Zhu, JinjinYang, ShuhuiQi, YadongGong, ZheZhang, HaitaoLiang, KaiyuShen, PanyangHuang, Yin-YuanZhang, ZheYe, WeilongYue, LeiFan, ShunwuShen, ShuyingMikos, Antonios G.Wang, XiumeiFang, Xiangqian2022-04-152022-04-152022Zhu, Jinjin, Yang, Shuhui, Qi, Yadong, et al.. "Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model." <i>Science Advances,</i> 8, no. 13 (2022) AAAS: https://doi.org/10.1126/sciadv.abk0011.https://hdl.handle.net/1911/112100Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes (P16INK4a/P21) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir-29b-5p, which was functionalized by conjugating a stem cell–homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.engThis is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.Journal articlesciadv-abk0011https://doi.org/10.1126/sciadv.abk0011