Wang Xiaoju, Molino Binbin Zhang, Pitkänen Sanna, Ojansivu Miina, Xu Chunlin, Hannula Markus, Hyttinen Jari, Miettinen Susanna, Hupa Leena, Wallace Gordon
Johan Gadolin Process Chemistry Centre, Åbo Akademi University, Piispankatu 8, 20500 Turku, Finland.
ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, University of Wollongong, Northfields Avenue, Wollongong, New South Wales 2522, Australia.
ACS Biomater Sci Eng. 2019 Sep 9;5(9):4496-4510. doi: 10.1021/acsbiomaterials.9b00105. Epub 2019 Aug 2.
The local delivery of Cu from copper-doped bioactive glass (Cu-BaG) was combined with 3D printing of polycaprolactone (PCL) scaffolds for its potent angiogenic effect in bone tissue engineering. PCL and Cu-BaG were, respectively, dissolved and dispersed in acetone to formulate a moderately homogeneous ink. The PCL/Cu-BaG scaffolds were fabricated via direct ink writing into a cold ethanol bath. The architecture of the printed scaffolds, including strut diameter, strut spacing, and porosity, were investigated and characterized. The PCL/Cu-BaG scaffolds showed a Cu-BaG content-dependent mechanical property, as the compressive Young's modulus ranged from 7 to 13 MPa at an apparent porosity of 60%. The ion dissolution behavior in simulated body fluid was evaluated, and the hydroxyapatite-like precipitation on the strut surface was confirmed. Furthermore, the cytocompatibility of the PCL/Cu-BaG scaffolds was assessed in human bone marrow stem cell (hBMSC) culture, and a dose-dependent cytotoxicity of Cu was observed. Here, the PCL/BaG scaffold induced the higher expression of late osteogenic genes and in comparison to the PCL scaffold. The doping of Cu in BaG elicited higher expression of the early osteogenic marker gene but decreased the expression of late osteogenic marker genes and in comparison to the PCL/BaG scaffold, demonstrating the suppressing effect of Cu on osteogenic differentiation of hBMSCs. In a coculture of hBMSCs and human umbilical vein endothelial cells, both the PCL/BaG and PCL/Cu-BaG scaffolds stimulated the formation of a denser tubule network, compared to the PCL scaffold. Meanwhile, only slightly higher gene expression of was observed with the PCL/Cu-BaG scaffold than with the PCL/BaG scaffold, indicating the potent angiogenic effect of the released Cu.
将铜掺杂生物活性玻璃（Cu-BaG）中的铜局部递送与聚己内酯（PCL）支架的3D打印相结合，以发挥其在骨组织工程中强大的血管生成作用。分别将PCL和Cu-BaG溶解并分散在丙酮中，以配制适度均匀的墨水。通过直接墨水书写将PCL/Cu-BaG支架制备到冷乙醇浴中。对打印支架的结构，包括支柱直径、支柱间距和孔隙率进行了研究和表征。PCL/Cu-BaG支架表现出与Cu-BaG含量相关的力学性能，在表观孔隙率为60%时，压缩杨氏模量范围为7至13 MPa。评估了在模拟体液中的离子溶解行为，并证实了支柱表面有类羟基磷灰石沉淀。此外，在人骨髓干细胞（hBMSC）培养中评估了PCL/Cu-BaG支架的细胞相容性，并观察到铜的剂量依赖性细胞毒性。在此，与PCL支架相比,PCL/BaG支架诱导了晚期成骨基因和的更高表达。与PCL/BaG支架相比，在BaG中掺杂铜引发了早期成骨标记基因的更高表达，但降低了晚期成骨标记基因和的表达，表明铜对hBMSCs成骨分化有抑制作用。在hBMSCs和人脐静脉内皮细胞的共培养中，与PCL支架相比，PCL/BaG和PCL/Cu-BaG支架均刺激形成了更密集的小管网络。同时，与PCL/BaG支架相比，PCL/Cu-BaG支架仅观察到略高的基因表达，表明释放的铜具有强大的血管生成作用。
