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收集并失活转化生长因子-β1水凝胶用于青光眼滤过术后抗瘢痕治疗

Collecting and deactivating TGF-β1 hydrogel for anti-scarring therapy in post-glaucoma filtration surgery.

作者信息

Wang Ruiqi, Chen Boyang, Wei Haiying, Yan Wei, Wu Yuping, Wang Cao, Zhang Bosong, Liu Fengzhen, Tian Hui, Chen Xiongbiao, Tian Weiming

机构信息

School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150080, Heilongjiang Province, People's Republic of China.

The First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Harbin, 150001, Heilongjiang Province, PR China.

出版信息

Mater Today Bio. 2022 Apr 18;14:100260. doi: 10.1016/j.mtbio.2022.100260. eCollection 2022 Mar.

Abstract

Scar formation can lead to glaucoma filtration surgery (GFS) failure, wherein transforming growth factor (TGF)-β is the core regulator. To reducing scar formation, this paper presents our study on the design of hydrogels to deactivate TGF-β1. We hypothesized that excess TGF-β1 can be removed from aqueous humor through the addition of oxidized hyaluronic acid (O-HA) hydrogels that are seeded with decorin (O-HA ​+ ​D). Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to demonstrate the adsorption properties of O-HA ​+ ​D hydrogel, thus reducing the TGF-β1 concentration in aqueous humor. In the light that collagen contraction in human Tenon's capsule fibroblasts (HTFs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs) can be activated by TGF-β1 and β2, we performed the quantitative analysis of polymerase chain reaction to determine the effect of O-HA ​+ ​D on the type I collagen, fibronectin, and angiogenesis. Our results illustrate that O-HA ​+ ​D can inhibit the increase of α-SMA expression in HTF induced by TGF-β1 and that O-HA ​+ ​D can inhibit the production of collagen I and fibronectin in HTF treated with TGF-β1. Furthermore, we performed in vivo studies by employing a rabbit model, where rabbits were treated with hydrogels post GFS. Our results demonstrate that, as compared with other groups, the rabbits treated with O-HA ​+ ​D had the greatest reduction in inflammatory cells with reduced level of collagen in wounds. Taken together, the present study paves the way toward the treatment of post-glaucoma fibrosis following surgery.

摘要

瘢痕形成可导致青光眼滤过手术(GFS)失败,其中转化生长因子(TGF)-β是核心调节因子。为减少瘢痕形成,本文介绍了我们关于设计水凝胶以失活TGF-β1的研究。我们假设通过添加接种了核心蛋白聚糖的氧化透明质酸(O-HA)水凝胶(O-HA + D),可以从房水中去除过量的TGF-β1。进行免疫组织化学和酶联免疫吸附测定(ELISA)以证明O-HA + D水凝胶的吸附特性,从而降低房水中的TGF-β1浓度。鉴于TGF-β1和β2可激活人眼球筋膜成纤维细胞(HTF)中的胶原收缩以及人脐静脉内皮细胞(HUVEC)的血管生成,我们进行了聚合酶链反应定量分析,以确定O-HA + D对I型胶原、纤连蛋白和血管生成的影响。我们的结果表明,O-HA + D可抑制TGF-β1诱导的HTF中α-SMA表达的增加,并且O-HA + D可抑制用TGF-β1处理的HTF中I型胶原和纤连蛋白的产生。此外,我们通过使用兔模型进行了体内研究,在青光眼滤过手术后给兔子注射水凝胶。我们的结果表明,与其他组相比,用O-HA + D处理的兔子炎症细胞减少最多,伤口处的胶原水平降低。综上所述,本研究为青光眼术后纤维化的治疗铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a436/9061788/12acb3c4535f/gr1.jpg

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