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Chinese Medicine · 2022 ·Vol. 17 ·期 1 ·1-17 · IF 4.546

Improvement of polydopamine-loaded salidroside on osseointegration of titanium implants

Yi Qingqing,Liang Pengchen,Liang Dongyu,Cao Liou,Sha Shuang,Jiang Xinquan,Chang Qing

Background Microarc oxidation (MAO) on the surface of medical pure titanium can improve its histocompatibility, and loading drugs on the surface can resist excessive intimal hyperplasia.Methods In this study, salidroside (SAL) was loaded on the surface of porous titanium (Ti) with polydopamine (PDA) carrier. The effects of SAL on the osteogenesis and angiogenesis of Ti implants were studied by phalloidin staining, alizarin red staining, ALP staining, wound-healing assay, cell transwell assay, matrigel tube formation, and osteogenic and angiogenic genes and proteins expression detected by PCR and western blot in vitro. The bone defect model experiments in rats was established in vivo including X-ray, micro CT, hematoxylin and eosin staining (HE), immunohistochemistry (IHC), Goldner's trichrome analysis, Safranin O-fast green staining and determination of contents of TNF-α and IL-6 in serum.Results EDS and EDS mapping showed that SAL could be loaded on the surface of the MAO coating by PDA. A drug release experiment showed that SAL loaded on the Ti coating could release slowly and stably without sudden release risk. In vitro cell experiments showed that the SAL coating could promote the proliferation, morphology, calcification and alkaline phosphate activity of MC3T3-E1 cells. At the same time, it promoted the migration and tube formation of HUVEC cells. The SAL coating promoted osteogenesis and angiogenesis by promoting the expression of genes and proteins related to. In vivo experiments, HE and IHC showed that SAL significantly promoted the expression of COL-1 and CD31. Goldner's trichrome and Safranin O-fast green staining showed that SAL coating could increase the new bone tissue around the implantation site. The SAL coating had anti-inflammatory activity by reducing the levels of TNF-α and IL-6 in vivo.Conclusion Therefore, SAL could improve osteogenesis and angiogenesis in conjunction with the Ti-PDA coating.

研究领域: 生物材料 · 组织工程 · 骨科 · 药剂学
✓ 已验证 DOI PubMed 高影响因子
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Effect of oligonucleotide MT01 delivered by N-isopropylacrylamide modified polyethyleneimine for bone regeneration

Qian Zhang,Xingyuan Qu,Chen Liang,Hongyan Li,Siyu Du,Chang Wang,Yuandong Xie,Yi Zheng,Lei Wang

Objective: This study aimed to investigate the regulatory effect of N-isopropylacrylamide-modified polyethyleneimine (PEN)-delivered oligodeoxynucleotide (ODN) MT01 on bone regeneration in vitro and in vivo . Methods: A polyethylenimine (PEI) derivative, PEN, was constructed through Michael addition and employed as a carrier for ODN MT01 transfection. PEN/MT01 nanocomposites were characterized using agarose gel retardation assay, size distribution, zeta potential and transmission electron microscopy. The Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of PEN on cell viability. Alkaline phosphatase (ALP) staining was used to detect the osteogenic differentiation ability of PEN/MT01 nanocomposite. Real-time quantitative PCR (q RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulatory effects of PEN/MT01 nanocomposite on osteogenic differentiation gene expression. Rat model was observed using the skull defect method and verified using micro-computed tomography (CT), serum biochemical indices, hematoxylin and eosin (H&E) staining and Immunohistochemistry (IHC). Results: PEN had good biological properties and could deliver MT01 well to achieve efficient transmission of MT01. PEN/MT01 nanocomposites were effectively transfected into MC3T3-E1 cells at a ratio of 6.0. CCK-8 assay displayed that PEN had no cytotoxicity to MC3T3-E1 cells. Additionally, PEN/MT01 nanocomposites could promote the expression of osteogenic genes. In vivo results revealed that PEN/MT01 nanocomposites could promote bone regeneration more effectively than the other groups. Conclusion: PEN has good biocompatibility and low toxicity, which is a good carrier for ODN MT01. PEN-delivered MT01 can be potentially employed as a useful approach to achieving bone regeneration.

