Mechanism research on a bioactive resveratrol–PLA–gelatin porous nano-scaffold in promoting the repair of cartilage defect

Abstract

Fei Yu,1,* Ming Li,1,* Zhipeng Yuan,2,* Feng Rao,1 Xingxing Fang,1 Baoguo Jiang,1 Yongqiang Wen,2 Peixun Zhang1 1Department of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, China; 2School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China *These authors contributed equally to this work Background: Articular cartilage defects are difficult to treat, but drug-loaded tissue engineering scaffolds provide a possible treatment option for these types of injuries.Purpose: In this study, we designed a bioactive resveratrol–PLA–gelatin porous nano-scaffold using electrospinning, freeze drying, and uniform dispersion techniques to repair articular cartilage defects, and then investigated the possible mechanism behind the successful repair.Methods: We established an articular cartilage defect rat model with a 2 mm diameter wound in the middle of the knee joint femoral condyle non-weight-bearing area, with a depth reaching the full thickness of the subchondral bone. Postmodel specimens and micro computed tomography (CT) were used to observe any macroscopic morphological changes in the articular cartilage and subchondral bone, whereas multiple staining methods were used to observe all microcosmic morphological changes. Gross scores and Mankin scores were used to evaluate the repair condition. Immunohistochemical staining was employed to detect protein expression.Results: When the repair included the resveratrol–PLA–gelatin porous nano-scaffold, the repaired cartilage and subchondral bone were in better condition. The expression levels of SIRT1, type II collagen, and PI3K/AKT signaling pathway-related proteins (AKT, VEGF, PTEN, Caspase 9, and MMP13) changed significantly. The expression levels of SIRT1,AKT and type II collagen proteins increased significantly, while the expression levels of VEGF, PTEN, Caspase9 and MMP13 proteins decreased significantly compared with the repair included blank porous PLA–gelatin nano-scaffold and without scaffold.Conclusion: We designed a bioactive resveratrol–PLA–gelatin porous nano-scaffold with better performance, which promoted the repair of cartilage injury as a whole, and explained its possible mechanism in accelerating cartilage repair via the PI3K/AKT signaling pathway. Keywords: resveratrol, PLA–gelatin, nano-scaffold, PI3K/AKT signaling, cartilage defect

Keywords

• resveratrol
• PLA-Gelatin
• nano-scaffold
• PI3K/AKT signaling
• cartilage defect