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Preparation of gelatin hydrogels incorporating low-molecular-weight heparin for anti-fibrotic therapy

机译:含低分子量肝素的明胶水凝胶的制备,用于抗纤维化治疗

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The objective of this study is to design biodegradable hydrogels for the controlled release of low-molecular-weight heparin (LMWH) and evaluate the biological activity. Gelatin was cationized by chemically introducing ethylene diamine into the carboxyl groups in different conditions to obtain cationized gelatins. The cationized gelatin was mixed with the LMWH in aqueous solution to form the complex. Gelatin, together with the complex of LMWH and cationized gelatin, was dehydrothermally cross-linked for different time periods to prepare the gelatin hydrogel-incorporating complex. The hydrogel-incorporating complex was neither degraded in phosphate-buffered saline solution (PBS) at 37°C nor did it release the LMWH complex. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded to release the LMWH complex. The time profile of hydrogel degradation and the LMWH release depended on the condition of hydrogel cross-linking. The longer the cross-linking time period, the slower the hydrogel degradation and the subsequent LMWH release. The half-life period of LMWH release was in good correspondence with that of hydrogel degradation. It is possible that the LMWH was released as the result of hydrogel degradation. When applied to the mouse model of abdominal membrane fibrosis, the hydrogel system of LMWH release showed a promising anti-fibrotic effect.
机译:这项研究的目的是设计用于可控制释放的低分子量肝素(LMWH)的生物可降解水凝胶,并评估其生物活性。通过在不同条件下将乙二胺化学引入羧基中来使明胶阳离子化,以获得阳离子化明胶。将阳离子化明胶与LMWH在水溶液中混合以形成复合物。将明胶与LMWH和阳离子化明胶的复合物在不同时间段进行脱氢热交联,以制备掺有明胶水凝胶的复合物。掺有水凝胶的复合物既不会在37°C的磷酸盐缓冲盐溶液(PBS)中降解,也不会释放LMWH复合物。当置于含有胶原酶的PBS中时,水凝胶被酶降解以释放LMWH复合物。水凝胶降解和LMWH释放的时间曲线取决于水凝胶交联的条件。交联时间越长,水凝胶降解和随后的LMWH释放越慢。 LMWH释放的半衰期与水凝胶降解的半衰期良好对应。 LMWH可能由于水凝胶降解而释放。当应用于小鼠腹膜纤维化模型时,LMWH释放的水凝胶系统显示出有希望的抗纤维化作用。

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