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MATERIALS & DESIGN · 2021 · IF 7.991

Coaxial bioelectrospinning of P34HB/PVA microfibers biomimetic scaffolds with simultaneity cell-laden for improving bone regeneration

Long Yang,Yan Zhao,Dongbing Cui,Yufei Liu,Qiang Zou,Shunen Xu,Siwei Luo,Chuan Ye

Poorly functioning scaffold materials and limitations in material-cell construction technology remain problems in bone tissue engineering. Electrospinning has been proven to be a suitable and available technique for production of 3D biomimetic scaffolds. To overcome these problems and retain the advantages of electrospinning, bioelectrospinning has been proposed to provide guidance by micropattern, homogeneous cell distribution, and effective nutrient utilization. Herein, we fabricated poly (3-hydroxybutyrate-co-4-hydroxybutyrate)/poly (vinyl alcohol) (P34HB/PVA) with human bone mesenchymal stem cells (hBMSCs) to biomimetic core-shell microfiber/cells complex by coaxial bioelectrospinning. Characterization of the fiber materials revealed that coaxial electrospinning combined the advantages of the two materials. In vitro cellular assays showed that after bioelectrospinning, the cells and material could be simultaneously spun while maintaining cell activity. The material provided a good 3D microenvironment allowing cell adhesion, proliferation, and differentiation. Both the in vitro and in vivo tests indicated the formation of mineralized nodules in both the co-spun and co-axial groups, while the implants formed bone-like tissue after 16 weeks of implantation. This study shows that coaxial bioelectrospinning technology can be used to construct tissue-engineered bone. Our technique might be applied in the future to fabricate more complex tissue and organs.

CAS / MDL: 9002-89-5
研究领域: 生物材料学 · 组织工程学
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Journal of Inflammation Research · 2023 · IF 4.5

NEAT1/microRNA 339-5p/SPI1 Axis Feedback Loop Contributes to Osteogenic Differentiation in Acute Suppurative Osteomyelitis in Children

Dongsheng Zhu,Zhitao Zhu,Han Qi

Objective Long non-coding RNA plays an important role in osteogenic differentiation. Nuclear enriched abundant transcript 1 (NEAT1) has been revealed to promote osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs), but the underlying regulatory mechanism remains unknown in acute suppurative osteomyelitis of children.Methods Osteogenic medium (OM) was used to induce osteogenic differentiation. Quantitative real-time PCR and Western blotting were used to evaluate gene expression. The effects of NEAT1, microRNA 339–5p (miR-339-5p), and salmonella pathogenicity island 1 (SPI1) on osteogenic differentiation were assessed in vitro using alizarin red S staining assays and alkaline phosphatase activity. Interactions between NEAT1, miR-339-5p, and SPI1 were identified using immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation.Results During osteogenic differentiation, expression of NEAT1 was up-regulated in hBMSCs, and miR-339-5p level was down during osteogenic differentiation. Knockdown of NEAT1 reduced the osteogenic differentiation of hBMSCs, and down-regulation of miR-339-5p may counteract the effect of NEAT1 silencing. SPI1 was a target of miR-339-5p by luciferase reporter assay and was also a transcription factor of NEAT1 by chromatin immunoprecipitation. A positive NEAT1-miR-339-5p-SPI1 feedback loop was found to be present during osteogenic differentiation in hBMSCs.Conclusion It was the first study to reveal that the NEAT1-miR-339-5p-SPI1 feedback loop can promote osteogenic differentiation in hBMSCs and shed a new light on the role of NEAT1 during osteogenic differentiation.

