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Polymers · 2021 ·Vol. 13 ·期 14 ·2302 · IF 4.329

Photocuring Hyaluronic Acid/Silk Fibroin Hydrogel Containing Curcumin Loaded CHITOSAN Nanoparticles for the Treatment of MG-63 Cells and ME3T3-E1 Cells

Qingwen Yu,Zhiyuan Meng,Yichao Liu,Zehao Li,Xing Sun,Zheng Zhao

After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. In this study, the curcumin (Cur) loaded chitosan (CS) nanoparticles (CCNP) encapsulated silk fibroin (SF)/hyaluronic acid esterified by methacrylate (HAMA) (CCNPs-SF/HAMA) hydrogel for the osteosarcoma therapy and bone regeneration was developed by photocuring and ethanol treatment. The micro or nanofibers networks were observed in the CCNPs-SF/HAMA hydrogel. The FTIR results demonstrated that alcohol vapor treatment caused an increase in β-sheets of SF, resulting in the high compression stress and Young’s modulus of CCNPs-SF/HAMA hydrogel. According to the water uptake analysis, SF caused a slight decrease in water uptake of CCNPs-SF/HAMA hydrogel while CCNPs could enhance the water uptake of it. The swelling kinetic results showed that both the CCNPs and the SF increased the swelling ratio of CCNPs-SF/HAMA hydrogel. The accumulative release profile of CCNPs-SF/HAMA hydrogel showed that the release of Cur from CCNPs-SF/HAMA hydrogel was accelerated when pH value was decreased from 7.4 to 5.5. Besides, compared with CCNPs, the CCNPs-SF/HAMA hydrogel had a more sustainable drug release, which was beneficial for the long-term treatment of osteosarcoma. In vitro assay results indicated that CCNPs-SF/HAMA hydrogel with equivalent Cur concentration of 150 μg/mL possessed both the effect of anti-cancer and promoting the proliferation of osteoblasts. These results suggest that CCNPs-SF/HAMA hydrogel with superior physical properties and the bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.Keywords:curcumin;hyaluronic acid;silk fibroin;chitosan nanoparticle;MG-63 cells;MC3T3-E1 cells

研究领域: 生物医学工程 · 药学 · 材料科学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2019 · IF 6.044

Two novel polysaccharides from rhizomes of Cibotium barometz promote bone formation via activating the BMP2/SMAD1 signaling pathway in MC3T3-E1 cells

Dong Huang,Xin Hou,Dawei Zhang,Qian Zhang,Chunyan Yan

Cibotium barometz , an important traditional Chinese medicine, is used in strengthening bones and tendons. We found that C. barometz crude polysaccharides (CB70) could alleviate bone loss and markedly improve the biomechanical properties of OVX rats. Thus, to clarify biological active ingredient(s) of CB70, two homogeneous polysaccharides (CBP70-1-1 and CBP70-1-2) were purified from CB70. A combination of monosaccharide composition, FT-IR, GC–MS and NMR analysis indicated that CBP70-1-1 was composed of →6)-D-Gal p -(1→, D-Glc p -(1→, →3,6)-D-Man p -(1→, →4)-D-Glc p -(1→ and →6)-D-Glc p -(1→ with relative molecular weights of 12,724 Da, and CBP70-1-2 was composed of →4)-D-Glc p -(1→, D-Glc p -(1→, →3,6)-D-Man p -(1→, →6)-D-Gal p -(1→, →4,6)-D-Glc p -(1→ and →3)-L-Ara f -(1→ with relative molecular weights of 3611 Da. Morphological analyses revealed that CBP70-1-1 and CBP70-1-2 appeared as a sheet that were irregular in size and shape, while the surface of CBP70-1-1 was full of sharp protuberances and CBP70-1-2 was smooth. Furthermore, the effects of CBP70-1-1 and CBP70-1-2 on the proliferation, differentiation and mineralization of mouse pre-osteoblastic MC3T3-E1 cells were assessed via CCK-8 assay, alkaline phosphatase activity assay, and alizarin red-based assay, respectively. These results revealed that CBP70-1-1 and CBP70-1-2 significantly promoted the proliferation, differentiation and mineralization of MC3T3-E1 cells, even better than E2. More importantly, quantitative real-time PCR and Western blot analysis indicated that CBP70-1-2 pronouncedly promoted the expression of osteogenic-related marker genes ( Runx2, Osx, Ocn and Opn ) and proteins (BMP2, RUNX2, OSX and p-SMAD1), which implies that the osteogenic activity of CBP70-1-2 is accomplished mainly by activating the BMP2/SMAD1 signaling pathway. These findings suggest CBP70-1-2 as a potential natural anti-osteoporotic agent for pharmacotherapy.

