3D-bioprinted all-inclusive bioanalytical platforms for cell studies

Abstract

Innovative drug screening platforms should improve the discovery of novel and personalized cancer treatment. Common models such as animals and 2D cell cultures lack the proper recapitulation of organ structure and environment. Thus, a new generation of platforms must consist of cell models that accurately mimic the cells' microenvironment, along with flexibly prototyped cell handling structures that represent the human environment. Here, we adapted the 3D-bioprinting technology to develop multiple all-inclusive high throughputs and customized organ-on-a-chip-like platforms along with printed 3D-cell structures. Such platforms are potentially capable of performing 3D cell model analysis and cell-therapeutic response studies. We illustrated spherical and rectangular geometries of bio-printed 3D human colon cancer cell constructs. We also demonstrated the utility of directly 3D-bioprinting and rapidly prototyping of PDMS-based microfluidic cell handling arrays in different geometries. Besides, we successfully monitored the post-viability of the 3D-cell constructs for seven days. Furthermore, to mimic the human environment more closely, we integrated a 3D-bioprinted perfused drug screening microfluidics platform. Platform's channels subject cell constructs to physiological fluid flow, while its concave well array hold and perfused 3D-cell constructs. The bioapplicability of PDMS-based arrays was also demonstrated by performing cancer cell-therapeutic response studies. Traditionally, biomedical research has relied on animal models or two-dimensional (2D) cell cultures. Animal models, though one of the most commonly used systematic models, provide a limited understanding of humanspecific biology of different tissues. This is due to several reasons, such as fundamental differences between humans and animals 1 , low throughput studies, in addition to the ethical concerns 2. Animal testing is not costeffective, considering the cost to provide care, food, and shelter for the animals. Moreover, it is still possible that animal models can show promising results for drug treatments that can be harmful when tested on human subjects 3. On the other hand, despite the broad applications of 2D-cell cultures, these models only interact with their microenvironment in two dimensions, which in most cases cannot properly represent physiological conditions 4. Several studies have shown that 2D-cell constructs possessed altered cell polarity, mechanical cues, biochemical signals, and cell-cell interactions 5. Recently, there has been an emergence of three-dimensional (3D) cell models that better capture the complex cellular microenvironment than the conventional 2D models. 3D-models have shown improvement and relevance in vivo cell structure and function, where features such as the cell type, cell morphology, cell propagation, as well as, differentiation are more precisely represented 6-13. Furthermore, one should note that each year, billions of dollars are wasted because of preclinical 2D cell culture failure in predicting drug safety ...

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