Detachable Microneedle Patch for Local Delivery of TGF-β Inhibitor to Suppress Scar Formation

Abstract

Severe wounds often lead to delayed healing and fibrotic scar formation, primarily driven by dysregulated transforming growth factor beta (TGF-β) signaling, which causes excessive collagen accumulation. Current treatments face limitations, including poor drug delivery, systemic side effects, and patient compliance issues. To address these challenges, we developed a detachable microneedle (d-MN) patch made of biodegradable poly(lactic-co-glycolic acid) for the localized, sustained delivery of the selective TGF-β inhibitor EW-7197 directly into skin wounds. The patch features detachable drug-loaded tips that remain embedded in the tissue shortly after application, allowing for prolonged drug release without continuous attachment. Drug dosage was controlled by adjusting the tip size, and rapid detachment was confirmed within 1 min using ex vivo models. In vitro tests showed sustained EW-7197 release for up to 14 days. In vivo studies using a rat excisional wound model demonstrated that the d-MN patch reduced wound size by approximately 50% and suppressed fibrotic scar formation compared to the controls. This minimally invasive, patient-friendly approach effectively regulates TGF-β signaling to suppress fibrosis during the wound-healing process. Our findings indicate that EW-7197-loaded d-MN patches are a promising therapeutic strategy for improving healing outcomes and reducing fibrotic scar formation.