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ROS-Responsive Double-Layer Microneedles Enable Sequential Antibacterial and Immunomodulatory Therapy for Infected
Huifang Zhang1,2,3, Zhongke Wang1,2,3, Yujing Zhu4
1Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, China.
Theranostics
|December 8, 2025
Summary
A novel microneedle patch delivers drugs to combat infection, inflammation, and oxidative stress, significantly accelerating the healing of chronic wounds by regulating the wound environment and immune response.
Area of Science:
- Biomaterials Science
- Wound Healing Research
- Drug Delivery Systems
Background:
- Chronic wound healing is impeded by inflammation, infection, and oxidative stress.
- Current therapies face challenges in addressing these multifactorial issues.
- A multifunctional microneedle patch (MN@DOX+RES) was developed for synergistic therapeutic effects.
Purpose of the Study:
- To design and evaluate a dual-layer microneedle patch for treating chronically infected wounds.
- To investigate the patch's ability to deliver drugs, respond to reactive oxygen species (ROS), and modulate the wound microenvironment.
- To assess the combined antibacterial, anti-inflammatory, and antioxidant effects for enhanced wound healing.
Main Methods:
- Fabrication of a dual-layer microneedle patch with a drug-loaded backing layer and a ROS-responsive tip layer.
- In vitro assessment of mechanical properties, biocompatibility, antibacterial activity, antioxidant capacity, and macrophage polarization.
- In vivo evaluation of wound healing in infected rat skin models.
Main Results:
- The microneedle patch demonstrated effective skin penetration and mechanical strength.
- Significant inhibition of bacterial growth, free radical scavenging, and reduction of intracellular ROS.
- Enhanced M2 macrophage polarization, accelerated wound closure, and modulation of inflammatory/anti-inflammatory cytokines (IL-6, IL-10).
- Activation of the Keap1/Nrf2/HO-1 antioxidant pathway in vivo.
Conclusions:
- The MN@DOX+RES microneedle system offers an innovative strategy for chronic infected wound treatment.
- Combines dual-drug delivery, oxidative stress regulation, and immune modulation.
- Shows significant potential to overcome clinical challenges in wound healing.