研究领域: 药理学 · 分子生物学 · 中医药学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2019 · IF 2.442

Dopamine-assisted immobilization of peptide arginine–glycine–aspartic acid to enhance the cellular performances of MC3T3-E1 cells of carbon–carbon composites

Xiaoling Yang,Xue Liu,Qianqian Wu,Xu Lv,Bo Li,Hongzhe Sun,Wenfeng Xu,Xiaoling Liao

Due to their excellent biocompatibility and suitable elastic modulus, carbon–carbon composites have excellent prospects for a wide range of applications such as artificial joints and bone replacements. However, the hydrophobicity and poor bioactivity limit their application in bone repair and substitution. Herein, a two-step surface modification of carbon–carbon composites was proposed to overcome these disadvantages. A polydopamine (PDA) layer was first deposited on the surface of carbon–carbon composites, followed by covalent coupling with arginine–glycine–aspartic acid (RGD) in varying concentrations. The surface-modified materials were characterized using a variety of techniques including water contact angle, scanning electron microscopy, atomic force microscopy, and protein adsorption. In addition, the cellular proliferation, alkaline phosphatase activity, and real-time quantitative PCR (RT-PCR) analysis were further tested in vitro. The results indicated that polydopamine and RGD nanoparticles formed on the surface, which significantly enhanced the hydrophilicity following modification. The RGD–PDA-coated carbon–carbon composites exhibited excellent roughness, protein adsorption behavior, and uniform morphology when a concentration of 50 µg/mL RGD was used, unlike blank and polydopamine-modified carbon–carbon composites. The in vitro cell co-culture experiments demonstrated that proliferation and alkaline phosphatase expression in osteoblasts was greatly improved after RGD–PDA coating. The RT-PCR results revealed that the expression of differentiation markers (alkaline phosphatase and osteocalcin) in cells on the RGD–PDA-coated carbon–carbon composites was higher than that on the blank and polydopamine-modified carbon–carbon composites, indicating that the RGD–PDA coating could support cell proliferation and promote osteogenic differentiation of MC3T3-E1 cells. In particular, the cells cultured on this material grew linearly along the morphological features of the material, which was effective for the subsequent regulation of cell growth. Our study suggested that the RGD–PDA coating was an effective method of enhancing the hydrophobicity and the cellular bioactivity of carbon–carbon composites, thus extending applications of carbon–carbon composites to the bone repair field.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Alginate-modified mesoporous bioactive glass and its drug delivery, bioactivity, and osteogenic properties

Haiyan Yao,Jun Luo,Yunyun Deng,Zhihua Li,Junchao Wei

Mesoporous bioactive glass (MBG) is widely used in bone tissue repairing and drug loading. However, burst release of drug and poor compatibility with other materials limited its application. It is an effective way to modify MBG with a polymer brush to improve the properties. Herein, an alginate-modified MBG was prepared, and then, the effects of ALG on the properties of MBG were investigated. The results demonstrate that ALG could improve the drug loading efficiency, prolong drug release times, and make orderly deposition of apatite on the surface of MBG. Furthermore, MBG@ALG significantly promoted the osteogenic differentiation of MC3T3-E1 cells, demonstrating that surface modification of MBG by ALG can improve its properties, which will further broaden the application of MBG in tissue engineering.

