Gao Jushan, Wen Jinpeng, Hu Datao, Liu Kailai, Zhang Yuchen, Zhao Xinxin, Wang Ke
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
Bioact Mater. 2022 Feb 21;16:27-46. doi: 10.1016/j.bioactmat.2022.02.015. eCollection 2022 Oct.
Postsurgical adhesion is a common clinic disease induced by surgical trauma, accompanying serious subsequent complications. Current non-surgical approaches of drugs treatment and biomaterial barrier administration only show limited prevention effects and couldn't effectively promote peritoneum repair. Herein, inspired by bottlebrush, a novel self-fused, antifouling, and injectable hydrogel is fabricated by the free-radical polymerization in aqueous solution between the methacrylate hyaluronic acid (HA-GMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) monomer without any chemical crosslinkers, termed as H-HPMA hydrogel. The H-HPMA hydrogel can be tuned to perform excellent self-fused properties and suitable abdominal metabolism time. Intriguingly, the introduction of the ultra-hydrophilic HPMA chains to the H-HPMA hydrogel affords an unprecedented antifouling capability. The HPMA chains establish a dense hydrated layer that rapidly prevents the postsurgical adhesions and recurrent adhesions after adhesiolysis . The H-HPMA hydrogel can repair the peritoneal wound of the rat model within 5 days. Furthermore, an underlying mechanism study reveals that the H-HPMA hydrogel significantly regulated the mesothelial-to-mesenchymal transition (MMT) process dominated by the TGF-β-Smad2/3 signal pathway. Thus, we developed a simple, effective, and available approach to rapidly promote peritoneum regeneration and prevent peritoneal adhesion and adhesion recurrence after adhesiolysis, offering novel design ideas for developing biomaterials to prevent peritoneal adhesion.
术后粘连是一种由手术创伤引起的常见临床疾病,伴有严重的后续并发症。目前的药物治疗和生物材料屏障给药等非手术方法仅显示出有限的预防效果,无法有效促进腹膜修复。在此,受瓶刷启发,通过甲基丙烯酸酯透明质酸(HA-GMA)和N-(2-羟丙基)甲基丙烯酰胺(HPMA)单体在水溶液中进行自由基聚合,在无任何化学交联剂的情况下制备了一种新型的自融合、抗污且可注射的水凝胶,称为H-HPMA水凝胶。H-HPMA水凝胶可被调节以表现出优异的自融合性能和合适的腹腔代谢时间。有趣的是,将超亲水的HPMA链引入H-HPMA水凝胶赋予了前所未有的抗污能力。HPMA链形成了一个致密的水合层,可迅速防止术后粘连和粘连松解术后的复发性粘连。H-HPMA水凝胶可在5天内修复大鼠模型的腹膜伤口。此外,一项潜在机制研究表明,H-HPMA水凝胶显著调节了由TGF-β-Smad2/3信号通路主导的间皮-间充质转化(MMT)过程。因此,我们开发了一种简单、有效且可行的方法来快速促进腹膜再生,并防止腹膜粘连和粘连松解术后的粘连复发,为开发预防腹膜粘连的生物材料提供了新的设计思路。