Abstract
Negative Pressure Wound Therapy (NPWT) is a commonly employed clinical strategy for wound healing, yet its early-stage mechanisms remain poorly understood. To address this knowledge gap and overcome the limitations of human trials, we establish an NPWT C57BL/6JNarl mouse model to investigate the molecular mechanisms involved in NPWT. In this study, we investigate the intricate molecular mechanisms through which NPWT expedites wound healing. Our focus is on NPWT's modulation of inflammatory immune responses and the concurrent orchestration of multiple signal transduction pathways, resulting in shortened coagulation time and reduced inflammation. Notably, we observe a significant rise in dickkopf-related protein 1 (DKK-1) concentration during NPWT, promoting the differentiation of Hair Follicle Stem Cells (HFSCs) into epidermal cells, expediting wound closure. Under negative pressure, macrophages express and release DKK-1 cytokines, crucial for stimulating HFSC differentiation, as validated in animal experiments and in vitro studies. Our findings illuminate the inflammatory dynamics under NPWT, revealing potential signal transduction pathways. The proposed framework, involving early hemostasis, balanced inflammation, and macrophage-mediated DKK-1 induction, provides a novel perspective on enhancing wound healing during NPWT. Furthermore, these insights lay the groundwork for future pharmacological advancements in managing extensive wounds, opening avenues for targeted therapeutic interventions in wound care.