3D printing of interferonγ-preconditioned NSC-derived exosomes/collagen/chitosan biological scaffolds for neurological recovery after TBI  

作　　者：Chong Chen Zhe-Han Chang Bin Yao Xiao-Yin Liu Xiao-Wang Zhang Jun Liang Jing-Jing Wang Shuang-Qing Bao Meng-Meng Chen Ping Zhu Xiao-Hong Li 

机构地区：[1]Academy of Medical Engineering and Translational Medicine,Tianjin University,Tianjin,300072,China [2]Guangdong Cardiovascular Institute,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,Guangdong,510100,China [3]Guangdong Provincial Key Laboratory of Pathogenesis,Targeted Prevention and Treatment of Heart Disease,Guangzhou Key Laboratory of Cardiac Pathogenesis and Prevention,Guangzhou,Guangdong,510100,China [4]Tianjin Key Laboratory of Neurotrauma Repair,Characteristic Medical Center of People’s Armed Police Forces,Tianjin,300162,China [5]Department of Neurosurgery,West China Hospital,West China Medical School,Sichuan University,Chengdu,610041,Sichuan,China

出　　处：《Bioactive Materials》2024年第9期375-391,共17页生物活性材料（英文）

基　　金：supported by the National Key Research and Development Program of China(2021YFF1200800,2018YFA0108700);the National Natural Science Foundation of China(82171861,82170256,82101448);Guangdong Provincial Special Support Program for Prominent Talents(2021JC06Y656);Science and Technology Planning Project of Guangdong Province(2020B1111170011,2022B1212010010);Guangzhou Science and Technology Plan Project(202201000006);the Natural Science Foundation of Sichuan Province(24NSFSC3547).

摘　　要：The reconstruction of neural function and recovery of chronic damage following traumatic brain injury(TBI)remain significant clinical challenges.Exosomes derived from neural stem cells(NSCs)offer various benefits inTBI treatment.Numerous studies confirmed that appropriate preconditioning methods enhanced the targetedefficacy of exosome therapy.Interferon-gamma(IFN-γ)possesses immunomodulatory capabilities and is widelyinvolved in neurological disorders.In this study,IFN-γwas employed for preconditioning NSCs to enhance theefficacy of exosome(IFN-Exo,IE)for TBI.miRNA sequencing revealed the potential of IFN-Exo in promotingneural differentiation and modulating inflammatory responses.Through low-temperature 3D printing,IFN-Exowas combined with collagen/chitosan(3D-CC-IE)to preserve the biological activity of the exosome.The deliveryof exosomes via biomaterial scaffolds benefited the retention and therapeutic potential of exosomes,ensuring that they could exert long-term effects at the injury site.The 3D-CC-IE scaffold exhibited excellentbiocompatibility and mechanical properties.Subsequently,3D-CC-IE scaffold significantly improved impairedmotor and cognitive functions after TBI in rat.Histological results showed that 3D-CC-IE scaffold markedlyfacilitated the reconstruction of damaged neural tissue and promoted endogenous neurogenesis.Furthermechanistic validation suggested that IFN-Exo alleviated neuroinflammation by modulating the MAPK/mTORsignaling pathway.In summary,the results of this study indicated that 3D-CC-IE scaffold engaged in long-termpathophysiological processes,fostering neural function recovery after TBI,offering a promising regenerativetherapy avenue.

关 键 词：EXOSOMES Traumatic brain injury Interferonγ 3D printing Neural reconstruction 

分 类 号：R318[医药卫生—生物医学工程]