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PubMed | National Engineering Research Center for Biomaterials and Sichuan University
Type: | Journal: International journal of nanomedicine | Year: 2017

Zwitterionic polymers have unique features, such as good compatibility, and show promise in the application of drug delivery. In this study, the zwitterionic copolymers, poly(-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) with disulfide (PCL-ss-PMPC) or poly(-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) or without disulfide (PCL-PMPC) and with different block lengths in PCL-ss-PMPC, were designed. The designed copolymers were obtained by a combination of ring-opening polymerization and atom transferring radical polymerization. The crystallization properties of these polymers were investigated. The micelles were prepared based on the obtained copolymers with zwitterionic phosphorylcholine as the hydrophilic shell and PCL as the hydrophobic core. The size distributions of the blank micelles and the doxorubicin (DOX)-loaded micelles were uniform, and the micelle diameters were <100 nm. In vitro drug release and intracellular drug release results showed that DOX-loaded PCL-ss-PMPC micelles could release drugs faster responding to the reduction condition and the intracellular microenvironment in contrast to PCL-PMPC micelles. Moreover, in vitro cytotoxicity evaluation revealed that the designed copolymers possessed low cell toxicity, and the inhibiting effect of DOX-loaded phosphorylcholine micelles to tumor cells was related to the components of these copolymers. These results reveal that the reduction-responsive phosphorylcholine micelles with a suitable ratio of hydrophilic/hydrophobic units can serve as promising drug carriers.


Cheng L.,West China Hospital | Ye F.,West China Hospital | Yang R.,West China Hospital | Lu X.,West China Hospital | And 5 more authors.
Acta Biomaterialia | Year: 2010

Many studies have shown that calcium phosphate ceramics can induce bone formation in non-osseous sites without the application of any osteoinductive biomolecules, but the mechanisms of this phenomenon (intrinsic osteoinduction of bioceramics) remain unclear. In this study, we compared the intrinsic osteoinduction of porous hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) implanted in mice at different sites. In 30 mice the left fibula was fractured and the right fibula was kept intact. A porous HA/β-TCP cylinder was implanted into both the left (group 1) and right (group 2) leg muscles of each animal. In addition, two HA/β-TCP cylinders were bilaterally implanted into leg subcutaneous pockets (group 3) in each of the remaining 15 mice. New bone formation was studied in the three groups by histology, histomorphometry and immunostaining. In group 1 new bone was observed at week 6 and bone marrow appeared at week 12. In group 2 new bone was observed at week 8 and bone marrow appeared at week 12. The new bone area percentage in group 1 was significantly higher than in group 2 at both weeks 8 and 12. In contrast, group 3 did not show any new bone within the period studied. These differences were explained based on the location of the implants and thus their proximity to the osteogenic environment of fracture healing. The results support the hypothesis that intrinsic osteoinduction by calcium phosphate ceramics is the result of adsorption of osteoinductive substances on the surface. © 2009 Acta Materialia Inc.


Cheng L.,University of Sichuan | Lu X.,University of Sichuan | Shi Y.,University of Sichuan | Li L.,University of Sichuan | And 6 more authors.
Applied Surface Science | Year: 2012

