Biomimetic polydimethylsiloxane cell substrate design for enhanced in vitro cellular behavior

Abstract

Recent developments in cell-based therapies and toxicological investigations re veal the need for well-designed, stable and flexible cell substrates. Mimicking the natu ral cellular microenvironment by altering cell substrate properties (stiffness, topography and chemical/biochemical composition) can significantly affect cell-substrate interfacial characteristics and potentially influence cellular behavior. Hence, the main objective of this thesis is to design biomimetic Polydimethylsiloxane (PDMS) cell substrates to enhance in vitro behavior of target cell types. In the first study, simple and one-step surface modification of PDMS is successfully accomplished by the preparation of amino acid (histidine, His; and leucine, Leu) conjugated self-assembled monolayers (SAMs) for enhanced osteoblast proliferation, morphology, alkaline phosphatase activity and mineralization. In the second study, PDMS substrates with healthy myocardium-like stiffness are produced and modified with conventional [(3-aminopropyl)triethoxysilane, APTES; octadecyltrimethoxysilane, OTS] and amino acid (His, Leu) conjugated SAMs. Comparative effects of these substrates are investigated on induced pluripotent stem cell (iPSC) behavior and their differentiation into cardiomyocytes. The last study is de veloped by using PDMS with a cornea-friendly stiffness, corneal endothelial cell (CEC) microenvironment-mimetic white rose petal topography patterning and collagen IV or hyaluronic acid modification for enhanced CEC proliferation, morphology and increased phenotypic marker expression. All these biomimetic approaches demonstrate successful platforms to improve cell substrate properties of PDMS, rendering very promising tools for cell-based therapies, microfluidics, drug screening and organ-on-chip platforms.|Keywords : Polydimethylsiloxane, Biomimetic, Self-assembled monolayer, Osteoblasts, Induced pluripotent stem cells, Cardiomyocyte differentiation, Corneal endothelial cells.