Hydrogels loaded with microRNA(miRNA)have shown promise in bone-defect repair.Here,we present the first report of miRNA-loaded hydrogels containing bioactivities to treat steroid-induced osteonecrosis of the femoral h...Hydrogels loaded with microRNA(miRNA)have shown promise in bone-defect repair.Here,we present the first report of miRNA-loaded hydrogels containing bioactivities to treat steroid-induced osteonecrosis of the femoral head(SONFH),based on the mechanism of competing endogenous RNAs.Transcriptome sequencing of human bone marrow mesenchymal stem cells(HBMSCs)extracted from the proximal femoral bone marrow and subsequent functional assays revealed that the circSRPK1/miR-320a axis promotes HBMSCs osteogenic differentiation.By incorporating antagomir-320a(a miR-320a inhibitor)encapsulated in liposomes into injectable hyaluronic acid(HA)hydrogels,we constructed an injectable hydrogel,HA@antagomir-320a.This hydrogel demonstrated exceptional osteogenic properties,targeting multiple osteogenic pathways via CDH2 and Osterix and exhibited excellent in vitro biocompatibility.In vivo,it substantially enhanced bone formation in the osteonecrotic area of the femoral head.This injectable HA@antagomir-320a hydrogel,which exhibited exceptional biocompatibility and osteogenic properties in vivo and in vitro,offers a promising and minimally invasive solution for the treatment of SONFH.展开更多
基金supported by the Beijing Natural Science Foundation(L232006,J230001)National High-Level Hospital Clinical Research Funding(2022-PUMCH-C-036)+2 种基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-C&T-B-031)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program(2019ZLH206)National Natural Science Foundation of China(81871740,81871786,81630064,82302708,52335004,and 52275199).
文摘Hydrogels loaded with microRNA(miRNA)have shown promise in bone-defect repair.Here,we present the first report of miRNA-loaded hydrogels containing bioactivities to treat steroid-induced osteonecrosis of the femoral head(SONFH),based on the mechanism of competing endogenous RNAs.Transcriptome sequencing of human bone marrow mesenchymal stem cells(HBMSCs)extracted from the proximal femoral bone marrow and subsequent functional assays revealed that the circSRPK1/miR-320a axis promotes HBMSCs osteogenic differentiation.By incorporating antagomir-320a(a miR-320a inhibitor)encapsulated in liposomes into injectable hyaluronic acid(HA)hydrogels,we constructed an injectable hydrogel,HA@antagomir-320a.This hydrogel demonstrated exceptional osteogenic properties,targeting multiple osteogenic pathways via CDH2 and Osterix and exhibited excellent in vitro biocompatibility.In vivo,it substantially enhanced bone formation in the osteonecrotic area of the femoral head.This injectable HA@antagomir-320a hydrogel,which exhibited exceptional biocompatibility and osteogenic properties in vivo and in vitro,offers a promising and minimally invasive solution for the treatment of SONFH.
