Spatial-temporal control over biochemical cues in hydrogels to recapitulate dynamic tissues

Lu, Yung Hsiang (1), Fokina, Ana (2), Baker, Alexander (2), Shoichet, Molly (1, 2, 3)

(1) Institute of Biomaterials and Biomedical Engineering, University of Toronto

(2) Department of Chemical Engineering and Applied Chemistry, University of Toronto

(3) Department of Chemistry, University of Toronto

Hydrogels are traditionally designed as static systems for 3-dimensional (3D) cell culture. While this is an improvement from culturing on 2D tissue culture polystyrene, traditional hydrogels have been shown to be insufficient in modelling the dynamic nature of tissue during development and disease progression. Recently, there has been a push towards bioengineered hydrogel systems which enable spatial-temporal control over the presentation of biochemical signals to cells. Research groups, such as those led by Anseth, Burdick, and DeForest, have developed photo-chemical methods to spatially and temporally change either mechanical properties of hydrogels or presentation of biochemical cues. However, most of these systems use materials, such as polyethylene glycol, that are not physiologically relevant to the body. In addition, most of these designs focus on controlling the removal rather than the presentation of biochemical cues. The goal of this project was to develop a new, physiologically-relevant hydrogel system with reversible photochemically-caged proteins. As a proof of concept study, we controlled the presentation of epidermal growth factor (EGF) in hyaluronan (HA)-based hydrogels and analysed the effect of EGF on encapsulated breast cancer spheroids. HA has been shown to be overexpressed in the tumour microenvironment, and especially abundant around breast cancer. EGF has previously been shown to differentially affect different lines of breast cancer cells in terms of viability, invasion, and response to drug treatment. With photochemistry, we can control the spatial-temporal presentation of EGF to cells. This study serves as a first step towards validating our hydrogel platform to dynamically present a diverse range of biochemical cues in a variety of in vitro biological models.