Photodegradable Hydrogels for On‐Demand Modeling of Age‐Related Spatiotemporal ECM Deformation

ABSTRACT The extracellular matrix (ECM) plays a crucial role in regulating tissue behavior through a dynamic interplay of spatial and temporal cues. Dynamic materials capable of modulating these cues at relevant scales are essential for tackling current challenges in tissue engineering and addressing fundamental biological questions. In vision research, there is a notable lack of suitable in vitro systems to study ECM dynamics. To help fill this gap, we developed an easy‐to‐use, photosensitive poly(ethylene glycol)‐based hydrogel that can deform on demand to simulate ECM bulging, known as drusen, associated with the aging of the outer retina. Our findings demonstrate that variations in the size of these artificial drusen during culture impact morphometric parameters of the retinal pigment epithelium, offering new insights into its mechanical resilience to different drusen sizes. Notably, drusen formation in our system does not significantly affect the cellular actin cytoskeleton or polarity, which are often disrupted in conventional acute substrate deformation models, allowing the study of early aging before detectable pathology. In summary, we present a light‐tunable hydrogel platform that enables precise spatial mimicry of ECM topographical changes, offering a promising tool for investigating the mechanobiological aspects of dynamic cell–matrix interactions.