The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Hsing-wen Sung - One of the best experts on this subject based on the ideXlab platform.
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genipin crosslinked gelatin microspheres as a drug carrier for intramuscular administration in vitro and in vivo studies
Journal of Biomedical Materials Research Part A, 2003Co-Authors: Huangchien Liang, Wenhsiang Chang, Kojung Lin, Hsing-wen SungAbstract:Gelatin microspheres have been widely evaluated as a drug carrier. Nevertheless, gelatin dissolves rather rapidly in aqueous environments, making the use of the polymer difficult for the production of long-term delivery systems. This adverse aspect requires the use of a crosslinking agent in forming nonsoluble networks in microspheres. However, the use of crosslinking agents such as formaldehyde and Glutaraldehyde can lead to toxic side effects owing to residual crosslinkers. In an attempt to overcome this problem, a naturally occurring crosslinking agent (genipin) was used to crosslink gelatin microspheres as a biodegradable drug-delivery system for intramuscular administration. Glutaraldehyde was used as a control. In the in vitro study, the morphology, dynamic swelling, and antienzymatic degradation of test microspheres were evaluated. In the in vivo study, the biocompatibility and degradability of test microspheres were implanted in the skeletal muscle of a rat model via intramuscular injection. The results obtained in the study suggested that crosslinking of gelatin microspheres with Glutaraldehyde or genipin may produce distinct crosslinking structures. The water transport mechanism in both the Glutaraldehyde- and genipin-crosslinked gelatin microspheres exhibit anomalous behavior ranging from Fickian to Case-II extremes. The increase of the swelling diameter for the genipin-crosslinked microspheres was significantly less than that observed for the Glutaraldehyde-crosslinked microspheres. In the animal study, it was found that the degree in inflammatory reaction for tissues implanted with the genipin-crosslinked microspheres was significantly less than that implanted with the Glutaraldehyde-crosslinked microspheres. Additionally, the degradation rate of the genipin-crosslinked microspheres was significantly slower than their Glutaraldehyde-crosslinked counterparts. These results indicated that the genipin-crosslinked gelatin microspheres may be used as a long-acting drug carrier for intramuscular administration.
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genipin crosslinked gelatin microspheres as a drug carrier for intramuscular administration in vitro and in vivo studies
Journal of Biomedical Materials Research Part A, 2003Co-Authors: Huangchien Liang, Wenhsiang Chang, Kojung Lin, Hsing-wen SungAbstract:Gelatin microspheres have been widely evaluated as a drug carrier. Nevertheless, gelatin dissolves rather rapidly in aqueous environments, making the use of the polymer difficult for the production of long-term delivery systems. This adverse aspect requires the use of a crosslinking agent in forming nonsoluble networks in microspheres. However, the use of crosslinking agents such as formaldehyde and Glutaraldehyde can lead to toxic side effects owing to residual crosslinkers. In an attempt to overcome this problem, a naturally occurring crosslinking agent (genipin) was used to crosslink gelatin microspheres as a biodegradable drug-delivery system for intramuscular administration. Glutaraldehyde was used as a control. In the in vitro study, the morphology, dynamic swelling, and antienzymatic degradation of test microspheres were evaluated. In the in vivo study, the biocompatibility and degradability of test microspheres were implanted in the skeletal muscle of a rat model via intramuscular injection. The results obtained in the study suggested that crosslinking of gelatin microspheres with Glutaraldehyde or genipin may produce distinct crosslinking structures. The water transport mechanism in both the Glutaraldehyde- and genipin-crosslinked gelatin microspheres exhibit anomalous behavior ranging from Fickian to Case-II extremes. The increase of the swelling diameter for the genipin-crosslinked microspheres was significantly less than that observed for the Glutaraldehyde-crosslinked microspheres. In the animal study, it was found that the degree in inflammatory reaction for tissues implanted with the genipin-crosslinked microspheres was significantly less than that implanted with the Glutaraldehyde-crosslinked microspheres. Additionally, the degradation rate of the genipin-crosslinked microspheres was significantly slower than their Glutaraldehyde-crosslinked counterparts. These results indicated that the genipin-crosslinked gelatin microspheres may be used as a long-acting drug carrier for intramuscular administration. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 65A: 271–282, 2003
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A genipin-crosslinked gelatin membrane as wound-dressing material: in vitro and in vivo studies.
