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Du Q.,CAS Technical Institute of Physics and Chemistry | Du Q.,Sichuan University | Fu C.,CAS Technical Institute of Physics and Chemistry | Tie J.,Peking University | And 8 more authors.
Nanoscale | Year: 2015

Local and rapid heating by microwave (MW) irradiation is important in the clinical treatment of tumors using hyperthermia. We report here a new thermo-seed technique for the highly efficient MW irradiation ablation of tumors in vivo based on gelatin microcapsules. We achieved 100% tumor elimination in a mouse model at an ultralow power of 1.8 W without any side-effects. The results of MTT assays, a hemolysis test and the histological staining of organs indicated that the gelatin microcapsules showed excellent compatibility with the physiological environment. A possible mechanism is proposed for MW hyperthermia using gelatin microcapsules. We also used gelatin microcapsules capped with CdTe quantum dots for in vivo optical imaging. Our study suggests that these microcapsules may have potential applications in imaging-guided cancer treatment. © 2015 The Royal Society of Chemistry.


Xu Y.,Sichuan University | Li L.,452 Hospital of Chinese PLA | Yu X.,Sichuan University | Gu Z.,Sichuan University | Zhang X.,Sichuan University
Carbohydrate Polymers | Year: 2012

Biological tissues must be chemically fixed before they can be implanted in humans. To overcome the cytotoxicity of the current chemical reagents used to fix bioprostheses, a naturally occurring crosslinking agent, alginate dialdehyde (ADA), was employed to fix biological tissues in this feasibility study. In this work, the crosslinking characteristics and the cytotoxicity of ADA-fixed biological tissues were investigated. The results indicated that ADA-fixed tissues are in possession of the fixation index and mechanical strength comparable to glutaraldehyde-fixed counterparts and superior to polyepoxy-fixed counterparts. The histological examination confirmed that the natural structure of the tissues preserved well after ADA fixation. Moreover, the results obtained in the MTT study further indicated that the cytotoxicity of ADA-fixed tissues was significantly lower than that of glutaraldehyde-fixed and polyepoxy-fixed tissues. In conclusion, the results of this vitro study demonstrate that ADA is an effective agent in the fixation of biological tissue. © 2011 Elsevier Ltd. All rights reserved.


Xu Y.,Sichuan University | Li L.,452 Hospital of Chinese PLA | Wang H.,Sichuan University | Yu X.,Sichuan University | And 3 more authors.
Carbohydrate Polymers | Year: 2013

Biological tissues must be chemically fixed before they can be implanted in humans, due to the immediate degradation and presence of antigenicity of naturally derived tissues. To provide a crosslinking reagent which is cytocompatible and may prepare biocompatible fixed tissues, a novel crosslinking agent, alginate dialdehyde (ADA), was employed to fix biological tissues by our group. The study was to evaluate the cytocompatibility of ADA for biological tissue fixation. Glutaraldehyde and genipin counterparts were used as controls. The result suggested that the cytotoxicity of ADA was significantly lower than that of glutaraldehyde and genipin. Additionally, in the evaluation of cytotoxicity of fixed tissue itself and the residues, as well as the cell adhesion property, ADA-fixed tissue was significantly superior to its glutaraldehyde counterpart and comparable to its genipin counterpart. The results obtained in this study demonstrate that ADA is a cytocompatible crosslinking reagent for biological tissue fixation. © 2012 Elsevier Ltd. All rights reserved.


Xu Y.,Sichuan University | Huang C.,Sichuan University | Li L.,452 Hospital of Chinese PLA | Yu X.,Sichuan University | And 4 more authors.
Carbohydrate Polymers | Year: 2013

Biological tissues must be chemically fixed before they can be implanted in humans as tissue engineering scaffolds. To provide an ideal tissue engineering scaffold material, which is biodegradable and cytocompatible, a novel crosslinking agent, alginate dialdehyde (ADA), was employed to fix biological tissues by our group. The study mainly investigated the enzymatic degradation of ADA fixed biological tissues in vitro. Glutaraldehyde, the most commonly used crosslinking agent for biological tissue fixation, was employed as a control. The results suggested that, the ADA fixation could enhance the resistance against enzymatic degradation of biological tissues effectively. Meanwhile, compared to glutaraldehyde-fixed tissues, the ADA-fixed tissues could also degrade gradually over time. Moreover, the ADA crosslinking reagent itself had a stimulatory effect on cell proliferation when at an appropriate concentration. The results obtained in this study demonstrate that ADA fixation might provide a successful example of the biodegradable scaffold materials in tissue engineering.


