Format

Send to

Choose Destination
J Clin Med. 2019 Oct 4;8(10). pii: E1626. doi: 10.3390/jcm8101626.

A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling.

Author information

1
Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. liqiang.zhang@asu.edu.
2
Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. jyaron@asu.edu.
3
Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. agonza49@asu.edu.
4
Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. 789sew@gmail.com.
5
Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. Jacki.Kilbourne@asu.edu.
6
Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. Shelley.Haydel@asu.edu.
7
Chemical Engineering, Arizona State University, Tempe, AZ 85287, USA. Kaushal.Rege@asu.edu.
8
Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. grantmcf@asu.edu.
9
Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. arlucas5@asu.edu.
10
Chemical Engineering, Arizona State University, Tempe, AZ 85287, USA. arlucas5@asu.edu.

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.

KEYWORDS:

hydrogel; immune modulation; scarring; serpin; wound healing

PMID:
31590323
DOI:
10.3390/jcm8101626
Free full text

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI)
Loading ...
Support Center