4.8 Article

Antimicrobial Peptide-Tether Dressing Able to Enhance Wound Healing by Tissue Contact

Journal

ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 21, Pages 24213-24228

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c06601

Keywords

wound dressing; LL37 NPs; antimicrobial activity; diabetic wounds; keratin expression; inflammatory response

Funding

  1. ERA Chair project (ERA@UC) through the EU Horizon 2020 program [669088]
  2. FCT [IF/00539/2015, POCI-01-0145-FEDER-029414]
  3. LightImplant [PTDC/CTM-CTM/1719/2021]
  4. Compete 2020 [47081]
  5. BluePharma award (2016)

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Currently, there is a lack of effective therapeutic dressings in the market that can prevent bacterial infection and promote skin regeneration in diabetic patients. A study has evaluated the antimicrobial and pro-regenerative effect of LL37 peptide immobilized in polyurethane-based wound dressings. The results showed that the LL37 peptide dressing effectively killed bacteria without inducing resistance and accelerated wound healing and re-epithelialization in diabetic mice.
No effective therapeutic dressings are currently available in the market that can prevent bacterial infection and simultaneously promote skin regeneration in diabetic patients. The lack of re-epithelization, prevalence of inflammation, and high risk of infection are hallmarks of non-healing wounds. Here, we have evaluated the antimicrobial and pro-regenerative effect of a relatively non-leaching LL37 peptide immobilized in polyurethane (PU)-based wound dressings (PU-adhesive-LL37 dressing). The PU-adhesive-LL37 (63 mu g LL37NPs/cm(2)) dressing killed Gram-positive and Gram-negative bacteria in human serum without inducing bacterial resistance after 16 antimicrobial test cycles in contrast to commercially available dressings with the capacity to release antimicrobial Ag ions. Importantly, type II diabetic mice (db/db mice) treated with the PU-adhesive-LL37 dressing for different periods of time (6 or 14 days) showed enhanced wound healing and re-epithelialization (i.e., high keratin 14/5 levels) and lower macrophage infiltration in the wounds compared to animals treated with PU. The wounds treated with PU-adhesive-LL37 dressings showed also low expression of pro-inflammatory cytokines such as TNF-alpha and IL6 after 6 days of treatment, indicating that they act as an anti-inflammatory dressing. Additionally, PU-adhesive-LL37 dressings do not induce acute inflammatory responses in the peripheral blood mononuclear cells (PBMCs) after 3 days of exposure, in contrast to controls. Taken together, PU-adhesive-LL37NP dressings might prevent the bacterial infections and facilitate wound healing by tissue contact, inducing re-epithelialization and anti-inflammatory processes in diabetic conditions.

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