Journal of biomaterials science. Polymer edition, 2003Co-Authors: Wenhsiang Chang, Yen Chang, Po-hong Lai, Hsing-wen SungAbstract:A naturally occurring crosslinking agent (genipin) was used in this study to crosslink gelatin hydrogel to develop a wound-dressing membrane. The study was to investigate the in vitro characteristics of the genipin-crosslinked gelatin membrane. The Glutaraldehyde-crosslinked counterpart, at a similar crosslinking degree, was used as control. Additionally, an in vivo experiment was undertaken to study the wound healings covered with the Glutaraldehyde- and genipin-crosslinked dressings in a rat model. The in vitro results obtained suggested that crosslinking of gelatin membranes with Glutaraldehyde or genipin may produce distinct crosslinking structures. The differences in crosslinking structure can significantly affect the mechanical property, water-vapor-transmission rate, swelling ratio, degradation against enzyme and cellular compatibility of the crosslinked membranes. In the in vivo study, it was found that the degree of inflammatory reaction for the wound treated with the genipin-crosslinked dressing was significantly less severe than that covered with the Glutaraldehyde-crosslinked dressing throughout the entire course of the study. Additionally, the healing rate for the wound treated with the genipin-crosslinked dressing was notably faster than its Glutaraldehyde-crosslinked counterpart.
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in vivo evaluation of cellular and acellular bovine pericardia fixed with a naturally occurring crosslinking agent genipin
Biomaterials, 2002Co-Authors: Yen Chang, Huangchien Liang, Chenchi Tsai, Hsing-wen SungAbstract:Abstract A cell extraction process was employed in the study to remove the cellular components from bovine pericardium, leaving a framework of largely insoluble collagen and elastin. It was hypothesized in the literature that this process may decrease the antigenic load (or increase the biocompatibility) within the material. Additionally, acellular tissues may provide a natural microenvironment for host-cell migration to regenerate the tissue. The study was to evaluate the biocompatibility of cellular and acellular bovine pericardia fixed with a naturally occurring crosslinking agent (genipin) implanted subcutaneously in a growing rat model. Additionally, the tissue regeneration rate in the genipin-fixed acellular tissue was investigated. The Glutaraldehyde-fixed counterparts were used as controls. The results indicated that the degrees in inflammatory reaction for the genipin-fixed cellular and acellular tissues were significantly less than their Glutaraldehyde-fixed counterparts. Additionally, it was noted that the inflammatory reactions for the Glutaraldehyde-fixed cellular and acellular tissues lasted much longer than their genipin-fixed counterparts. The tissue regeneration rate for the genipin-fixed acellular tissue was significantly faster than its Glutaraldehyde-fixed counterpart. The calcium content of each studied group, analyzed by atomic absorption, did not change significantly until at the 52nd week, postoperatively. The differences in calcium content between the cellular and acellular tissues were insignificant for both the Glutaraldehyde- and genipin-fixed groups throughout the entire course of the study. In summary, the biocompatibility of the genipin-fixed cellular and acellular tissues was superior to their Glutaraldehyde-fixed counterparts. The genipin-fixed acellular tissue provided a better microenvironment for tissue regeneration than its Glutaraldehyde-fixed counterpart, due to its low cytotoxicity. These results suggested that the genipin-fixed acellular tissue might be used as a tissue-engineering matrix in the clinical applications.
