Chronic wounds are a life-threatening condition characterized by the closure of damage. Chronic inflammation and impaired regeneration and repair lead to the pathological phenotype of chronic diabetic wounds, reducing the efficacy of drugs. This study found that epidermal stem cells (EpSCs) have poor proliferation and differentiation capabilities in the inflammatory microenvironment, which is a key factor causing delayed wound healing in chronic diabetic wounds. To address this issue, we designed a nanoscale cascade engineering workshop (Cu 5.4 O@LL-37/pDNA), which can simultaneously reshape the inflammatory microenvironment and activate EpSC functions, promoting rapid wound closure. The workshop adopted a core-shell structure design. The core is a super-small Cu 5.4 O nanozyme that can efficiently eliminate reactive oxygen species, enhance the inflammatory response, and transform the pathological wound microenvironment into an ecological niche promoting regeneration. The shell is composed of plasmid DNA (pDNA) and the antibacterial peptide LL-37 through electrostatic assembly, improving the gene transfection efficiency and effectively inhibiting bacterial infection. By leveraging the dual advantages of microenvironment modulation and structural design, this system significantly enhanced gene delivery, promoted the continuous expression of P311, and thereby accelerated the proliferation and differentiation of EpSCs. This nanotherapy reshapes the microenvironment and activates EpSC functions, accelerating re-epithelialization and wound closure in diabetic and infection models. This therapeutic strategy is a new method for achieving persistent and effective healing of chronic wounds. This research was published in Advanced Materials under the title "Nanocascade Engineering Workshop for Synergistic Microenvironment Reprogramming and EpSC Revitalization in Precise Diabetic Wound Therapy".
Reference News: DOI: 10.1002/adma.202522987