Jason P Hodde1, Michael C Hiles2, Dennis W Metzger3. 1. Cook Biotech Incorporated, 1425 Innovation Place, West Lafayette, IN, 47906, USA. Electronic address: Hodde@cookbiotech.com. 2. Cook Biotech Incorporated, 1425 Innovation Place, West Lafayette, IN, 47906, USA. Electronic address: Hiles@cookbiotech.com. 3. Department of Immunology and Microbial Disease, Albany Medical College, 47 New Scotland Avenue, Albany, NY, 12208, USA. Electronic address: metzged@mail.amc.edu.
Abstract
BACKGROUND: The SIS Wound Matrix (SISWM) has been shown to improve healing of chronic ulcers over standard of care. In this study, we tested the hypothesis that chronic venous ulcers responsive to treatment with SISWM would more closely mimic an acute wound state as opposed to unresponsive ulcers. METHODS: Serum and wound exudate were collected at baseline and then weekly for up to 12 weeks from 12 patients receiving multiple applications of the SISWM. Levels of matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-12), pro-inflammatory cytokines (IL-1β, TNF-α, IL-8), and transforming growth factor beta (TGF-β1) were evaluated. A variety of Th1/Th2 cytokines were also assayed, as were systemic anti-SIS and anti-α-gal antibody titers. RESULTS: Seven of the 12 patients eventually healed their wounds. Results showed significant decreases in MMP-1, MMP-2, MMP-3, MMP-9, TNF-α and IL-8, and significant increases in TGF-β1 in wounds responding to treatment with the SISWM versus wounds that did not respond to treatment. None of the 12 patients formed a measurable serum antibody response to the SISWM. CONCLUSIONS: These data show that SISWM does not lead to immune system recognition or sensitization to the matrix and that wounds that went on to heal following treatment were characterized by a more acute wound state. The study confirms that the wound environment is important to healing and that turning a wound toward an acute biochemical state is key to the healing process.
BACKGROUND: The SIS Wound Matrix (SISWM) has been shown to improve healing of chronic ulcers over standard of care. In this study, we tested the hypothesis that chronic venous ulcers responsive to treatment with SISWM would more closely mimic an acute wound state as opposed to unresponsive ulcers. METHODS: Serum and wound exudate were collected at baseline and then weekly for up to 12 weeks from 12 patients receiving multiple applications of the SISWM. Levels of matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-12), pro-inflammatory cytokines (IL-1β, TNF-α, IL-8), and transforming growth factor beta (TGF-β1) were evaluated. A variety of Th1/Th2 cytokines were also assayed, as were systemic anti-SIS and anti-α-gal antibody titers. RESULTS: Seven of the 12 patients eventually healed their wounds. Results showed significant decreases in MMP-1, MMP-2, MMP-3, MMP-9, TNF-α and IL-8, and significant increases in TGF-β1 in wounds responding to treatment with the SISWM versus wounds that did not respond to treatment. None of the 12 patients formed a measurable serum antibody response to the SISWM. CONCLUSIONS: These data show that SISWM does not lead to immune system recognition or sensitization to the matrix and that wounds that went on to heal following treatment were characterized by a more acute wound state. The study confirms that the wound environment is important to healing and that turning a wound toward an acute biochemical state is key to the healing process.
Authors: Ewa A Burian; Lubna Sabah; Tonny Karlsmark; Klaus Kirketerp-Møller; Christine J Moffatt; Jacob P Thyssen; Magnus S Ågren Journal: Int J Mol Sci Date: 2022-06-10 Impact factor: 6.208