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Stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin)
Journal of Biomedical Materials Research, 2001Co-Authors: Hsing-wen Sung, I. Lin Liang, Chiun Nan Chen, Rong-nan Huang, Hsiang Fa LiangAbstract:The study was undertaken to investigate the stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin) at distinct elapsed storage durations. The Glutaraldehyde-fixed counterpart was used as a control. Porcine pericardia procured from a slaughterhouse were used as raw materials. After fixation, the fixed tissues were sterilized in a graded series of ethanol solutions and thoroughly rinsed in phosphate buffered saline for 1 day, and then stored in a jar containing sterilized water. The samples were taken out and tested for their stability during the durations of 1day through 6 months after storage. The stability of each study group was tested by measuring its tensile strength, free-amino-group content, and denaturation temperature. Additionally, the cytotoxicity of each test sample and its corresponding storage solution were investigated in vitro using 3T3 fibroblasts. The results were examined using a microscope and 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that the stability of the genipin-fixed tissue during storage was superior to its Glutaraldehyde-fixed counterpart. The differences in stability between the genipin- and Glutaraldehyde-fixed tissues during storage may be caused by their differences in crosslinking structure. There was no apparent cytotoxicity for both the genipin-fixed tissue and its corresponding storage solution throughout the entire course of the study, whereas significant cytotoxicity was observed for both the Glutaraldehyde-fixed tissue and its storage solution. However, the cytotoxicity of the Glutaraldehyde-fixed tissue decreased with increasing elapsed storage duration, whereas that of its corresponding storage solution increased. This suggested that the toxic residues remaining in the Glutaraldehyde-fixed tissue leached out slowly into its corresponding storage solution during the course of storage.
Mario Lopezmoya - One of the best experts on this subject based on the ideXlab platform.
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optimizing Glutaraldehyde fixed tissue heart valves with chondroitin sulfate hydrogel for endothelialization and shielding against deterioration
Biomacromolecules, 2018Co-Authors: Mario Lopezmoya, Pedro Melgarlesmes, Jose M De La Torre Hernandez, Kumaran Kolandaivelu, Elazer R. Edelman, Mercedes BalcellsAbstract:Porcine Glutaraldehyde-fixed pericardium is widely used to replace human heart valves. Despite the stabilizing effects of Glutaraldehyde fixation, the lack of endothelialization and the occurrence of immune reactions contribute to calcification and structural valve deterioration, which is particularly significant in young patients, in whom valve longevity is crucial. This report shows an optimization system with which to enhance endothelialization of fixed pericardium to mimic the biological function of a native heart valve. The Glutaraldehyde detoxification, together with the application of a biodegradable methacrylated chondroitin sulfate hydrogel, reduces aldehydes cytotoxicity, increases the migration and proliferation of endothelial cells and the recruitment of endothelial cell progenitors, and confers thromboresistance in fixed pericardium. The combination of Glutaraldehyde detoxification and a coating with chondroitin sulfate hydrogel promotes in situ mechanisms of endothelialization in fixed peric...
Roberto Fernandezlafuente - One of the best experts on this subject based on the ideXlab platform.
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immobilization and stabilization of different β glucosidases using the Glutaraldehyde chemistry optimal protocol depends on the enzyme
International Journal of Biological Macromolecules, 2019Co-Authors: Diandra De Andrades, Roberto Fernandezlafuente, Natalia G Graebin, Marina Kimiko Kadowaki, Marco Antonio Zachia Ayub, Rafael C RodriguesAbstract:Three β-glucosidases (Pectinex Ultra SP-L, Pectinex Ultra Clear and homemade preparation from Aspergillus niger) were immobilized using different strategies: ionic adsorption on aminated (MANAE)-agarose beads at pH 5, 7, and 9, followed by biocatalysts modification with Glutaraldehyde, or on Glutaraldehyde pre-activated supports. The pH of the immobilization was altered to allow different enzyme molecule orientations on the support surface. The biocatalysts from Pectinex Ultra SP-L showed the highest thermal and operational stabilities when immobilized on MANAE-agarose-Glutaraldehyde at pH 7. The β-glucosidase from Pectinex Ultra Clear and from A. niger produced best results when immobilized on MANAE-agarose beads at pH 5 and 7, respectively, which was later treated with Glutaraldehyde. The best immobilization results using pre-activated supports were observed for the enzyme present in Pectinex Ultra SP-L, to which the highest thermal stabilities were obtained. Remarkably, the enzyme from A. niger, immobilized on MANAE-agarose at pH 9 and subsequently treated with Glutaraldehyde, produced the highest stabilization (approximately 560 times more stable than soluble enzyme at 60 °C). Results showed that optimal protocol for β-glucosidases immobilizations using the Glutaraldehyde chemistry must be individually tested and tailored to each type of enzyme.
