Topical Anti-inflammatories Improve Skin Graft Contraction After Stsg In A Porcine Excisional Wound Model.
David H. Tassin, MD, Rodney K. Chan, MD, Anders Carlsson, PhD, Christopher J. Corkins, MD.
US Army Institute of Surgical Research, San Antonio, TX, USA.
PURPOSE: The aim of this study was to improve long-term skin graft scarring and contraction using topical anti-inflammatories applied at the time of grafting. Resulting in part from exaggerated inflammation during healing, hypertrophic scarring and resultant contractures remain the most devastating long-term consequences of severe traumatic wounds or burns. These scars severely affect quality of life, psychosocial wellbeing, and function among injury survivors. Moreover, patients often require months to years of multimodal therapy to restore function and pre-injury cosmesis. Prevention of hypertrophic scarring, therefore, would have profound clinical implications among those with severe soft tissue injuries.
METHODS: 8 Red Duroc / Yorkshire crossbred swine each received 10 full thickness excisional wounds 6cm in diameter followed by split thickness skin grafting three days thereafter. Topical anti-inflammatories suspended in a chitosan based hydrogel were applied to the wounds from the day of grafting until post-op day 4 with the following groups: Plain STSG, hydrogel without drug, gentamicin, indomethacin, dexamethasone, indomethacin/dexamethasone combination, dexamethasone/gentamicin, and indomethacin/gentamicin. Wounds were serially assessed with two primary endpoints: Skin graft take at 14 days and contraction at 120 days. Data analysis was performed with one-way ANOVA for each endpoint with post-hoc two-sample t-test comparing individual groups.
RESULTS: The ANOVA revealed no statistical difference overall in skin graft take at 14 days between groups (p=0.075). Post-hoc t-test, though, showed that hydrogel alone worsened graft take compared to plain STSG (81% vs 91%, p= 0.0018); similarly, numerous drug treatment groups differed from STSG alone on post-hoc t-tests, but none differed from carrier alone. At 120 days, ANOVA again revealed no significant effect on wound contraction overall (p=0.11). There was a trend for hydrogel alone to worsen contraction compared to plain STSG (wounds 46% of original size compared to 54%, p=0.093). Post-hoc t-tests, though, reveal improved contraction at 120 days with gentamicin (wounds 53% of original size, p=0.019), indomethacin (62% of original size, p=0.0059), and indomethacin/dexamethasone (57% of original size, p=0.0092) compared to hydrogel alone (46% of original size). No drug treatment groups differed from plain STSG in contraction at 120 days.
CONCLUSION: In this porcine excisional wound model, topical anti-inflammatories dampened the initial inflammatory response during wound healing and led to improved long-term wound contraction. More specifically, application of anti-inflammatory drugs immediately following STSG lessened wound contraction compared to hydrogel carrier alone. Our hydrogel carrier tended to worsen short-term graft take and long-term wound contraction, but the drugs themselves do not appear to affect short-term graft take. Methods to reduce long-term skin graft contracture are an appealing means of preventing the devastating sequelae of hypertrophic scarring. This work suggests a role for topical anti-inflammatory medications in improving long-term contraction after STSG, but the optimal delivery method is still unknown.
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