A multifunctional parathyroid hormone-related supramolecular peptide-loaded dual network hydrogel for radiation-induced wound repair

Radiation-induced wounds (RIWs), frequently resulting from radiotherapy, adversely affect clinical outcomes and patient care due to excessive reactive oxygen species (ROS) production, persistent inflammation, and ensuing cellular senescence. This study presents an innovative multifunctional dual-network hydrogel that integrates P1R16, a supramolecular parathyroid hormone-related peptide, into a matrix composed of quaternized chitosan (QCS), oxidized hyaluronic acid (OHA), and paramylon (PM). The hydrogel was designed to address key challenges in RIWs management, including bacterial infection, oxidative stress, cellular senescence, vascularization and tissue regeneration. Its antibacterial properties stem from QCS and PM, while the Schiff-base reaction and ether bonds enhance self-healing and mechanical stability. P1R16 contributes to reducing radiation-induced oxidative damage, inflammation, and senescence, promoting cell viability and facilitating wound healing. A rat model with RIWs demonstrated that QOP@P1R16 effectively accelerates skin regeneration via antibacterial, antioxidant, anti-senescence, and angiogenesis mechanisms. These findings suggest that QOP@P1R16 represents a promising therapeutic strategy for RIWs and other radiation-induced tissue injuries.