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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Soy Peptide Ameliorate TGF-β1-Mediated Osteoblast Differentiation through Smad and MAPK Signaling Pathways

Kuaitian Wang,Mengqi Jian,Yuhang Chen,Mengdi Du,Zhenhua Wang,Bo Xu,Ning Tang,Yongqiang Cheng,Jing Gan

The aim of this study was to determine the osteogenic activity and mechanism of soybean peptide VVELLKAFEEKF (SOP) and the potential relationship between SOP and transforming growth factor-β1 (TGF-β1). The results show that SOP promotes MC3T3-E1 cell proliferation by altering cell progression. SOP induced cell differentiation and mineralization in a dose-dependent manner at 0.7–7 μM. Moreover, SOP stimulates osteoblast differentiation, which may be achieved through the activation of p38-MAPK and Smad2/3 signaling pathways. Furthermore, treatment with a TβRI inhibitor (SB525334) inhibited the phosphorylation levels of p38 and Smad2/3, which indicates the involvement of TβRI in the process of osteoblast differentiation caused by SOP. Besides, in non-FBS-cultured MC3T3-E1 cells, SOP and TGF-β1 promoted the phosphorylation of Smad2/3 and alkaline phosphatase (ALP) activity, but the effect was lost when SOP was incubated separately, indicating that SOP stimulated osteoblast differentiation by promoting TGF-β1 activity. In vivo, SOP significantly restores bone mineral density loss and behavioral deficits in a model of glucocorticoid-induced osteoporosis (GIOP) in zebrafish. These results suggest that SOP may have the function of promoting bone remodeling and may be used as a potential active factor for functional food development to prevent osteoporosis.

CAS / MDL: 9004-67-5
研究领域: 生物学 · 药理学 · 医学研究
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2020 · IF 4.872

Effects of cadmium on osteoblast cell line: Exportin 1 accumulation, p-JNK activation, DNA damage and cell apoptosis

Ling Ou,Haixia Wang,Zhidi Wu,Panpan Wang,Li Yang,Xiaoyun Li,Kehuan Sun,Xiaofeng Zhu,Ronghua Zhang

Cadmium is an environmental metal pollutant that has been a focus of research in recent years, which is reported to cause bone disease; however, its skeletal toxicity and the mechanism involved are not yet fully known. Therefore, this study used MC3T3-E1 subclone 14 cells to determine the mechanism of cadmium toxicity on bone. Cadmium chloride (Cd) significantly reduced cell viability in a concentration-dependent manner. Exposure to Cd inhibited osteoblast-related proteins (Runx2, Col-1, STC2) and decreased alkaline phosphatase (ALP) activity. Cd caused Exportin-1 accumulation and induced DNA damage. Cd significantly down-regulated caspase 9 and induced cleaved-PARP, cleaved-caspase 3 protein level. Treatment with JNK inhibitor, SP600125, suppressed cadmium-induced elevation in the ratio of phosphorylation of JNK to JNK. Inhibition of caspase with pan-caspase inhibitor, Z-VAD-FMK, prevented MC3T3-E1 subclone 14 cells from cadmium-induced reduction of Runx2, STC2, caspase 9, and accumulation of cleaved PARP and cleaved caspase 3. Cd-induced cell survival enhanced by SP600125 but rescued by Z-VAD-FMK or KPT-335. These results suggest that cadmium cytotoxicity on bone involved exportin 1 accumulation, phosphorylation of JNK, induction of DNA damage and pro-apoptosis, which was induced by activation of caspase-dependent pathways.

CAS / MDL: 10108-64-2
研究领域: 毒理学 · 细胞生物学 · 环境科学
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Stability, biomechanics and biocompatibility analysis following different preparation strategies of hierarchical zeolite coatings on titanium alloy surfaces

