In situ microenvironment remodeling using a dual-responsive system: photodegradable hydrogels and gene activation by visible light

A 3D microenvironment with dynamic cell-biomaterial interactions was developed using a dual-responsive system for in situ microenvironment remodeling and control of cellular function. A visible-light-responsive polymer was utilized to prepare a hydrogel with photodegradation properties, enabling in situ microenvironment remodeling. Additionally, a vascular endothelial growth factor (VEGF) gene activation unit that was responsive to the same wavelength of light was incorporated to support the potential application of the system in regenerative medicine. Following light exposure, the mechanical properties of the photodegradable hydrogel gradually deteriorated, and product analysis confirmed the degradation of the hydrogel, and thereby, 3D microenvironment remodeling. In situ microenvironment remodeling influenced stem cell proliferation and enlargement within the hydrogel. Furthermore, stem cells engineered to express light-activated VEGF and incorporated into the dual-responsive system were applied to wound healing and an ischemic hindlimb model, proving their potential application in regenerative medicine.