Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration

Wound healing progresses through many key cellular activities, including fibroblast and keratinocyte proliferation and angiogenesis. This study explored the wound-healing potential of reactive oxygen species (ROS)-generating hyaluronic acid (HA) hydrogels. We fabricated a chlorin e6–conjugated HA (Ce6-HA) hydrogel that generates ROS when subjected to irradiation from an LED light source. In vitro studies revealed that the ROS generated by the Ce6-HA hydrogels enhanced the proliferation of fibroblasts and keratinocytes. Further, the fibroblasts were found to have high levels of intracellular ROS, elevated expression of p-ERK1/2, p-p38 MAPK, p-Akt, and cyclin D1 proteins, and enhanced collagen deposition. Moreover, the Ce6-HA hydrogel also promoted endothelial angiogenesis in vitro . In vivo studies demonstrated the ROS-generating HA hydrogels significantly improved wound closure and tissue regeneration compared to control groups. The Ce6-HA hydrogel-treated group exhibited accelerated wound healing, with enhanced fibroblast proliferation, increased keratinocyte proliferation, and better angiogenesis. Histopathological and immunohistochemical analyses showed elevated levels of key growth factors and signaling molecules, which are critical to wound healing. The controlled ROS generation from the Ce6-HA hydrogels activated broader molecular pathways necessary for effective skin tissue repair. Therefore, ROS-triggering HA hydrogels could be a viable approach to accelerate recovery and reduce scarring in clinical settings. This study investigates a hyaluronic acid hydrogel conjugated with chlorin e6 (Ce6-HA), which generates ROS upon exposure to LED light. In vitro experiments were conducted using fibroblasts, keratinocytes, and endothelial cells to evaluate the cellular responses. In vivo studies demonstrated that the Ce6-HA hydrogel significantly enhanced wound closure and tissue regeneration. Histological analysis further confirmed elevated expression of growth factors and wound healing related markers. • A Ce6-conjugated HA hydrogel was developed to release ROS under red LED light for controlled wound therapy. • ROS release promoted both fibroblast growth and keratinocyte activation, enhancing skin regeneration. • The hydrogel stimulated angiogenesis, leading to improved vascularization and faster tissue repair. • Histological analysis confirmed enhanced cellular activity and reduced inflammation in ROS-treated wounds. • ROS-releasing HA hydrogels show strong therapeutic potential for wound healing by accelerating recovery.