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杂交生物活性水凝胶通过部分肝切除术后激活枯否细胞和细胞外基质重塑促进肝脏再生。

Hybrid Bioactive Hydrogel Promotes Liver Regeneration through the Activation of Kupffer Cells and ECM Remodeling After Partial Hepatectomy.

机构信息

Department of Liver Surgery and Liver Transplantation, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China.

Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai, 200127, P. R. China.

出版信息

Adv Healthc Mater. 2024 Jul;13(17):e2303828. doi: 10.1002/adhm.202303828. Epub 2024 Apr 21.

Abstract

Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self-repairing mixed hydrogel (OH/Cu/SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with OH, demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage-regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.

摘要

部分肝切除术是一种重要的外科技术,用于治疗晚期肝脏疾病,如肝肿瘤,以及进行活体供肝移植。然而,术后并发症如出血、腹部粘连、伤口感染和肝再生不足等,都构成了重大挑战,增加了发病率和死亡率。开发了一种自修复混合水凝胶(OH/Cu/SCCK),其中包含源自人脐带间充质干细胞(HUMSCs)的干细胞衍生细胞因子(SCCK),并用传统中药丹参酮 IIA(TSA)处理。这种 SCCK 与 OH 联合使用,对枯否细胞激活和细胞外基质(ECM)重塑具有显著作用。这导致分泌关键生长因子,促进肝细胞和内皮细胞的增殖,从而促进部分肝切除后的肝再生和修复。此外,水凝胶具有调节巨噬细胞的特性,可有效减轻切口区域的炎症和氧化应激损伤,为术后肝再生创造最佳环境。水凝胶的可注射性和强粘附性可在切口部位迅速止血,其物理屏障功能可防止术后腹部粘连。此外,水凝胶中加入的 Cu 提供了全面的抗菌作用,可预防多种类型的细菌,并降低手术后感染的机会。

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