Injectable chitosan microspheres resisting inflammatory and oxidativestress for ameliorating intervertebral disc degeneration  

具有抗炎抗氧化作用的可注射壳聚糖微球用于缓解椎间盘退变

作　　者：Lin Huang Wantao Wang Lei Liu Wenzheng Ma Jinghao Fan Dan Zhou Lei Zhao Zhaomin Zheng Hongmei Liu Decheng Wu 黄林;王挽涛;刘磊;马文政;范景皓;周丹;赵磊;郑召民;刘洪梅;吴德成(Guangdong Provincial Key Laboratory of Advanced Biomaterials,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen 518055,China;Department of Spine Surgery,The First Affiliated Hospital,Pain Research Center,Sun Yat-sen University,Guangzhou 510080,China)

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

出　　处：《Science China Materials》2025年第2期610-625,共16页中国科学(材料科学)(英文版)

基　　金：supported by the Ministry of Science and Technology of China (2020YFA0908900);National Natural Science Foundation of China (21935011);Shenzhen Science and Technology Innovation Commission (KQTD20200820113012029, JCYJ20220530114409020, and 20231115134555001);Guangdong Provincial Key Laboratory of Advanced Biomaterials (2022B1212010003)。

摘　　要：The treatment of intervertebral disc (IVD) degeneration remains a significant challenge due to the uniqueischemic structure of the IVD, which comprises the scavengingof inflammatory cytokines, alleviation of cellular oxidativestress responses, restoration of nuclei pulposus (NP) cell viability,and recovery of IVD biomechanical function. Herein,we developed an injectable microsphere (CS-MnO_(2)@PC) byincorporating chitosan microspheres (CS) with manganesedioxide (MnO_(2)) nanozymes and celecoxib encapsulated inPluronic F-127 (PC) nanosized micelles, via in situ redox orSchiff base reaction. The hybrid carrier demonstrates robustcapabilities in scavenging free radicals, alleviating extracellularoxidative stress, and reducing inflammatory cytokinesin NP cells, as evidenced by RT-qPCR and immunofluorescence staining assays. In vivo evaluations further indicatethat this hybrid carrier helps preserve NP hydration andthe lamellar structure of the annulus fibrosus (AF), as confirmed by radiological analysis and histological staining evaluations.These injectable chitosan microspheres, combiningnanozymes and nanosized drug micelles, represent a promising therapeutic strategy for degenerative IVD.由于椎间盘(IVD)特殊缺血性的组织结构,治疗椎间盘退变是一项巨大的挑战.椎间盘退变的治疗是一个复杂的过程,包括调节细胞炎症因子和氧化应力,恢复髓核细胞活性,并重建椎间盘生物力学功能.在此,我们构建了一种MnO_(2)纳米酶和celecoxib药物胶束共同负载的可注射壳聚糖微球(CSMnO_(2)@PC).体外细胞实验证明,这种复合微球具有较好的自由基清除、缓解细胞氧化应力、降低髓核细胞中炎症因子的表达等功能.体内实验进一步表明,该混合载体可以维持纤维环(AF)组织的板层结构和髓核(NP)组织的水合状态,这已通过影像学和组织切片学评估得以证实.这种纳米酶和药物胶束共同负载的可注射壳聚糖微球为治疗椎间盘退变提供了一种有效策略.

关 键 词：chitosan microsphere nanozymes inflammatory relieving oxidative stress regulation intervertebral disc degeneration 

分 类 号：O63[理学—高分子化学]