研究领域: 材料科学 · 生物医学工程 · 组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Orthopaedic Surgery and Research · 2024 ·Vol. 19 ·期 1 ·1-13 · IF 2.8

Asperuloside alleviates osteoporosis by promoting autophagy and regulating Nrf2 activation

Huang Fenglan,Wang Yiteng,Liu Jinzhu,Cheng Ye,Zhang Xiaonan,Jiang Haoli

Background Osteoporosis is a metabolic bone disease that has a common occurrence in postmenopausal women. Asperuloside (ASP) has been reported to exert anti-inflammatory and anti-oxidative effects in numerous diseases, such as rheumatoid arthritis and acute lung injury. However, whether ASP plays a role in osteoporosis has not been addressed.Methods In vivo, ovariectomy (OVX) was used to induce mouse osteoporosis. Then, the mice were treated with 20 and 40 mg/kg ASP. In vitro, MC3T3-E1 cells were treated with 0, 1, 10, 20, 40 and 80 µM ASP. We chose 20 and 40 µM for further experiments due to no significant effects on cell viability.Results The data indicated that ASP reduced osteoporosis in OVX mice and promoted osteogenic differentiation and mineralization in MC3T3-E1 cells. In addition, we explored that ASP protected against osteoporosis via inducing autophagy and activating Nrf2.Conclusion ASP alleviates OVX-induced osteoporosis by promoting autophagy and regulating Nrf2 activation.

研究领域: 药理学 · 骨骼生物学 · 医学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

From Solution to Biointerface: Graphene Self-Assemblies of Varying Lateral Sizes and Surface Properties for Biofilm Control and Osteodifferentiation

Zhaojun Jia,Yuying Shi,Pan Xiong,Wenhao Zhou,Yan Cheng,Yufeng Zheng,Tingfei Xi,Shicheng Wei

Bringing multifunctional graphene out of solution through facile self-assembly to form 2D surface nanostructures, with control over the lateral size and surface properties, would be an intriguing accomplishment, especially in biomedical fields where biointerfaces with functional diversity are in high demand. Guided by this goal, in this work, we built such graphene-based self-assemblies on orthopedic titanium, attempting to selectively regulate bacterial activities and osteoblastic functions, which are both crucial in bone regeneration. Briefly, large-area graphene oxide (GO) sheets and functionalized reduced GO (rGO) micro-/nanosheets were self-assembled spontaneously and controllably onto solid Ti, through an evaporation-assisted electrostatic assembly process and a mussel-inspired one-pot assembly process, respectively. The resultant layers were characterized in terms of topological structure, chemical composition, hydrophilicity, and protein adsorption properties. The antibacterial efficacies of the assemblies were examined by challenging them with pathogenic Staphylococcus aureus (S. aureus) bacteria that produce biofilms, whereby around 50% antiadhesion effects and considerable antibiofilm activities were observed for both layer types but through dissimilar modes of action. Their cytocompatibility and osteogenic potential were also investigated. Interfaced with MC3T3-E1 cells, the functionalized rGO sheets evoked better cell adhesion and growth than GO sheets, whereas the latter elicited higher osteodifferentiation activity throughout a 28-day in vitro culture. In this work, we showed that it is technically possible to construct graphene interface layers of varying lateral dimensions and surface properties and confirmed the concept of using the obtained assemblies to address the two major challenges facing orthopedic clinics. In addition, we determined fundamental implications for understanding the surface–biology relationship of graphene biomaterials, in efforts to better design and more safely use them for future biomedicine.

