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载有 FGFR2 修饰的脂肪源性干细胞的双改性硫酸化细菌纤维素支架材料在尿道重建中的临床应用。

Clinical application of a double-modified sulfated bacterial cellulose scaffold material loaded with FGFR2-modified adipose-derived stem cells in urethral reconstruction.

机构信息

Department of Urology, Peking University First Hospital, Beijing, 100034, China.

Institution of Urology, Peking University, Beijing, 100034, China.

出版信息

Stem Cell Res Ther. 2022 Sep 6;13(1):463. doi: 10.1186/s13287-022-03164-9.

Abstract

BACKGROUND

Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification.

METHODS

First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip.

RESULTS

The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs.

CONCLUSIONS

Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

摘要

背景

尿道狭窄和重建是泌尿外科领域的棘手难题之一。组织工程和生物材料的不断发展为此问题提供了新的治疗思路。细菌纤维素(BC)是一种优秀的生物材料,具有易得性和强可塑性。此外,脂肪源性干细胞(ADSCs)通过定向修饰可以增强其伤口愈合能力。

方法

本研究首先通过物理钻孔和磺化处理使 BC 更有利于细胞附着和降解。我们测试了这些材料的相关力学性能。之后,我们将成纤维细胞生长因子受体 2(FGFR2)修饰的 ADSCs 附着在材料上,构建用于组织工程的尿道。然后,我们在雄性新西兰兔模型中验证了这一发现,并在手术后 1 和 3 个月进行了免疫组织化学和成像检查。同时,我们通过生物信息学和细胞因子芯片检测 FGFR2 的潜在生物学功能。

结果

结果表明,该复合材料具有优异的可修复性,且这种能力与血管生成有关。本研究中的新型复合材料为尿道重建提供了新的思路和治疗方法。初步机制表明,FGFR2 通过促进 ADSCs 分泌血管内皮生长因子 A(VEGFA),促进血管生成和组织修复。

结论

双修饰磺化细菌纤维素支架与 FGFR2 修饰 ADSCs 相结合,为尿道狭窄患者提供了新的治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a226/9450280/9b14f9b5d449/13287_2022_3164_Fig1_HTML.jpg

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