National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
Biomater Adv. 2022 Sep;140:213030. doi: 10.1016/j.bioadv.2022.213030. Epub 2022 Jul 15.
Nowadays, the three-dimensional (3D) printed calcium phosphate (CaP) ceramics have well-designed geometric structure, but suffer from relative weak osteoinductivity. Surface modification by incorporating bone morphogenetic protein-2 (BMP2) onto scaffolds is considered as an efficient approach to improve their bioactivity. However, high dose and uncontrolled burst release of BMP2 may cause undesired side effect. In the present study, porous BCP ceramics with inverse face-centred cube structure prepared by digital light processing (DLP)-based 3D printing technique were used as the substrates. BMP2 proteins were loaded in the self-assembled Heparin/PEI nanogels (NP/BMP2), and then immobilized onto BCP substrates through the intermediate mussel-derived bioactive dopamine and dihydroxyphenylacetic acid (DA/DOPAC) coating layers to construct functional BCP/layer/NP/BMP2 scaffolds. Our results showed that Heparin/PEI nanogel was a potent delivery system for BMP2, and BCP/layer/NP/BMP2 scaffolds exhibited the high loading capacity, controlled release rate, and sustained local delivery of BMP2. In vitro cell experiments with bone marrow stromal cells (BMSCs) found that BCP/layer/NP/BMP2 could promote cell proliferation, facilitate cell spreading, accelerate cell migration, up-regulate expression of osteogenic genes, and improve synthesis of osteoblast-related proteins. Moreover, the murine intramuscular implantation model suggested that BCP/layer/NP/BMP2 had a superior osteoinductive capacity, and the rat femoral condyle defect repair model showed that BCP/layer/NP/BMP2 could enhance in situ bone repair and regeneration. These findings demonstrate that the incorporation of BMP2 loaded Heparin/PEI nanogels to 3D printed scaffolds holds great promise in fabricating bone graft with a superior biological performance for orthopedic application.
如今，三维（3D）打印的磷酸钙（CaP）陶瓷具有精心设计的几何结构，但骨诱导活性相对较弱。将骨形态发生蛋白-2（BMP2）掺入支架被认为是提高其生物活性的有效方法。然而，BMP2 的高剂量和不可控的突释可能会引起不良的副作用。在本研究中，使用基于数字光处理（DLP）的 3D 打印技术制备的具有反面心立方结构的多孔 BCP 陶瓷作为基底。BMP2 蛋白被装载在自组装的肝素/PEI 纳米凝胶（NP/BMP2）中，然后通过中间贻贝衍生的生物活性多巴胺和二羟基苯乙酸（DA/DOPAC）涂层固定在 BCP 基底上，构建功能性 BCP/层/NP/BMP2 支架。我们的结果表明，肝素/PEI 纳米凝胶是 BMP2 的有效递送系统，BCP/层/NP/BMP2 支架具有高载药量、控释率和持续的 BMP2 局部递送。与骨髓基质细胞（BMSCs）的体外细胞实验发现，BCP/层/NP/BMP2 可以促进细胞增殖，促进细胞铺展，加速细胞迁移，上调成骨基因表达，并提高成骨细胞相关蛋白的合成。此外，小鼠肌肉内植入模型表明，BCP/层/NP/BMP2 具有优越的成骨能力，大鼠股骨髁缺损修复模型表明，BCP/层/NP/BMP2 可以增强原位骨修复和再生。这些发现表明，将负载 BMP2 的肝素/PEI 纳米凝胶掺入 3D 打印支架中，有望为骨科应用制造具有优异生物性能的骨移植物。
