Research Institute for Biomaterials, Tech Institute for Advanced Materials, College of Materials Science and Engineering, Nanjing Tech University, Nanjing 211816, China.
NJTech-BARTY Joint Research Center for Innovative Medical Technology, Nanjing 210000, China.
Biomater Sci. 2022 Aug 9;10(16):4479-4491. doi: 10.1039/d2bm00632d.
Although significant breakthroughs have been achieved in constructing complex tissue/organ models , the progress of 3D bioprinting has long been subjected to trade-offs between the printability and biocompatibility of bioinks. Methacrylated hyaluronic acid (HAMA) has been widely adopted for 3D bioprinting due to its limited immunogenicity and simple synthetic method. However, the challenges arising from HAMA are its limited mechanical properties, low printing resolution, inhomogeneity networks, and the accumulation of reactive oxygen species (ROS) during polymerization. Here, these limitations are addressed by developing a thiol-norbornene photoclick polysaccharide-based bioink (HC-HN), which is prepared through the modification of hyaluronic acid with norbornene functional groups (Nor) and cysteamine hydrochloride (Cys). Compared with traditional HAMA, the HC-HN bioink a step-growth polymerization mechanism can realize increased viscoelastic properties, reduced ROS accumulation, and superior shape fidelity in a range of complex structures by 3D embedded bioprinting. To further confirm its potential in 3D bioprinting applications, the HC-HN bioink is employed to print a liver model , which shows higher albumin secretion and urea production. Furthermore, a markedly increased sensitivity to drug-induced hepatotoxicity is observed in the bioprinted liver model compared to the 2D culture. Therefore, the proposed photoclick HC-HN bioink expands the palette of available polysaccharide-based bioinks and greatly extends the biofabrication window to broaden the application opportunities of 3D bioprinting.
尽管在构建复杂的组织/器官模型方面已经取得了重大突破，但 3D 生物打印的进展长期以来一直受到生物墨水的可打印性和生物相容性之间的权衡。甲基丙烯酰化透明质酸（HAMA）由于其免疫原性有限且合成方法简单，已被广泛用于 3D 生物打印。然而，HAMA 带来的挑战是其机械性能有限、打印分辨率低、网络不均匀以及聚合过程中活性氧（ROS）的积累。在这里，通过开发一种巯基-降冰片烯光点击多糖基生物墨水（HC-HN）来解决这些限制，该生物墨水是通过用降冰片烯官能团（Nor）和半胱胺盐酸盐（Cys）修饰透明质酸制备的。与传统的 HAMA 相比，HC-HN 生物墨水具有逐步聚合机制，通过 3D 嵌入式生物打印可以实现更高的粘弹性、减少 ROS 积累和更优异的复杂结构形状保真度。为了进一步证实其在 3D 生物打印应用中的潜力，将 HC-HN 生物墨水用于打印肝脏模型，结果显示其白蛋白分泌和尿素生成更高。此外，与 2D 培养相比，在生物打印的肝脏模型中观察到对药物诱导的肝毒性的敏感性显著增加。因此，所提出的光点击 HC-HN 生物墨水扩展了可用多糖基生物墨水的调色板，并大大扩展了生物制造窗口，从而拓宽了 3D 生物打印的应用机会。
