Aptamer-Modified\nTetrahedral Framework Nucleic Acid\nSynergized with TGF-β3 to Promote Cartilage Protection in Osteoarthritis\nby Enhancing Chondrogenic Differentiation of MSCs

Characterized by progressive and\nirreversible degeneration of the articular cartilage (AC), osteoarthritis\n(OA) is the most common chronic joint disease, and there is no cure\nfor OA at present. Recent studies suggest that enhancing the recruitment\nof endogenous mesenchymal stem cells (MSCs) to damaged cartilage is\na promising therapeutic strategy for cartilage repair. Tetrahedral\nframework nucleic acid (tFNA) is a novel DNA nanomaterial and has\nshown great potential in the field of biomedical science. Transforming\ngrowth factor-beta 3 (TGF-β3), a vital member of the highly\nconserved TGF-β superfamily, is considered to induce chondrogenesis.\nA 66-base DNA aptamer named HM69 is reported to identify and recruit\nMSCs. In this study, aptamer HM69-modified tFNAs were successfully\nself-assembled and used to load TGF-β3 when the disulfide bonds\ncombined. We confirmed the successful synthesis of the final composition,\nHM69-tFNA@TGF-β3 (HTT), by PAGE, dynamic light scattering, and\natomic force microscopy. The results of in vitro experiments showed\nthat HTT effectively induced MSC proliferation, migration, and chondrogenic\ndifferentiation. In addition, HTT-treated MSCs were shown to protect\nthe OA chondrocytes. In DMM mice, the injection of HTT improved the\ntherapeutic outcome of mouse pain symptoms and AC degeneration. In\nconclusion, this study innovatively used the disulfide bonds combined\nwith TGF-β3 and tFNA, and an additional sequence HM69 was loaded\non tFNA for the better-targeted recruitment of MSCs. HTT demonstrated\nits role in promoting the chondrogenesis of MSCs and cartilage protection,\nindicating that it might be promising for OA therapy.