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Glutaraldehyde in bio catalysts design a useful crosslinker and a versatile tool in enzyme immobilization
RSC Advances, 2014Co-Authors: Oveimar Barbosa, Rafael C Rodrigues, Claudia Ortiz, Angel Berenguermurcia, Rodrigo Torres, Roberto FernandezlafuenteAbstract:Glutaraldehyde is one of the most widely used reagents in the design of biocatalysts. It is a powerful crosslinker, able to react with itself, with the advantages that this may bring forth. In this review, we intend to give a general vision of its potential and the precautions that must be taken when using this effective reagent. First, the chemistry of the Glutaraldehyde/amino reaction will be commented upon. This reaction is still not fully clarified, but it seems to be based on the formation of 6-membered heterocycles formed by 5 C and one O. Then, we will discuss the production of intra- and inter-molecular enzyme crosslinks (increasing enzyme rigidity or preventing subunit dissociation in multimeric enzymes). Special emphasis will be placed on the preparation of cross-linked enzyme aggregates (CLEAs), mainly in enzymes that have low density of surface reactive groups and, therefore, may be problematic to obtain a final solid catalyst. Next, we will comment on the uses of Glutaraldehyde in enzymes previously immobilized on supports. First, the treatment of enzymes immobilized on supports that cannot react with Glutaraldehyde (only inter and intramolecular cross-linkings will be possible) to prevent enzyme leakage and obtain some enzyme stabilization via cross-linking. Second, the cross-linking of enzymes adsorbed on aminated supports, where together with other reactions enzyme/support crosslinking is also possible; the enzyme is incorporated into the support. Finally, we will present the use of aminated supports preactivated with Glutaraldehyde. Optimal Glutaraldehyde modifications will be discussed in each specific case (one or two Glutaraldehyde molecules for amino group in the support and/or the protein). Using preactivated supports, the heterofunctional nature of the supports will be highlighted, with the drawbacks and advantages that the heterofunctionality may have. Particular attention will be paid to the control of the first event that causes the immobilization depending on the experimental conditions to alter the enzyme orientation regarding the support surface. Thus, Glutaraldehyde, an apparently old fashioned reactive, remains the most widely used and with broadest application possibilities among the compounds used for the design of biocatalyst.
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different mechanisms of protein immobilization on Glutaraldehyde activated supports effect of support activation and immobilization conditions
Enzyme and Microbial Technology, 2006Co-Authors: Lorena Betancor, Fernando Lopezgallego, Aurelio Hidalgo, Noelia Alonsomorales, Gisela Dellamoraortiz Cesar Mateo, Roberto Fernandezlafuente, Jose M GuisanAbstract:Abstract The precise control of the conditions during support activation with Glutaraldehyde has enabled the modification of the amino groups of the matrix with one or two Glutaraldehyde molecules. Moreover, the use of aminated supports implies that below each Glutaraldehyde molecule, there are amino groups and, therefore, these supports could be considered as heterofunctional matrices; an anion exchanger bearing Glutaraldehyde groups for covalent immobilization. Thus, by using several enzymes as models, it has been found that at low ionic strength the protein immobilization on Glutaraldehyde activated supports proceeds via a first ionic interchange of the protein on the amino groups of the support, followed by the covalent reaction. Moreover, the dimeric form of Glutaraldehyde seems to be much more reactive than its monomeric counterpart, permitting the immobilization of proteins even at very high ionic strength. Although in all cases the immobilization of the enzymes on both monomer and dimeric matrices promoted a significant increment in the enzyme stability, it was found that the stabilization depends on the degree of activation (monomer or dimer), and it is necessary to analyze each individual enzyme before selecting any of the immobilization protocols.