研究领域: 分子生物学 · 细胞生物学 · 医学遗传学 · 儿科
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2021 · IF 3.575

LncRNA NONHSAT009968 inhibits the osteogenic differentiation of hBMMSCs in SA-induced inflammation via Wnt3a

Hongjie Wen,Zhong Chen,Yi Cui,Yongqing Xu

Osteomyelitis is one of the most challenging diseases in the field of orthopedics for its complex pathogenesis and unsatisfactory treatment. The mechanism underlying its occurrence and development is still unclear. In our previous study, we found that long non-coding RNA (lncRNA) NONHSAT009968 inhibited the ability of osteogenic differentiation in staphylococcal protein A (SPA)-treated human bone marrow mesenchymal stem cells (hBMMSCs), but the underlying mechanism remains unclear. The current study was aimed at elucidating the possible mechanism of NONHSAT009968 in regulating osteogenic differentiation and bone defect repairability of hBMMSCs under infection. It was revealed that Wnt3a played a key role in promoting osteogenic differentiation of hBMMSCs treated with SPA in vitro. In addition, NONHSAT009968 inhibited osteogenic differentiation of hBMMSCs treated with SPA via Wnt3a, both in vivo and in vitro. In sum, the results suggested that lncNONHSAT009968 inhibited osteogenic differentiation of hBMMSCs in SA-induced inflammation through Wnt3a, which may have affected the occurrence and development of osteomyelitis. This study might provide novel insights regarding osteomyelitis and infectious bone defects.

研究领域: 骨科 · 分子生物学 · 干细胞研究 · 炎症
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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Glucosamine-modified polyethylene glycol hydrogel-mediated chondrogenic differentiation of human mesenchymal stem cells

Hang Yao,Jingchen Xue,Qunfang Wang,Renjian Xie,Weichang Li,Sa Liu,Jinglei Cai,Dajiang Qin,Dong-An Wang,Li Ren

Glucosamine (GA) is an important cartilage matrix precursor for the glycosaminoglycan biochemical synthesis, and has positive effects on cartilage regeneration, particularly in osteoarthritis therapy. However, it has not been used as a bioactive group in scaffolds for cartilage repair widely. In this study, we synthesized modified polyethylene glycol (PEG) hydrogel with glucosamine and then encapsulated human bone mesenchymal stem cells (hBMSCs) in the hydrogel to induce the differentiation of hBMSCs into chondrocytes in three-dimensional culture. The GA-modified PEG hydrogels promoted the chondrogenesis of hBMSCs, particularly in the concentration of 5   mM and 10   mM. The subcutaneous transplantation of 10   mM GA-modified hydrogels with hBMSCs formed cartilage-like blocks in vivo for 8   weeks. Importantly, with glucosamine increase, the modified hydrogels down-regulated the fibrosis and hypertrophic cartilage markers in protein level. Therefore, glucosamine modified PEG hydrogels facilitated the chondrogenesis of hBMSCs, which might represent a new method for cartilage repair using a tissue-engineering approach.

研究领域: 组织工程 · 再生医学 · 干细胞研究 · 材料科学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS · 2024 ·Vol. 112 ·期 1 ·e35366 · IF 3.2

Effects of aligned PLGA/SrCSH composite scaffolds on in vitro growth and osteogenic differentiation of human mesenchymal stem cells

Lichu Liu,Pin Luo,Honghong Liao,Kuangyang Yang,Shenyu Yang,Mei Tu

Strontium (Sr) has important functions in bone remodeling. Incorporating strontium-doped α-calcium sulfate hemihydrate (SrCSH) into poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds were expected to increase its bio-activity and provide a potential material for bone tissue engineering. In the present study, Sr-containing aligned PLGA/SrCSH fibrous scaffolds similar to the architecture of natural bone were prepared via wet spinning. CCK-8 assay revealed that Sr-containing scaffolds possessed better bioactivity and supported favorable cell growth effectively. The aligned PLGA/SrCSH fibers exerted a contact effect on cell attachment, inducing regular cell alignment and influencing a series of cell behaviors. Releasing of high concentration Sr from a-PLGA/SrCSH scaffolds could induce high expression levels of BMP-2, increase ALP activity and upregulate RUNX-2 expression, and further promote the expressions of COL-I and OCN and the maximum mineralization. This study demonstrated that Sr and ordered structure in a-PLGA/SrCSH fibrous scaffolds could synergistically enhance the osteogenic differentiation of umbilical cord mesenchymal stem cells (UCMSCs) by regulating cell arrangement and expressions of osteogenic genes.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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Journal of Orthopaedic Surgery and Research · 2023 ·Vol. 18 ·期 1 ·1-15 · IF 2.6