Chang Liu,Jiaxin Zhang,Xin Zhao,Mingwei Xu,He Liu,Hongming Zhou

Traditional titanium alloy implant surfaces are inherently smooth and often lack effective osteoinductive properties. To overcome these limitations, coating technologies are frequently employed to enhance the efficiency of bone integration at the implant–host bone interface. Hierarchical zeolites, characterized by their chemical stability, can be applied to 3D-printed porous titanium alloy (pTi) surfaces as coating. The resulting novel implants with a “microporous-mesoporous-macroporous” spatial gradient structure can influence the behavior of adjacent cells; thereby, promoting the integration of bone at the implant interface. Consequently, a thorough exploration of various preparation methods is warranted for hierarchical zeolite coatings with respect to biocompatibility, coating stability, and osteogenesis. In this study, we employed three methods: in situ crystal growth, secondary growth, and layer-by-layer assembly, to construct hierarchical zeolite coatings on pTi, resulting in the development of a gradient structure. The findings of this investigation unequivocally demonstrated that the LBL-coating method consistently produced coatings characterized by superior uniformity, heightened surface roughness, and increased hydrophilicity, as well as increased biomechanical properties. These advantages considerably amplified cell adhesion, spreading, osteogenic differentiation, and mineralization of MC3T3-E1 cells, presenting superior biological functionality when compared to alternative coating methods. The outcomes of this research provide a solid theoretical basis for the clinical translation of hierarchical zeolite coatings in surface modifications for orthopedic implants.

CAS / MDL: 1341-49-7 26062-79-3
研究领域: 材料科学 · 生物医学工程 · 骨科 · 表面工程
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JOURNAL OF MOLECULAR STRUCTURE · 2016 · IF 1.78

Structure design and fabrication of porous hydroxyapatite microspheres for cell delivery

Ruijing Li,Kexin Chen,Geng Li,Guoxiang Han,Sheng Yu,Juming Yao,Yurong Cai

Porous microspheres fabricated from bioceramics have great potential for cell delivery in injectable tissue engineering application. The size and structure of pores in the microspheres are important for the effective protection and transportation of cells. In this study, porous hydroxyapatite microspheres are fabricated through the water-in-oil emulsion method followed by a calcination treatment at the high temperature. Both self-made resorcinol-formaldehyde (RF) composite spheres and camphene are used as pore-forming agents to produce big pores corresponding to the size of RF spheres and connected channel among big pores in hydroxyapatite matrix. The properties of the microspheres are characterized using X-ray diffraction, thermogravimetry analysis, universal material machine, field emission scanning electron microscopy . Cell assays are carried out to evaluate the cellular compatibility of the microspheres. The results showed that the hydroxyapatite microspheres with controllable pore structure and high porosity could be fabricated by this method, which have better strength to resist the compressive force. The microspheres are conducive to support adhesion, proliferation and differentiation of MC3T3-E1 cells. The results indicate that the obtained porous hydroxyapatite microspheres can be a permeable microenvironment for cell delivery in injectable tissue engineering.

研究领域: 生物材料 · 组织工程 · 生物陶瓷 · 细胞生物学
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CERAMICS INTERNATIONAL · 2020 · IF 3.83

Facile synthesis, antibacterial mechanisms and cytocompatibility of Ag–MnFe2O4 magnetic nanoparticles

P. Ning,C.C. Liu,Y.J. Wang,X.Z. Li,R. Ranjithkumar,Z.H. Gan,Y.Y. Wu,T. Fu

Magnetic MnFe 2 O 4 nanoparticles containing 0, 1 and 3 at.% silver, respectively were synthesized by one-pot sol-gel method for antibacterial applications in biomedical fields. Material characterizations indicate that MnFe 2 O 4 begins crystallization at 134 °C and oxidation at 450 °C, the grain size and agglomeration degree increase with the silver content and silver exists as metallic state for the particles. The saturation magnetization decreases with the sintering temperature and slightly increases with the silver content, with the maximum of 50.0 emu/g obtained. Antibacterial tests by plate counting and PI-Hoechst 33342 staining suggest that the antibacterial activity of Ag–MnFe 2 O 4 nanoparticles is silver content-dependent. Silver ions concentration measurement, β-galactosidase activity assay and transmission electron microscopic observation show that the antibacterial activity is dominated by the actions of the released silver ions, rather than the membrane cell impairment or reactive oxygen species-induced oxidative stress mechanism. MC3T3-E1 cell test demonstrates the best cytocompatibility of the nanoparticles with 3 at.% silver, which is likely related to the reduced cell endocytosis of the aggregated particles. The combination of magnetism , antibacterial activity and biocompatibility would make Ag–MnFe 2 O 4 nanoparticles a potential multi-functional material in various biomedical applications.