CAS / MDL: 9012-36-6
研究领域: 生物材料 · 生物医学工程 · 组织工程 · 分子生物学 · 骨科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2024 · IF 2.3

Copper ion-doped multifunctional hydrogel with mild photothermal enhancement promotes vascularized bone regeneration

Chao Han,Dingsong Lu,Suoping Yang,Chong Liu,Feng Guo,Kai Zhang,Peng Li

The design and construction of a new and excellent synthetic graft is of great significance in the field of bone defect repair and reconstruction. In this study, a dopamine modified chitosan hydrogel doped with Cu ions with a mild photothermal effect was designed to provide a better microenvironment to advance the bone repair via promote the angiogenesis and osteogenesis. Characterizations showed the successful synthesis of the material while it also presented excellent biocompatibility and mild photothermal effect under the irradiation of near-infrared light. Further, it could enhance the angiogenesis of HUVECs cells through promoting the ability of migration and tube formation and enhance the osteogenic differentiation of MC3T3-E1 cells via increasing the content of vital osteogenic factors including Runx2, Col-1, OPN, OCN, OSX, etc. The in vivo experiment also testified that it could promote the bone defect repair in rat models. These results indicate the multifunctional hydrogel is an ideal material for the treatment of bone defects and has good clinical application potential.

研究领域: 生物材料 · 组织工程 · 再生医学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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CERAMICS INTERNATIONAL · 2025 · IF 5.6

Surface modification of silicon nitride ceramics by secondary phase removal for improved biomedical performance

Bo Qiao,Liran Dong,Jie Zhang,Yanbo Shan,Lingkai Liu,Yuanwei Chao,Kexin Chen,Ning Wen

Silicon nitride (Si 3 N 4 ) is considered a potential material for biomedical implants due to its mechanical strength and biocompatibility. However, the presence of a glassy phase may affect osseointegration by potentially leading to ion release and altered surface wettability, among other effects. In this study, a surface modification method using molten NaOH was employed to remove the secondary phase and improve surface characteristics. The treated samples (N-SN) showed increased surface roughness and exposure of crystalline planes, which are associated with enhanced cell adhesion. In vitro experiments indicated that N-SN supported the proliferation and osteogenic differentiation of MC3T3-E1 preosteoblasts, with up-regulated expression of osteogenic marker genes such as ALP, Col-1, OPN, and Runx-2. In a Beagle dog mandible model, N-SN implants formed direct bone contact and newly formed bone tissue without evident inflammatory response, suggesting improved osseointegration. This surface treatment approach may provide a practical option for enhancing the bioactivity of Si 3 N 4 ceramics in orthopedic and dental applications.

CAS / MDL: 1344-28-1
研究领域: 生物医学工程 · 材料科学 · 牙科植入物 · 骨科 · 陶瓷材料
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LIFE SCIENCES · 2018 · IF 3.234

Myricetin ameliorates glucocorticoid-induced osteoporosis through the ERK signaling pathway