Bone tissue engineering (BTE) is approached via implantation of autogenous mesenchymal stem cells (MSCs), marrow cells, or platelet-rich plasma, etc. To the contrary, gene therapy combining with the bone marrow (BM) has not been often reported. This study was performed to investigate whether a modified BTE method, that is, the BM and a recombinant human bone morphogenetic protein-2 adenovirus (Ad.hBMP-2) gene administering in hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramics could accelerate the healing of segmental defects in the rabbit radius. In our study, ceramics were immersed in the adenovirus overnight, and half an hour before surgery, autologous BM aspirates were thoroughly mixed with the ceramics; at the same time, a 15-mm radius defect was introduced in the bilateral forelimbs of all animals, after that, this defect was filled with the following: (1) Ad.hBMP-2 + HA/β-TCP + autologous BM (group 1); (2) HA/β-TCP + Ad.hBMP-2 (group 2); (3) HA/β-TCP alone (group 3); (4) an empty defect as a control (group 4). Histological observation and μ-CT analyses were performed on the specimens at weeks 2, 4, 8, and 12, respectively. In group 1, new bone was observed at week 4 and BM appeared at week 12, in groups 2 and 3, new bone was observed at week 8 and it was more mature at week 12, in contrast, the defect was not bridged in group 4 at week 12. The new bone area percentage in group 1 was significantly higher than that in groups 2 and 3. Our study indicated that BM combined with hBMP-2 adenovirus and porous ceramics could significantly increase the amount of newly formed bone. And this modified BTE method thus might have potentials in future clinical application. © 2012 Elsevier B.V. All rights reserved.


Chen S.J.,University of Sichuan | Chen S.J.,National Engineering Research Center for Biomaterials | Yu H.Y.,University of Sichuan | Yang B.C.,University of Sichuan | Yang B.C.,National Engineering Research Center for Biomaterials
Journal of Biomedical Materials Research - Part A | Year: 2013

Electrospining method was used to prepare bioactive TiO2 fibers films in this study. The acetic acid/ethanol/tetrabutyl titanate/ polyvinylpyrrolidone (PVP) solvent system was used as precursor for the electrospining. The TiO2 fiber structures (including its fiber diameter, morphology, and phase composition) could be controlled by changing feeding rate, PVP concentration and sinter temperature. The fiber films were subjected to simulated body fluid soaking experiments and MG63 cells culture experiments to study their bioactivity. According to the X-ray diffraction and MTT assay results, the fiber containing with anatase showed better apatite formation ability than that without anatase at the early stage, while cell proliferated on anatase-rutile TiO2 fiber was better than that on other samples (p < 0.05). Some string beads in the fiber were beneficial for apatite formation, while the cell proliferated best on the fiber film without string beads (p < 0.05). The fiber with a diameter of 200 nm had the best apatite formation ability and osteoblast compatibility (p < 0.05). The results showed that the TiO2 fiber film structure had great influence on its bioactivity. It indicated that the electronspining method is an effective way to prepare bioactive titania fiber films, and it is possible to control the structure of the films in the spinning process to optimize the bioactivity of TiO2 fiber. © 2012 Wiley Periodicals, Inc.


Xiao M.,University of Sichuan | Xiao M.,National Engineering Research Center for Biomaterials | Biao M.,University of Sichuan | Biao M.,National Engineering Research Center for Biomaterials | And 5 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2016

Bone morphogenetic protein 2 (BMP-2) is important for regulating the osteogenic differentiation of mesenchymal stem cells and the response of bone tissue. It adsorbs on the surface of biomedical implants immediately and plays a role of mediator between the materials surfaces and the host cells. Studies usually connect the material surface properties and the new bone formation directly. However, interaction between the adsorbed BMP-2 on the implant surface and the cells in the tissue is the key to explaining the osteogenic properties of the material. So, in this article, we investigated the conformational and functional changes induced by the surface modified titanium metals. We found that the α-helix and β-sheet structure of rhBMP-2 can be well maintained on the anodic oxidation treated titanium surface. The osteogenic function of rhBMP-2 can sustain for a relatively long time even though there is less amount adhere to the surface compared with that on the acid alkali treated titanium. Surface properties, especially the morphology enable a larger amount of rhBMP-2 to adsorb to the surface of the acid alkali treated titanium, but the conformation of the protein is severely influenced. The percentage of α-helix structure is also significantly decreased so that the efficacy of rhBMP-2 is only maintained in the early time. This study indicated that different surface modification of the surface could regulate the structure of rhBMP-2 and then further influence its osteogenic function. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1882–1893, 2016. © 2016 Wiley Periodicals, Inc.


