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

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/m2 (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/m2 NANO dressing. Thinner dressings (10 and 20 g/m2), 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/m2 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/m2 NANO was comparable to Jelonet. Dressing thickness influenced healing quality in the porcine model. Partial-thickness wounds treated with 10-20 g/m2 NANO dressings showed superior outcomes compared with 30 g/m2, with negligible systemic LPPO exposure. In the clinical case, a 15 g/m2 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.