Shuli Fan,Xiang Gao,Peng Chen,Xu Li

Myricetin has been reported to promote osteogenic differentiation and inhibit osteoclastogenesis. The aim of this study was to investigate the potential effects of myricetin on glucocorticoid-induced osteoporosis (GIOP) both in vivo and in vitro . Male Sprague-Dawley (SD) rats were given dexamethasone (DEX, 0.1 mg/kg, s.c.) once daily and myricetin (1 mg/kg or 2.5 mg/kg, i.p.) once every other day for a total of five weeks. Body weight was recorded once a week. Bone mineral density (BMD), the activities or levels of bone turnover markers, and histological changes were assessed. MC3T3-E1 cells were incubated with DEX (1 μM) and myricetin (20 μM). Osteoblast proliferation, differentiation and mineralization were evaluated. U0126 was added to evaluate the involvement of the ERK signaling pathway. The results showed that myricetin increased body weight gain and inhibited DEX-induced reduction in BMD, enhanced alkaline phosphatase (ALP) activity, and upregulated osteocalcin (OCN), bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) levels, whereas reduced tartrate-resistant acid phosphatase (TRAP) activity and C-terminal telopeptide of type I collagen (CTx) level. In addition, myricetin ameliorated histological changes in the femurs. In our in vitro studies, myricetin promoted osteoblast differentiation and mineralization in DEX-treated MC3T3-E1 cells, accompanied by increases in BMP2, Runx2, ALP, OCN, collagen type I alpha 1 (COL1A1) and osteopontin (OPN) levels. The promotion effects of myricetin on osteogenic differentiation and matrix mineralization were reversed by U0126. These results suggest that myricetin may alleviate DEX-induced osteoporosis by promoting osteogenic differentiation and matrix mineralization via the ERK signaling pathway.

CAS / MDL: 109511-58-2 50-02-2
研究领域: 药理学 · 骨科 · 细胞生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE · 2024 · IF 3.3

Supplementation with carnosine, a food-derived bioactive dipeptide, alleviates dexamethasone-induced oxidative stress and bone impairment via the NRF2 signaling pathway

Xi-you Li,Xiao-yuan Gu,Xiao-min Li,Jian-gang Yan,Xin-liang Mao,Qin Yu,Yu-lan Du,Hiroshi Kurihara,Chang-Yu Yan,Wei-xi Li

BACKGROUND Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone-induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo , as well as MC3T3-E1 cells in vitro . RESULTS Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone-exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3-E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense-1 (HO-1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone-induced oxidative stress. CONCLUSION Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry.

CAS / MDL: 2997-92-4
研究领域: 药理学 · 生物化学 · 细胞生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Molecular Medicine Reports · 2020 ·Vol. 22 ·期 4 ·2741-2752 · IF 2.1

Gallium ions promote osteoinduction of human and mouse osteoblasts via the TRPM7/Akt signaling pathway

Mingyang Yu,Yunguang Wang,Yao Zhang,Daping Cui,Guishan Gu,Dewei Zhao

Gallium (Ga) ions have been widely utilized for biomedical applications; however, their role in osteoblast regulation is not completely understood. The aim of the present study was to investigate the potential effect of Ga ions on osteoinduction in two osteoblast cell lines and to explore the underlying mechanisms. Human hFOB1.19 and mouse MC3T3‑E1 osteoblasts were treated with Ga nitride (GaN) at different concentrations, and the degree of osteoinduction was assessed. Ga ion treatment was found to increase alkaline phosphatase activity and accelerate calcium nodule formation, as assessed using ALP activity assay and Alizarin red S staining. Moreover, upregulated expression levels of osteogenic proteins in osteoblasts were identified using western blotting and reverse transcription‑quantitative PCR. Western blotting was also performed to demonstrate that the biological action of Ga ions was closely associated with the transient receptor potential melastatin 7/Akt signaling pathway. Furthermore, it was found that Ga ions did not cause osteoblast apoptosis, as indicated via flow cytometry, but promoted osteoclast proliferation, migration or invasion. The present study investigated the potential role of Ga ions in regulating osteoinduction of osteoblasts, thereby providing a promising strategy for the treatment of osteoporosis.

CAS / MDL: 25617-97-4
研究领域: 生物医学工程 · 细胞生物学 · 分子生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

Transcription factor 7-like 2 promotes osteogenic differentiation and boron-induced bone repair via lipocalin 2

Chengcheng Yin,Xiaoshi Jia,Qin Zhao,Zifan Zhao,Jinyang Wang,Yufeng Zhang,Zhi Li,Hongchen Sun,Zubing Li

