Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor  

作　　者：Congyi Shen Jian Wang Guangfeng Li Shuyue Hao Yan Wu Peiran Song Yafei Han Mengmeng Li Guangchao Wang Ke Xu Hao Zhang Xiaoxiang Ren Yingying Jing Ru Yang Zhen Geng Jiacan Su 

机构地区：[1]Institute of Translational Medicine,Shanghai University,Shanghai,200444,China [2]Organoid Research Center,Shanghai University,Shanghai,200444,China [3]School of Medicine,Shanghai University,Shanghai,200444,China [4]School of Life Sciences,Shanghai University,Shanghai,200444,China [5]National Center for Translational Medicine(Shanghai)SHU Branch,Shanghai University,Shanghai,200444,China [6]Department of Orthopedics,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200092,China [7]Department of Orthopedics,Shanghai Zhongye Hospital,Shanghai,200941,China [8]Second Affiliated Hospital of Soochow University,Departments of Rheumatology and Immunology,Soochow,215000,China

出　　处：《Bioactive Materials》2024年第5期429-444,共16页生物活性材料（英文）

基　　金：supported by the National Key Research and Development Program of China(No.2022YFB3804300);Integrated Project of Major Research Plan of National Natural Science Foundation of China(92249303);Key Project of the National Natural Science Foundation of China(82230071);National Natural Science Foundation of China(32101084).

摘　　要：Osteoarthritis(OA),a common degenerative disease,is characterized by high disability and imposes substantial economic impacts on individuals and society.Current clinical treatments remain inadequate for effectively managing OA.Organoids,miniature 3D tissue structures from directed differentiation of stem or progenitor cells,mimic native organ structures and functions.They are useful for drug testing and serve as active grafts for organ repair.However,organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth.Hydrogel microspheres,with tunable physical and chemical properties,show promise in cartilage tissue engineering by replicating the natural microenvironment.Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration,we developed a novel RGD-SF-DNA hydrogel microsphere(RSD-MS)via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA.The RSD-MSs exhibited uniform size,porous surface,and optimal swelling and degradation properties.In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells(BMSCs)proliferation,adhesion,and chondrogenic differentiation.Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis.Moreover,in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors(COPs)significantly enhanced cartilage regeneration.In conclusion,RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids,offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.

关 键 词：Silk fibroin-DNA hydrogel MICROSPHERE CHONDROGENESIS Cartilage organoid Cartilage repair 

分 类 号：R318[医药卫生—生物医学工程]