A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling.
hydrogel
immune modulation
scarring
serpin
wound healing
Journal
Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588
Informations de publication
Date de publication:
04 Oct 2019
04 Oct 2019
Historique:
received:
08
08
2019
revised:
25
09
2019
accepted:
30
09
2019
entrez:
9
10
2019
pubmed:
9
10
2019
medline:
9
10
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31590323
pii: jcm8101626
doi: 10.3390/jcm8101626
pmc: PMC6832452
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIH HHS
ID : 1RC1HL100202
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing financial interests.
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