研究领域: 生物材料 · 生物医学工程 · 材料科学 · 表面化学
✓ 已验证 DOI PubMed 高影响因子
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INDUSTRIAL CROPS AND PRODUCTS · 2018 · IF 3.849

Structural elucidation and osteogenic activities of two novel heteropolysaccharides obtained from water extraction residues of Cibotium barometz

Dong Huang,Mengliu Zhang,Wei Chen,Dawei Zhang,Xinluan Wang,Huijuan Cao,Qian Zhang,Chunyan Yan

Cibotium barometz is a tropical and subtropical plant, mainly distributed in the Malaysian Peninsula and southern China. In China, C. barometz has tremendous commercial value in horticultural and medicinal applications. In the present study, alkaline soluble crude polysaccharides (CBBs) were extracted from water extraction residues of C. barometz with sodium hydroxide solution. After deproteinization and dialysis, CBBs were isolated and purified via DEAE-52 cellulose and Sephadex G-75 gel filtration chromatography to obtain two polysaccharide fractions (CBBP-2 and CBBP-3), with relative molecular weights of 10.7 kDa and 1.23 × 10 2  kDa, respectively. Chemical methods and nuclear magnetic resonance (NMR) studies indicated that CBBP-2 was composed of →4)- α - d -Glc p -(1→, →3)- α - l - R ha p -(1→, →3)- α - l -Ara f -(1→, →6)- β - d -Gal p -(1→, →3,6)- α - d -Man p -(1→ and α - d -GalA p -(1→, and CBBP-3 was composed of →6)- β - d -Gal p -(1→, →3)- α - l - R ha p -(1→, →3)- α - l -Fuc p -(1→, →3)- α - l -Ara f -(1→, →3,6)- α - d -Man p -(1→, β - d -GalA p -(1→ and α - d -Gal p -(1→. Morphological and conformational analyses indicated that CBBP-2 had a fragmented and sawdust-like structure. CBBP-3 had a neuron-like morphology, with a number of dendritic branches. Neither CBBP-2 nor CBBP-3 had a triple helix structure. Furthermore, MC3T3-E1 cells were selected to evaluate the osteogenic activities of CBBP-2 and CBBP-3 in an in vitro anti-osteoporosis assay, and the results revealed that CBBP-2 significantly promoted the differentiation of MC3T3-E1 cells at concentrations of 9.4 μM and 18.8 μM and promoted osteogenic mineralization at a low concentration at 4.7 μM. Overall, the systematic extraction, purification, structure identification and bioactivity assays of CBBP-2 and CBBP-3 showed that CBBP-2 could potentially be used as an anti-osteoporotic activity ingredient, with applications in health care and pharmaceutical industries.

CAS / MDL: 50-28-2
研究领域: 药理学 · 生物化学 · 分子生物学
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2022 · IF 3.682

Highly resilient porous polyurethane composite scaffolds filled with whitlockite for bone tissue engineering

Jingjing Du,Yang Zhang,Jiaqi Wang,Mengjie Xu,Miao Qin,Xiumei Zhang,Di Huang

The present work is intended to provide a base for further investigation of the composite scaffolds for bone tissue engineering, and whitlockite/polyurethane (WH/PU) scaffolds, in particular. WH Ca18Mg2(HPO4)2(PO4)12 was successfully prepared by means of a chemical reaction between Ca(OH)2, Mg(OH)2 and H3PO4. WH/PU scaffolds were synthesized via in situ polymerization. Synthesized WH particles and WH/PU composite scaffolds were characterized using FTIR, XRD, SEM and EDS. The porosity of scaffolds was calculated by the liquid displacement method. The water contact angle of scaffolds was tested. Mechanical characterization of WH/PU composite scaffolds was evaluated according to monotonic and cyclic compression examination. MC3T3-E1 cells were employed to evaluate the cytocompatibility of scaffolds. The results showed that WH and PU were completely integrated into composite biomaterials. The maximum compressive strength and elastic modulus of WH/PU composite scaffold reached up to 5.2 and 14.1 MPa, respectively. WH/PU composite scaffold had maximum 73% porosity. The minimum contact angle of WH/PU composite scaffold was 89.16°. WH/PU composite scaffolds have a good elasticity. Cyclic compression tests showed that scaffold could recover 90% of its original shape 1 h after removing the load. WH/PU composite scaffolds exhibited a high affinity to MC3T3-E1 cells. WH/PU composite scaffolds significantly promoted proliferation and alkaline phosphatase activity of MC3T3-E1 cells when compared to those grown on tissue culture well plates. It is suggested that the WH/PU scaffolds might be suitable for the application of bone tissue engineering.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-13 · IF 4.259

