Antioxidant MOF Nanozyme-Engineered Periodontal Ligament Stem Cells Promote Diabetic Wound Healing.

Abstract

Diabetic chronic wounds, as a prevalent and serious complication of diabetes, pose serious threats to patient health and survival, underscoring the urgent need for effective therapeutic strategies. Stem cell therapy has emerged as a promising approach, but its efficacy is often compromised by the hostile wound microenvironment, characterized by excessive reactive oxygen species and persistent inflammation. To address this challenge, we developed a nanozyme-based engineering strategy to enhance the therapeutic potential of periodontal ligament stem cells (PDLSCs) based on a bimetallic CuNi-MOF nanozyme exhibiting dual superoxide dismutase- and catalase-like activities. In vitro experiments demonstrated that, the CuNi-MOF nanozyme effectively alleviated oxidative stress and reduced cellular senescence in PDLSCs. Mechanistic investigation revealed the involvement of the JNK/ERK signaling axis in this protective effect. In a diabetic wound model, nanozyme-engineered PDLSCs (E-PDLSCs), exhibited superior healing compared with untreated PDLSCs. Specifically, E-PDLSCs significantly accelerated re-epithelialization, enhanced collagen deposition, and promoted angiogenesis, while also modulating inflammatory cytokine levels and macrophage polarization. Overall, this study presents a cell engineering strategy that integrates antioxidant nanozymes with stem cells for chronic wound treatment, extending the potential applications of nanozyme in regenerative medicine.