An anti-senescence hydrogel with pH-responsive drug release for mitigating intervertebral disc degeneration and low back pain  

作　　者：Wantao Wang Lei Liu Wenzheng Ma Lei Zhao Lin Huang Dan Zhou Jinghao Fan Jianru Wang Hongmei Liu Decheng Wu Zhaomin Zheng 

机构地区：[1]Department of Spine Surgery,The First Affiliated Hospital,Sun Yat-sen University Guangzhou,510080,People's Republic of China [2]Pain Research Center,Sun Yat-sen University,Guangzhou,510080,People's Republic of China [3]Guangdong Provincial Key Laboratory of Advanced Biomaterials,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,People's Republic of China

出　　处：《Bioactive Materials》2024年第11期355-370,共16页生物活性材料（英文）

基　　金：National Natural Science Foundation of China(82072490 and 21935011);Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029);Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).

摘　　要：Oxidative stress and aging lead to progressive senescence of nucleus pulposus(NP)cells,resulting in intervertebral disc(IVD)degeneration(IVDD).In some cases,degenerative IVD can further cause low back pain(LBP).Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD.However,the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs.Here,we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl(GP)with quercetin to alleviate IVDD by removing senescent NP cells.The hydrogel exhibited injectability,biodegradability,prominent biocompatibility and responsive release of quercetin under pathological conditions.In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells.In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models,indicating a potential therapeutic approach for ameliorating IVDD and LBP.This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD,providing a new strategy for IVDD treatment.

关 键 词：Intervertebral disc degeneration Low back pain SENESCENCE QUERCETIN HYDROGEL 

分 类 号：R681.5[医药卫生—骨科学]