摘要
The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.
基金
financially supported by the National Key Research and Development Program of China(2018YFA0703003)
National Natural Science Foundation of China(82072429,52125501,82371590)
the Program for Innovation Team of Shaanxi Province(2023-CX-TD-17)
the Key Research&Development Program of Shaanxi Province(2024SF-YBXM-355,2020SF-093,2021LLRH-08)
the Natural Science Foundation of Henan Province(222300420358)
the Postdoctoral Project of Shaanxi Province(2023BSHYDZZ30)
the Postdoctoral Fellowship Program of CPSF(GZB20230573)
the Institutional Foundation of the First Affiliated Hospital of Xi’an Jiaotong University(2019ZYTS-02)
the Fundamental Research Funds for the Central Universities.
