Synthesis of Polymeric Hydrogel for 3D Cell Culturing

Abstract

Over the past decade there has been high interest in understanding cell behaviour in an in vivo setting and with that hydrogel have been drawn into light. Hydrogels have been used in a wide scope of applications such as tissue engineering and stem cell differentiation being the key examples.1, 2 However, the main application which peaked scientist interest is their functionality as an extracellular matrix (ECM) mimic.3 It has been widely accepted that cell behaviour (proliferation, migration, invasion) is influenced by the surrounding environment. That is, a 2 dimensional environment provides different biological cues to a cell compared to a 3 dimensional environment. One of the main factors which come into play is mechanotransduction; the influence of mechanical forces on a cell which translate into electrochemical stimuli.4 Understanding cell response to different environments will be critical in developing a cell culturing platform that resembles the in vivo settings. This thesis outlines 3 bodies of work; each contributing to the development of the next hydrogel. The first hydrogel is based on traditional formation whereby a stimulus (light) is used to cause gelation. Understanding the promise and limitation of the light based hydrogel a borax based hydrogel was developed. The premise of the borax hydrogel was to use commercially available chemicals to form the ECM mimics with options to change various components to introduce other biological stimulus i.e. peptide crosslinkers. Finally, a maleimide based hydrogel was developed in conjunction with a 3D printer and commercially available chemicals. Automation and pre-made chemicals remove inconsistencies and provide commercial advantage. This is the first report of an “off the shelf” ECM mimic which can be printed and manipulated specifically for various cell types.