Aligned membranes regulate wound healing via MMP12 secreted by macrophages

Aligned electrospinning membranes (Align) have demonstrated the potential to enhance wound healing by establishing a regenerative microenvironment surrounding the wound; However, the precise mechanism underlying its facilitation of healing remains unclear. To elucidate aligned electrospun fiber membrane's role in accelerating wound healing and improving its quality, we conducted a comprehensive analysis. Firstly, in vivo experiments confirmed that Align promotes wound healing. Through combined bulk RNA sequencing and single-cell RNA sequencing, we identified that MMP12+ macrophages exhibit high expression of MMP12 during the early stage of wound remodeling, thereby inhibiting fibroblast migration and reducing scar formation after wound closure. Finally, both in vitro and in vivo experiments further validated the role of MMP12 in promoting wound healing and suppressing fibroblast migration. Our findings reveal that Align effectively enhances skin wound healing by upregulating MMP12 expression while inhibiting fibroblast migration. These insights provide valuable knowledge on how Align promotes efficient scar-free wound healing and serve as a theoretical foundation for developing more effective biological dressings.