Architected Hydrogels for Functional Tissue Engineering Applications

The functionality of many biological tissues relies on their highly sophisticated architecture. Recent advances have enabled in vitro generation of human organoid models through 3D stem cell culture in animal-derived protein hydrogels. However, these oversimplified materials often lack in vivo-like microarchitecture and mechanical stimuli to support in vitro tissue formation. As such, there is an imperative need to develop architected hydrogels that can be integrated with 3D cell culture and microfluidic technologies to provide native-like dynamic 3D environments promoting multicellular self-organization and tissue maturation. In this review article, we provide an overview of the design and properties of architected hydrogels and highlight their integration with other bioengineering tools for functional tissue engineering. Firstly, we discuss the structural and physical properties in natural nanofibrillar hydrogels and synthetic analogues with non-linear elasticity. We then provide a comparative summary of different methods to generate macroporous hydrogels that facilitate mass transport, cell-cell communication, and tissue maturation in 3D. Next, we investigate examples of 3D printed hydrogels with complex tissue-mimicking architectures and discuss emerging applications of architected hydrogels in tissue engineering, organ-on-chip technology and mechanobiology. Lastly, existing challenges and future directions in developing architected hydrogels towards functional tissue engineering are highlighted.