I am interested in using photo-responsive hydrogels to provide controlled biophysical cues to direct the morphogenesis and differentiation of intestinal organoids and intestinal monolayers. Intestinal organoids are three dimensionally structured tissue constructs that when cultured under the appropriate matrix and biochemical cues in 3D hydrogels form crypt structures highly reminiscent of the crypt-villi axis present in-vivo. Importantly the formation of these crypts can be precisely controlled through biophysical cues via spatiotemporal softening of the hydrogel they are grown within to give differentiated organoids resembling the native intestine. However, the lifetime of these differentiated organoids is limited as dead cells accumulate within the lumen leading to a necrotic core.
When these same cell types are cultured in 2D they give rise to monolayers that spontaneously differentiate to give rise to the stochastic formation of crypt zones (comprising stem cells and Paneth cells) and villi zones (comprising differentiated cells). I am interested in providing biophysical cues to these developing monolayers through the spatiotemporal softening of the hydrogel they are grown on to control and guide their differentiation.