CAS / MDL: 369-07-3
研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 微生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2020 · IF 4.389

Enhanced cellular osteogenic differentiation on CoFe2O4/P(VDF-TrFE) nanocomposite coatings under static magnetic field

Bolin Tang,Xiaojun Shen,Yaru Yang,Zhi Xu,Jie Yi,Yongbo Yao,Miao Cao,Yalin Zhang,Hongqin Xia

Cellular responses can be regulated and manipulated through combining stimuli-responsive biomaterial with external stimulus. In this present, the magneto-responsive CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were designed to understand cell behaviors of preosteoblasts, as well as get insight into the underlying mechanism of osteogenic differentiation under static magnetic field (SMF). CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings with differential magnetic property (low, medium and high magnetization) were prepared by incorporation of different mass fraction of CoFe 2 O 4 nanoparticles (6%, 13 %, 20 %) into P(VDF-TrFE) matrix. Cell experiments indicated that all nanocomposite coatings with the assistance of SMF could promote the cell attachment, proliferation and osteogenic differentiation of MC3T3-E1 cells. Among different nanocomposite coatings, low magnetization coating (6%) showed a higher ALP activity and gene expression of Runx2, Col-I, OCN. Molecular biology assays demonstrated that the combination of nanocomposite coatings and SMF could significantly up-regulate the expression level of α2β1 integrin and p-ERK. Whereas, the addition of inhibitor U0126 down-regulated sharply the expression level of p-ERK, which indicated that cellular osteogenic differentiation of MC3T3-E1 cells was governed through α2β1 integrin-mediated MEK/ERK signaling pathways during CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were combined with SMF. This work provided a promising strategy to enhance cellular osteogenic differentiation through a remote-control manner, which exhibited great potential in the application of bone tissue repair and regeneration.

研究领域: 生物材料 · 组织工程 · 细胞生物学 · 磁性材料 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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Materials Science & Engineering C-Materials for Biological Applications · 2013 · IF 2.404

Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering

Junmin Qian,Weijun Xu,Xueqing Yong,Xinxia Jin,Wei Zhang

In this study, biomorphic poly( dl -lactic- co -glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164   ±   52   μm and 13   ±   8   μm, respectively, with a porosity of 89.3   ±   1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400   μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering.

CAS / MDL: 1306-06-5 12167-74-7
研究领域: 生物材料 · 组织工程 · 生物医学工程
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FOOD RESEARCH INTERNATIONAL · 2023 · IF 8.1

Effects of ethanol pretreatment on osteogenic activity and off-flavors in blue mussel (Mytilus edulis L.) enzymatic hydrolysates

Xinyu Qiao,Han Li,Yunjiao Ma,Xianbing Xu,Junjie Yi,Hesham R. El-Seedi,Ming Du

Aquatic protein hydrolysates have many biological activities, but the off-flavor seriously decreases their commercial acceptability. Therefore, it is important to invest in finding an effective deodorization of aquatic hydrolysates that do not affect activities. In this study, ethanol pretreatment of mussel was applied to establish a new method to deodorize the blue mussel ( Mytilus edulis L. ) hydrolysates. LC-MS and GC–MS analysis results showed that 87.34% of fatty acids, 83.94% of aldehydes, most volatile flavor compounds including aldehydes, ketones, alcohols, acids, and hydrocarbons were decreased after ethanol pretreatment. Besides, it was found that the enzymatic hydrolysates of mussel with or without ethanol pretreatment showed high osteogenic activity, which induced an increase of 33.65 ± 4.36% and 31.77 ± 5.45% in MC3T3-E1 cell growth. These results suggest that ethanol pretreatment has beneficial potential for improving the flavor aspects of blue mussel peptides which may have the potential to stimulate bone regeneration and formation.

CAS / MDL: 108-94-1 67-68-5
研究领域: 海洋生物学 · 食品科学 · 生物技术
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LANGMUIR · 2018 · IF 3.789

Bioinspired Surface Functionalization for Improving Osteogenesis of Electrospun Polycaprolactone Nanofibers

Kuan Zhang,Yi Wang,Tao Sun,Bo Wang,Hongyu Zhang

Electrospun nanofibers, with a typical interconnected porous structure mimicking the extracellular matrix, are commonly used in bone tissue engineering. However, to the best of our knowledge, few studies have been reported to investigate the enhancement of osteogenesis capability of electrospun polycaprolactone (PCL) nanofibers based on bioinspired surface functionalization. In this study, a universal and versatile approach was proposed to spontaneously modify the electrospun PCL nanofibers with bioactive nano-hydroxyapatite (nHA), using dopamine as an effective bioadhesive agent. The evaluation of scanning electron microscopy, energy-dispersive spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and surface wettability indicated that nHA was successfully coated onto electrospun nanofibers (PCL-PDHA). Furthermore, in vitro cell experiment including adhesion, proliferation, and osteogenic capability and in vitro biomineralization test in simulated body fluid revealed that the PCL-PDHA nanofibers were biocompatible to MC3T3-E1 cells, and the osteogenesis and biomineralization capabilities were greatly improved in comparison with that of PCL nanofibers. In summary, the facile bioinspired surface functionalization method introduced in the present study, due to its universality and versatility, not only can be used to improve osteogenesis of electrospun nanofibers but also can be regarded as an avenue to achieve other predesigned purposes in biomedical engineering.