Yue C.,University of Sichuan | Yue C.,National Engineering Research Center for Biomaterials | Yang B.,University of Sichuan | Yang B.,National Engineering Research Center for Biomaterials
Journal of Bionic Engineering | Year: 2014

Titanium metals and its alloy have been widely used in hard tissue repairing fields due to their good biocampatibility and mechanical properties. However, bioinert response and biomaterial associated infections are the main problems for their clinical application. In this study, we chose titanium plates treated with anodic oxidation (AO-Ti), alkali-heat (AH-Ti) and acid-alkali (AA-Ti) methods, which have been proved to be bioactive in vivo, to culture with Staphylococcus aureus and Escherichia coli to investigate the interaction between bioactive titanium surfaces and biofilm. We used X-ray diffraction (XRD), Scanning Electron Microscope (SEM), roughness measurement to study the physical-chemical properties of the as-received bioactive titanium surfaces, and Confocal Laser Scanning Microscope (CLSM) was employed to study the properties of biofilm formed on the biomaterial surfaces. The results indicate that the titanium surface subjected to anodic oxidation treatment is unfavorable for the formation of biofilm in vitro because the titania (TiO2) coating formed by anodizing has superior antimicrobial property than the other surfaces. Therefore, anodic oxidation surface modification is effective to endow titanium surface with bioactivity and antimicrobial property, which has the potential to improve the successful rate of the clinical application of titanium implants. © 2014 Jilin University.


Hu X.N.,University of Sichuan | Hu X.N.,National Engineering Research Center for Biomaterials | Yang B.C.,University of Sichuan | Yang B.C.,National Engineering Research Center for Biomaterials
Journal of Biomedical Materials Research - Part A | Year: 2014

The conformation change of bovine serum albumin (BSA) induced by bioactive titanium surfaces, including acid-alkali-treated titanium (AA-Ti) and alkali-heat-treated titanium (AH-Ti), was studied, and its effects on the activity of MC3T3-E1 cell were evaluated. Pure titanium metal (P-Ti) was used as control. The AA-Ti could adsorb more BSA on its surface than AH-Ti and P-Ti. The α-helix part of the protein adsorbed on P-Ti has weakly decreased compared with native BSA, and it dramatically decreased on AA-Ti and AH-Ti. The β-sheet segment of proteins adsorbed on P-Ti and AH-Ti had obviously increased. Much more tryptophan residues were exposed after the protein conformation changed when it interacted with AH-Ti, and some tryptophan residues were enveloped after it interacted with AA-Ti and P-Ti. AA-Ti has more tryptophan residues enveloped than P-Ti. All titanium surfaces induced tyrosine residues exposed, especially for the P-Ti. The higher ratio of COO -/NH3 + for the proteins on P-Ti and AA-Ti indicated an orientation of proteins on P-Ti and AA-Ti, which makes more COO- exposed. The lower ratio of COO-/NH3 + on AH-Ti indicates that more NH3 + is exposed on its surface. The cell proliferation ability on different treated titanium surfaces coated with BSA followed by the order: P-Ti > AA-Ti > AH-Ti, which indicated that the protein conformation change on different bioactive titanium surfaces has great effect on the cell activity. Our results showed that the different biological response of bioactive titanium metals might depend on the protein conformation change induced by the surface structure. © 2013 Wiley Periodicals, Inc.


