软骨
细胞生物学
血管内皮生长因子A
化学
血管生成
下调和上调
脚手架
组织工程
生物医学工程
血管内皮生长因子
血管内皮生长因子受体
癌症研究
解剖
生物
医学
生物化学
基因
作者
Yi Chen,Wei Chen,Yiming Ren,Shuling Li,Miao Liu,Jiahua Xing,Yudi Han,Youbai Chen,Ran Tao,Lingli Guo,Xiang Sui,Quanyi Guo,Shuyun Liu,Han Yan
标识
DOI:10.1016/j.ijbiomac.2022.09.065
摘要
Cartilage is an important tissue that is widely found in joints, ears, nose and other organs. The limited capacity to regenerate makes cartilage reconstruction an urgent clinical demand. Due to the avascular nature of cartilage, we hypothesized that inhibition of vascularization contributes to cartilage formation. Here, we used VEGFa siRNA to inhibit the infiltration of the local vascular system. Optimized lipid nanoparticles were prepared by microfluidics for the delivery of siRNA. Then, we constructed a tissue engineering scaffold. Both seed cells and VEGFa siRNA-LNPs were loaded in a GELMA hydrogel. Subcutaneous implantation experiments in nude mice indicate that this is a promising strategy for cartilage reconstruction. The regenerated cartilage was superior, with significant upregulation of SOX9, COL-II and ACAN. This is attributed to an environment deficient in oxygen and nutrients, which facilitates cartilage formation by upregulating HIF-1α and FOXO transcription factors. In conclusion, a GelMA/Cells+VEGFa siRNA-LNPs scaffold was constructed to achieve superior cartilage regeneration.
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