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Microenvironment-responsive Cu-phenolic networks coated nanofibrous dressing with timely macrophage phenotype
Tianhua Xiao1, Jiamin Liu1, Yuanxin Li1
1Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Department of Orthopaedic Surgery, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) infection is a pressing clinical issue that impedes wound healing. Pro-inflammatory M1 macrophages is required to clear bacteria and recruit various cell types during the initial phase of wound healing, but timing of this process is crucial. Herein, a microenvironment-responsive nanofibrous dressing capable of timely macrophage phenotype transition in vivo is constructed by coating copper ions (Cu2+)-polydopamine (PDA) networks on poly (ε-caprolactone) fiber (PCL-fiber) membrane. During the initial post-implantation period, the nanofibrous dressing show pH-sensitive Cu2+ release in the acidic infection microenvironment. The release Cu2+ have a direct killing effect on MRSA, and promote the proinflammatory M1 phenotype of macrophages to enhance the antibacterial macrophage response. Later, PDA to become a reactive oxygen species (ROS) scavenger when in microenvironments with elevated ROS levels, which conferred the dressing with an immunomodulatory activity that convert M1 macrophages into M2 macrophages. In vivo examination in an MRSA infected full-thickness skin wounds of rat model demonstrates that this dressing significantly facilitated infection eradication and wound healing through modulating local inflammatory phenotype. Overall, this study offers a simple and effective approach for timely manipulation of inflammation progression to promote infected wound healing.
Insights
This study developed a smart nanofibrous dressing that releases copper ions to kill MRSA and promote M1 macrophages, then scavenges ROS to shift macrophages to M2, enhancing infected wound healing.
Area of Science:
- Biomaterials Science
- Immunology
- Wound Healing Research
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) infections pose a significant challenge to effective wound healing.
- The balance of macrophage phenotypes (M1 and M2) is critical for managing infection and promoting tissue repair.
- Current treatments often struggle to modulate the inflammatory response dynamically during the healing process.
Purpose of the Study:
- To engineer a microenvironment-responsive nanofibrous dressing for dynamic immunomodulation in MRSA-infected wounds.
- To investigate the dual role of copper ions and polydopamine in controlling macrophage phenotypes and bacterial load.
- To evaluate the efficacy of the developed dressing in promoting wound healing in a preclinical MRSA infection model.
Main Methods:
- Fabrication of poly(ε-caprolactone) (PCL) nanofibrous membranes coated with copper ion (Cu²⁺)-polydopamine (PDA) networks.
- Assessment of pH-sensitive Cu²⁺ release and ROS scavenging properties of the dressing.
- In vitro evaluation of macrophage phenotype modulation and antibacterial activity.
- In vivo testing in a rat full-thickness skin wound model with MRSA infection.
Main Results:
- The Cu²⁺-PDA/PCL dressing exhibited pH-sensitive Cu²⁺ release, directly killing MRSA and promoting pro-inflammatory M1 macrophages.
- The PDA component acted as a reactive oxygen species (ROS) scavenger, facilitating the transition of M1 to M2 macrophages.
- In vivo studies demonstrated significant infection eradication and accelerated wound healing in the MRSA-infected rat model.
Conclusions:
- The developed nanofibrous dressing effectively manages the inflammatory microenvironment in infected wounds.
- This approach enables timely manipulation of macrophage phenotypes, transitioning from antibacterial M1 to pro-resolving M2.
- The study presents a promising strategy for enhancing the healing of MRSA-infected wounds through dynamic immunomodulation.
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