Nan M.,University of Sichuan | Nan M.,National Engineering Research Center for Biomaterials | Yangmei C.,University of Sichuan | Yangmei C.,National Engineering Research Center for Biomaterials | And 2 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2014

Reactive oxygen plays an important role in the pathogenesis of many serious illnesses, including bony cancer. Recently, it has been suggested that hydrogen (H2), a selective antioxidant, can effectively scavenge free radicals. Biomedical magnesium (Mg) used for bone defect repair in the surgery of bony cancer could release H2 because of the degradation, so Mg might have the potential to prevent bony cancer from metastasis and recurrence. In this study, alkali-heat treatment method was employed to modify the surface structure of Mg metal, so as to control the degradation of Mg metal and the H2 releasing rate. Then the released H2 was introduced to the Fenton Reaction system to detect its effect on scavenging free radicals. The modified Mg metal was employed as the substrate for bone cancer cell culture to study the effect of the H2 releasing on scavenging free radicals in the cells. It is found that the H2 released from the Mg degradation could scavenge free radicals both in the Fenton Reaction system and bone cancer cells. The effect on the scavenging free radical is proportional to the rate of H2 releasing. It suggested that Mg might be a potential material with anti-bone cancer properties. It is hopeful to both repair the bone defect and prevent bony cancer from metastasis and recurrence for the bony cancer patients by biomedical Mg metal. © 2013 Wiley Periodicals, Inc.


Chen Y.,University of Sichuan | Chen Y.,National Engineering Research Center for Biomaterials | Xiao M.,University of Sichuan | Xiao M.,National Engineering Research Center for Biomaterials | And 4 more authors.
Journal of Materials Chemistry B | Year: 2015

H2 is a therapeutic agent for tumors because it could scavenge free radicals, which is one of the causes for this disease in the human body. Biomedical magnesium (Mg) could release H2 in the biodegradation process, thus it might have antitumor properties. In this study, Mg metal (P-Mg) was subjected to anodic oxidation plus heat treatment to get AO-HT-Mg covered with MgO. In SBF experiments AO-HT-Mg showed bioactivity as it could induce calcium phosphate deposition. The MgO layer played a protective role in the biodegradation process and controlled the H2 releasing rate. In MRMT-1 rat breast carcinoma cell culture experiments, both P-Mg and AO-HT-Mg could inhibit free radical expression in the cells, and AO-HT-Mg showed higher inhibiting ability. In the animal experiments with 72 mice divided into 4 groups, both P-Mg and AO-HT-Mg could inhibit tumor growth. After implantation in the animals, P-Mg showed higher inhibiting ability at the initial stage, and AO-HT-Mg showed higher inhibiting ability after 26 days. The tumor inhibiting properties depended on H2 releasing rates. The results confirm Mg metal has antitumor properties in vivo, and it is possible to optimize its antitumor properties by surface modification. © The Royal Society of Chemistry 2015.


Wang Q.Q.,University of Sichuan | Wang Q.Q.,National Engineering Research Center for Biomaterials | Li W.,University of Sichuan | Yang B.C.,University of Sichuan | Yang B.C.,National Engineering Research Center for Biomaterials
Journal of Biomedical Materials Research - Part A | Year: 2011

To study the regulation on the biocompatibility of titanium metal surface structure, the interaction between the collagen and the titanium surface structure were studied with titanium surfaces subjected to anodic oxidation and acid-alkali treatment. The cell response on the treated surfaces was studied in vitro experiments of MG63 osteoblasts. The effects of different collagen adsorption ability on the biomineralization were investigated with simulated body fluid (SBF) experiment and osteoblasts culture experiments in a mineralization culture medium. It was found that the collagen adsorption ability was controlled by the wettability. The acid-alkali treated titanium could adsorb much more collagen on its surface. The abilities of cell attachment and proliferation were improved after collagen soaking. The apatite formation ability was inhibited in SBF after collagen adsorption on the surfaces, but improved in cell-involved situation. The ALP and OCN activity of MG63 cells assay showed the collagen on the titanium surface could enhance the bioactivity of the cells, which could accelerate the biomineralization process in cell culture experiments. The result indicated that the different adsorption ability of type I collagen could regulate the biocompatibility of titanium metal surface. It is possible to optimize the biocompatibility of the titanium metals by using suitable surface modification method. Copyright © 2011 Wiley Periodicals, Inc.

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