研究领域: 生物医学工程 · 组织工程 · 材料科学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Osteogenic and antibacterial PLLA membrane for bone tissue engineering

Haiyan Yao,Jiaolong Wang,Yunyun Deng,Zhihua Li,Junchao Wei

Insufficient bone regeneration and bacterial infection are two major concerns of bone repair materials. Poly-L-lactic acid (PLLA) have been widely used in bone tissue engineering (BTE), however, lack of osteogenic and antibacterial properties have greatly limit its clinical application. Herein, PLLA membrane was firstly treated with polydopamine (PDA), and then modified with ε-polylysine (ε-PL) and alginate (ALG) via layer-by-layer method. The (ε-PL/ALG)n composite layer coated PLLA ( [email protected] (ε-PL/ALG)n) could facilitates the adhesion and osteoblast differentiation of MC3T3-E1 cells. Furthermore, [email protected] (ε-PL/ALG) n presents an effective antibacterial efficacy against S. aureus and E. coli , and the bacterial survival rates of S. aureus and E. coli on [email protected] (ε-PL/ALG) 10 were 21.5 ± 3.5 % and 13 ± 2.1 %, respectively. This work provides a promising method to design PLLA materials with osteogenic and antibacterial activity simultaneously. Furthermore, the method is also an optional choice to construct multifunctional coatings on the other substrate.

研究领域: 生物医学工程 · 材料科学 · 组织工程
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APL Materials · 2024 ·Vol. 12 ·期 9 · IF 5.3

Magnetic casein/CaCO3/Fe3O4 microspheres stimulate osteogenic differentiation

Zhang Mingjie,Li Xiaolei,Lin Han

The quality of life is significantly impacted by bone defects, which calls for the creation of optimum restorative materials with particular qualities. Current repair materials, such as metal alloys, polymer scaffolds, and bone cement, have a number of drawbacks, such as poor fracture toughness, non-degradability, and insufficient osteogenic ability. To address these challenges, we designed a novel magnetic casein/CaCO 3 /Fe 3 O 4 microspheres (CCFM), combining biodegradability, osteoinductivity, osteoconductivity, and osteogenesis properties together. In vitro studies confirmed the outstanding biocompatibility and osteogenic differentiation effects on MC3T3-E1 cells of CCFM, highlighting their potential as a promising bone regeneration platform for clinical applications. As a novel bone repair material with superparamagnetic properties, CCFM not only possess good osteoinductivity, osteoconductivity, and osteogenesis properties but also can remain in the lesion location for a long time under an external magnetic field, representing a significant advancement in the field of bone tissue engineering and offering new possibilities for effective bone defect remediation and patient care.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科
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Materials Science & Engineering C-Materials for Biological Applications · 2021 · IF 7.328

Biofunctionalization of electrospun fiber membranes by LbL-collagen/chondroitin sulfate nanocoating followed by mineralization for bone regeneration

Jing Zheng,Naureen Rahman,Longfei Li,Jingshuang Zhang,Haozhe Tan,Yun Xue,Yu Zhao,Jiliang Zhai,Nana Zhao,Fujian Xu,Liqun Zhang,Rui Shi,Yuri Lvov,Jiajia Xue

It is of great significance to develop osteoinductive artificial scaffold for bone repair and regeneration. We constructed a biomimetic apatite interface on electrospun polycaprolactone fibers by combining layer-by-layer (LbL) nanocoating with mineralization to fabricate an osteoinductive artificial scaffold. After polydopamine modification, cationic type-І collagen and anionic chondroitin sulfate were sequentially adsorbed on the fiber surface. The fibers coated with the multilayer components served as the precursor matrix to induce apatite deposition. By adjusting the number of the layers and duration of mineralization, the nanoscale morphology of composite fibers was optimized. When ten bilayers of the collagen and chondroitin sulfate were deposited onto the fibers followed by one day-mineralization, the obtained polycaprolactone–apatite composite scaffolds significantly promoted the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. In a subcutaneous implantation in mice, this composite fiber membrane enhanced in vivo ectopic osteogenesis. Our nano-architectural scaffolds were able to mimic the composition and structure of the bone matrix to a certain extent, holding great potential for bone repair and regeneration.

CAS / MDL: 75-89-8
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨再生
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