【作者】 王玮； 孙亮； 刘文广；

【Author】 WANG Wei;SUN Liang;LIU Wenguang;School of Materials Science and Engineering,Tianjin Key Laboratory of Composite and Functional Materials,Tianjin University;

【机构】 天津大学材料科学与工程学院,材料复合与功能化重点实验室；

【摘要】 <正>关节处的炎症因子表达是导致关节炎的最重要原因,因而抑制关节处炎症的表达能很好地缓解并治疗关节炎。白藜芦醇(Res)有抗炎症、抗氧化、抗癌症和调节免疫等功能,Res可以对前炎性细胞因子如白介素-1β、肿瘤坏死因子产生抑制作用,进而Res可以对关节炎具有治疗和预防的作用。但是Res本身水溶性很差、在血液中代谢速率快等问题抑制其作为药物的直接使用。本研究中将Res接枝到聚丙烯酸上(PAA-Res),构建大分子药物,能够显著更多还原

【Abstract】 Inflammatory factor overexpression is the major cause of cartilage and osteochondral damages.Resveratrol(Res) is known for its anti-inflammatory,antioxidant and immunmodulatory properties.However,these effects are hampered by its water insolubility and quick metabolism in vivo.To optimize its therapeutic efficacy in this study,Res was grafted to polyacrylic acid(PAA) to obtain a macromolecular drug PAA-Res,which was then incorporated into atelocollagen hydrogels to fabricate anti-inflammatory cell-free scaffolds(Coll/Res) with improved mechanical strengths.The Coll/Res scaffolds demonstrated the ability to capture the DPPH free radicals.Both pure atelocollagen(Coll) and Coll/Res scaffolds could maintain their original shape for 6 weeks in PBS.The scaffolds were degraded by collagenase in several days,and the degradation rate was slowed down by Res loading.The Coll and Coll/Res scaffolds with excellent cytoeompatibility were shown to promote the proliferation and maintain the normal phenotype of the seeded chondrocytes and BMSCs.In addition,the Coll/Res scaffold exhibited the capacity to protect the chondrocytes and BMSCs against reactive oxygen species(ROS).The acellular Coll/Res scaffolds were transplanted into the rabbit osteochondral defects.After implantation for 2,4,6 weeks,the samples were retrieved for quantitative real-time polymerase chain reaction(qRT-PCR),and the inflammatory related genes IL-1β,MMP-13,COX-2 and bone and cartilage related genes SOX-9,aggrecan,CollⅡ,and Coll Ⅰ were determined.Compared with the untreated defects,the inflammatory related genes were down-regulated and those bone and cartilage related genes were upregulated by filling the defect with an anti-inflammatory scaffold.After 12 weeks,the osteochondral defects were completely repaired by Coll/Res scaffold,and the neo-cartilage integrated well with its surrounding tissue and subchondral bone.Immunohistochemical and glycosaminoglycans(GAGs) staining confirmed the distribution of Coll II and GAGs in the regenerated cartilage.The anti-inflammatory acellular Coll/Res scaffolds are convenient to administer in vivo,holding a greater potential for future clinical applications.更多还原