Modulation of Macrophage ferroptosis under the guide of infrared thermography promotes the healing of pressure injuries

Chronic inflammation resulting from an imbalance of M1/M2 macrophages in the inflammatory phase was found to be caused by over-activation of ferroptosis in the PIs. During the early phase of inflammation (days 0–3), excessive infiltration of M1-like macrophages resulted in a decrease in wound temperature on day 3 (green line). During the late phase of inflammation (days 4–7), there was a delayed transition from M1-like to M2-like macrophages, resulting in a delayed decrease in wound temperature on day 7 (red line). Enrichment of M1-like macrophages with inducible nitric oxide synthase (iNOS)/NO• targeted 15LOX can alter their susceptibility to ferroptosis when ferroptosis is overactivated in the PIs. M2-like macrophages gain resistance to ferroptosis when empowered by NO• donors, thereby promoting angiogenesis and wound repair. IRT can be used to identify the timing of macrophage activation and their transition to pro- or anti-inflammatory states by showing wound temperature. This finding indicates that modulation of macrophage ferroptosis based on the temperature signal has the potential to impact chronic inflammation, which in turn promotes the healing of PIs. • This non-invasive skin evaluation tool can be valuable in guiding inflammation modulation by targeting ferroptosis molecular level to promote the healing of PIs. • Two patterns of wound temperature change were observed using IRT as a result of the difference in M1/M2 macrophage phenotype sensitivity to ferroptosis. • Guided modulation of M2-like macrophage resistance to ferroptosis in wound by IRT-suggested temperature changes significantly promotes PIs healing. Accurately recognizing and regulating the transition time of macrophages to a pro- (M1-like) or anti-inflammatory (M2-like) state is essential for improving chronic inflammation in pressure injuries (PIs). This study aimed to evaluate the effectiveness of infrared thermography (IRT) in measuring wound temperature of PIs for the purpose of guiding treatment in regulating chronic inflammation. The healing process of 21 patients with PIs was monitored using IRT prospectively followed for 30 days. The wound temperature changing pattern of different healing outcomes were analyzed and calculated the optimal wound temperature range to guide the treatment time of anti-inflammation for 100 patients with PIs accurately. Additionally, the molecular mechanisms underlying the observed temperature changes in a mouse model of PI were investigated, and the effect of IRT-guided chronic inflammation targeting ferroptosis modulation on PIs was validated. The application of IRT to monitor PIs temperatures outside the 36.23 °C to 37.37 °C range is indicative of a potential risk indicator, which allows for the timely guidance of treatment to markedly enhance the efficacy of PIs healing outcomes. This wound temperature change was also observed during the process of PIs healing in mice, as a result of the imbalance of M1-like/M2-like macrophages and the subsequent chronic inflammation. Mechanically, evidence indicates that ferroptosis is hyperactivated in PIs, and the enrichment of M1-like macrophages with iNOS/NO• can enhance their resistance to ferroptosis compared with M2-like macrophages, resulting in the imbalance of M1-like/M2-like macrophages and subsequent alteration of wound temperature. The modulation of M2-like macrophage resistance to ferroptosis in PIs by NO• donors, suggesting by IRT-monitored temperature changes, has been demonstrated to significantly improve chronic inflammation. This establishes a foundation for the application of IRT to direct a therapeutic strategy for the precise promotion of PIs healing.