Enhancement of incisional wound healing by thrombin conjugated iron oxide nanoparticles.
ABSTRACT Thrombin has been clinically used for topical hemostasis and wound management for more than six decades. The half-life of thrombin in human plasma is shorter than 15s due to close control by inhibitors. In order to stabilize the thrombin, it was bound to maghemite (gamma-Fe(2)O(3)) nanoparticles, as demonstrated in previous work. The aim of the present study was to examine the efficiency of the bound thrombin for wound healing applications compared to the free thrombin. For this purpose incisional wounds on rat skin were treated with a mixture of fibrinogen, CaCl(2) solution and free or bound thrombin. The wounds' edges were then approximated by skin staples. The control incisional wounds were closed with staples only. In the course of 28 days of healing the highest values of skin tensile strength were observed following treatment with the bound thrombin. Significantly lower values of tensile strength were observed following treatment with the free thrombin, and the lowest values were obtained following treatment with staples only. The histological findings correlate with the mechanical strength measurements, which demonstrate the most advanced stages of healing following treatment with the bound thrombin.
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Article: Inflammation and wound healing.[show abstract] [hide abstract]
ABSTRACT: Cutaneous wound healing is a complex process involving several overlapping phases. While we have made great strides in understanding these various phases, there is still much to learn about the cells and soluble mediators that are involved in a successful wound healing event. The current review describes the immuno/inflammatory cells and some less commonly studied soluble mediators involved in the adult healing response.Frontiers in Bioscience 02/2007; 12:2993-9. · 3.29 Impact Factor
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ABSTRACT: Thrombin is the product of the hemostatic response essential to the conversion of fibrinogen to fibrin. In addition, it is also responsible for the aggregation of blood platelets in the formation of the "platelet plug" as well as the activation of factor VIII, factor V, factor XI, factor XIII and protein C. The action of thrombin is not confined to the hemostatic response as it also has a critical function in the wound healing process by stimulating 'mitogenic' events through interaction with cell surface receptors. In this review, we consider the various biological activities of thrombin as they relate to current therapeutic use. While there has been considerable interest in the development of fibrin sealant products, there has been considerably less interest in documenting the continuing use of thrombin as a therapeutic. The use of thrombin for topical hemostasis and the treatment of pseudoaneurysms will be discussed in detail. It is concluded that the use of thrombin as a drug will not only continue but also will significantly increase. However, the availability of a safe human thrombin preparation will be critical for the continued use of thrombin as a therapeutic.Thrombosis and Haemostasis 06/2004; 91(5):851-60. · 6.09 Impact Factor
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ABSTRACT: To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.Journal of Clinical Investigation 06/1992; 89(5):1469-77. · 12.81 Impact Factor