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载 bFGF 和 SDF-1 的几丁质水凝胶促进内源性间充质干细胞归巢改善压力性尿失禁。

Chitin-based hydrogel loaded with bFGF and SDF-1 for inducing endogenous mesenchymal stem cells homing to improve stress urinary incontinence.

机构信息

Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, People's Republic of China.

College of Chemistry & Molecular Sciences, Wuhan University, Hubei Engineering Center of Natural Polymers-based Medical Materials, Wuhan, 430072, People's Republic of China.

出版信息

Carbohydr Polym. 2023 Nov 1;319:121144. doi: 10.1016/j.carbpol.2023.121144. Epub 2023 Jun 29.

Abstract

Nonoperative treatments for Stress Urinary Incontinence (SUI) represent an ideal treatment method. Mesenchymal stem cell (MSCs) treatment is a new modality, but there is a lack of research in the field of gynecological pelvic floor and no good method to induce internal MSC homing to improve SUI. Herein, we develop an injectable and self-healing hydrogel derived from β-chitin which consists of an amino group of quaternized β-chitin (QC) and an aldehyde group of oxidized dextran (OD) between the dynamic Schiff base linkage.it can carry bFGF and SDF-1a and be injected into the vaginal forearm of mice in a non-invasive manner. It provides sling-like physical support to the anterior vaginal wall in the early stages. In the later stage, it slowly releasing factors and promoting the homing of MSCs in vivo, which can improve the local microenvironment, increase collagen deposition, repair the tissue around urethra and finally improve SUI (Scheme 1). This is the first bold attempt in the field of pelvic floor using hydrogel mechanical support combined with MSCs homing and the first application of chitin hydrogel in gynecology. We think the regenerative medicine approach based on bFGF/SDF-1/chitin hydrogel may be an effective non-surgical approach to combat clinical SUI.

摘要

非手术治疗压力性尿失禁(SUI)是一种理想的治疗方法。间充质干细胞(MSCs)治疗是一种新方法,但在妇科盆底领域的研究还比较缺乏,也没有很好的方法来诱导内源性 MSC 归巢以改善 SUI。在这里,我们开发了一种可注射的和自修复的水凝胶,它来源于β-壳聚糖,由季铵化β-壳聚糖(QC)的氨基和氧化葡聚糖(OD)的醛基之间的动态席夫碱键组成。它可以携带 bFGF 和 SDF-1a,并以非侵入性的方式注射到小鼠的阴道前臂中。它在早期为前阴道壁提供类似吊带的物理支撑,在后期缓慢释放因子并促进 MSC 在体内归巢,从而改善局部微环境,增加胶原蛋白沉积,修复尿道周围组织,最终改善 SUI(方案 1)。这是在盆底领域首次尝试使用水凝胶机械支撑结合 MSC 归巢,也是壳聚糖水凝胶在妇科的首次应用。我们认为基于 bFGF/SDF-1/壳聚糖水凝胶的再生医学方法可能是治疗临床 SUI 的一种有效非手术方法。

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