<p>Diabetic wounds impose a heavy medical burden on patients due to the persistent high blood sugar environment and susceptibility to bacterial infections, especially multidrug-resistant bacteria. To address this critical issue, we designed&#xa0;and&#xa0;synthesized&#xa0;a photothermally active hydrogel. Epigallocatechin gallate (EGCG) was stabilized within a carboxymethyl chitosan (CMCS) and 2-formylphenylboronic acid (2-FPBA) dual-dynamic network via Schiff base and borate ester bonds to form the EGCG—CMCS (EC) hydrogel, while puerarin (PUE) was encapsulated in polydopamine (PDA) nanospheres to enhance its solubility, yielding the PDA-PUE nanospheres. In the 808&#xa0;nm NIR band, the nanospheres in this composite indicated a high photothermal conversion efficiency (65.7%) and a regular spherical shape with a particle size of approximately 223&#xa0;nm. In vitro, PDA-PU@EC + NIR&#xa0;inhibited&#xa0;MDR&#xa0;<i>Escherichia coli</i>&#xa0;(MDR <i>E. coli</i>)&#xa0;and&#xa0;MDR&#xa0;<i>Staphylococcus aureus</i>&#xa0;(MDR&#xa0;<i>S. aureus</i>)&#xa0;by greater than 98%, as&#xa0;verified&#xa0;by membrane disruption shown by live/dead staining and scanning electron microscopy. In&#xa0;MDR&#xa0;<i>Staphylococcus aureus</i>-infected diabetic mice, it&#xa0;accelerated&#xa0;wound closure (97% by day 11),&#xa0;reduced inflammatory response (as evidenced by significantly decreased fluorescence intensities of IL−6 to 17 ± 2% and TNF-<i>α</i> to 22% of control levels on day 7), and promoted angiogenesis (with marked upregulation of VEGF and CD31 expression), and promoted collagen deposition, outperforming controls. Biosafety tests&#xa0;confirmed&#xa0;low hemolysis (&lt; 5%) and negligible organ toxicity. This work&#xa0;presented&#xa0;a potentially effective strategy to deal with the complex microenvironment of diabetic wound infections, providing a new way of thinking about the effective combination of natural polyphenols, herbal components and photothermal substances.</p>

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Epigallocatechin gallate-inspired dual-powered hydrogel synergistically promotes diabetic wound healing through photothermal enhancement of antimicrobial agents

  • Wanzhen Li,
  • Lixiang Fan,
  • Hua Liu,
  • Lin Gui,
  • Longbao Zhu,
  • Ping Song,
  • Zuchun Zhao,
  • Fei Ge,
  • Weiwei Zhang

摘要

Diabetic wounds impose a heavy medical burden on patients due to the persistent high blood sugar environment and susceptibility to bacterial infections, especially multidrug-resistant bacteria. To address this critical issue, we designed and synthesized a photothermally active hydrogel. Epigallocatechin gallate (EGCG) was stabilized within a carboxymethyl chitosan (CMCS) and 2-formylphenylboronic acid (2-FPBA) dual-dynamic network via Schiff base and borate ester bonds to form the EGCG—CMCS (EC) hydrogel, while puerarin (PUE) was encapsulated in polydopamine (PDA) nanospheres to enhance its solubility, yielding the PDA-PUE nanospheres. In the 808 nm NIR band, the nanospheres in this composite indicated a high photothermal conversion efficiency (65.7%) and a regular spherical shape with a particle size of approximately 223 nm. In vitro, PDA-PU@EC + NIR inhibited MDR Escherichia coli (MDR E. coli) and MDR Staphylococcus aureus (MDR S. aureus) by greater than 98%, as verified by membrane disruption shown by live/dead staining and scanning electron microscopy. In MDR Staphylococcus aureus-infected diabetic mice, it accelerated wound closure (97% by day 11), reduced inflammatory response (as evidenced by significantly decreased fluorescence intensities of IL−6 to 17 ± 2% and TNF-α to 22% of control levels on day 7), and promoted angiogenesis (with marked upregulation of VEGF and CD31 expression), and promoted collagen deposition, outperforming controls. Biosafety tests confirmed low hemolysis (< 5%) and negligible organ toxicity. This work presented a potentially effective strategy to deal with the complex microenvironment of diabetic wound infections, providing a new way of thinking about the effective combination of natural polyphenols, herbal components and photothermal substances.