3D bio-printed biphasic scaffolds with dual modification of silk fibroin for the integrated repair of osteochondral defects
3D bio-printed biphasic scaffolds with dual modification of silk fibroin for the integrated repair of osteochondral defects
复制标题
丝素蛋白双重修饰的3D生物打印双相支架用于骨软骨缺损的综合修复
DOI：
10.1039/d1bm00535a
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发表时间：
2021-05-13
影响因子：
6.6
通讯作者：
Wang, Jinwu
中科院分区：
文献类型：
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作者：
Deng, Changxu;Yang, Jin;Wang, Jinwu
骨软骨缺损的修复仍然是一个挑战，尤其是透明软骨的再生。甲状旁腺激素（PTH）可抑制软骨细胞的肥大，维持透明软骨的表型。本研究旨在构建基于丝素蛋白双重修饰的具有机械梯度的生物打印双相支架，用于骨软骨缺损的整体修复。简单地说，SF分别接枝PTH （SF-PTH）和用甲基丙烯酸酐（SF- ma）共价固定。接下来，明胶甲基丙烯酰（GM）与SF-PTH或SF-MA混合作为生物墨水用于关节软骨和软骨下骨再生。最后，采用生物3D打印技术构建GM + SF-PTH/GM + SF-MA骨软骨双相支架，并植入兔骨软骨缺损模型。本研究首次合成了SF-PTH生物墨水。体外实验结果表明，GM + SF-MA生物墨水具有良好的力学性能，而GM + SF-PTH生物墨水抑制软骨细胞肥大，有利于透明软骨细胞外基质的生成。重要的是，成功构建了具有机械梯度的集成GM + SF-PTH/GM + SF-MA双相支架。体内实验结果表明，GM + SF-PTH/GM + SF-MA支架能在很大程度上促进骨软骨缺损的再生，维持透明软骨的表型。综上所述，我们的研究结果表明，生物3D打印构建的集成GM + SF-PTH/GM + SF-MA双相支架有望成为治疗骨软骨缺损的新策略。
Repair of osteochondral defects is still a challenge, especially the regeneration of hyaline cartilage. Parathyroid hormone (PTH) can inhibit the hypertrophy of chondrocytes to maintain the phenotype of hyaline cartilage. Here, we aimed to construct a bio-printed biphasic scaffold with a mechanical gradient based on dual modification of silk fibroin (SF) for the integrated repair of osteochondral defects. Briefly, SF was grafted with PTH (SF-PTH) and covalently immobilized with methacrylic anhydride (SF-MA), respectively. Next, gelatin methacryloyl (GM) mixed with SF-PTH or SF-MA was used as a bio-ink for articular cartilage and subchondral bone regeneration. Finally, the GM + SF-PTH/GM + SF-MA osteochondral biphasic scaffold was constructed using 3D bioprinting technology, and implanted in a rabbit osteochondral defect model. In this study, the SF-PTH bio-ink was synthesized for the first time. In vitro results indicated that the GM + SF-MA bio-ink had good mechanical properties, while the GM + SF-PTH bio-ink inhibited the hypertrophy of chondrocytes and was beneficial for the production of hyaline cartilage extracellular matrix. Importantly, an integrated GM + SF-PTH/GM + SF-MA biphasic scaffold with a mechanical gradient was successfully constructed. The results in vivo demonstrated that the GM + SF-PTH/GM + SF-MA scaffold could promote the regeneration of osteochondral defects and maintain the phenotype of hyaline cartilage to a large extent. Collectively, our results indicate that the integrated GM + SF-PTH/GM + SF-MA biphasic scaffold constructed by 3D bioprinting is expected to become a new strategy for the treatment of osteochondral defects.