Boron-containing mesoporous bioactive glass (B-MBG) scaffolds could be capable of promoting osteogenesis by activating Wnt/β-catenin signaling pathway during the process of bone defect repair. Despite this, more involving molecular controls are still largely unclear. In the present study, we identified that the downstream of Wnt/β-catenin signaling pathway named transcription factor 7-like 2 (TCF7L2) served as a key effector to promote boron-induced bone regeneration and osteogenesis through lipocalin 2 (LCN2). TCF7L2 was highly expressed in osteoblasts when treated with B-MBG scaffold extraction than MBG. LCN2, as a secreted bone factor, positively affected osteogenic differentiation of MC3T3-E1 and osteogenesis in vivo , which could be induced by TCF7L2. In addition, interference of TCF7L2 decreased the osteogenic differentiation of osteoblasts. Finally, we identified that rLCN2 could rescue the poor ability of osteogenic differentiation of MC3T3-E1 whose Tcf7l2 gene was knocked down by lentiviral transfection of shRNA. Our findings provide some new insights into the molecular controls of boron-associated bone regeneration and potential therapeutic targets for the treatment of bone defects.

CAS / MDL: 130-22-3
研究领域: 生物医学工程 · 分子生物学 · 骨科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2021 · IF 6.4

Templated Three-Dimensional Engineered Bone Matrix as a Model for Breast Cancer Osteolytic Bone Metastasis Process

Manman Sun,Ke Huang,Xueshi Luo,Hong Li

Purpose Bone metastasis is one of the common causes of death relative to breast cancer. However, the evolvement of bone niche in cancer progression remains poorly understood. A three-dimensional (3D) engineered bone matrix was developed as an effective biomimetic model to explore the mechanism relative to bone cancer metastasis. Methods In the study, a 3D engineered bone matrix was developed via cell biomineralization templated by a biomimetic collagen template. The process of bone metastasis relative to breast cancer was investigated by co-culturing breast cancer MDA-MB-231-GFP cells with pre-osteogenic MC3T3-E1 cells on the 3D bone matrix. Results A typical bone matrix was obtained, where mineralized collagen fibers were packed into the bundle to form a 3D engineered bone matrix. As the cancer cells were invading along the way vertical to the alignment of mineralized collagen fiber, the bone matrix gradually became thinner, accompanied with the erosion of Col I and the loss of calcium and phosphorus. As a result, the disassembled structure of mineralized collagen fiber was observed, which may be attributed to osteolytic bone metastasis. Conclusion An engineered 3D bone-like matrix was successfully prepared via cell mineralization, which can act as a model for bone metastasis process. The study revealed mineralized collagen fiber disassembled at nanoscale relative to breast cancer cells.

CAS / MDL: 50-81-7
研究领域: 癌症生物学 · 生物医学工程 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioengineered · 2022 · IF 6.832

Preparation of a nanopearl powder/C-HA (chitosan-hyaluronic acid)/rhBMP-2 (recombinant human bone morphogenetic protein-2) composite artificial bone material and a preliminary study of its effects on MC3T3-E1 cells

Wenbo Zhang,Pu Xu,Yanan Cheng,Yanlan Yang,Qiuhua Mao,Zuogeng Chen

A nanopearl powder/C-HA (chitosan-hyaluronic acid)/rhBMP-2 (recombinant human bone morphogenetic protein-2) composite artificial bone material was prepared, and its biological properties were evaluated. The nanopearl powder/C-HA/rhBMP-2 composite porous artificial bone material was prepared using the freeze-drying method after the nanopearl powder was prepared using mechanical ball milling. The particle was measured with a transmission electron microscope, its surface morphology and pore size were observed under a scanning electron microscope. The porosity of the artificial bone was determined using pycnometry, a compression performance test was conducted with a universal testing machine, and XRD (X-ray diffraction) patterns were recorded to examine the crystal form of the pearl powder in the composite artificial bone. Finally, the artificial bone was cocultured with mouse MC3T3-E1 cells to investigate its effects on cell proliferation and differentiation and the expression of osteogenesis-related genes. The pearl powder prepared in this experiment had a particle size in the nanometer range. This nanopearl powder, along with C-HA and rhBMP-2, was compounded into the nanopearl powder/C-HA/rhBMP-2 composite artificial bone, showing pore sizes of 188.53 ± 15.32 μm, a porosity of 86.43 ± 2.78% and a compressive strength of 0.342 ± 0.024 MPa. Notably, rhBMP-2 was released from the artificial bone in a sustained manner. Moreover, this artificial bone promoted the adhesion, proliferation, and differentiation of MC3T3-E1 cells and upregulated the expression of ColαI (collagen α1), OCN (osteocalcin), OPN (osteopontin) and Runx2 (runt-related gene 2). Conclusively, this nanopearl powder/C-HA/rhBMP-2 composite artificial bone material showed good performance and cytocompatibility, suggesting that it can be used for bone tissue engineering.

