Micro-injection molded, poly(vinyl alcohol)-calcium salt templates for precise customization of 3D hydrogel internal architecture
Micro-injection molded, poly(vinyl alcohol)-calcium salt templates for precise customization of 3D hydrogel internal architecture
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DOI：
10.1016/j.actbio.2019.04.050
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发表时间：
2019-09-01
影响因子：
9.7
通讯作者：
Ashton, Randolph S.
中科院分区：
文献类型：
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作者：
McNulty, Jason D.;Marti-Figueroa, Carlos;Ashton, Randolph S.
在组织工程应用中，水凝胶整料的牺牲模塑是用于产生3D模具以控制组织形态的通用技术。通过诸如溶剂浇铸和热挤出/纤维拉伸的系列工艺制造的先前牺牲模板可用于在快速聚合的本体固化水凝胶内有效地模制内部几何形状。然而，它们在控制扩散受限的离子交联水凝胶（如藻酸盐）的几何形状方面表现出较差的性能。在这里，我们描述了使用聚（乙烯醇）-钙盐模板（PVOH-Ca）制造的微注塑成型，一个平行的大规模生产过程中，方便地铸造内的散装固化水凝胶和离子交联的海藻酸盐水凝胶的内部几何形状。发现钙盐溶解度是优化聚合物复合材料的可制造性、机械性能和模板溶解时释放的钙量的关键因素。计量学和计算机断层扫描（CT）分析表明，模板的钙释放能够在藻酸盐水凝胶内精确铸造微尺度通道几何形状（6.4 +/- 7.2%平均误差）。组装模块化PVOH钙模板，以塑造藻酸盐水凝胶内的三维通道网络，以证明工程的可扩展性。此外，该平台用于创建水凝胶模具，用于工程化人胚胎干细胞（hESC）衍生的神经上皮类器官，其具有微型仿生圆柱形形态。因此，注射成型的PVOH-Ca模板有助于定制水凝胶牺牲成型，其可用于生成具有复杂内部微观结构的3D水凝胶，用于各种组织工程应用。之前通过系列工艺制造的牺牲材料已用于有效地在快速聚合、批量固化水凝胶中模制内部几何形状。然而，它们在扩散受限的离子交联水凝胶（例如藻酸盐）内的模塑几何形状中表现出较差的性能。我们描述了使用聚（乙烯醇）-钙盐模板（PVOH-Ca）制造的微注塑成型，一个无与伦比的大规模生产过程中，方便地铸造内的散装固化水凝胶和离子交联的海藻酸盐水凝胶的内部几何形状。从PVOH-Ca模板释放的钙使得能够精确地牺牲成型藻酸盐水凝胶，并且该过程是生物相容的。此外，我们证明了其用于设计hPSC衍生的神经上皮类器官的形态，并且可以组装模块化PVOH-Ca模板设计以实现水凝胶内部结构的可扩展的3D定制。(C)2019 Acta Materialia Inc.爱思唯尔有限公司出版
In tissue engineering applications, sacrificial molding of hydrogel monoliths is a versatile technique for creating 3D molds to control tissue morphology. Previous sacrificial templates fabricated by serial processes such as solvent casting and thermal extrusion/fiber drawing can be used to effectively mold internal geometries within rapidly polymerizing, bulk curing hydrogels. However, they display poorer performance in controlling the geometry of diffusion limited, ionically cross-linked hydrogels, such as alginate. Here, we describe the use of poly(vinyl alcohol)-calcium salt templates (PVOH-Ca) fabricated by micro-injection molding, a parallel mass-production process, to conveniently cast internal geometries within both bulk curing hydrogels and ionically cross-linked alginate hydrogels. Calcium salt solubility was discovered to be a critical factor in optimizing the polymer composite's manufacturability, mechanical properties, and the quantity of calcium released upon template dissolution. Metrological and computed tomography (CT) analysis showed that the template's calcium release enables precise casting of microscale channel geometries within alginate hydrogels (6.4 +/- 7.2% average error). Assembly of modular PVOH-Ca templates to mold 3D channel networks within alginate hydrogels is presented to demonstrate engineering scalability. Moreover, the platform is used to create hydrogel molds for engineering human embryonic stem cell (hESC)-derived neuroepithelial organoids of a microscale, biomimetic cylindrical morphology. Thus, injection molded PVOH-Ca templates facilitate customization of hydrogel sacrificial molding, which can be used to generate 3D hydrogels with complex internal microscale architecture for diverse tissue engineering applications.Statement of SignificanceSacrificial molding of hydrogel monoliths is a versatile technique for creating 3D molds for tissue engineering applications. Previous sacrificial materials fabricated by serial processes have been used to effectively mold internal geometries within rapidly polymerizing, bulk curing hydrogels. However, they display poor performance in molding geometry within diffusion limited, ionically cross-linked hydrogels, e.g. alginate. We describe the use of poly(vinyl alcohol)-calcium salt templates (PVOH-Ca) fabricated by micro-injection molding, an unparalleled mass-production process, to conveniently cast internal geometries within both bulk curing hydrogels and ionically cross-linked alginate hydrogels. Calcium release from the PVOH-Ca templates enables precise sacrificial molding of alginate hydrogels and the process is biocompatible. Moreover, we demonstrate its use to engineer the morphology of hPSC-derived neuroepithelial organoids, and modular PVOH-Ca template designs can be assembled to enable scalable 3D customization of hydrogel internal architecture. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd.