Thickness‐Dependent Healing Effects of Polycaprolactone Electrospun Nanofiber Dressings (Loaded With Lipophosphonoxin) in Partial‐Thickness Skin Wounds

ABSTRACT Polycaprolactone (PCL) electrospun nanofiber dressings loaded with lipophosphonoxin (LPPO) have shown antibacterial activity and pro‐healing potential. To optimize dressing thickness for partial‐thickness skin wounds and evaluate translational relevance. We compared PCL dressings with areal weights of 10, 20, and 30 g/m 2 (with or without 7 wt.% LPPO) in a porcine model using partial‐thickness wounds. Standard comparators were Aquacel Ag + (antibacterial control) and Jelonet (standard control). Healing was assessed macroscopically and histologically (hematoxylin and eosin, keratins‐10 and ‐14 immunohistochemistry). Systemic LPPO exposure was measured by LC–MS/MS in plasma and liver. A clinical case (STSG donor site) used a 15 g/m 2 NANO dressing. Thinner dressings (10 and 20 g/m 2 ), whether unloaded (NANO) or LPPO‐loaded (NANO‐LPPO), supported rapid re‐epithelialization from wound edges and hair follicles and yielded complete closure in wounds, comparable to controls. The 30 g/m 2 variants of both NANO and NANO‐LPPO were associated with persistent inflammation and delayed re‐epithelialization. LC–MS/MS showed plasma concentrations of LPPO below the quantification limit and very low liver levels. The clinical case mirrored the porcine findings: timely re‐epithelialization of the STSG donor site with 15 g/m 2 NANO was comparable to Jelonet. Dressing thickness influenced healing quality in the porcine model. Partial‐thickness wounds treated with 10–20 g/m 2 NANO dressings showed superior outcomes compared with 30 g/m 2 , with negligible systemic LPPO exposure. In the clinical case, a 15 g/m 2 NANO dressing supported timely re‐epithelialization of the STSG donor site, comparable to standard care. These findings justify further clinical development of PCL NANO‐LPPO dressings.