✓ 已验证 DOI PubMed 高影响因子
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Nano Research · 2024 · IF 9.5

Enhancing osteogenic bioactivities of coaxial electrospinning nano-scaffolds through incorporating iron oxide nanoparticles and icaritin for bone regeneration

Wang Peng,Wang Qianjin,Wu Dengxian,Zhang Yunyang,Kang Shixiong,Wang Xucai,Gu Jiayu,Wu Hao,Xu Zhihong,Jiang Qing

Bone tissue engineering provides a promising strategy for the treatment of bone defects. Nonetheless, the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive properties. Here, we proposed to endow nano-scaffold (NS) constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles (IONPs) and icaritin (ICA). Four types of nano-scaffolds (NS, ICA@NS, NS-IONPs and ICA@NS-IONPs) were prepared. The incorporation of ICA and IONPs minimally impact their surface morphological and chemical properties. IONPs enhanced the mechanical properties of NS scaffolds, including hardness, tensile strength, and elastic modulus. In vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase (ALP) activity level, expressions of osteogenesis-related genes and proteins as well as mineralized nodule formation. Mechanistic investigations revealed that MEK/ERK (MAP kinase-ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK)) signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@NS-IONPs. Furthermore, the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone regeneration. Therefore, IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering.

CAS / MDL: 67-68-5 24980-41-4
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 生物材料
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CELL BIOCHEMISTRY AND BIOPHYSICS · 2024 · IF 1.8

Alpha-lipoic Acid Prevents Bone Loss in Type 2 Diabetes and Postmenopausal Osteoporosis Coexisting Conditions by Modulating the YAP/Glut4 Pathway

Xu Lei,Zhang Chunfang,Bao Jiawu,Han Guozhu,Wang Changyuan,Cai Yuanqing,Xu Gang,Sun Huijun,Liu Mozhen

This study aims to characterize the bone-protecting effects of Alpha-lipoic acid (ALA), a potent antioxidant, against the detrimental effects of the coexistence of type 2 diabetes mellitus (T2DM) and postmenopausal osteoporosis (POP) and identify the possible mechanisms with particular reference to its modulation of YAP/Glut4 pathway. The T2DM and POP coexisting model was induced in mice by high fat diet (HFD) + Streptozocin (STZ) + ovariectomy (OVX). The mice in the treatment groups were given ALA for 10 weeks. In the in vitro study, MC3T3-E1 cells were induced with 500 μM methylglyoxal for 24 h with or without pretreatment with ALA for 24 h. The oxidative and antioxidative biomarkers, bone microarchitecture, histo-morphology, and related protein expression of apoptosis, osteogenic differentiation and the YAP/Glut4 pathway were detected. The results showed ALA could improve glucose tolerance, inhibit oxidative stress and apoptosis and alleviate bone loss. Further study by siRNA technology revealed that the YAP/Glut4 pathway was implicated in the pathogenesis of bone loss due to the coexistence of T2DM and POP. Taken together, the present study has demonstrated for the first time that ALA exerts potent protective effects against bone loss in T2DM and POP coexisting conditions by modulating the YAP/Glut4 pathway.

CAS / MDL: 78-98-8
研究领域: 内分泌学 · 药理学 · 分子生物学 · 病理生理学 · 骨生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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