Enhancing Cell Proliferation and Osteogenic Differentiation of MC3T3-E1 Pre-osteoblasts by BMP-2 Delivery in Graphene Oxide-Incorporated PLGA/HA Biodegradable Microcarriers

Fu Chuan,Yang Xiaoyu,Tan Shulian,Song Liangsong

Lack of bioactivity has seriously restricted the development of biodegradable implants for bone tissue engineering. Therefore, surface modification of the composite is crucial to improve the osteointegration for bone regeneration. Bone morphogenetic protein-2 (BMP-2), a key factor in inducing osteogenesis and promoting bone regeneration, has been widely used in various clinical therapeutic trials. In this study, BMP-2 was successfully immobilized on graphene oxide-incorporated PLGA/HA (GO-PLGA/HA) biodegradable microcarriers. Our study demonstrated that the graphene oxide (GO) facilitated the simple and highly efficient immobilization of peptides on PLGA/HA microcarriers within 120 min. To further test in vitro , MC3T3-E1 cells were cultured on different microcarriers to observe various cellular activities. It was found that GO and HA significantly enhanced cell adhesion and proliferation. More importantly, the immobilization of BMP-2 onto the GO-PLGA/HA microcarriers resulted in significantly greater osteogenic differentiation of cells in vitro , as indicated by the alkaline phosphate activity test, quantitative real-time polymerase chain reaction analysis, immunofluorescence staining and mineralization on the deposited substrates. Findings from this study revealed that the method to use GO-PLGA/HA microcarriers for immobilizing BMP-2 has a great potential for the enhancement of the osseointegration of bone implants.

研究领域: 生物医学工程 · 组织工程 · 骨再生 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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POLYMER SCIENCE SERIES B · 2022 ·Vol. 64 ·期 4 ·487-499 · IF 1.023

Fabrication of Bone Morphogenic Protein-2 and Icariin-Containing Sustained-Release Microcapsule and Evaluation of its Osteogenic Differentiation Capacity in MC3T3-E1 Cells

Zhen Hua,Cheng Jian,Shi Dong-jian,Chen Ji-wei,Peng Hong-cheng,Liu Ming-ming

Abstract The delivery of cytokines and Chinese medicines using biodegradable microspheres may promote bone regeneration. We designed a sustained-release microcapsule containing bone morphogenetic protein-2 (BMP2) and icariin (ICA) and evaluated its effects on osteogenic differentiation in MC3T3-E1 cells. ICA was preloaded onto sodium alginate-grafted phenylboronic acid (Alg-PBA) particles. Alg-PBA-ICA was used to coat the surface of SiO 2 -NH 2 colloids by electrostatic interaction, and then SiO 2 colloids were etched using HF. The Alg-PBA-ICA vesicles were immersed in a BMP2 solution, and Alg-PBA-ICA/BMP2 microcapsules were obtained. The optimal concentration of ICA and BMP2 for osteogenic differentiation induction was selected. We evaluated the microcapsules' osteogenic differentiation capacity. The microcapsules displayed intact morphology without obvious broken debris. The size of Alg-PBA-ICA@SiO 2 microcapsules was 210 ± 2 nm; the surface charge was –15.70 ± 2.12 mV. BMP2 (100 ng/mL) combined with 10 nM ICA had the strongest effect on cell behavior. The osteo-inductive effect at this concentration was stronger than that of the other combinations. The mRNA and protein expression levels of osteogenic genes increased after treatment with the microcapsules following 7 days of stimulation. This new drug delivery system has powerful osteo-inductive effects on MC3T3-E1 cells.

