Temperature-Responsive Hydrogel System Integrating Wound Temperature Monitoring and On-demand Drug Release for Sequentially Inflammatory Process Regulation of Wound Healing

Wound healing faces challenges like inflammation, infection, and limited monitoring capabilities, and traditional dressings often lack the ability to promote healing or provide real-time wound status updates. Early pro-inflammatory responses help clear pathogens and damaged tissue, while timely anti-inflammatory modulation aids tissue regeneration, making sequential inflammation regulation crucial. Additionally, wound temperature, a key infection biomarker, enables real-time monitoring for effective management. We propose a temperature-responsive hydrogel dressing capable of two-stage sequential drug release and wound temperature monitoring. The hydrogel, composed of poly( N -isopropylacrylamide) (PNIPAM) and dopamine/methacrylated-modified hyaluronic acid (HA–MA–DA), allows temperature-based drug release control, sequential regulating pro-inflammatory and anti-inflammatory stages in wound healing. Interleukin-8 (IL-8), a pro-inflammatory molecule, is encapsulated into hydrogel matrix and rapidly released to trigger the initial inflammatory response. Furthermore, photothermally responsive and erastin-loaded polydopamine@PNIPAM nanoparticles (E-PD NPs) are incorporated to release the anti-inflammatory drug erastin upon near-infrared light exposure, terminating inflammation through cytosolic burial, and thus achieve anti-inflammatory effects at the second stage of wound healing. Furthermore, a bluetooth module enables real-time wound temperature monitoring. Combining sequential drug release with temperature monitoring, our hydrogel dressing addresses significant gaps in current wound healing technologies and offers new insights into personalized therapeutic interventions.