Kim Yun Ah, Chun So Young, Park Sung-Bin, Kang Eunyoung, Koh Won-Gun, Kwon Tae Gyun, Han Dong Keun, Joung Yoon Ki
Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Korea.
Biomater Sci. 2020 Oct 7;8(19):5427-5440. doi: 10.1039/d0bm00871k. Epub 2020 Sep 3.
Fibroblast-derived extracellular matrix (fECM)-supported scaffolds made up of poly(lactic-co-glycolic acid) were prepared with the enhanced preservation of ECM components by composites with magnesium hydroxide nanoparticles (MH NPs), and were applied for the renal tissue regeneration. MH NP utilization resulted in an increased ECM protein amount, decreased scaffold degradation, and surface hydrophilic modification. These effects were correlated with the improved adhesion and viability of renal proximal tubule epithelial cells on the scaffold. In vivo experiments demonstrated effects of fECM and MH NPs on renal regeneration. The number of glomeruli was the largest in the ECM scaffold with MH NPs as compared to the pristine scaffold and ECM scaffold without MH NPs. Quantitative PCR analysis exhibited less inflammation (IL-1β, TNF-α, and IL-6) and fibrosis-related (vimentin, collagen I, and α-SMA) markers, whereas opposite results were found in regeneration-related markers (Pax2, vWf, Wt1, and Emx2). The concentration of renal function-related molecules, creatinine and blood urea nitrogen diminished in the ECM scaffold with MH NPs. All results indicate that MH NPs utilization for the renal regenerative scaffold is effective for in vitro and in vivo environments and is, therefore, a good model for regeneration of kidneys and other tissues, and organs.
由聚乳酸-乙醇酸共聚物制成的成纤维细胞衍生细胞外基质(fECM)支持的支架,通过与氢氧化镁纳米颗粒(MH NPs)复合,能增强细胞外基质成分的保留,并应用于肾组织再生。MH NPs的使用导致细胞外基质蛋白量增加、支架降解减少以及表面亲水性修饰。这些效应与肾近端小管上皮细胞在支架上的粘附和活力改善相关。体内实验证明了fECM和MH NPs对肾再生的作用。与原始支架和不含MH NPs的ECM支架相比,含MH NPs的ECM支架中肾小球数量最多。定量PCR分析显示炎症(IL-1β、TNF-α和IL-6)和纤维化相关(波形蛋白、胶原蛋白I和α-SMA)标志物较少,而在再生相关标志物(Pax2、vWf、Wt1和Emx2)中则发现相反的结果。含MH NPs的ECM支架中与肾功能相关的分子肌酐和血尿素氮浓度降低。所有结果表明,将MH NPs用于肾再生支架在体外和体内环境中均有效,因此是肾脏及其他组织和器官再生的良好模型。