Smart wound dressings for accelerated scar-free wound healing

Abstract

Wound healing is a complex process comprising four main stages: hemostasis, inflammation, proliferation, and remodeling. Disruptions at any stage can lead to delayed healing, chronic wounds, or excessive scar formation. This project leverages nanotechnology to develop strategies that modulate different phases of wound healing, promoting tissue regeneration. Nanotechnology enables the manipulation of the wound healing trajectory through various chemical and physical cues to accelerate healing while minimizing scar formation. This study focuses on two key approaches: (1) infection prevention to reduce inflammation-related healing delays and (2) responsive delivery of an anti-scar drug within the critical window of scar formation. For infection prevention, a theranostic biosensor was developed. The biosensor integrates a hemicyanine dye that undergoes a color change upon detecting bacterial lipase, allowing early and visible identification of bacterial presence. Additionally, it incorporates responsive nanoparticles that release antibacterial agents selectively in environments with elevated reactive oxygen species (ROS), ensuring targeted bacterial elimination. For anti-scar drug delivery, solid lipid nanoparticles (SLNs) were engineered for targeted drug release during the early stages of scar formation. Since premature or delayed drug delivery can interfere with normal healing, a biomarker overexpressed specifically during scar formation was identified. SLNs were functionalized with a ligand targeting this marker. To prevent premature drug release, a cage-like protein coating was applied to the SLNs, enhancing stability until the optimal release window. These strategies enabled early bacterial detection at low concentrations, selective bacterial elimination in ROS-rich environments, and precise delivery of anti-scar drugs to cells overexpressing connective tissue growth factor (CTGF), a biomarker specific to scar formation. By modulating different wound healing stages, this study aims to accelerate healing while minimizing scarring. However, further in vivo studies are essential to validate the clinical potential of these approaches.