Targeting local glucocorticoid metabolism with a silk fibroin microneedle for more effective hypertrophic scar repair

Abstract

Hypertrophic scars (HS) are pathological cutaneous scars characterized by excessive collagen deposition and fibrosis. Intralesional glucocorticoid injections remain the standard treatment for HS, but it is often associated with side effects. In this study, we developed a novel silk fibroin microneedle (SF-MN) loaded with prednisone for localized delivery and glucocorticoid metabolism. The SF-MNs were fabricated using 10 % (w/v) silk fibroin. Prednisone-loaded SF-MNs were characterized by SEM and evaluated for biocompatibility, mechanical strength, and preclinical efficacy. Overall, the results demonstrated that the SF-MN enhanced local expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a specific enzyme that converting inactive glucocorticoids to its active form. SF-MN also achieved sustained in vitro release of prednisone over 7 days. Once released into local tissue, prednisone was rapidly converted to its active form, prednisolone. In the animal study, prednisone-SF-MNs effectively prevented scar formation during wound healing. Moreover, in the HS model, the prednisone-SF-MN accelerated scar remodelling, resulting in smaller scar size and decreased fibrosis. This targeted delivery strategy optimizes local glucocorticoid metabolism, enhance drug penetration, and minimize side effects associated with active glucocorticoid administration. These findings highlight the potential of SF microneedle-based drug delivery for improving HS treatment and support its future clinical translation.

Keywords: Glucocorticoids metabolism; Hypertrophic scar; Silk fibroin microneedle.