Wang Y.,Sichuan University | Wang X.,Sichuan University | Li L.,452 Hospital of Chinese PLA | Gu Z.,Sichuan University | Yu X.,Sichuan University
RSC Advances | Year: 2014

Initial burst release of drugs is a major shortcoming which needs to be addressed in treating osteomyelitis by using drug delivery systems (DDS). The aim of this study was to develop a novel DDS for reducing initial burst release based on the combination of chitosan (CS) microspheres and calcium polyphosphate/chitosan/aldehyde alginate (CPP/CS/ADA) composite scaffolds. CS microspheres and CPP/CS/ADA composite scaffolds were characterized by FTIR spectroscopy, a laser particle size analyzer and SEM in order to reveal their composition, size distribution and surface morphology. Tetracycline hydrochloride (TC), as a model drug in the study, was encapsulated in CS microspheres, which further combined with CPP/CS/ADA composite scaffolds to form new DDS. Then the in vitro drug release was studied in detail. The kinetics of the drug release was also systematically studied. The results indicate that this new microspheres/scaffold compound system has a promising potential to reduce initial drug burst release effectively and prolong drug release time even for 30 days. © 2014 the Partner Organisations.


Gu Z.,Sichuan University | Xie H.,University of Sichuan | Li L.,452 Hospital of Chinese PLA | Zhang X.,Sichuan University | And 2 more authors.
Journal of Materials Science: Materials in Medicine | Year: 2013

The key factor for regenerating large segmental bone defects through bone tissue engineering is angiogenesis in scaffolds. Attempts to overcome this problem, it is a good strategy to develop a new scaffold with bioactivity to induce angiogenesis in bone tissue engineering. In our previous research, the ability of strontium-doped calcium polyphosphate (SCPP) to stimulate the release of angiogenic growth factors from cultured osteoblasts was studied. This study was performed to determine the ability of SCPP to induce angiogenesis within in vitro co-culture model of human umbilical vein endothelial cells (HUVEC) and osteoblasts co-cultured. The bioactivity of developed scaffolds to induce angiogenesis in vivo was also researched in this paper. Co-cultured model has been developed in vitro and then cultured with SCPP scaffold as well as calcium polyphosphate (CPP) scaffold and hydroxylapatite (HA) scaffold. The results showed that the optimal ratio of HUVEC and osteoblasts co-cultured model for in vitro angiogenesis was 5:1. The model could maintain for more than 35 days when cultured with the scaffold and show the best activity at 21st day. Compared with those in CPP and HA scaffold, the formation of tube-like structure and the expression of platelet endothelial cell adhesion molecule in co-cultured model is better in SCPP scaffold. The in vivo immunohistochemistry staining for VEGF also showed that SCPP had a potential to promote the formation of angiogenesis and the regeneration of bone. SCPP scaffold could be served as a potential biomaterial with stimulating angiogenesis in bone tissue engineering and bone repair. © Springer Science+Business Media New York 2013.


Gu Z.,Sichuan University | Gu Z.,Suzhou University | Zhang X.,Sichuan University | Li L.,452 Hospital of Chinese PLA | And 4 more authors.
Materials Science and Engineering C | Year: 2013

The development of suitable bioactive three-dimensional scaffold for the promotion of bone regeneration is critical in bone tissue engineering. The purpose of this study was to investigate in vivo osteogenesis of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds for bone repair, as well as the relationship between osteogenic properties of SCPP scaffolds and the secretion of bFGF and VEGF from osteoblasts stimulated by SCPP. Besides, the advantages of scaffolds seeded with mesenchymal stem cells (MSCs) for bone repair were also studied. Firstly, the bone repair evaluation of scaffolds was performed on a rabbit segmental bony defects model over a period of 16 weeks by histology combined with X-ray microradiography. And then, in order to avoid the influence from the other factors such as hypoxia which emerge in vivo study and affect the secretion of VEGF and bFGF from host cells, human osteoblast-like cells (MG63) were seeded to SCPP, CPP and HA scaffolds in vitro to determine the ability of these scaffolds to stimulate the secretion of angiogenic growth factors (VEGF and bFGF) from MG63 and further explore the reason for the better osteogenic properties of SCPP scaffolds. The histological and X-ray microradiographic results showed that the SCPP scaffolds presented better osteogenic potential than CPP and HA scaffolds, when combined with MSCs, the SCPP scaffolds could further accelerate the bone repair. And the amounts of VEGF measured by ELISA assay in SCPP, CPP and HA groups after cultured for 7 days were about 364.989 pg/mL, 244.035 pg/mL and 232.785 pg/mL, respectively. Accordingly, the amounts of bFGF were about 27.085 pg/mL, 15.727 pg/mL and 8.326 pg/mL. The results revealed that the SCPP scaffolds significantly enhanced the bFGF and VEGF secretion compared with other scaffolds. The results presented in vivo and in vitro study demonstrated that the SCPP could accelerate bone formation through stimulating the secretion of VEGF and bFGF from osteoblasts, making it attractive for bone regeneration. © 2012 Elsevier B.V.


