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<p>Drug-resistant bacterial infections, exacerbated by antibiotic resistance and biofilm resilience, disrupt tissue repair through dysregulated inflammation and impaired regeneration. Neutrophil extracellular traps (NETs) play a crucial role in endogenous immunity by entrapping and eliminating pathogens, inspiring the development of synthetic biomaterials that replicate this function. However, current synthetic NETs face challenges in complexity, biocompatibility, structural integrity and effectiveness. Here, we present a NETs-mimicking hydrogel composed of reversible lysozyme amyloid flexible nanofibrils (FFs) enabling pathogen elimination and tissue regeneration. The FFs therein self-assemble from natural egg-white lysozyme endowing these nanoNETs with bioactivity against pathogens, and when duly labeled to respond to near-infrared irradiation, they disassemble into unfolded lysozyme monomers with antimicrobial activity. Notably, the hydrogel disassembly is followed by the controlled release of pre-dissolved Mg²⁺ ions, reprogramming macrophages toward a pro-regenerative phenotype and mitigating inflammation. In both murine and porcine models, these biocompatible nanoNETs demonstrate excellent antibacterial performance, accelerating healing of wounds infected by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Moreover, these nanoNETs boost in-vivo healing of MRSA-infected periprosthetic joints, preserving osteogenic and regenerative microenvironments. These results build on the reversible nature of flexible amyloids to introduce stimuli-responsive biocompatible nanoNETs with significant potential for antimicrobial and regenerative therapies in bacterial-resistant infections.</p>

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Photo-reversible amyloid nanoNETs for regenerative antimicrobial therapies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月10日

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  • Qize Xuan,
  • Hui Li,
  • Yuan Gao,
  • Xinchi Qiao,
  • Yifan Feng,
  • Xinyu Yu,
  • Jiazhe Cai,
  • Tonghui Jin,
  • Bin Liu,
  • Mohammad Peydayesh,
  • Jiaqi Su,
  • Peter Fischer,
  • Ping Wang,
  • Chao Chen,
  • Jiangtao Zhou,
  • Raffaele Mezzenga

摘要

Drug-resistant bacterial infections, exacerbated by antibiotic resistance and biofilm resilience, disrupt tissue repair through dysregulated inflammation and impaired regeneration. Neutrophil extracellular traps (NETs) play a crucial role in endogenous immunity by entrapping and eliminating pathogens, inspiring the development of synthetic biomaterials that replicate this function. However, current synthetic NETs face challenges in complexity, biocompatibility, structural integrity and effectiveness. Here, we present a NETs-mimicking hydrogel composed of reversible lysozyme amyloid flexible nanofibrils (FFs) enabling pathogen elimination and tissue regeneration. The FFs therein self-assemble from natural egg-white lysozyme endowing these nanoNETs with bioactivity against pathogens, and when duly labeled to respond to near-infrared irradiation, they disassemble into unfolded lysozyme monomers with antimicrobial activity. Notably, the hydrogel disassembly is followed by the controlled release of pre-dissolved Mg²⁺ ions, reprogramming macrophages toward a pro-regenerative phenotype and mitigating inflammation. In both murine and porcine models, these biocompatible nanoNETs demonstrate excellent antibacterial performance, accelerating healing of wounds infected by methicillin-resistant Staphylococcus aureus (MRSA). Moreover, these nanoNETs boost in-vivo healing of MRSA-infected periprosthetic joints, preserving osteogenic and regenerative microenvironments. These results build on the reversible nature of flexible amyloids to introduce stimuli-responsive biocompatible nanoNETs with significant potential for antimicrobial and regenerative therapies in bacterial-resistant infections.