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Jiani Zheng, Hongguo Xie,
Weiting Yu,
Mingqian Tan,
Faquan Gong,
Xiudong Liu,
Feng Wang,
Guojun Lv,
Wanfa Liu,
Guoshuang Zheng,
Yan Yang,
Weiyang Xie,
Xiaojun Ma
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ABSTRACT: Alginate/chitosan/alginate (ACA) hydrogel microcapsules were modified with methoxy poly(ethylene glycol) (MPEG) to improve protein repellency and biocompatibility. Increased MPEG surface graft density (n(S)) on hydrogel microcapsules was achieved by controlling the grafting parameters including the buffer layer substrate, membrane thickness, and grafting method. X-ray photoelectron spectroscopy (XPS) model was employed to quantitatively analyze n(S) on this three-dimensional (3D) hydrogel network structure. Our results indicated that neutralizing with alginate, increasing membrane thickness, and in situ covalent grafting could increase n(S) effectively. ACAC(PEG) was more promising than ACC(PEG) in protein repellency because alginate supplied more -COO(-) negative binding sites and prevented MPEG from diffusing. The n(S) increased with membrane thickness, showing better protein repellency. Moreover, the in situ covalent grafting provided an effective way to enhance n(S), and 1.00 ± 0.03 chains/nm(2) was achieved, exhibiting almost complete immunity to protein adsorption. This antifouling hydrogel biomaterial is expected to be useful in transplantation in vivo.
Langmuir 08/2012; 28(37):13261-73. · 4.19 Impact Factor
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Ying Ma,
Ying Zhang,
Shan Zhao,
Yu Wang,
Siran Wang,
Yan Zhou,
Na Li, Hongguo Xie,
Weiting Yu,
Yang Liu,
Wei Wang,
Xiaojun Ma
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ABSTRACT: Microencapsulation has been a promising approach for drug delivery, cell implantation, cell-based gene therapy and large-scale cell culture. To make use of microcapsules more effectively, it is important to accurately construct the microcapsule membranes with desired properties including a certain thickness, strength, and so forth. To date single factor experiments have been widely used, however, they are time-consuming to obtain the desired membrane preparation conditions. Response surface methodology (RSM) is a mathematical and statistical technique for building empirical models that gained importance for optimizing reacting conditions. In this study, three signifficant effect factors that affect alginate-based microcapsule membrane properties, including membrane thickness, swelling degree, and mechanical stability, were determined with Plackett-Burman method, and then three empirical models were built to optimize the preparation conditions of the microcapsule membranes according to the responses of these three signifficant effect factors respectively with RSM. These models can be used to predict the characteristics of microcapsules under different membrane preparation conditions, which provide a guide for optimizing the microencapsulation technology.
Journal of Biomedical Materials Research Part A 03/2012; 100(4):989-98. · 2.63 Impact Factor
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ABSTRACT: The up-regulation of VEGF interrelated to tumor angiogenesis provides a target for tumor treatment. We describe the feasibility of using chitosan nanoparticles for successful VEGF-siRNA delivery to finally reduce the VEGF level in a mouse melanoma model in vitro. The chitosan/VEGF-siRNA (CTS/siRNA) nanoparticles were prepared with a size of 110-200nm and zeta potential of ~20mV. Moreover, the stable nanoparticles can successfully transport VEGF-siRNA into cells, and release siRNA for VEGF gene silencing.
Journal of Controlled Release 11/2011; 152 Suppl 1:e160-1. · 5.73 Impact Factor
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Journal of Controlled Release 11/2011; 152 Suppl 1:e246-8. · 5.73 Impact Factor
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ABSTRACT: Aggregating into multicellular spheroids within alginate–poly-L-lysine–alginate (APA) microcapsules is important in maintaining the cellular viability and specific functions. However, in the absence of a vascular network, cells in the core of large-sized spheroids are gradually necrotic because of oxygen transfer limitations. In this study, a novel APA microcapsule embedded with three-dimensional fibrous scaffolds (called APA-FS) was proposed to eliminate cellular necrosis by regulating cells to form multi-small spheroids. HepG2 cells were embedded within the APA-FS to form spheroids and the state of these spheroids was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay, glucose/lactate metabolism, live/dead staining, and hematoxylin and eosin staining. Comparing with the conventional APA microcapsules, the cells within APA-FS organized into multi-small spheroids. The size of these spheroids depended on the concentration of fibrous scaffolds embedded within the microcapsules. In the APA-FS embedded with 5% (v/v) fibrous scaffolds, the average size of cellular spheroids was controlled below 100 microm and the cellular viability was increased by 50% than the control. The results of live/dead staining and hematoxylin and eosin staining showed that the improved cellular viability might be attributed to the decreased necrosis in the core of these spheroids. The improved viability of cells demonstrated the efficiency of this technology. These findings implied that this system might provide a more suitable culture environment for a variety of tissue engineering applications.
