Drug and chemical development along with safety tests rely on the use of numerous clinical models. This is a lengthy process where animal testing is used as a standard for pre-clinical trials. However, these models often fail to represent human physiopathology. This may lead to poor correlation with results from later human clinical trials. Organ-on-a-Chip (OOAC) systems are engineered microfluidic systems, which recapitulate the physiochemical environment of a specific organ by emulating the perfusion and shear stress cellular tissue undergoes in vivo and could replace current animal models. The success of culturing cells and cell-derived tissues within these systems is dependent on the scaffold chosen; hence, scaffolds are critical for the success of OOACs in research. A literature review was conducted looking at current OOAC systems to assess the advantages and disadvantages of different materials and manufacturing techniques used for scaffold production; and the alternatives that could be tailored from the macro tissue engineering research field.