Direct 3D Bioprinting of Tough and Antifatigue Cell-Laden Constructs Enabled by a Self-Healing Hydrogel Bioink

Three-dimensional (3D) extrusion bioprinting has emerged as one of the most promising biofabrication technologies for preparing biomimetic tissue-like constructs. The successful construction of cell-laden constructs majorly relies on the development of proper bioinks with excellent printability and cytocompatibility. Bioinks based on gelatin methacryloyl (GelMA) have been widely explored due to the excellent biocompatibility and biodegradability and the presence of the arginine-glycine-aspartic acid (RGD) sequences for cell adhesion. However, such bioinks usually require low-temperature or ionic cross-linking systems to solidify the extruded hydrogel structures, which results in complex processes and limitations to certain applications. Moreover, many current hydrogel-based bioinks, even after chemical cross-linking, hardly possess the required strength to resist the mechanical loads during the implantation procedure. Herein, we report a self-healing hydrogel bioink based on GelMA and oxidized dextran (OD) for the direct printing of tough and fatigue-resistant cell-laden constructs at room temperature without any template or cross-linking agents. Enabled by dynamic Schiff base chemistry, the mixed GelMA/OD solution showed the characteristics of a dynamic hydrogel with shear-thinning and self-supporting behavior, which allows bridging the 5 mm gap and efficient direct bioprinting of complex constructs with high shape fidelity. After photo-cross-linking, the resulting tissue constructs exhibited excellent low cell damage, high cell viability, and enhanced mechanical strength. Moreover, the GelMA/OD construct could resist up to 95% compressive deformation without any breakage and was able to maintain 80% of the original Young's modulus during long-term loading (50 cycles). It is believed that our GelMA/OD bioink would expand the potential of GelMA-based bioinks in applications such as tissue engineering and pharmaceutical screening.