Vascularized Bone-Mimetic Hydrogel Constructs by 3D Bioprinting to Promote Osteogenesis and Angiogenesis
Vascularized Bone-Mimetic Hydrogel Constructs by 3D Bioprinting to Promote Osteogenesis and Angiogenesis
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DOI：
10.3390/ijms20051096
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Yang, Yunzhi
中科院分区：
文献类型：
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作者：
Anada, Takahisa;Pan, Chi-Chun;Yang, Yunzhi
骨是一种高度血管化的组织，具有独特而复杂的结构。长骨由外周皮质壳和内部高度血管化的骨髓腔组成，皮质壳包含血管穿透通道网络。生物打印是一种强大的工具，可以实现细胞和生物材料的快速和精确的空间图案化。在这里，我们开发了一种两步数字光处理技术，以制造基于磷酸八钙（OCP）、人脐静脉内皮细胞（HUVEC）球体和甲基丙烯酸明胶（GelMA）水凝胶的仿骨3D水凝胶结构。骨模拟3D水凝胶结构设计为由外周含OCP的GelMA环（模拟皮质壳）和中心含HUVEC球状体的GelMA环（模拟骨髓间隙）组成。我们进一步证明，OCP，这是均匀地嵌入在GelMA，刺激间充质干细胞的成骨分化。我们改进了球状体培养装置的设计，以促进大量HUVEC球状体的快速形成，将其包埋到不同浓度的GelMA水凝胶中。结果表明，GelMA的浓度调节源自HUVEC球状体的毛细血管样结构的形成程度。这种具有仿生双环结构的细胞负载水凝胶基骨构建体有可能用于骨组织工程。
Bone is a highly vascularized tissue with a unique and complex structure. Long bone consists of a peripheral cortical shell containing a network of channels for vascular penetration and an inner highly vascularized bone marrow space. Bioprinting is a powerful tool to enable rapid and precise spatial patterning of cells and biomaterials. Here we developed a two-step digital light processing technique to fabricate a bone-mimetic 3D hydrogel construct based on octacalcium phosphate (OCP), spheroids of human umbilical vein endothelial cells (HUVEC), and gelatin methacrylate (GelMA) hydrogels. The bone-mimetic 3D hydrogel construct was designed to consist of a peripheral OCP-containing GelMA ring to mimic the cortical shell, and a central GelMA ring containing HUVEC spheroids to mimic the bone marrow space. We further demonstrate that OCP, which is evenly embedded in the GelMA, stimulates the osteoblastic differentiation of mesenchymal stem cells. We refined the design of a spheroid culture device to facilitate the rapid formation of a large number of HUVEC spheroids, which were embedded into different concentrations of GelMA hydrogels. It is shown that the concentration of GelMA modulates the extent of formation of the capillary-like structures originating from the HUVEC spheroids. This cell-loaded hydrogel-based bone construct with a biomimetic dual ring structure can be potentially used for bone tissue engineering.