Significance: Extracellular matrix (ECM) stiffness is an influential factor in many biological processes. Temporal changes in ECM stiffness are observed in cancer, cardiovascular disease, and wound healing, and are likely involved in disease progression. However, no cell culture systems exist to appropriately model temporal changes in ECM stiffness to determine the biological relevance and mechanisms involved. Here, we present a 3D hydrogel cell culture system in which the matrix stiffness can be tuned by light. Our approach offers both spatial and temporal control of stiffness, is compatible with cell culture, and can be used transdermally for in vivo applications. This system is amenable to many applications to investigate the influence of matrix stiffness on cell behavior and fate.

Inflammation is triggered by an insult or injury to the cells of the body and is a healthy and productive step towards healing. Persistent inflammation, however, is a dysregulated response and can lead to a host of unwanted disease states. The death of cells by necrosis is known to initiate inflammation, while the programmed death of cells by apoptosis limits the inflammatory response. We propose here that there exists a spectrum of cell living, aging, dying, and death states that have differential effects on inflammatory disease.