Soluble CD83 Accelerates Wound Healing and Attenuates Inflammatory Responses Induced by Chronic Wound Fluid in a Human 3D in Vitro Wound Healing Model.

Chronic wounds, as defined by prolonged inflammation and impaired healing, represent a major and growing healthcare challenge worldwide. Currently, only limited therapeutic options are available to address this condition. This study investigates the potential of soluble CD83 (sCD83), an immunomodulatory molecule, to facilitate wound healing in a human in vitro wound model. This model incorporates keratinocytes, fibroblasts, and macrophages in a three-dimensional skin construct and was exposed to chronic wound fluid (CWF) to induce an inflammatory and impaired-healing environment. Treatment with sCD83 resulted in a significant acceleration of wound closure, enhanced macrophage polarisation towards a pro-regenerative phenotype, and an increase in the production of growth factors such as VEGF and TGF-β. These effects were also observed under inflammatory conditions induced by CWF, which otherwise impaired healing and sustained a pro-inflammatory environment. Furthermore, sCD83 enhanced markers associated with epidermal stem cell activity and diminished the expression of pro-inflammatory mediators, underscoring its immunomodulatory and pro-regenerative properties within this human 3D in vitro model. Together, these results demonstrate that sCD83 can attenuate inflammatory responses and improve regenerative processes in a CWF-induced impaired healing environment in vitro. Our findings provide the basis for further preclinical studies to unravel the clinical potential of sCD83 as a novel treatment option for chronic and hard-to-heal wounds.