研究领域: 生物医学工程 · 药学 · 细胞生物学
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POLYMER TESTING · 2023 · IF 5.1

Fabrication of carboxymethyl chitosan-strontium chondroitin sulfate composites for potential bone regeneration

Meixin Li,Lei Xu,Fenbo Ma,Bin Tang,Chenghe Qin

Large bone defects have been a major healthcare concern. These defects are difficult to heal because of the chronic inflammatory environment surrounding the injury area. Osteoconductive composites with anti-inflammatory effects could provide a substrate to support cell growth and guide bone defect repair. Here, we synthesized a biofunctional composite that combined carboxymethyl-chitosan (CMCS) and strontium chondroitin sulfate (SrCS), for potential use in bone regeneration. We hypothesized that the as-prepared CMCS-SrCS composites could stimulate osteogenic activity and suppress inflammatory responses. The resultant composites displayed uniformly porous structures and good swelling capacity. The effect of the composites on MC3T3-E1 cells was investigated in vitro and the live cells showed favorable viability. Moreover, the RT-PCR results indicated that the CMCS-SrCS composites could suppress inflammatory responses and promote the osteogenic differentiation of MC3T3-E1 cells. These results suggested the CMCS-SrCS composites should have osteoconductive characteristics. Thus, we believe that the developed CMCS-SrCS composites should be a promising skeletal candidate for regenerative engineering applications.

研究领域: 生物医学工程 · 材料科学 · 再生医学
✓ 已验证 DOI 高影响因子
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Food & Function · 2023 · IF 6.1

Effect of the phosphorylation structure in casein phosphopeptides on the proliferation, differentiation, and mineralization of osteoblasts and its mechanism

Wanying Zhong,Jian He,Wen Huang,Guangling Yin,Guo Liu,Yong Cao,Jianyin Miao

Our previous studies have shown that highly phosphorylated casein phosphopeptides (residues 1–25) P5 could efficiently bind calcium and promote intestinal calcium absorption, and enhanced bone development in rats. The purpose of this study was to investigate the effect of the phosphorylation structure in P5 on the proliferation, differentiation, and mineralization of osteoblasts (MC3T3-E1) and its mechanism. P5 was obtained by high-performance liquid chromatography (HPLC) and non-phosphorylated peptide P5-0 was obtained by chemical synthesis. Compared with the control group, the proliferation rate of MC3T3-E1 cells treated by P5 was 1.10 times that of P5-0 at 200 μg mL−1. P5 caused the cell cycle retention of MC3T3-E1 cells in the G2/M phase, while P5-0 had no significant difference in the G2/M phase. MC3T3-E1 cells incubated with P5 showed stronger alkaline phosphatase (ALP) activity than with P5-0, suggesting a tendency to promote cellular differentiation. Compared to the P5-0 treatment group, the P5 treatment group at concentrations of 10 μg mL−1 showed significant differences in the mineralization rates (p < 0.05). P5 significantly upregulated the expressions of Runx2, ALP, ColIα1, and OCN compared with the control group (p < 0.05). In addition, in silico molecular docking showed that the binding force of the P5-EGFR complex was stronger than that of the P5-0-EGFR complex, which was significantly related to the phosphorylation structure in P5 and might be an important reason for osteoblast proliferation. In conclusion, the phosphorylation structure and amino acid composition in P5 stimulated the osteogenic activity of MC3T3-E1 cells, and could be expected to be a functional food for the prevention of osteoporosis.

CAS / MDL: 76-05-1
研究领域: 营养学 · 骨骼生物学 · 细胞生物学 · 分子生物学
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