%0 Journal Article
%T DNA Tetrahedron Delivering miR-21-5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis.
%A Qi L
%A Hong S
%A Zhao T
%A Yan J
%A Ge W
%A Wang J
%A Fang X
%A Jiang W
%A Shen SG
%A Zhang L
%J Adv Healthc Mater
%V 0
%N 0
%D 2024 Jul 9
%M 38979868
%F 11.092
%R 10.1002/adhm.202401275
%X Compromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As the most abundant bone-related miRNA, miRNA-21-5p plays a crucial role in inducing osteogenic and angiogenic differentiation. However, highly efficient miR-21-5p delivery still confronts challenges including poor cellular uptake and easy degradation. Herein, TDN-miR-21-5p nanocomplex is constructed based on DNA tetrahedral (TDN) and has great potential in promoting osteogenesis and alleviating senescence of senescent bone marrow stem cells (O-BMSCs), simultaneously enhancing angiogenic capacity of senescent endothelial progenitor cells (O-EPCs). Of note, the activation of AKT and Erk signaling pathway may direct regulatory mechanism of TDN-miR-21-5p mediated osteogenesis and senescence of O-BMSCs. Also, TDN-miR-21-5p can indirectly mediate osteogenesis and senescence of O-BMSCs through pro-angiogenic growth factors secreted from O-EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN and TDN-miR-21-5p to fabricate delivery scaffolds. TDN-miR-21-5p@GelMA scaffold exhibits greater bone repair with increased expression of osteogenic- and angiogenic-related markers in senescent critical-size cranial defects in vivo. Collectively, TDN-miR-21-5p can alleviate senescence and induce osteogenesis and angiogenesis in senescent microenvironment, which provides a novel candidate strategy for senescent bone repair and widen clinical application of TDNs-based gene therapy.