Development of a superior in vitro model for drug hepatoxicity screening through 3D printing of crosslinkable biopolymers.

Developing drugs is a time- and cost-intensive process. During drug development, different phases are required for a drug to finally reach the market. During the discovery and development phase, thousands of compounds are synthesized, of which the most appropriate reach the preclinical phase. During this phase, in vitro and in vivo tests are performed in an attempt to track toxicity. Due to ethical as well as economic constraints, there is a clear need for more reliable in vitro toxicity tests in an attempt to enable proper selection of compounds entering the clinical phase. During my PhD research, I will focus on developing such a 3D model to evaluate drug toxicity earlier on in the drug development trajectory. Certain biopolymers will be chemically functionalized to enable crosslinking after 3D printing. The scaffolds will be optimized regarding scaffold specific properties such as composition, pore architecture and coating material. Subsequent the scaffolds will be tuned towards liver-specific properties. Those scaffolds will be used to support the adhesion and proliferation of human skin-derived precursor cells (hSKP). These stem cells will be differentiated towards hepatocyte-like cells in order to deal with the poor quality (cfr. not representative for human hepatocytes) of commercially available cell lines and the lack of availability of human hepatocytes. hSKP cells are isolated from the foreskin of boys who ondergo circumsision.