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Functional Self-Similar Polyether-Polyester Mimicking Host Defense Peptides Enable Prolonged Antimicrobial Activity.

Shuting Huang1, Yushen Qian1, Jia Wei2

  • 1School of Material Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.

ACS Macro Letters
|April 21, 2026
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Summary
This summary is machine-generated.

New functional self-similar polymers mimic host defense peptides (HDPs) for potent, long-lasting antimicrobial activity. These biocompatible polymers overcome degradation issues, offering a promising solution for chronic wound infections and antibiotic resistance.

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Antimicrobial Research

Background:

  • Chronic wounds are susceptible to bacterial infections, necessitating long-term antimicrobial treatments.
  • Host defense peptides (HDPs) and cationic polymers show antimicrobial promise but are often degraded by proteases, limiting their efficacy.
  • Developing stable antimicrobial agents is crucial for combating drug-resistant bacteria in chronic wound settings.

Purpose of the Study:

  • To design and synthesize novel cationic polyether-polyester-mimicking polymers with sustained antimicrobial activity.
  • To evaluate the antimicrobial efficacy, biocompatibility, and stability of these polymers against protease-mediated degradation.
  • To explore the potential of these functional self-similar polymers for treating chronic wound infections.

Main Methods:

  • Synthesis of a series of cationic polyether-polyester-mimicking copolymers.
  • Antimicrobial activity testing against various bacteria, including determination of minimum inhibitory concentrations (MICs).
  • Enzymatic degradation studies to assess polymer stability and retained activity.
  • In vivo evaluation of antibacterial performance and safety in mouse models.

Main Results:

  • The optimal copolymer, P8, demonstrated broad-spectrum antimicrobial activity with MICs as low as 0.5 μg/mL.
  • P8 maintained significant antimicrobial activity after enzymatic degradation, with an MIC of 16 μg/mL.
  • The rational design of the copolymer backbone and hydrophobic side chains contributed to superior performance.
  • P8 exhibited potent in vivo antibacterial efficacy and excellent safety in mouse models.

Conclusions:

  • Functional self-similar polymers offer a promising strategy for developing long-lasting antimicrobial agents.
  • These polymers effectively address the challenge of protease-mediated degradation, enhancing therapeutic potential.
  • The developed materials show potential for clinical applications in treating bacterial resistance and chronic wound infections with prolonged, low-toxicity antibacterial therapies.