Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota

Michelle Vang Mouritzen, Marija Petkovic, Katrine Qvist, Steen Seier Poulsen, Susana Alarica, Ermelindo Leal, Louise Torp Dalgaard, Nuno Empadinhas, Eugenia Carvalho, Håvard Jenssen*

*Corresponding author

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Bovine lactoferricin (LFcinB) has antimicrobial and immunomodulatory properties; however, the effects on diabetic wound healing remain poorly understood. The wound healing potential of LFcinB was investigated with in vitro, ex vivo, and in vivo models. Cell migration and proliferation were tested on keratinocytes and on porcine ears. A type 1 diabetic mouse model was also used to evaluate wound healing kinetics, bacterial diversity patterns, and the effect of LFcinB on oxidative stress, macrophage phenotype, angiogenesis, and collagen deposition. LFcinB increased keratinocyte migration in vitro (p < 0.05) and ex vivo (p < 0.001) and improved wound healing in diabetic mice (p < 0.05), though not in normoglycemic control mice. In diabetic mouse wounds, LFcinB treatment led to the eradication of Bacillus pumilus, a decrease in Staphylococcus aureus, and an increase in the Staphylococcus xylosus prevalence. LFcinB increased angiogenesis in diabetic mice (p < 0.01), but this was decreased in control mice (p < 0.05). LFcinB improved collagen deposition in both diabetic and control mice (p < 0.05). Both oxidative stress and the M1-to-M2 macrophage ratios were decreased in LFcinB-treated wounds of diabetic animals (p < 0.001 and p < 0.05, respectively) compared with saline, suggesting a downregulation of inflammation in diabetic wounds. In conclusion, LFcinB treatment demonstrated noticeable positive effects on diabetic wound healing. Topical delivery of bovine lactoferricin (LFcinB) has antimicrobial and immunomodulatory actions and improves wound closure and changes the bacterial diversity of diabetic wounds. Hallmarks of diabetic wound healing impairments like inflammation, oxidative stress, disrupted angiogenesis, and collagen deposition improved by LFcinB indicate its therapeutic potential.

Original languageEnglish
JournalMolecular Therapy - Methods & Clinical Development
Volume20
Issue number20
Pages (from-to)726-739
Number of pages14
ISSN2329-0501
DOIs
Publication statusPublished - 12 Mar 2021

Keywords

  • bacterial diversity
  • bovine lactoferricin
  • collagen deposition
  • diabetes
  • immunomodulation
  • inflammatory cytokines
  • macrophage polarization
  • wound healing

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