Research

Manfredi San Germano

Development of novel 3D cell culture system microfluidics plaform for drug screening and tissue engineering

Manfredi San Germano - 2nd year PhD

Abstract

Current medical research aims to test new therapies as well as diagnostics tests on animals before delivering them to humans and in turn, basic research is first tested in-vitro before translating it to animal trials. This jump from in-vitro to in-vivo has ethical as well as scientific challenges as animals get killed and it is not easy to test isolated responses in uncontrolled environments that in-vivo models offer. 3D cell cultures are limited by the diffusion of oxygen and nutrients throughout the tissue. This is typically about 200-300 microns, limiting the generation of tissue in-vitro to few tissues such as skin or poorly vascularised cartilage. Blood vessels keep tissues perfused and are the bottleneck in many tissue engineering developments. Current in vitro systems do not fully represent in-vivo conditions of microenvironments to test new versus existing therapies. Tissue models are currently being perfused with artificial pre-fabricated micro channels or porous material allowing nutrient and oxygen diffusion. These may unable to grow cells in a 3D setting but lack in basic physiological delivery channels - blood vessels - that are fundamental in evaluating pharmacokinetics of new molecules. The ability to grow a microenvironment mimicking closely in-vivo conditions would bring significant advancements to both drug discovery as well as tissue engineering. Functional 3D tissue models that are subject to biochemical, electrical and mechanical stimuli can be used to mimic closely pathology of degenerative myopathies as well as grow tissue for surgical procedures. Microfluidics offer a flexible engineering approach to design controlled experiments closely monitoring 3D microenvironment. This intermediate step between 2D in vitro and in vivo assays can help tease out microenvironmental cues involved in successful delivery of therapies and tissue growth/formation."