Silk Fibroin-histamine Dressing Accelerates Healing In Full Thickness Mice Wounds
Deepanjan Ghosh1, Sudhakar Godeshala1, Jacquelyn Kilbourne1, David J. Dicaudo2, Kaushal Rege1.
1Arizona State University, Tempe, AZ, USA, 2Mayo Clinic, Scottsdale, AZ, USA.
Wound healing typically follows a programmed sequence which involves hemostasis, inflammation, proliferation and remodeling. In this work, we show local delivery of histamine, an immune modulator in combination with silk fibroin (SF) film resulting in faster closure of wounds in BALB/c mice when compared to wounds closed with conventional wound dressing (Tegaderm). Histamine was applied topically on 3.5 mm full thickness wounds and covered with either Tegaderm or a SF-gold nanorods (GNRs) film and irradiated with 800 nm near infrared laser (NIR) laser. Significant reduction in wound area and improved tissue biomechanical properties was observed in histamine treated wounds. SF-GNRs film-histamine treated wounds showed complete wound closure (p-value <0.0001, n=10) and higher tissue strength (p-value <0.01, n=6) compared to Tegaderm-histamine treated wounds at day 7 post-wounding. Immunohistological analyses also showed that SF-GNRs film-histamine treatment promoted angiogenesis (CD31+ cells, p-value <0.05, n=4) and myofibroblast mediated wound contraction (aSMA+, p-value <0.05, n=4). This also resulted in the increased epidermal thickness (Pan-cytokeratin, p-value <0.01, n=4) and reduced proliferation (Ki67+ cells, p-value <0.01, n=4) compared to Tegaderm-histamine treated wounds. IL-1beta and IL-6 levels in serum samples showed significant increased at day 1 post wounding and reduced to basal level at day 3 in SF-GNRs-histamine treated wounds showing a robust early inflammatory response to set the stage for subsequent proliferation and remodeling. We conclude that SF-GNRs film was effective in promoting wound healing and in combination with single histamine dose it outperformed clinically approved polyurethane wound dressing.
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