Temperature-Programmable Deformable Microneedles for Scar-Free Healing of Infective Wounds via Sensory Nerve Regeneration

Abstract

Infectious wound healing remains a complex challenge, complicated by bacterial infections, inflammation, and sensory nerve damage, which hinder healing and contribute to excessive scarring. For refractory wound healing, a temperature-programmable deformable microneedle (TPDM) is constructed, which can program at 85 °C through changes in time to maintain the shape for a corresponding period of time at 27 °C before returning to its original shape. In addition, his deformation is not temperature related, but rather caused by the separation of water phases to prevent skin burns from high temperatures and secondary impacts. The microneedles are characterized using scanning electron microscopy, transmission electron microscopy, and Nile red staining. Their antibacterial efficacy is confirmed through co-culture with methicillin-resistant Staphylococcus aureus (MRSA). In vitro, it promoted keratinocyte migration and facilitated sensory nerve regeneration. Furthermore, they significantly reduced scar-associated Engrailed-1 (EN-1)-positive fibroblasts and macrophages, which are key contributors to fibrotic responses. In vivo, it accelerated wound healing, reduced the accumulation of EN-1-positive fibroblasts and collagen I, and enhanced sensory nerve density and mitochondrial activity at the wound site. TPDM exhibits strong antibacterial properties against MRSA, promoting sensory nerve regeneration and reduces scarring, offering a promising therapeutic strategy for improving the healing of infectious wounds.