Ultrasound-Responsive Hydrogels for Accelerated Wound Healing through Programmable Microenvironment Modulation

Wound healing involving persistent inflammation and fibrosis is driven by reactive oxygen species (ROS) and Yes-associated protein (YAP), often leading to scars. A polyvinyl alcohol/alginate ultrasound-responsive hydrogel was developed, containing free epigallocatechin gallate (EGCG) in the matrix and EGCG-verteporfin (VP) nanoparticles embedded in the hydrogel network. Free EGCG is released rapidly, whereas EGCG-VP nanoparticles release is triggered by ultrasound. In vitro, this system reduced ROS by ∼69%. Western blot revealed ∼71% reduction in α-smooth muscle actin and ∼47% in YAP. In vivo, it promoted wound closure in rats. This system enables programmable modulation of the wound microenvironment.