1539 A paradigm shift: Inflammatory response in chronic wounds halts progression of healing

Chronic wounds (CW), including diabetic foot ulcers (DFU) and venous leg (VLU) represent a major clinical challenge worldwide urgently needing better therapeutic solutions. The current paradigm describes chronic as “stuck in inflammatory phase” which acute progresses through other phases of healing. This was based on studies comparing human CW to intact skin from animal models that poorly resemble condition. To decipher the role inflammation CW, we performed RNAseq DFU (n=13) VLU (n=11) compared them (n=8) obtained three days post-wounding at peak phase. We identified immune signaling pathways suppressed wounds. revealed suppression TREM1/FOXM1 pathway (p=0.01), contributing decreased macrophage/neutrophil recruitment function, confirmed mouse model prospective patients. Transcriptional data immunostaining leukocyte populations pro-inflammatory M1 macrophages VLUs. Furthermore, genes important for cell were (p=0.001), by qPCR. Diminished response coupled with increased production cortisol, potent anti-inflammatory factor wound healing inhibitor. Taken together demonstrated de-regulated pro- signals, poor cells two types revealing shift lack appropriate does not reach renders incapable progressing Our underscore new treatment strategy VLU: stimulate an wound-like into