Tissue Engineering Part C Methods 10/2010; 16(5):1023-32. · 4.64 Impact Factor
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ABSTRACT: Microencapsulation of recombinant cells is a novel means for gene therapy. However, one of the major concerns is the relationship between the permeability of microcapsule and cell growth. Many studies have focused on the permeability of empty microcapsule, but little is known about the effect of the cell growth on the permeability of a cell-contained microcapsule. A combination of fluorescence labeled protein and confocal laser scanning microscope (CLSM) provides the information about the permeability changes during the cell growth. A decrease of membrane permeability was detected on the 14th day. Meanwhile, membrane surface protein fouling was also investigated. A significant increase of membrane surface protein content was detected on the 21st day. In order to study the effect of the permeability changes on the cell viability, the membrane of cell-contained microcapsules with different permeability was set up by incubating gel beads in poly-L-lysine for 5 and 30 min, respectively, to mimic the bovine serum albumin cutoff, and a retard of cell growth was found in 7 days' culture. These results showed that the protein fouling of the microcapsule membrane caused by the cell growth may be an important factor to influence cell viability.
Journal of Biomedical Materials Research Part A 08/2008; 90(3):773-83. · 2.63 Impact Factor
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ABSTRACT: Oral administration of artificial cell microcapsules entrapping live bacterial cells is a promising approach in disease therapy. However, the current technology of microcapsules limits this approach. In this study, alginate-chitosan-alginate (ACA) microcapsules entrapping live bacterial cells were prepared with the purpose of oral delivery for therapy, and their in vitro and in vivo properties were investigated. Genetically engineered Escherichia coli DH5 were used as the model bacterial strain. ACA microcapsules remained intact and stable in simulated gastrointestinal fluid and the entrapped bacteria cells survived and grew normally. Moreover, ACA microcapsules were more stable than alginate-polylysine-alginate microcapsules in the rat gastrointestinal tract, which was attributed to the enhanced resistance of the ACA microcapsules to enzymatic digestion. Therefore, these results reinforce the potential of ACA microcapsules for the therapeutic oral delivery of live bacterial cells.
Journal of Bioscience and Bioengineering 06/2008; 105(6):660-5. · 1.79 Impact Factor
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ABSTRACT: Oxidation reactions of alginate solution with H2O2 were performed under different conditions to prepare low molecular weight alginate, and its potential application for tissue engineering was investigated. H2O2 oxidation is an effective method for alginate depolymerization with the rate depending on reaction time, temperature, solution pH and H2O2 concentration. The structure analyses by FT-IR, elemental analysis and 13C NMR indicated that, the rupture of glucoside bonds in alginate chains into low molecular weight polymers is the basic process during H2O2 depolymerization. Oxidation of alginate under weak oxidation conditions (H2O2 0.6% (w/v), 50 °C, 1 h) did not significantly interfere in the formation of ionic junctions with calcium ions. The cross-linked alginate scaffold prepared from the obtained alginate under these conditions showed faster degradation rate than that from the unmodified alginate, due to the lower molecular weight of oxidized alginate and the formed aldehyde groups susceptible to hydrolysis.
Carbohydrate Polymers 79(3):660-664. · 3.63 Impact Factor
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ABSTRACT: Polyelectrolyte complexes (PECs) have been the focus of an expanding number of studies for their wide use. This study investigated the characteristics and biodegradation of chitosan–alginate PECs prepared by freeze-drying a precipitate from sufficient mixtures of the two polymers. The analyses of X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) suggested that the partial protonated amine groups of chitosan reacted with the carboxylate groups of alginate and thus strong PECs were formed. After incubating in lysozyme solution, the PECs showed high ability of enzyme adsorption, and low degradation rate in spite of different degrees of deacetylation of chitosan, due to the strong interaction between chitosan and alginate and the hindrance of closely adsorbed lysozyme.
Polymer Degradation and Stability 94(1):1-6. · 2.77 Impact Factor