Chronic, nonhealing diabetic foot ulcers do not follow the normal, orderly progression of events seen in healthy acute wounds. Many theories have been proposed to explain the observed pathophysiologic state of these wounds. Traditionally, chronic DFUs have been considered to be trapped in a persistent inflammatory state, with impaired transition toward pro-resolution macrophage phenotypes.. Graphically, this is displayed as a prolongation of the bell shaped curve of “inflammation” following hemostasis, and preceding healing. The cells within and at the edge of chronic wounds have been described as senescent, which aligns with the observation that aggressive debridement can support healing. One inconsistency was observed with the use of fibroblasts and keratinocytes that were made replicatively senescent via exposure to radiation. Spraying these living, senescent cells onto the surface of a chronic VLU promoted much better rates of healing (Kirsner 2016). How can senescent cells be the answer if cellular senescence is the problem? More recent single-cell analyses of human DFUs have challenged the conventional M1/M2 paradigm, identifying distinct cellular states associated with healing and nonhealing wounds, including enrichment of inflammatory macrophage populations in healers (Theocharidis et al., 2022). This session will reconsider the conventional view of inflammation in DFUs, explore how the nature and timing of inflammatory responses influence healing, and discuss novel therapeutic approaches that harness, rather than simply suppress, inflammation.<br><br>
Sponsored by Flen Health.