School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China.
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, China.
Acta Biomater. 2022 Oct 1;151:163-173. doi: 10.1016/j.actbio.2022.08.001. Epub 2022 Aug 6.
Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.
术后腹膜粘连是手术后常见的并发症，发病率高。除了改善手术操作外，药物治疗和物理屏障是预防术后腹膜粘连的两种主要方法。单一的防粘连方法往往效果不理想，屏障治疗与防粘连药物的联合应用受到了更多的关注。本研究首先证明了补体激活异常与腹膜损伤和炎症反应有关。相应地，阻断 C5a-C5aR 轴反应能有效减轻炎症反应。因此，我们创新性地开发了一种针对腹膜粘连的木葡聚糖衍生物（mXG）水凝胶与静脉注射抗 C5a 受体抗体（anti-C5aRab）的联合治疗方法，并采用小鼠侧壁缺损-盲肠擦伤模型系统评估了其治疗效果。体外和体内实验表明，mXG 水凝胶具有良好的生物相容性和可降解性，可作为安全的防粘连屏障。结果表明，抗 C5aRab 治疗可通过减少中性粒细胞浸润和磷酸化 Smad2 的表达，显著抑制腹膜粘连。综上所述，mXG 水凝胶与抗 C5aRab 联合应用具有优异的防粘连性能，在预防腹膜粘连方面具有广阔的临床应用前景。
术后腹膜粘连是手术后亟待解决的问题。先前开发了一种可生物降解和热可逆的木葡聚糖衍生物（mXG）水凝胶，可有效预防术后腹膜粘连，但仍可观察到明显的炎症反应和增殖。此外，补体激活异常与多种炎症性疾病有关。我们证明了补体激活异常参与了腹膜粘连。在这项工作中，mXG 水凝胶和静脉注射抗 C5a 受体抗体（anti-C5aRab）被整合在一起以解决腹膜粘连问题。anti-C5aRab 减少了炎症反应。此外，mXG 水凝胶易于使用，并能有效地将伤口表面隔离在局部损伤部位。总体而言，这种联合治疗显著提高了防粘连效果。