Inhibiting KCNMA1-AS1 promotes osteogenic differentiation of HBMSCs via miR-1303/cochlin axis

Lin Yuan,Dai Hanhao,Yu Guoyu,Song Chao,Liu Jun,Xu Jie

ObjectiveOsteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform.Materials and methodsIn this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteogenic induction were used to examine the effect of identified ceRNA networks on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs).Results miR-1303 was lowly expressed, while cochlin (COCH) and KCNMA1-AS1 were highly expressed in the osteoporosis subjects. COCH knockdown improved the osteogenic differentiation of HBMSCs. Meanwhile, COCH inhibition compensated for the suppression of osteogenic differentiation of HBMSCs by miR-1303 knockdown. Further, KCNMA1-AS1 knockdown promoted osteogenic differentiation of HBMSCs through downregulating COCH by sponging miR-1303.Conclusion sOur findings suggest that the KCNMA1-AS1/miR-1303/COCH axis is a promising biomarker and therapeutic target for osteoporosis.

研究领域: 分子生物学 · 基因组学 · 干细胞研究 · 骨骼生物学 · 治疗靶点
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CHEMICAL ENGINEERING JOURNAL · 2018 · IF 6.735

Halloysite nanotubes coated 3D printed PLA pattern for guiding human mesenchymal stem cells (hMSCs) orientation

Fan Wu,Jingqi Zheng,Zhixiong Li,Mingxian Liu

Three-dimensional (3D) printed polymer scaffolds can build engineered tissue constructs with complex and hierarchical structures, mechanical and biological heterogeneity. However, the interactions between the scaffolds and cells should be optimally designed for their practical application. In this work, 3D printed polylactic acid (PLA) pattern was functionalized by a polydopamine (PDA) interlayer to firmly bond the halloysite nanotubes (HNTs) on the surfaces of the PLA pattern for guiding cell orientation. A series of 3D printed PLA patterns with different stripe widths were characterized by scanning electron microscopy (SEM), polarized light microscopy (POM), 3D optical profiler and so on. The successful introduction of HNTs on PLA pattern was verified by field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analyzer (TGA). The HNTs coating could effectively improve roughness and hydrophilicity of PLA pattern. In addition, in vitro human mesenchymal stem cells (hMSCs) culture experiments suggested that 3D printed PLA patterns with different strip widths exhibited different ability to induce cell orientation. The smaller the stripe width of the PLA pattern, the more suitable for cell orientation. When the layer height was set to 0.05 mm, the effect of inducing cell orientation was optimal. Meanwhile, the 3D printed PLA pattern with HNTs coating was more suitable for the adhesion and proliferation of cells. This works provides a general routine for improving the cell affinity of 3D printed PLA structure by the simple coating of nanoparticles, which shows the promising application in cell culture scaffolds, wound healing materials, and biosensors.

CAS / MDL: 62-31-7 77-86-1
研究领域: 生物材料 · 组织工程 · 细胞生物学 · 纳米技术
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Materials Science & Engineering C-Materials for Biological Applications · 2018 · IF 5.08

Formation and in vitro/in vivo performance of “cortex-like” micro/nano-structured TiO2 coatings on titanium by micro-arc oxidation

