Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration  

作　　者：Liang Zhou Feng Cai Hongyi Zhu Yichang Xu Jincheng Tang Wei Wang Ziang Li Jie Wu Zhouye Ding Kun Xi Liang Chen Yong Gu 

机构地区：[1]Department of Orthopedics Surgery,Orthopedic Institute,The First Affiliated Hospital of Soochow University,Soochow University,899 Pinghai Road,Suzhou,Jiangsu,215006,PR China

出　　处：《Bioactive Materials》2024年第7期132-152,共21页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China (82072438,82272501,81972078,82120108017,82102589,82372484,82302683);Natural Science Foundation of Jiangsu Province (BK20211504);Social Development Project of Jiangsu Province (BE2021646);Jiangsu Province"333 Project"talent project (2069999);Suzhou Gusu Health Talent Program (GSWS2020001,GSWS2021009,GSWS2021007);Jiangsu Innovative and Enterpreneurial Talent Program (JSSCBS20211570);Medical Health Science and Technology Innovation Program of Suzhou (SKY2022119).

摘　　要：Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration(IVDD).Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc.This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1(TGF-β1)(T-NNPs)onto the surface of methacrylic acid gelatin anhydride microspheres(GM)via amide bonds.The nanoparticle-microsphere complex(GM@T-NNPs)sustained the long-term release of T-NNPs with excellent cell-like functions,effectively bound to pro-inflammatory cytokines,and improved the release kinetics of TGF-β1,maintaining a 36 day-acting release.GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro,downregulated the expression of inflammatory factors and matrix metalloproteinase,and upregulated the expression of collagen-II and aggrecan.GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model.The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

关 键 词：Intervertebral disc degeneration Nucleus pulposus Hydrogel microsphere Neutrophil membrane Drug release kinetics Cell membrane-coated mimic 

分 类 号：R681.5[医药卫生—骨科学]