The desired organ in micro-tissue models of organ-on-a-chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural-based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural-based biomaterials and summarize recent reports on their applications in the design and fabrication of micro-tissue models. This article will help bioengineers select the proper biomaterials based on developing new technologies to meet clinical expectations and improve patient outcomes fusing disease modeling.hydrogels, micro-tissue, natural biopolymers, organ-on-a-chip
| INTRODUCTIONEngineered micro-tissue models have been used to resemble extracellular matrix (ECM) and natural tissues, with intensive applications ranging from drug injection to sample separation and detection on a single platform. 1 These models can be added to organs-on-chips (OoCs) to precisely monitor cell media across microchannels ranging in size from tens to hundreds of microns. 2 The microchannel has a Berivan Cecen and Ayca Bal-Ozturk contributed equally.