Three-dimensional (3D) bioprinting based on microgel: design, properties, and applications

Microgel-based bioinks, comprising densely packed microgel particles, are emerging biomaterials that advance 3D bioprinting technologies due to their customizable physical and biological properties. These bioinks enable the fabrication of complex three-dimensional structures that partially reproduce some features of the natural extracellular matrix (ECM), thereby supporting improved cellular viability, proliferation, and tissue regeneration compared to traditional materials. This review focuses on the design strategies, properties, and characterizations of microgel-based bioinks, highlighting their transformative role in diverse biomedical applications, including tissue engineering, regenerative medicine, and disease modeling. We first introduce fabrication methods used to produce microgels with tunable properties. The development of functionalized microgel-based bioinks for various 3D bioprinting techniques is then summarized, with a focus on structural design and property control, including rheological, mechanical, biological properties as well as printability. Integration of functional components, such as conductive materials, to develop stimulus-responsive microgels is also discussed, offering pathways to create dynamic and adaptive structures for advanced biomedical applications. Furthermore, we critically review the application of 3D-printed microgel-based structures in engineering complex tissues and constructing in vitro disease models, demonstrating their ability to support diverse cellular environments, including skin, bone, liver, and neural systems. These platforms also facilitate drug screening and tissue repair. Lastly, future perspectives are provided to tackle the challenges in the ongoing development and practical applications of microgel-based. Advancements in microgel design and preparation, innovative fabrication strategies, and a mechanistic understanding of microgel-cell interactions are expected to further facilitate 3D bioprinting using microgel-based bioinks for tissue engineering and regenerative medicine.