Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model

• DOI: 10.1126/sciadv.abk0011
• Publication Date: 2022-03-30T17:57:25Z
• Authors: Jinjin Zhu; Shuhui Yang; Yadong Qi; Zhe Gong; Haitao Zhang; Kaiyu Liang; Panyang Shen; Yin-Yuan Huang; Zhe Zhang; Weilong Ye; Lei Yue; Shunwu Fan; Shuying Shen; Antonios G. Mikos; Xiumei Wang; Xiangqian Fang
• Keywords: Cartilage, Articular; MicroRNAs; Stem Cells; Osteoarthritis; Animals; Regeneration; Hydrogels; Biomedicine and Life Sciences; Rats

Osteoarthritis (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 (

P16 INK4a /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.