Comparison of structure, strength and cytocompatibility of a fibrin matrix supplemented either with tranexamic acid or aprotinin

Fürst, Walter; Banerjee, Asmita; Redl, Heinz

doi:10.1002/jbm.b.30711

Cited by 33 publications

(23 citation statements)

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“…Although differences can be seen with FESEM based on the type of hemostat used, the fibrin morphology and incorporation of red blood cells between clots formed with clopidogrel donor blood and those of the controls were similar. The clots formed with fibrin sealant were similar to those seen previously [40,41] as well as those formed with the thrombin based gelatin matrix hemostat [42]. Therefore, not only does the use of thrombin attenuate the impact of clopidogrel by initiating platelet activation while retaining normal clot kinetics and strength, it also facilitates structurally similar clots when used in combination with gelatin matrix and fibrin sealant hemostats.…”

Section: Discussionsupporting

confidence: 78%

Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the presence of clopidogrel

et al. 2014

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BackgroundPlatelet inhibitors are commonly used to reduce the risk of atherothrombotic events. The aim of this study was to determine the impact of platelet inhibitors, specifically clopidogrel and aspirin, on clot kinetics, strength, and/or structure during the use of thrombin based gelatin matrices and fibrin sealants.MethodsBlood was collected and heparinized from donors on clopidogrel (and aspirin) and age matched control donors. Blood component analysis, whole blood platelet aggregometry, and activated clotting time (ACT) were used to monitor compliance to therapy and identify any differences between donor groups. Clot kinetics and strength were analyzed using thrombelastography (TEG). Field Emission Scanning Electron Microscopy (FESEM) was used to analyze clot structure.ResultsBlood component profiles were similar for both donor groups. Aggregometry indicated that aggregation response to adenosine diphosphate (ADP) for clopidogrel donors was 12% of that for the controls (p = 0.0021), an expected result of clopidogrel induced platelet inhibition. However, blood from both donor groups had an elevated thrombin induced aggregation response. Heparinization of donor blood resulted in similarly elevated ACTs for both donor groups. TEG results indicated similar clot kinetics and strength between clopidogrel and control donor groups for blood alone and when clotting was induced using thrombin based gelatin matrices and fibrin sealants. FESEM images supported TEG findings in that similar morphologies were observed in ex vivo formed clots from both donor groups when thrombin based gelatin matrices and fibrin sealants were used.ConclusionThese results suggest that platelet inhibitors do not negatively impact clot kinetics, strength, and structure when clotting is initiated with thrombin based gelatin matrices and fibrin sealants.

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Section: Discussionsupporting

confidence: 78%

Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the presence of clopidogrel

et al. 2014

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“…Autografts were fixed with skin staples using a disposable skin stapler or with a two-component fibrin sealant [18]. …”

Section: Methodsmentioning

confidence: 99%

A porcine model of full-thickness burn, excision and skin autografting

Branski¹,

Mittermayr²,

Herndon³

et al. 2008

Burns

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Acute burn wounds often require early excision and adequate coverage to prevent further hypothermia, protein and fluid losses, and the risk of infection. Meshed autologous skin grafts are generally regarded as the standard treatment for extensive full-thickness burns. Graft take and rate of wound healing, however, depend on several endogenous factors. This paper describes a standardized reproducible porcine model of burn and skin grafting which can be used to study the effects of topical treatments on graft take and re-epithelialization.Procedures provide a protocol for successful porcine burn wound experiments with special focus on pre-operative care, anesthesia, burn allocation, excision and grafting, postoperative treatment, dressing application, and specimen collection. Selected outcome measurements include percent area of wound closure by planimetry, wound assessment using a clinical assessment scale, and histological scoring.The use of this standardized model provides burn researchers with a valuable tool for the comparison of different topical drug treatments and dressing materials in a setting that closely mimics clinical reality. KeywordsBurn; Burn excision; Wound healing; Reconstruction; Autograft BackgroundStandard treatment for severe burns currently includes early excision and adequate coverage to prevent hypothermia, protein and fluid loss, and risk of exogenous infection [1]. Autologous meshed split-thickness skin grafts are generally regarded as the standard treatment for extensive full-thickness burns. Early wound healing with concomitant wound closure is a major factor in patient outcome and infection control.To determine new treatment options which enhance and accelerate wound healing, many investigators rely on animal models to closely observe the healing process. Many animal models have been described in the literature, mostly involving rodents and pigs, with different *Corresponding author. Tel.: +1 409 770 6742; fax: +1409 770 6919. E-mail address: majeschk@utmb.edu (M.G. Jeschke). 1 Authors contributed equally to this manuscript. [2][3][4][5][6]. However, there has been no large animal model described which would encompass a burn excision and autografting, for an extended observation of over 2 weeks, to closely monitor the wound healing progress and its mechanisms. This paper presents a porcine model for the assessment of multiple treatments and quantification of differences in burn wound healing. Conflict of interest statement Procedures Basic and study guidelinesPigs have been used as models for wound healing studies due to their structural and functional resemblance to human skin. The thickness of porcine skin differs greatly depending on the location (pig epidermis: 30-140 μm; Human epidermis: 50-120 μm) [7]. Further, the vascularization of human and porcine skin is similar [8], with both human and pig having about 95% collagen and 2% elastic fibers in their extracellular matrix. This composition presents similar elastic components which is paramount in wound contraction [9]....

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“…In these therapies, premature fibrinolysis not only leads to decreased treatment efficacy, but can additionally result in recurrent bleeding, leakage, or tissue dehiscence [5]. As such, many commercial fibrin sealants are stabilized with fibrinolysis inhibitors, such as the protein aprotinin or the small molecules tranexamic acid and ε-aminocaproic acid.…”

Section: Introductionmentioning

confidence: 99%

Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials

et al. 2017

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Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine origin of aprotinin. Here, we aimed to develop a human-derived substitute to aprotinin. Based on sequence homology analyses, we identified the Kunitz-type protease inhibitor (KPI) domain of human amyloid-β A4 precursor protein as being a potential candidate. While KPI has a lower intrinsic anti-fibrinolytic activity than aprotinin, we reasoned that its efficacy is additionally limited by its fast release from fibrin material, just as aprotinin’s is. Thus, we engineered KPI variants for controlled retention in fibrin biomaterials, using either covalent binding through incorporation of a substrate for the coagulation transglutaminase Factor XIIIa or through engineering of extracellular matrix protein super-affinity domains for sequestration into fibrin. We showed that both engineered KPI variants significantly slowed plasmin-mediated fibrinolysis in vitro, outperforming aprotinin. In vivo, our best engineered KPI variant (incorporating the transglutaminase substrate) extended fibrin matrix longevity by 50%, at a dose at which aprotinin did not show efficacy, thus qualifying it as a competitive substitute of aprotinin in fibrin sealants.

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Comparison of structure, strength and cytocompatibility of a fibrin matrix supplemented either with tranexamic acid or aprotinin

Cited by 33 publications

References 23 publications

Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the presence of clopidogrel

Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the presence of clopidogrel

A porcine model of full-thickness burn, excision and skin autografting

Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials

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