Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing  

作　　者：Jintao Li Haolin Ke Xiangcheng Lei Jiexin Zhang Zhicheng Wen Zhisheng Xiao Huabin Chen Juncheng Yao Xuan Wang Zhengnong Wei Hongrui Zhang Weilun Pan Yan Shao Yitao Zhao Denghui Xie Chun Zeng 

机构地区：[1]Department of Sports Medicine,Center for Orthopedic Surgery,Orthopedic Hospital of Guangdong Province,The Third School of Clinical Medicine,Southern Medical University,The Third Affiliated Hospital of Southern Medical University,Guangzhou,Guangdong,China [2]Department of Orthopedics,Academy of Orthopedics⋅Guangdong Province,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases,The Third Affiliated Hospital of Southern Medical University,Guangzhou,Guangdong,China [3]Department of Spine Surgery,Center for Orthopedic Surgery,The Third Affiliated Hospital of Southern Medical University,Guangzhou,Guangdong,China [4]The Second School of Clinical Medicine,Zhujiang Hospital,Southern Medical University,Guangzhou,China [5]Department of Laboratory Medicine,Nanfang Hospital,Southern Medical University,Guangzhou,510515,China

出　　处：《Bioactive Materials》2024年第6期62-82,共21页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China[grant numbers:82302639,81974327,81974328 and 82372358];National Students’Platform for Innovation and Entrepreneurship Training Program of China[grant number:No.202212121004];Natural Science Funds for Distinguished Young Scholar of Guangdong province[grant number:2022B1515020044];the Natural Science Foundation of Guangdong Province[grant number:2022A1515011101].

摘　　要：Tendon-bone interface injuries pose a significant challenge in tissue regeneration,necessitating innovative approaches.Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries.In this study,we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions(Mg^(2+)).We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles(Mg-PC)through a self-assembly process and integrated them into a two-component hydrogel.The hydrogel was composed of dopamine-modified hyaluronic acid(Dop-HA)and F127.To ensure controlled release and mitigate the“burst release”effect of Mg^(2+),we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel.This crosslinking strategy extended the release window of Mg^(2+)concentrations for up to 56 days.The resulting hydrogel(Mg-PC@Dop-HA/F127)exhibited favorable properties,including injectability,thermosensitivity and shape adaptability,making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites.Furthermore,the hydrogel sustained the release of Mg^(2+)and Procyanidins,which attracted mesenchymal stem and progenitor cells,alleviated inflammation,and promoted macrophage polarization towards the M2 phenotype.Additionally,it enhanced collagen synthesis and mineralization,facilitating the repair of the tendon-bone interface.By incorporating multilevel metal phenolic networks(MPN)to control ion release,these hybridized hydrogels can be customized for various biomedical applications.

关 键 词：Magnesium Metal-phenolic networks Self-assembly process Controlled release IMMUNOMODULATION Tendon-bone interface 

分 类 号：R318[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]