin, GelDA, and graphene oxide nanosheet composite bioink loaded with bone marrow mesenchymal stem cells was prepared and used for bioprinting. The physicochemical properties, biocompatibility, and osteogenic roles of the bioink and 3D bioprinted artificial periosteum were then systematically evaluated. The results showed that the developed bioink showed good thermosensitivity and printability and could be used to build 3D bioprinted artificial periosteum with satisfactory cell viability and high adhesion. Finally, the 3D bioprinted artificial periosteum could effectively enhance osteogenesis both in vitro and in vivo. Thus, the developed 3D bioprinted artificial periosteum can prompt new bone formation and provides a promising strategy for bone defect repair.
研究领域:
组织工程
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生物医学工程
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再生医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2022
·
IF 3.682
Hongwei Pan,Wanxin Li,Yue Qu,Simei Li,Ayixiemu Yusufu,Jia Wang,Lihua Yin
Bone defects caused by trauma or tumor are a significant challenge in clinical practice. Hydrogel-based tissue engineering has been considered an effective strategy. This study successfully formed a series of injectable hydrogels by enzyme-catalyzed crosslinking hyaluronic acid-tyramine (HA-TA) and sodium alginate-tyramine (ALG-TA) under physiological conditions in the presence of both horseradish peroxidase and hydrogen peroxide. The morphology, mechanical properties, swelling properties, and biodegradation properties of hydrogels were investigated. The results showed that the mechanical properties, swelling properties and biodegradation of HA/ALG hydrogels varied with the precursor solution concentration. Furthermore, the proliferation and osteogenic differentiation of BMSCs within the HA/ALG hydrogels were evaluated in vitro. The results illustrated that the hydrogels could offer an excellent microenvironment for BMSCs growth and promote osteogenic differentiation. Therefore, the injectable hydrogels can be used as an effective 3 D scaffold for bone repair and regeneration.
研究领域:
组织工程
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生物医用材料
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再生医学
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 8
·1725-1738
·
IF 7
Xin Sun,Xin Jiao,Zengguang Wang,Jie Ma,Tianchang Wang,Dan Zhu,Han Li,Liang Tang,Heyue Li,Changde Wang,Yiming Li,Chen Xu,Jinwu Wang,Yaogai Gan,Wenjie Jin
Cellular bioactivity and tissue regeneration can be affected by coatings on tissue-engineered scaffolds. Using mussel-inspired polydopamine (PDA) is a convenient and effective approach to surface modification. Therefore, 3D-printed β-tricalcium phosphate (β-TCP) scaffolds were coated with PDA in this study. The effects of the scaffolds on the adhesion and osteogenic differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro and on new-bone formation in vivo were investigated. The potential mechanisms and related differential genes were assessed using mRNA sequencing. It was seen that PDA coating increased the surface roughness of the 3D-printed β-TCP scaffolds. Furthermore, it prompted the adhesion and osteogenic differentiation of seeded BMSCs. mRNA sequencing analysis revealed that PDA coating might affect the osteogenic differentiation of BMSCs through the calcium signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway, etc. Moreover, the expression of osteogenesis-related genes, such as R-spondin 1 and chemokine c-c-motif ligand 2, was increased. Finally, both the 3D-printed β-TCP scaffolds and PDA-coated scaffolds could significantly accelerate the formation of new bone in critical-size calvarial defects in rats compared with the control group; and the new bone formation was obviously higher in the PDA-coated scaffolds than in β-TCP scaffolds. In summary, 3D-printed β-TCP scaffolds with a PDA coating can improve the physicochemical characteristics and cellular bioactivity of the scaffold surface for bone regeneration. Potential differential genes were identified, which can be used as a foundation for further research.
研究领域:
生物材料
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组织工程
·
干细胞生物学
·
分子生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Zengzilu Xia,Huiwen Zhang,Qing Li,Chao Yi,Zhijian Xing,Zizhen Qin,Huilin Zhao,Jing Jing,Chuanrong Zhao,Kaiyong Cai
Electrical stimulation has been used clinically as an adjunct therapy to accelerate the healing of bone defects, and its mechanism requires further investigations. The complexity of the physiological microenvironment makes it challenging to study the effect of electrical signal on cells alone. Therefore, an artificial system mimicking cell microenvironment in vitro was developed to address this issue. In this work, a novel electrical stimulation system was constructed based on polypyrrole nanowires (ppyNWs) with a high aspect ratio. Synthesized ppyNWs formed a conductive network in the composited hydrogel which contained modified gelatin with methacrylate, providing a conductive cell culture matrix for bone marrow mesenchymal stem cells. The dual-network conductive hydrogel had improved mechanical, electrical, and hydrophilic properties. It was able to imitate the three-dimensional structure of the cell microenvironment and allowed adjustable electrical stimulations in the following system. This hydrogel was integrated with cell culture plates, platinum electrodes, copper wires, and external power sources to construct the artificial electrical stimulation system. The optimum voltage of the electrical stimulation system was determined to be 2 V, which exhibited remarkable biocompatibility. Moreover, this system had significant promotion in cell spreading, osteogenic makers, and bone-related gene expression of stem cells. RNA-seq analysis revealed that osteogenesis was correlated to Notch, BMP/Smad, and calcium signal pathways. It was proven that this biomimetic system could regulate the osteogenesis procedure, and it provided further information about how the electrical signal regulates osteogenic differentiations.
