Kang Zhanrong, Li Dejian, Shu Chaoqin, Du Jianhang, Yu Bin, Qian Zhi, Zhong Zeyuan, Zhang Xu, Yu Baoqing, Huang Qikai, Huang Jianming, Zhu Yufang, Yi Chengqing, Ding Huifeng
Department of Orthopaedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
State Key Laboratory of High-Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China.
Front Bioeng Biotechnol. 2021 Nov 16;9:749221. doi: 10.3389/fbioe.2021.749221. eCollection 2021.
Polyethylene terephthalate (PET)-based artificial ligaments are one of the most commonly used grafts in anterior cruciate ligament (ACL) reconstruction surgery. However, the lack of favorable hydrophilicity and cell attachment for PET highly impeded its widespread application in clinical practice. Studies found that surface modification on PET materials could enhance the biocompatibility and bioactivity of PET ligaments. In this study, we immobilized bone morphogenetic protein-2 (BMP-2) on the surface of PET ligaments mediated by polydopamine (PDA) coating and investigated the bioactivation and graft-to-bone healing effect of the modified grafts and . In this study, we prepared the PDA coating and subsequent BMP-2-immobilized PET artificial ligaments. Scanning electron microscopy (SEM) was used to analyze the morphological changes of the modified grafts. In addition, the surface wettability properties of the modified ligaments, amount of immobilized BMP 2, and the release of BMP-2 during a dynamic period up to 28 days were tested. Then, the attachment and proliferation of rat bone mesenchymal stem cells (rBMSCs) on grafts were examined by SEM and Cell Counting Kit-8 (CCK-8) assay, respectively. Alkaline phosphatase (ALP) assay, RT-PCR, and Alizarin Red S staining were performed to test the osteoinduction property. For experiments, an extra-articular graft-to-bone healing model in rabbits was established. At 8 weeks after surgery, biomechanical tests, micro-CT, and histological staining were performed on harvested samples. A surface morphological analysis verified the success of the PDA coating. The wettability of the PET artificial ligaments was improved, and more than 80% of BMP-2 stably remained on the graft surface for 28 days. The modified grafts could significantly enhance the proliferation, attachment, as well as expression of ALP and osteogenic-related genes, which demonstrated the favorable bioactivity of the grafts immobilized with BMP-2 . Moreover, the grafts immobilized with BMP-2 at a concentration of 138.4 ± 10.6 ng/cm could highly improve the biomechanical properties, bone regeneration, and healing between grafts and host bone after the implantation into the rabbits compared with the PDA-PET group or the PET group. The immobilization of BMP-2 mediated by polydopamine coating on PET artificial ligament surface could enhance the compatibility and bioactivity of the scaffolds and the graft-to-bone healing .
聚对苯二甲酸乙二酯(PET)基人工韧带是前交叉韧带(ACL)重建手术中最常用的移植物之一。然而,PET缺乏良好的亲水性和细胞附着性,这严重阻碍了其在临床实践中的广泛应用。研究发现,对PET材料进行表面改性可以提高PET韧带的生物相容性和生物活性。在本研究中,我们通过聚多巴胺(PDA)涂层介导将骨形态发生蛋白-2(BMP-2)固定在PET韧带表面,并研究了改性移植物的生物活化和移植物与骨的愈合效果。在本研究中,我们制备了PDA涂层以及随后固定有BMP-2的PET人工韧带。使用扫描电子显微镜(SEM)分析改性移植物的形态变化。此外,测试了改性韧带的表面润湿性、固定的BMP-2量以及在长达28天的动态期间BMP-2的释放情况。然后,分别通过SEM和细胞计数试剂盒-8(CCK-8)测定法检测大鼠骨髓间充质干细胞(rBMSCs)在移植物上的附着和增殖情况。进行碱性磷酸酶(ALP)测定、RT-PCR和茜素红S染色以测试成骨诱导特性。对于实验,建立了兔关节外移植物与骨愈合模型。术后8周,对收获的样本进行生物力学测试、显微CT和组织学染色。表面形态分析证实了PDA涂层的成功。PET人工韧带的润湿性得到改善,超过80%的BMP-2在移植物表面稳定保留28天。改性移植物可显著增强rBMSCs的增殖、附着以及ALP和骨相关基因的表达,这表明固定有BMP-2的移植物具有良好的生物活性。此外,与PDA-PET组或PET组相比,以138.4±10.6 ng/cm的浓度固定有BMP-2的移植物在植入兔体内后可显著改善生物力学性能、骨再生以及移植物与宿主骨之间的愈合情况。通过聚多巴胺涂层介导将BMP-2固定在PET人工韧带表面可增强支架的相容性和生物活性以及移植物与骨的愈合。