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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Antimicrobial Therapy

Background:

  • Drug-resistant bacterial infections impede tissue repair via inflammation and impaired regeneration.
  • Neutrophil extracellular traps (NETs) are crucial for immunity, inspiring synthetic biomaterial development.
  • Existing synthetic NETs struggle with complexity, biocompatibility, and effectiveness.

Purpose of the Study:

  • To create a NETs-mimicking hydrogel for pathogen elimination and tissue regeneration.
  • To address limitations of current synthetic NETs in treating resistant bacterial infections.

Main Methods:

  • Fabrication of a hydrogel from reversible lysozyme amyloid flexible nanofibrils (FFs).
  • Near-infrared irradiation triggers FF disassembly into antimicrobial lysozyme monomers.
  • Controlled release of Mg²⁺ ions to reprogram macrophages and reduce inflammation.

Main Results:

  • The nanoNETs hydrogel demonstrated potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).
  • Accelerated healing of infected wounds and periprosthetic joints in murine and porcine models.
  • Preservation of osteogenic and regenerative microenvironments during healing.

Conclusions:

  • Reversible flexible amyloids enable stimuli-responsive, biocompatible nanoNETs.
  • These nanoNETs show significant potential for antimicrobial and regenerative therapies.
  • The developed hydrogel offers a promising strategy for combating bacterial-resistant infections.