School of Biological and Health Systems Engineering, Arizona State University, 550 East Orange Street, Tempe, Arizona 85281, United States.
ACS Biomater Sci Eng. 2022 Sep 12;8(9):4002-4013. doi: 10.1021/acsbiomaterials.2c00640. Epub 2022 Aug 31.
Biofabrication methods capable of generating complex, three-dimensional, cell-laden hydrogel geometries are often challenging technologies to implement in the clinic and scaled manufacturing processes. Hydrogel injection molding capitalizes on the reproducibility, efficiency, and scalability of the injection molding process, and we adapt this technique to biofabrication using a library of natural and synthetic hydrogels with varied crosslinking chemistries and kinetics. We use computational modeling to evaluate hydrogel library fluid dynamics within the injection molds in order to predict molding feasibility and cytocompatibility. We evaluate the reproducibility of hydrogel construct molding and extraction and establish criteria for the selection of hydrogels suitable for injection molding. We demonstrate that hydrogel injection molding is capable of generating complex three-dimensional cell-laden construct geometries using diverse hydrogel materials and that this platform is compatible with primary human islet encapsulation. These results highlight the versatility and feasibility of hydrogel injection molding as a biofabrication technique with potential applications in the clinic and biomanufacturing.
生物制造方法能够生成复杂的三维、细胞填充的水凝胶结构，通常是在临床和规模化制造过程中具有挑战性的技术。水凝胶注塑成型利用了注塑成型过程的可重复性、效率和可扩展性，我们使用具有不同交联化学和动力学的天然和合成水凝胶库来适应这种技术的生物制造。我们使用计算建模来评估注塑模具中水凝胶库的流体动力学，以预测成型可行性和细胞相容性。我们评估水凝胶结构的可重复性和提取，并建立适用于注塑成型的水凝胶选择标准。我们证明了水凝胶注塑成型能够使用多种水凝胶材料生成复杂的三维细胞填充结构，并且该平台与原代人胰岛的封装兼容。这些结果突出了水凝胶注塑成型作为一种生物制造技术的多功能性和可行性，具有在临床和生物制造中的潜在应用。
