摘要
Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and the diverse biological and mechanical properties across the tissue.Conventional repair strategies do not replicate the complex zonal characteristics within the meniscus,resulting in suboptimal outcomes.In this study,we introduce an innovative fetal/adult and stiffness-tunable meniscus decellularized extracellular matrix(DEM)-based hydrogel system designed for precision repair of heterogeneous,zonal-dependent meniscus injuries.By syn-thesizing fetal and adult DEM hydrogels,we identified distinct cellular responses,including that hydrogels with adult meniscus-derived DEM promote more fibrochondrogenic phenotypes.The incorporation of methacrylated hyaluronic acid(MeHA)further refined the mechanical properties and injectability of the DEM-based hydrogels.The combination of fetal and adult DEM with MeHA allowed for precise tuning of stiffness,influencing cell differentiation and closely mimicking native tissue environments.In vivo tests confirmed the biocompatibility of hydrogels and their integration with native meniscus tissues.Furthermore,advanced 3D bioprinting techniques enabled the fabrication of hybrid hydrogels with biomaterial and mechanical gradients,effectively emulating the zonal properties of meniscus tissue and enhancing cell integration.This study represents a significant advance in meniscus tissue engineering,providing a promising platform for customized regenerative therapies across a range of heterogeneous fibrous connective tissues.
基金
supported by the National Institutes of Health(K01 AR07787,R21 R077700,P30 AR069619,R01 AR056624,R01 HL163168)
National Science Foundation(CMMI 1548571)
Department of Veterans Affairs(CReATE Motion Center,I50 RX004845)in the United States
supported by the Korea Health Technology R&D Project through the Korea Health Industry Develop-ment Institute(KHIDI)funded by the Ministry of Health and Welfare(HI19C1095)
National R&D Program through the National Research Foundation of Korea(NRF)funded by Ministry of Science and ICT(RS-2024-00405574)in the Republic of Korea.
