Microfabricated and multilayered PLGA structure for the development of co-cultured in vitro liver models

Abstract One of the main advantages of having an in vitro model is the possibility of reducing toxic effects of drugs on human body and evaluate their response to pharmacological treatments to improve the efficacy of a patient-specific therapy. The limitation of such in vitro model is the use of monolayer hepatocytes cultures that show some problems of protein secretion and hepatic functionality. In order to overcome these drawbacks, we present two innovative multilayer structures based on micro-stamped poly(lactic-co-glycolic acid) (PLGA) structures and hepatocytes and fibroblast co-cultures. In particular, the first model consisted of 1 up to 5 layers of PLGA seeded with the previously cited co-culture, while the second model consisted of various sandwich structures of PLGA functionalised (or not) with collagen and seeded with hepatocytes and/or fibroblasts. A mechanical analysis, contact angle and surface charge density measurements were carried out. After these preliminary tests, a metabolic analysis was performed evaluating glucose consumption and urea and albumin production over a culture period of 11 days. Results showed promising application of these in vitro liver models, in particular considering the field of cirrhotic liver treatment.