Wound Healing Society

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Exogenously Administered Xenogenic Plasminogen Localizes To A Burn Wound Without Negatively Impacting Natural Plasminogen Production
Robert D. Smith, Jr., Kyle Monger, Abdulnaser Alkhalil, Lauren T. Moffatt, Jeffrey W. Shupp.
The Burn Center, MedStar Washington Hospital Center, Washington, DC, USA.

Background: Plasminogen is a proenzyme that plays a role in fibrin clot degradation, extracellular matrix remodeling, and regulation of inflammation following cutaneous injury, such as a burn. It has been proposed that plasminogen may be useful as a drug to improve wound healing and prevent burn conversion. Before introducing exogenous plasminogen for this purpose, it is important to first investigate its ability to localize to the site of injury. Methods: Sprague-Dawley rats received deep partial thickness comb burns and were treated with plasma-derived human plasminogen via subcutaneous (SC) or intravenous (IV) injection. Saline injection was used in control animals. Animals were treated at hours 4, 12, 24, 36, and 48 post injury. At each timepoint, blood and biopsies from burned and unburned interspace skin were collected. Four days post injury, animals were necropsied and tissues preserved. Tissue and plasma were assayed for human and rat plasminogen using ELISA. Results: Human plasminogen was quantified in the rat plasma, burned tissue, and interspace tissue of SC and IV treated groups. Burned and interspace tissue from the SC treatment group had more human plasminogen than the IV treated group at hour 24 (n=3, p < 0.005). No difference in rat plasminogen localization to burned tissue was observed (n=3, p ≥ 0.35). There was an increase in rat plasminogen localization to interspace tissue at day four in IV treated group compared to sham (n=3, p < 0.02). The amount of rat plasminogen present in the liver was unchanged (n=3, p ≥ 0.82). Conclusions: Xenogenic plasminogen can successfully localize in a host to burn-injured and healthy tissue. Both the SC and IV routes of administration are effective at delivering xenogenic plasminogen to the injury site without negatively impacting host endogenous plasminogen production.

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