School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
Biofabrication. 2019 Mar 28;11(2):025011. doi: 10.1088/1758-5090/ab063f.
Gelatin methacryloyl (GelMA) is a versatile biomaterial that has been shown to possess many advantages such as good biocompatibility, support for cell growth, tunable mechanical properties, photocurable capability, and low material cost. Due to these superior properties, much research has been carried out to develop GelMA as a bioink for bioprinting. However, there are still many challenges, and one major challenge is the control of its rheological properties to yield good printability. Herein, this study presents a strategy to control the rheology of GelMA through partial enzymatic crosslinking. Unlike other enzymatic crosslinking strategies where the rheological properties could not be controlled once reaction takes place, we could, to a large extent, keep the rheological properties stable by introducing a deactivation step after obtaining the optimized rheological properties. Ca-independent microbial transglutaminase (MTGase) was introduced to partially catalyze covalent bond formation between chains of GelMA. The enzyme was then deactivated to prevent further uncontrolled crosslinking that would render the hydrogel not printable. After printing, a secondary post-printing crosslinking step (photo crosslinking) was then introduced to ensure long-term stability of the printed structure for subsequent cell studies. Biocompatibility studies carried out using cells encapsulated in the printed structure showed excellent cell viability for at least 7 d. This strategy for better control of rheological properties of GelMA could more significantly enhance the usability of this material as bioink for bioprinting of cell-laden structures for soft tissue engineering.
明胶甲基丙烯酰（GelMA）是一种用途广泛的生物材料，具有良好的生物相容性、支持细胞生长、可调机械性能、光固化能力和低材料成本等优点。由于这些优越的性能，已经进行了大量的研究来开发 GelMA 作为生物打印的生物墨水。然而，仍然存在许多挑战，其中一个主要挑战是控制其流变性能以获得良好的可印刷性。在此，本研究提出了一种通过部分酶交联来控制 GelMA 流变性的策略。与其他酶交联策略不同，一旦反应发生，就无法控制流变性能，我们可以通过在获得优化的流变性能后引入失活步骤，在很大程度上保持流变性能的稳定性。非 Ca 依赖性微生物转谷氨酰胺酶（MTGase）被引入以部分催化 GelMA 链之间的共价键形成。然后将酶失活以防止进一步的不受控制的交联，从而使水凝胶无法打印。打印后，引入二次后打印交联步骤（光交联），以确保打印结构的长期稳定性，以便进行后续的细胞研究。使用封装在打印结构中的细胞进行的生物相容性研究表明，细胞活力至少在 7 天内保持良好。这种更好地控制 GelMA 流变性能的策略可以更显著地提高该材料作为生物墨水用于软组织工程中细胞负载结构的生物打印的可用性。