Yada Li,Weiqiang Wang,Huiying Liu,Jingwu Lei,Jingying Zhang,Hongzhi Zhou,Min Qi

A novel “cortex-like” micro/nano dual-scale structured TiO 2 coating was prepared on a titanium surface by micro-arc oxidation (MAO) with tetraborate electrolytes. This structure, which combines microslots with nanopores, exhibits super hydrophilicity. This coating modified the surface structure, chemistry, and hydrophilicity in a one-step treatment. Evolution of the coating together with its surface and structure properties was studied. We propose a forming mechanism of the dual-scale structure in which the oxides formed during the MAO discharge dissolve in the tetraborate electrolytes, leaving little or no deposition outside the discharge channels. We performed in vitro tests using human bone marrow-derived mesenchymal stem cells (hBMSCs) that compared this coating with a “volcano-like” MAO coating and a commercial sandblasted, large-grit and acid-etched (SLA) coating. The adhesion, morphology, proliferation, and differentiation of hBMSCs, together with the matrix mineralization, were investigated. Results suggest that the “cortex-like” structure significantly promotes the adhesion, spreading, and differentiation of cells and increases the matrix mineralization. In vivo tests with mongrel dogs showed an excellent osseointegration of the “cortex-like” coating. The combination of the dual-scale structure and the hydrophilicity of the “cortex-like” TiO 2 coating synergistically resulted in an outstanding cytocompatibility and osseointegration, which may facilitate a higher level of implant success.

CAS / MDL: 12007-60-2
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 材料科学
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 34 ·7153-7163 · IF 4.543

Aspirin enhances the osteogenic and anti-inflammatory effects of human mesenchymal stem cells on osteogenic BFP-1 peptide-decorated substrates

Yan Li,Zuyuan Luo,Xiao Xu,Yongliang Li,Siqi Zhang,Ping Zhou,Yi Sui,Minjie Wu,En Luo,Shicheng Wei

Several bone diseases, including arthritis, fracture and osteoporosis, have a pathophysiologically important inflammatory component. Sustained inflammation can result in delayed bone healing. Therefore, to promote bone repair, it is important to inhibit inflammatory bone erosion and suppress pro-inflammatory mediators. In this study, aspirin significantly enhanced immunomodulation and osteogenic differentiation in human mesenchymal stem cells (hMSCs). Additionally, an osteogenic BFP-1 peptide-decorated substrate (PS-PEP) enhanced osteogenic differentiation of aspirin-treated hMSCs compared to a pristine substrate. Alkaline phosphatase assay, quantitative real-time polymerase chain reaction, immunostaining and Alizarin Red S staining revealed that aspirin-treated hMSCs cultured on PS-PEP exhibited enhanced osteogenesis compared with untreated cells. Thus, we report here that the anti-inflammatory and osteogenic effects of aspirin promote the activity and osteogenesis of hMSCs. The combination of aspirin and an osteogenic BFP-1 peptide-decorated substrate suppresses the production of pro-inflammatory mediators and promotes osteogenic differentiation of hMSCs; therefore, this novel strategy has potential for application in cell therapy and bone tissue engineering.

研究领域: 药理学 · 干细胞生物学 · 组织工程 · 骨再生
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Science Advances · 2021 ·Vol. 7 ·期 40 · IF 14.143

Iron oxide nanoparticles augment the intercellular mitochondrial transfer–mediated therapy

Ting Huang,Tianyuan Zhang,Xinchi Jiang,Ai Li,Yuanqin Su,Qiong Bian,Honghui Wu,Ruyi Lin,Ni Li,Hongcui Cao,Daishun Ling,Jinqiang Wang,Yasuhiko Tabata,Zhen Gu,Jianqing Gao

The transfer of mitochondria between cells has recently been revealed as a spontaneous way to protect the injured cells. However, the utilization of this natural transfer process for disease treatment is so far limited by its unsatisfactory transfer efficiency and selectivity. Here, we demonstrate that iron oxide nanoparticles (IONPs) can augment the intercellular mitochondrial transfer from human mesenchymal stem cells (hMSCs) selectively to diseased cells, owing to the enhanced formation of connexin 43–containing gap junctional channels triggered by ionized IONPs. In a mouse model of pulmonary fibrosis, the IONP-engineered hMSCs achieve a remarkable mitigation of fibrotic progression because of the promoted intercellular mitochondrial transfer, with no serious safety issues identified. The present study reports a potential method of using IONPs to enable hMSCs for efficient and safe transfer of mitochondria to diseased cells to restore mitochondrial bioenergetics.

