Smart wound healing via a microenvironment-adaptive catalytic platform with multienzyme-like activities

Area of Science:

• Biomaterials Science
• Nanotechnology
• Regenerative Medicine

Background:

• Chronic wound management faces challenges from microenvironment shifts and antibiotic resistance.
• Current therapies lack adaptability to dynamic healing stages.
• Need for intelligent systems that switch therapeutic functions based on wound status.

Purpose of the Study:

• To engineer a pH-gated, smart nanozyme platform (ZIF-8-TA@Cu_s) for adaptive wound management.
• To investigate the platform's dual functionality: antibacterial and pro-regenerative.
• To evaluate the therapeutic efficacy in infected chronic wound models.

Main Methods:

• Fabrication of a pH-responsive nanozyme platform integrating ZIF-8, tannic acid, and Cu2O/CuO heterojunction.
• In vitro assessment of catalytic activities (peroxidase-like, antioxidant) under varying pH conditions.
• In vivo evaluation in a Staphylococcus aureus-infected mouse wound model, assessing bacterial clearance, inflammation modulation, and tissue regeneration.

Main Results:

• The nanozyme platform demonstrated pH-dependent catalytic activity, generating reactive oxygen species (ROS) under acidic conditions and scavenging ROS under neutral conditions.
• In vivo studies showed superior bacterial eradication compared to levofloxacin and effective resolution of inflammation via M2 macrophage polarization.
• Significant enhancement in angiogenesis, collagen deposition, and overall tissue regeneration leading to accelerated wound healing.

Conclusions:

• The engineered ZIF-8-TA@Cu_s nanozyme platform offers a novel, adaptive therapeutic strategy for infected chronic wounds.
• Its intelligent microenvironment-sensing mechanism allows autonomous switching between antibacterial and pro-regenerative functions.
• This multimodal therapeutic approach represents a significant advancement beyond traditional drug delivery systems for complex wound healing.