研究领域:
生物医学工程
·
细胞生物学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Jiamin Zhang,Xuzhao He,Xiaoyi Chen,Yongjun Wu,Lingqing Dong,Kui Cheng,Jun Lin,Huiming Wang,Wenjian Weng
High performance of biomaterial surfaces provides a sound basis to mediate cellular growth behavior. In this work, we attempted to incorporate both positive and negative magnetostriction particles of CoFe 2 O 4 (CFO) and Tb x Dy 1−x Fe 2 alloy (TD) into piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for forming high magnetoelectric effect films, on which osteogenic differentiation could be dynamically mediated by a magnetic-field-induced surface potential (φ ME ).The negatively poled film with TD/CFO volume ratio of 1:4 (1T4C) showed a highest magnetoelectric effect with φ ME of −171 mV at 2800 Oe. Compared with CFO/P(VDF-TrFE) and TD/P(VDF-TrFE) films, the φ ME increased about 213% and 173%, respectively. This could result from that P(VDF-TrFE) dipole domains receive a larger off-axial stress caused by the distribution characteristic of CFO and TD in P(VDF-TrFE), consequently to facilitate P(VDF-TrFE) dipole domain rearrangement. When MSCs were cultured on 1T4C film for 7 or 14 days, the magnetic actuation was setup to begin at the 4th or 8th day after the culture. The 7-day osteogenic differentiation was hardly affected for magnetic actuation at 4th day, moreover, the 14-day differentiation was significantly enhanced for magnetic actuation at 8th day. The enhancement appears just at a relatively late period of the cell growth, probably because the cells need a steady change in cell membrane potential to disassociate pairs of β-catenin and E-cadherin and activate osteogenic-related signaling pathway. This work could provide an alternative way to promote performance for magnetoelectric materials, and get insight into understanding of interactions of surface potential with cells.
研究领域:
生物材料学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Xiaojun Long,Xiaozhao Wang,Lili Yao,Suya Lin,Jiamin Zhang,Wenjian Weng,Kui Cheng,Huiming Wang,Jun Lin
Graphene (Gr) presents promising applications in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Light illumination is regarded as a spatiotemporally controllable, easily applicable, and noninvasive mean to modulate material responses. Herein, Gr-transferred silicon (Gr/Si) with a Schottky junction is utilized to evaluate the visible-light-promoted osteogenic differentiation of BMSCs. Under light illumination, light-induced charges, owing to the formation of the Schottky junction at the interface of Gr and Si, accumulated on the surface and then changed the surface potential of Gr/Si. The Schottky junction and surface potential at the interface of Gr and Si was measured by photovoltaic test and scanning Kelvin probe microscopy. Alkaline phosphatase (ALP) activity and quantitative real-time polymerase chain reaction (PCR) measurement showed that such variations of surface improved the osteogenic differentiation of BMSCs, and the activation of the voltage-gated calcium channels through surface potential and accumulation of cytosolic Ca2+ could be the reason. Moreover, X-ray photoelectron spectroscopy characterization showed that surface charge could also affect BMSCs differentiation through the promotion or inhibition of the adsorption of osteogenic growth factors. Such light-promoted osteogenic differentiation of BMSCs on Gr/Si may have huge potential for biomedical materials or devices for bone regeneration application.
研究领域:
生物材料学
·
医学工程
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2024
·
IF 12.4
Maojiao Li,Qi Tang,Chengcheng Liao,Zhuo Wang,Siyuan Zhang,Qingqing Liang,Cheng Liang,Xiaodong Liu,Jingyi Zhang,Weidong Tian,Li Liao
Rationale: Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs undergo apoptosis shortly after transplantation and produce apoptotic extracellular vesicles (ApoEVs). This study aims to clarify the potential role of ApoEVs from apoptotic MSCs in ameliorating osteoporosis and molecular mechanism. Methods: In this study, Dio-labeled bone marrow mesenchymal stem cells (BMSCs) were injected into mice to track BMSCs apoptosis and ApoEVs production. ApoEVs were isolated from BMSCs after inducing apoptosis, the morphology, size distribution, marker proteins expression of ApoEVs were characterized. Protein mass spectrometry analysis revealed functional differences in proteins between ApoEVs and BMSCs. BMSCs were adopted to test the cellular response to ApoEVs. Ovariectomy mice were used to further compare the ability of ApoEVs in promoting bone formation. SiRNA and lentivirus were used for gain and loss-of-function assay. Results: The results showed that BMSCs underwent apoptosis within 2 days after being injected into mice and produce a substantial quantity of ApoEVs. Proteomic analysis revealed that ApoEVs carried a diverse functional array of proteins, and easily traversed the circulation to reach the bone. After being phagocytized by endogenous BMSCs, ApoEVs efficiently promoted the proliferation, migration, and osteogenic differentiation of BMSCs. In an osteoporosis mouse model, treatment of ApoEVs alleviated bone loss and promoted bone formation. Mechanistically, ApoEVs carried Ras protein and activated the Ras/Raf1/Mek/Erk pathway to promote osteogenesis and bone formation in vitro and in vivo . Conclusion: Given that BMSC-derived ApoEVs are high-yield and easily obtained, our data underscore the substantive role of ApoEVs from dying BMSCs to treat bone loss, presenting broad implications for cell-free therapeutic modalities.
研究领域:
干细胞生物学
·
骨生物学
·
再生医学
·
分子生物学
✓ 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）