School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, 639798, Singapore.
Biofabrication. 2019 Feb 25;11(2):025008. doi: 10.1088/1758-5090/ab03ed.
Biofabrication technologies have endowed us with the capability to fabricate complex biological constructs. However, cytotoxic biofabrication conditions have been a major challenge for their clinical application, leading to a trade-off between cell viability and scalability of biofabricated constructs. Taking inspiration from nature, we proposed a cell protection strategy which mimicks the protected and dormant state of plant seeds in adverse external conditions and their germination in response to appropriate environmental cues. Applying this bioinspired strategy to biofabrication, we successfully preserved cell viability and enhanced the seeding of cell-laden biofabricated constructs via a cytoprotective pyrogallol (PG)-alginate encapsulation system. Our cytoprotective encapsulation technology utilizes PG-triggered sporulation and germination processes to preserve cells, is mechanically robust, chemically resistant, and highly customizable to adequately match cell protectability with cytotoxicity of biofabrication conditions. More importantly, the facile and tunable decapsulation of our PG-alginate system allows for effective germination of dormant cells, under typical culture conditions. With this approach, we have successfully achieved a biofabrication process which is reproducible, scalable, and provided a practical solution for off-the-shelf availability, shipping and temporary storage of fabricated bio-constructs.
生物制造技术使我们能够制造复杂的生物结构。然而，细胞毒性的生物制造条件一直是其临床应用的主要挑战，导致细胞活力和生物制造结构的可扩展性之间存在权衡。受自然启发，我们提出了一种细胞保护策略，模拟植物种子在不利的外部条件下的保护和休眠状态，以及它们对适当环境线索的发芽。将这种仿生策略应用于生物制造，我们成功地通过一种细胞保护的邻苯三酚（PG）-海藻酸盐包封系统来保持细胞活力并增强细胞负载的生物制造结构的播种。我们的细胞保护包封技术利用 PG 触发的孢子形成和发芽过程来保护细胞，具有机械强度、化学抗性和高度可定制性，可以充分匹配细胞保护能力和生物制造条件的细胞毒性。更重要的是，我们的 PG-海藻酸盐系统的简单和可调的去封装允许休眠细胞在典型的培养条件下有效发芽。通过这种方法，我们成功地实现了一种可重复、可扩展的生物制造过程，并为现成的、可运输的和临时存储制造的生物结构提供了一种实用的解决方案。
