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3D 缺氧模拟和抗粘连水凝胶促进肾损伤修复和再生的新血管形成。

3D hypoxia-mimicking and anti-synechia hydrogel enabling promoted neovascularization for renal injury repair and regeneration.

作者信息

Zhang Yuehang, Yu Lei, Qiu Renjie, Cao Lisha, Ye Genlan, Lin Rurong, Wang Yongqin, Wang Guobao, Hu Bianxiang, Hou Honghao

机构信息

Division of Nephrology, State Key Lab for Organ Failure Research, National Clinical Research Center of Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.

Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.

出版信息

Mater Today Bio. 2023 Jun 7;21:100694. doi: 10.1016/j.mtbio.2023.100694. eCollection 2023 Aug.

Abstract

renal tissue engineering is promising yet challenging for renal injury repair and regeneration due to the highly vascularized structure of renal tissue and complex high-oxidative stress and ischemic microenvironment. Herein, a novel biocompatible 3D porous hydrogel (DFO-gel) with sustained release capacity of hypoxia mimicking micromolecule drug deferoxamine (DFO) was developed for renal injury repair. and experimental results demonstrated that the developed DFO-gels can exert the synchronous benefit of scavenging excess reactive oxygen species (ROS) regulating inflammatory microenvironment and promoting angiogenesis for effective renal injury repair by up-regulating hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). The neogenesis of neonatal glomerular- and tubular-like structures in the implanted areas in the partially nephrectomized rats also suggested the potential for promoting renal injury repair and regeneration. This multifunctional hydrogel can not only exhibit the sustained release and promoted bio-uptake capacity for DFO, but also improve the renal injured microenvironment by alleviating oxidative and inflammatory stress, accelerating neovascularization, and promoting efficient anti-synechia. We believe this work offers a promising strategy for renal injury repair and regeneration

摘要

由于肾组织高度血管化的结构以及复杂的高氧化应激和缺血微环境,肾组织工程在肾损伤修复和再生方面虽前景广阔但也颇具挑战。在此,我们开发了一种新型生物相容性三维多孔水凝胶(DFO-凝胶),其具有模拟缺氧小分子药物去铁胺(DFO)的缓释能力,用于肾损伤修复。实验结果表明,所开发的DFO-凝胶可通过上调缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF),发挥清除过量活性氧(ROS)、调节炎症微环境和促进血管生成的协同作用,实现有效的肾损伤修复。部分肾切除大鼠植入区域新生肾小球样和肾小管样结构的形成也表明其具有促进肾损伤修复和再生的潜力。这种多功能水凝胶不仅能展现出DFO的缓释和促进生物摄取能力,还能通过减轻氧化和炎症应激、加速新血管形成以及促进高效抗粘连来改善肾损伤微环境。我们相信这项工作为肾损伤修复和再生提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115f/10279555/bbdbc0ec91e2/ga1.jpg

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