上海交通大学学报（医学版）2025，Vol.45Issue(7)：829-837,9.DOI:10.3969/j.issn.1674-8115.2025.07.004
负载牛磺熊去氧胆酸的光交联明胶水凝胶支架在兔膝关节软骨缺损修复中的效能
Efficacy of photo-crosslinked gelatin hydrogel scaffolds loaded with tauroursodeoxycholic acid on knee cartilage defect repair in a rabbit model
摘要
Abstract
Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.关键词
软骨缺损/骨关节炎/牛磺熊去氧胆酸/甲基丙烯酸酐化明胶/软骨细胞/组织工程Key words
cartilage defect/osteoarthritis/tauroursodeoxycholic acid/gelatin methylacrylated/chondrocyte/tissue engineering分类
医药卫生引用本文复制引用
魏祥,魏凌飞,徐纯峰,高玉洁,聂萍,于德栋..负载牛磺熊去氧胆酸的光交联明胶水凝胶支架在兔膝关节软骨缺损修复中的效能[J].上海交通大学学报（医学版）,2025,45(7):829-837,9.基金项目
国家自然科学基金(32101094,52175422,82100965). National Natural Science Foundation of China(32101094,52175422,82100965). （32101094,52175422,82100965）
