Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.
Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, No. 2999, People North Road, Shanghai 201620, China.
Biomater Sci. 2021 Jul 13;9(14):4891-4903. doi: 10.1039/d1bm00535a.
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.
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）可以抑制软骨细胞的肥大，从而维持透明软骨的表型。在这里，我们旨在构建一种基于丝素蛋白（SF）双重修饰的具有机械梯度的生物打印双相支架，用于骨软骨缺损的综合修复。简而言之，SF 分别与 PTH 接枝（SF-PTH）和与甲基丙烯酰酐共价固定（SF-MA）。接下来，将明胶甲基丙烯酰（GM）与 SF-PTH 或 SF-MA 混合用作关节软骨和软骨下骨再生的生物墨水。最后，使用 3D 生物打印技术构建 GM + SF-PTH/GM + SF-MA 骨软骨双相支架，并将其植入兔骨软骨缺损模型中。在这项研究中，首次合成了 SF-PTH 生物墨水。体外结果表明，GM + SF-MA 生物墨水具有良好的机械性能，而 GM + SF-PTH 生物墨水抑制了软骨细胞的肥大，有利于透明软骨细胞外基质的产生。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。体内结果表明，GM + SF-PTH/GM + SF-MA 支架能够促进骨软骨缺损的再生，并在很大程度上保持透明软骨的表型。总之，我们的研究结果表明，通过 3D 生物打印构建的集成 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。
