A Multifunctional MOF Heterojunction for Combating Antibiotic Resistance and Promoting Regenerative Immunity

Area of Science:

• Biomaterials Science
• Nanotechnology
• Infectious Disease Research

Background:

• Antimicrobial resistance (AMR) and dysregulated immune responses complicate infected wound treatment.
• Existing therapies face challenges in overcoming drug resistance and modulating the inflammatory microenvironment.

Purpose of the Study:

• To develop a hierarchically engineered microreactor (SK@hZnO@ZIF-8, SZZ) addressing both AMR and immune dysregulation in infected wounds.
• To investigate the synergistic bactericidal and immunomodulatory effects of the SZZ system.

Main Methods:

• Fabrication of a pH-responsive, nanostructured ZIF-8 shell microreactor encapsulating Shikonin (SK) and Zn2+.
• In vitro assessment of stimuli-responsive drug release and efficacy against Methicillin-resistant Staphylococcus aureus (MRSA).
• In vivo evaluation of SZZ's impact on infection clearance, immune cell polarization (M2 macrophages), and tissue regeneration.

Main Results:

• SZZ achieved >99.9% MRSA eradication, overcoming drug resistance with sustained efficacy (>95% over 20 passages).
• The system successfully shifted the immune microenvironment from pro-inflammatory to pro-reparative by promoting M2 macrophage polarization.
• In vivo studies demonstrated complete infection clearance and significant tissue regeneration within 7 days, including increased collagen deposition and hair follicle formation.

Conclusions:

• The SZZ microreactor offers a synergistic therapeutic strategy for infected wounds by combining targeted antimicrobial delivery with immunomodulation.
• This nanoscale gating mechanism on a microscale platform presents a promising paradigm for resolving infection and orchestrating complex biological repair processes.