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enzyme stabilization by Glutaraldehyde crosslinking of adsorbed proteins on aminated supports
Journal of Biotechnology, 2005Co-Authors: Fernando Lopezgallego, Lorena Betancor, Aurelio Hidalgo, Noelia Alonsomorales, Jose M Guisan, Cesar Mateo, Gisela Dellamoraortiz, Roberto FernandezlafuenteAbstract:The stabilization achieved by different immobilization protocols have been compared using three different enzymes (glutaryl acylase (GAC), D-aminoacid oxidase (DAAO), and glucose oxidase (GOX)): adsorption on aminated supports, treatment of this adsorbed enzymes with Glutaraldehyde, and immobilization on Glutaraldehyde pre-activated supports. In all cases, the treatment of adsorbed enzymes on amino-supports with Glutaraldehyde yielded the higher stabilizations: in the case of GOX, a stabilization over 400-fold was achieved. After this treatment, the enzymes could no longer be desorbed from the supports using high ionic strength (suggesting the support-protein reaction). Modification of the enzymes immobilized on supports that did not offer the possibility of react with Glutaraldehyde showed the same stability that the non modified preparations demonstrating that the mere chemical modification did not have effect on the enzyme stability. This simple strategy seems to permit very good results in terms of immobilization rate and stability, offering some advantages when compared to the immobilization on Glutaraldehyde pre-activated supports.
Mercedes Balcells - One of the best experts on this subject based on the ideXlab platform.
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optimizing Glutaraldehyde fixed tissue heart valves with chondroitin sulfate hydrogel for endothelialization and shielding against deterioration
Biomacromolecules, 2018Co-Authors: Mario Lopezmoya, Pedro Melgarlesmes, Jose M De La Torre Hernandez, Kumaran Kolandaivelu, Elazer R. Edelman, Mercedes BalcellsAbstract:Porcine Glutaraldehyde-fixed pericardium is widely used to replace human heart valves. Despite the stabilizing effects of Glutaraldehyde fixation, the lack of endothelialization and the occurrence of immune reactions contribute to calcification and structural valve deterioration, which is particularly significant in young patients, in whom valve longevity is crucial. This report shows an optimization system with which to enhance endothelialization of fixed pericardium to mimic the biological function of a native heart valve. The Glutaraldehyde detoxification, together with the application of a biodegradable methacrylated chondroitin sulfate hydrogel, reduces aldehydes cytotoxicity, increases the migration and proliferation of endothelial cells and the recruitment of endothelial cell progenitors, and confers thromboresistance in fixed pericardium. The combination of Glutaraldehyde detoxification and a coating with chondroitin sulfate hydrogel promotes in situ mechanisms of endothelialization in fixed peric...
Elazer R. Edelman - One of the best experts on this subject based on the ideXlab platform.
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optimizing Glutaraldehyde fixed tissue heart valves with chondroitin sulfate hydrogel for endothelialization and shielding against deterioration
Biomacromolecules, 2018Co-Authors: Mario Lopezmoya, Pedro Melgarlesmes, Jose M De La Torre Hernandez, Kumaran Kolandaivelu, Elazer R. Edelman, Mercedes BalcellsAbstract:Porcine Glutaraldehyde-fixed pericardium is widely used to replace human heart valves. Despite the stabilizing effects of Glutaraldehyde fixation, the lack of endothelialization and the occurrence of immune reactions contribute to calcification and structural valve deterioration, which is particularly significant in young patients, in whom valve longevity is crucial. This report shows an optimization system with which to enhance endothelialization of fixed pericardium to mimic the biological function of a native heart valve. The Glutaraldehyde detoxification, together with the application of a biodegradable methacrylated chondroitin sulfate hydrogel, reduces aldehydes cytotoxicity, increases the migration and proliferation of endothelial cells and the recruitment of endothelial cell progenitors, and confers thromboresistance in fixed pericardium. The combination of Glutaraldehyde detoxification and a coating with chondroitin sulfate hydrogel promotes in situ mechanisms of endothelialization in fixed peric...
