A virus-derived immune modulating serpin accelerates wound closure with improved collagen remodeling

Liqiang Zhang, Jordan Yaron, Amanda M. Tafoya, Sarah E. Wallace, Jacquelyn Kilbourne, Shelley Haydel, Kaushal Rege, Douglas McFadden, Alexandra Lucas

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases and inflammation, in a mouse excisional wound model. Saline or recombinant Serp-1 were applied directly to wounds as single doses of 1 µg or 2 µg or as two 1 µg boluses. A chitosan-collagen hydrogel was also tested for Serp-1 delivery. Wound size was measured daily for 15 days and scarring assessed by Masson’s trichrome, Herovici’s staining, and immune cell dynamics and angiogenesis by immunohistochemistry. Serp-1 treatment significantly accelerated wound healing, but was blocked by urokinase-type plasminogen activator (uPAR) antibody. Repeated dosing at a lower concentration was more effective than single high-dose serpin. A single application of Serp-1-loaded chitosan-collagen hydrogel was as effective as repeated aqueous Serp-1 dosing. Serp-1 treatment of wounds increased arginase-1-expressing M2-polarized macrophage counts and periwound angiogenesis in the wound bed. Collagen staining also demonstrated that Serp-1 improves collagen maturation and organization at the wound site. Serp-1 has potential as a safe and effective immune modulating treatment that targets thrombolytic proteases, accelerating healing and reducing scar in deep cutaneous wounds.

Original languageEnglish (US)
Article number1626
JournalJournal of Clinical Medicine
Volume8
Issue number10
DOIs
StatePublished - Oct 2019

Keywords

  • Hydrogel
  • Immune modulation
  • Scarring
  • Serpin
  • Wound healing

ASJC Scopus subject areas

  • Medicine(all)

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