Bilayer Pcl/Gelma Microneedle Patch Codelivers Deferoxamine and Primed Mesenchymal Stem Cell Secretome for Enhanced Diabetic Wound Repair Publisher



Sepanjnia A ; Farzin A ; Rezaei A ; Seyhoon I ; Arab M ; Verdi J
Source: Biomaterials Advances Published:2027

Abstract

Chronic diabetic wounds remain refractory to healing due to persistent inflammation, impaired re-epithelialization, extracellular matrix dysregulation, and microvascular dysfunction. Here, we report a mechanically robust and biologically integrated microneedle (MN) platform composed of a poly(ε-caprolactone) (PCL) core and a gelatin methacryloyl (GelMA) coating, engineered for the localized compartmentalized co-delivery of deferoxamine (DFO) and mesenchymal stem cell-derived conditioned medium (CM). By leveraging a dual-reservoir architecture—incorporating fresh liquid CM within the GelMA shell and lyophilized CM within the structural PCL core—the platform achieves complementary biphasic release kinetics while preserving the biological integrity of labile growth factors. In a diabetic wound model using Wistar rats, treatment with a bioactive MN platform significantly accelerated re-epithelialization, resolved chronic inflammation, and increased collagen deposition by approximately 40% compared to untreated and blank MN controls. Furthermore, vascular assessment on day 14 revealed a qualitative increase in CD31-positive vascular structures within the treated wounds. Notably, microneedles co-loaded with DFO and CM markedly improved key healing parameters compared with untreated diabetic wounds, with several parameters approaching those observed in non-diabetic control tissues at the 14-day endpoint. Mechanistically, these findings are consistent with a hierarchical healing process in which restoration of immune homeostasis promotes epithelialization and extracellular matrix remodeling, followed by enhanced vascularization. Collectively, these results indicate that spatially compartmentalized MN-mediated co-delivery of DFO and CM may represent a promising strategy for activating endogenous regenerative pathways and enhancing tissue repair in diabetic wounds. This approach may also provide a scalable therapeutic platform for improving the impaired healing capacity associated with diabetes. Copyright © 2026. Published by Elsevier B.V.