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An Injectable and Antifouling Self-fused Supramolecular Hydrogel for Preventing Postoperative and Recurrent Adhesion
Chemical Engineering Journal ( IF 13.3 ) Pub Date : 2020-09-22 , DOI: 10.1016/j.cej.2020.127096
Xiaoye Zhao , Jianhai Yang , Yang Liu , Jushan Gao , Ke Wang , Wenguang Liu

Abdominal adhesion is a serious complication of abdominal surgery. Existing barrier hydrogels are severely limited in the prevention of adhesions due to their poor controllability and long retention time in vivo. Here, we fabricate a supramolecular hydrogel (PNAGA-PHPMA) by copolymerization of N-acryloyl glycinamide (NAGA), a hydrogen bonding monomer, and highly hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA). The injectable PNAGA-PHPMA hydrogel cross-linked by reversible hydrogen bonds exhibits tunable rheological properties, preferable self-fused ability governed by H-bonds, excellent antifouling capability, and on-demand retention time in vivo. Squeezed out of a syringe to the abdominal cavity, the fragmented gel pieced self-fused into an intact hydrogel, thus demonstrating an efficient inhibitory effect on postoperative abdominal adhesions and recurrent adhesions after adhesiolysis. The molecular mechanism studies reveal that the hydrogel significantly downregulates fibrosis-related cytokines (TGF-β1 and Fibrinogen) and pro-inflammatory cytokines (TNF-α and IL-6), regulates the fibrinolytic system balance (t-PA and PAI-1), and inhibits the activity of Erk1/2 and p38 kinase in the mitogen-activated protein kinase (MAPK) signaling pathway, thereby showing an excellent anti-fibrotic and anti-inflammatory effect. This injectable and antifouling self-fused supramolecular hydrogel has a profound clinical significance for the prevention of postoperative adhesions and recurrent adhesions.



中文翻译:

可注射和防污的自融合超分子水凝胶,用于预防术后和复发性粘连

腹部粘连是腹部手术的严重并发症。现有的屏障水凝胶由于其可控性差和在体内的保留时间长,在防止粘连方面受到严重限制。在这里,我们通过共聚N-丙烯酰基甘氨酰胺(NAGA),氢键单体和高亲水性N-(2-羟丙基)甲基丙烯酰胺(HPMA)来制造超分子水凝胶(PNAGA-PHPMA )。通过可逆氢键交联的可注射PNAGA-PHPMA水凝胶具有可调节的流变性质,受H键控制的自熔性佳,出色的防污能力和体内按需保留时间从注射器中将其挤出腹腔,将破碎的凝胶自融为一块完整的水凝胶,从而证明对粘膜溶解后的术后腹腔粘连和复发性粘连具有有效的抑制作用。分子机理研究表明,水凝胶可显着下调与纤维化相关的细胞因子(TGF-β1和纤维蛋白原)和促炎性细胞因子(TNF-α和IL-6),调节纤溶系统的平衡(t-PA和PAI-1) ,并抑制有丝分裂原活化蛋白激酶(MAPK)信号传导途径中的Erk1 / 2和p38激酶的活性,从而显示出优异的抗纤维化和抗炎作用。这种可注射且防污的自融合超分子水凝胶对于预防术后粘连和复发性粘连具有深远的临床意义。

更新日期:2020-09-22
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