Iron-quercetin-incorporated PCL/PEO nanofibrous scaffolds for ADSC secretome modulation and in vitro regenerative responses.

Chronic and non-healing wounds remain a major clinical challenge due to impaired angiogenesis and insufficient regenerative signaling. Although mesenchymal stem cell (MSC)-derived secretomes offer promise as cell-free therapeutics, clinical translation is hindered by limited regenerative potency and poor localization. Here, we translated Iron-Quercetin complex (IronQ) into a scaffold-integrated priming platform by developing IronQ-incorporated polycaprolactone/poly(ethylene oxide) (PCL/PEO) electrospun nanofibers for adipose-derived stem cell (ADSC) culture and secretome modulation. The optimized PCL/PEO (3:1) scaffold exhibited favorable architecture, mechanical properties, cytocompatibility, and pH-/temperature-responsive IronQ release. Proteomic and cytokine analyses demonstrated that nanofibrous scaffold-based culture, together with IronQ-mediated biochemical stimulation, was associated with changes in ADSC secretory profiles involving extracellular matrix organization and regenerative pathways, with increased levels of selected regenerative mediators, including VEGF-A, HGF, FGF-21, PDGF-AA, SDF-1α, and CCL-2. Functionally, conditioned medium generated from ADSCs cultured on the IronQ-containing scaffold enhanced endothelial proliferation and vascular network formation, as well as fibroblast responses associated with tissue repair in vitro. These findings support the potential of this bioactive nanofibrous platform as a scaffold-based strategy for modulating ADSC paracrine responses relevant to wound-healing applications.