Bio-mimicked hierarchical 2D and 3D structures from natural templates: applications in cell biology

Intricate structures of natural surfaces and materials have amazed people over the ages. The unique properties of various surfaces also created interest and curiosity in researchers. In the recent past, with the advent of superior microscopy techniques, we have started to understand how these complex structures provide superior properties. With that knowledge, scientists have developed various bio-mimicked and bio-inspired surfaces for different non-biological applications. In the last two decades, we have also started to learn how structures of the tissue microenvironment influence cell function and behaviour, both in physiological and pathological conditions. Hence, it became essential to decipher the role and importance of structural hierarchy in the cellular context. With advances in microfabricated techniques, such complex structures were made by superimposing features of different dimensions. However, the fabricated topographies are far from matching the complexities present in vivo. Hence, the need of biomimicking the natural surfaces for cellular applications was felt. In this review, we discuss a few examples of hierarchical surfaces found in plants, insects, and vertebrates. Such structures have been widely biomimicked for various applications but rarely studied for cell-substrate interaction and cellular response. Here, we discuss the research work wherein 2D hierarchical substrates were prepared using biomimicking to understand cellular functions such as adhesion, orientation, differentiation, and formation of spheroids. Further, we also present the status of ongoing research in mimicking 3D tissue architecture using de-cellularised plant-based and tissue/organ-based scaffolds. We will also discuss 3D printing for fabricating 2D and 3D hierarchical structures. The review will end by highlighting the various advantages and research challenges in this approach. The biomimicked in-vivo like substrate can be used to better understand cellular physiology, and for tissue engineering.