Coaxial electrohydrodynamic printing of core–shell microfibrous scaffolds with layer-specific growth factors release for enthesis regeneration  

作　　者：Lang Bai Meiguang Xu Zijie Meng Zhennan Qiu Jintao Xiu Baojun Chen Qian Han Qiaonan Liu Pei He Nuanyang Wen Jiankang He Jing Zhang Zhanhai Yin 

机构地区：[1]Department of Orthopaedics,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,People’s Republic of China [2]State Key Laboratory for Manufacturing Systems Engineering,Xi’an Jiaotong University,Xi’an 710049,People’s Republic of China [3]Frontier Institute of Science and Technology,Xi’an Jiaotong University,Xi’an 710049,People’s Republic of China [4]Department of Surgery of Spine and Spinal Cord,Henan Provincial People’s Hospital,Zhengzhou 450003,People’s Republic of China [5]Key Laboratory of Resource Biology and Biotechnology in Western China,Ministry of Education.School of Medicine,Northwest University,Xi’an 710069,People’s Republic of China

出　　处：《International Journal of Extreme Manufacturing》2024年第5期220-238,共19页极端制造（英文）

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.

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.

关 键 词：coaxial electrohydrodynamic printing core-shell structures microfibrous scaffolds growth factors enthesis regeneration 

分 类 号：R318.08[医药卫生—生物医学工程]