Gu Z.,Sichuan University | Xie H.,University of Sichuan | Huang C.,Sichuan University | Li L.,452 Hospital of Chinese PLA | Yu X.,Sichuan University
International Journal of Biological Macromolecules | Year: 2013

The objective of this work was to prepare chitosan/silk fibroin (CS/SF) blending membranes crosslinked with alginate dialdehyde (ADA) as wound dressings and to evaluate the physical properties and biocompatibility of the membranes. The morphology of membrane was observed by scanning electron microscopy (SEM) which showed that the well consistency of these two compositions. Further, the stability, water absorption and water vapor permeability of the ADA fixed CS/SF membranes could meet the needs of wound dressing. Furthermore, the biocompatibility of ADA fixed membranes was investigated by MTT assays and SEM in vitro, and the membranes were found to promote the cell attachment and proliferation. These results suggest that ADA fixed CS/SF blending membranes with a suitable ratio could be a promising candidate for wound healing applications. © 2013 Elsevier B.V.


Wang X.,Sichuan University | Wang Y.,Sichuan University | Li L.,452 Hospital of Chinese PLA | Gu Z.,Sichuan University | Yu X.,Sichuan University
Carbohydrate Polymers | Year: 2014

The aim of this study was to evaluate the crosslinking effect of dialdehyde carboxymethyl cellulose (DCMC) on decellularized porcine aortas. Before implanted, biological tissues must be chemically modified to avoid rapid enzymatic degradation and serious immune response. To overcome limitations like high cytotoxicity and susceptibility to calcification caused by glutaraldehyde (GA), a traditional crosslinking reagent, dialdehyde carboxymethyl cellulose (DCMC) was employed to fix biological tissues. The crosslinking characteristics and cytotoxicity of aortas fixed by DCMC were all investigated. The results indicated that DCMC-fixation significantly increased the mechanical strength and the capacity of enzymatic hydrolytic resistance of tissues. The histological examination showed that the microcosmic structures of tissues were all preserved well after DCMC fixation. In addition, the data obtained from MTT assay confirmed that the cytotoxicity of DCMC-fixed tissues was significantly lower than glutaraldehyde-fixed counterparts. In a word, the present study demonstrated DCMC might be an effective crosslinking reagent for biological tissue fixation with low cytotoxicity. © 2014 Elsevier Ltd. All rights reserved.


Huang C.,Sichuan University | Li L.,452 Hospital of Chinese PLA | Yu X.,Sichuan University | Gu Z.,Sichuan University | Zhang X.,Guangdong Medical Devices Quality Surveillance and Test Institute
Biomedical Materials (Bristol) | Year: 2014

Aseptic loosening is a common cause of joint implant failure in humans. In order to enhance implant stability, we need to develop a new material that not only promotes the wear resistance of components of an artificial joint, but also possesses the pharmaceutical efficacy of protecting patients against aseptic loosening. Strontium-doped calcium polyphosphate (SCPP) has been found to have this potential ability. The goal of this study is to respectively quantify the levels of TNF (for macrophages), receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) (for osteoblasts) when osteoblasts and macrophages are challenged with various particles (including SCPP). In this study, the osteoblasts ROS 17/2.8 and macrophages RAW 264.7 were challenged with various wear particles (8% SCPP, the molar percentage of Sr in SCPP is 8%, UHMWPE, hydroxyapatite (HA) and CPP). The secretion of TNF (from RAW 264.7), OPG and RANKL protein (from ROS 17/2.8) was analyzed by ELISA. The OPG and RANKL mRNA from ROS 17/2.8 was detected by RT-PCR. The data of ELISA indicated that the amount of TNF challenged with 8% SCPP particles was more than three-fold lower than that of all other test groups. The ratio of OPG/RANKL in the 8% SCPP group was significantly increased compared to that of all other test groups. The results of OPG and RANKL mRNA expression showed the same tendency as the ELISA results. In general, this study showed that 8% SCPP particles can inhibit the expression of TNF and RANKL, promote the expression of OPG so that SCPP can inhibit bone resorption and promote bone formation, and then inhibit aseptic loosening. Thus SCPP could be a promising material for the construction of artificial joints. © 2014 IOP Publishing Ltd.

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