研究领域: 纳米技术 · 细胞生物学 · 再生医学 · 治疗学
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BMC MUSCULOSKELETAL DISORDERS · 2024 ·Vol. 25 ·期 1 ·1-10 · IF 2.2

Knockdown of the UL-16 binding protein 1 promotes osteoblast differentiation of human mesenchymal stem cells by activating the SMAD2/3 pathway

Lai Zhen,Li Mingming,Yang Xiaodong,Xian Zhenjie

Osteoporosis is caused by the imbalance of osteoblasts and osteoclasts. The regulatory mechanisms of differentially expressed genes (DEGs) in pathogenesis of osteoporosis are of significant and needed to be further investigated. GSE100609 dataset downloaded from Gene Expression Omnibus (GEO) database was used to identified DEGs in osteoporosis patients. KEGG analysis was conducted to demonstrate signaling pathways related to enriched genes. Osteoporosis patients and the human mesenchymal stem cells (hMSCs) were obtained for in vivo and in vitro resaerch. Lentivirus construction and viral infection was used to knockdown genes. mRNA expression and protein expression were detected via qRT-PCR and western blot assay separately. Alkaline phosphatase (ALP) activity detection, alizarin Red S (ARS) staining, and expression of bone morphogenetic protein 2 (BMP2), osteocalcin (OCN) and Osterix were evaluated to determine osteoblast differentiation capacity. UL-16 binding protein 1 (ULBP1) gene was upregulated in osteoporosis and downregulated in differentiated hMSCs. Knockdown of ULBP1 increased ALP activity, mineralization ability evaluated by ARS staining, expression of BMP2, OCN and Osterix in differentiated hMSCs. Furthermore, rescue experiment demonstrated that suppressed ULBP1 boosted osteoblast differentiation by activating TNF-β signaling pathway. Knockdown of ULBP1 gene could promoted osteoblast differentiation by activating TNF-β signaling pathway in differentiated hMSCs. ULBP1 may be a the Achilles’ heel of osteoporosis, and suppression of ULBP1 could be a promising treatment for osteoporosis.

CAS / MDL: 50-00-0
研究领域: 分子生物学 · 干细胞研究 · 骨骼生物学 · 基因组学
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Journal of Materials Chemistry B · 2014 ·Vol. 3 ·期 8 ·1612-1623 · IF 0

Effects of functional groups on the structure, physicochemical and biological properties of mesoporous bioactive glass scaffolds

Shichang Zhao,Jianhua Zhang,Min Zhu,Yadong Zhang,Zhongtang Liu,Yanyu Ma,Yufang Zhu,Changqing Zhang

Functionalization of biomaterials with specific functional groups is one of the most straightforward strategies to induce specific cell responses to biomaterials. In this study, thiol (SH) and amino (NH2) functional groups have been successfully modified on the surfaces of mesoporous bioactive glass (MBG) scaffolds to form thiol-functionalized MBG (SH-MBG) and amino-functionalized MBG (NH2-MBG) scaffolds by a post-grafting technique. The effects of the functional groups on the structure, physicochemical and biological properties of MBG scaffolds were systematically investigated. The results showed that the functionalization of MBG scaffolds did not change their structures, and the SH-MBG and NH2-MBG scaffolds still had hierarchical pore architecture (macropores of 300–500 μm and mesopores of 3.5–4 nm) and high porosity (84–86%), similar to the MBG scaffolds. Furthermore, the SH-MBG and NH2-MBG scaffolds possessed similar apatite mineralization ability and biocompatibility compared to the MBG scaffolds. Importantly, the SH-MBG and NH2-MBG scaffolds significantly stimulated adhesion, proliferation and differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Therefore, functionalization of MBG scaffolds with SH and NH2 functional groups would be a viable way to tailor the surface characteristics for stimulating biological responses of hBMSCs, and the functionalized MBG scaffolds would be a promising bioactive material for bone tissue engineering applications.

CAS / MDL: 4420-74-0
研究领域: 材料科学 · 生物材料 · 组织工程 · 细胞生物学
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