Local Delivery of Glabridin by Biomolecular Microneedle to Accelerate Infected Wound Healing.

Applying antibacterial polymers and pro-regenerative small molecules are two individual strategies for accelerating wound healing. However, integrating those two unique approaches into one therapeutic platform that meets clinical requirements is still a challenge. Herein, a series of antibacterial gelatin methacrylate (GelMA)/ε-polylysine (ε-PL) composite hydrogels (termed as GP-n HGs, n = 0, 10, 20 and 30, respectively) were innovatively fabricated by ultraviolet light (UV) crosslinking. The GP-n HGs were proved to be broad-spectrum antibacterial and biocompatible. Among those GP-n HGs, the GP-20 HG was selectively processed into microneedle following a mold-casting method. Then, the glabridin was loaded into those needles to produce composite microneedle termed GP-20@Gla MN. An S. aureus-infected full-thickness defect model in rats was created to evaluate the wound-healing effect of GP-20@Gla MN. Furthermore, an RNA sequencing assay was performed to explore the possible molecular mechanisms of glabridin in promoting tissue regeneration, and many positive routes have been summarized. This work is of significant novelty in fulfilling complex clinical needs by simultaneously optimizing the advanced microneedles' chemical compositions and physical structures. This work will provide a promising therapeutic platform for treating infected and chronic wounds. This article is protected by copyright. All rights reserved.