fibrin and Burns

Topics: Blood Coagulation; Burns; Chronic Disease; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Tests; Hemostasis; Humans; Leukemia; Purpura, Thrombotic Thrombocytopenic; Thrombin

Topics: Alpha-Globulins; Animals; Basal Metabolism; Blood Proteins; Burns; Carbon Isotopes; Dogs; Environmental Exposure; Fibrin; Fibrinogen; Fractures, Bone; gamma-Globulins; Humans; Iodine Isotopes; Nitrogen; Nitrogen Isotopes; Paralysis; Postoperative Complications; Proteins; Rats; Serum Albumin; Serum Albumin, Radio-Iodinated; Temperature; Wounds and Injuries

These studies establish that the staphylococcal clumping test is superior to the tanned red cell hemagglutination inhibition immunoassay for monitoring fibrin split product concentration in burn sera. It is strongly suggested that the principal circulating degradation product is a complex of soluble fibrin monomer with fragment D. Finally, there does not appear to be any effect on measured fibrin split product concentration in sera of burn patients receiving prophylactic heparin or aspirin.

Topics: Aspirin; Burns; Disseminated Intravascular Coagulation; Drug Evaluation; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Heparin; Humans; Immunoassay; Prospective Studies; Staphylococcus

The shortage of corneal donors has prompted the development of tissue-engineered corneal grafts as an alternative solution. Currently, amniotic membranes with good biocompatibility are widely used as scaffolds for loading stem cells in the treatment of corneal injury. However, this approach has its limitations. In this study, BMSCs were induced to differentiate into corneal epithelial cells

Topics: Animals; Bone Marrow Cells; Burns; Corneal Injuries; Epithelial Cells; Fibrin; Fibrosis; Inflammation; Mesenchymal Stem Cells; Rats

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Bone Marrow; Bone Marrow Cells; Burns; Collagen; Fibrin; Humans; Hydrogels; Mesenchymal Stem Cells; Mice; Pseudomonas aeruginosa; Rats; Wound Healing; Wound Infection

The current standard of care for patients with severe large-area burns consists of autologous skin grafting or acellular dermal substitutes. While emerging options to accelerate wound healing involve treatment with allogeneic or autologous cells, delivering cells to clinically relevant wound topologies, orientations, and sizes remains a challenge. Here, we report the one-step in situ formation of cell-containing biomaterial sheets using a handheld instrument that accommodates the topography of the wound. In an approach that maintained cell viability and proliferation, we demonstrated conformal delivery to surfaces that were inclined up to 45° with respect to the horizontal. In porcine pre-clinical models of full-thickness burn, we delivered mesenchymal stem/stromal cell-containing fibrin sheets directly to the wound bed, improving re-epithelialization, dermal cell repopulation, and neovascularization, indicating that this device could be introduced in a clinical setting improving dermal and epidermal regeneration.

Topics: Animals; Biocompatible Materials; Burns; Cell Differentiation; Cell Proliferation; Fibrin; Humans; Mesenchymal Stem Cells; Skin; Skin Transplantation; Skin, Artificial; Swine; Wound Healing

Infection control is necessary for improved burn wound regeneration. In this study contact burn wounds were induced on the dorsum of the rats and were infected with Pseudomonas aeruginosa (107cfu/ml of saline) and left overnight (12-14 hours) to establish the infection. After 12 hours, the wounds were treated with PEGylated fibrin hydrogel containing 50 mgs of silver sulfadiazine (SSD) loaded chitosan microsphere (SSD-CSM-FPEG). On day 9, SSD-CSM-FPEG treated burn wounds further received adipose derived stem cell (5×104 ASCs cells/ml) embedded in PEGylated fibrin hydrogel. Wounds were assessed for the healing outcomes such as neovascularization, granulation tissue formation, wound closure and collagen maturation. Analysis of bacterial load in the burn wound biopsies, demonstrated that SSD-CSM-FPEG significantly reduced bacterial infection, while overt infection was still observed in the untreated groups on day 14. Sequential treatment of infected wounds with SSD-CSM-FPEG followed by ASC-FPEGs (SSD-CSM-ASC-FPEG) significantly reduced bacterial colonization (9 log reduction) and pro-inflammatory cytokine (TNF-α) expression. A significant increase in neovascularization markers; NG2 and vWF was also observed. Histological analysis indicated the wounds treated with SSD-CSM-ASC-FPEG increased amount of dermal collagen matrix deposition, a thicker granulation tissue on day 21 and more mature collagen on day 28. This work demonstrates that the sequential treatment of infected burn wounds with SSD-CSM-FPEG followed by ASC-FPEG reduces bacterial infection as well as promotes neo-vascularization with improved matrix remodeling.

Topics: Adipocytes; Animals; Anti-Infective Agents, Local; Burns; Chitosan; Fibrin; Hydrogels; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Microspheres; Models, Animal; Rats; Rats, Inbred Strains; Silver Sulfadiazine; Skin; Stem Cells; Wound Healing; Wound Infection

While early excision and grafting has revolutionized burn wound care, autologous split-thickness skin grafts are sometimes unavailable. Tissue-engineered skin substitutes have generated great interest but have proven inadequate. Therefore, the development of novel biomaterials to replace/augment skin grafting could improve burn patient outcomes. Herein, we establish the effects of debridement on deep-partial thickness burns and subsequently examine the effects of 3 different hydrogels on healing. Burns were created on the dorsum of pigs and 4 days after, the eschar was either left intact or debrided for treatment with collagen, PEGylated fibrinogen (PEG-fibrin) or PEGylated autologous platelet-free plasma (PEG-PFP) hydrogels. Wounds were photographed, scored, and biopsied for histology on postburn days 7, 10, 14, and 28. Compared with nondebrided wounds, debridement improved wound color and suppleness but accelerated contraction. Debridement also significantly reduced the number of neutrophils in the wound bed at days 10 and 14 postburn. Treatment with any hydrogel transiently mitigated contraction, with the PEG-fibrin group displaying less contraction on day 28. All hydrogels were visible histologically for up to 10 days, with significant cellular and blood vessel infiltration observed in PEG-fibrin hydrogels. Collagen and PEG-fibrin hydrogels reduced neutrophils and macrophages in surrounding granulation tissue on day 7, while PEG-fibrin hydrogels contained less immune cells. These data suggest that a single hydrogel application at the time of debridement has immunomodulatory properties that aid in wound healing. Ultimately, these hydrogels may be combined with other biomaterials, cells, or biologics for replacing/augmenting skin substitutes.

Topics: Animals; Burns; Collagen; Debridement; Disease Models, Animal; Female; Fibrin; Hydrogels; Plasma; Polyethylene Glycols; Swine; Wound Healing

Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU) for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked immunosorbent assay and was elevated on day 14 after thermal injury, and was higher in patients who developed sepsis. sGPVI levels were associated with sepsis, and the value for predicting sepsis was increased in combination with platelet count and Abbreviated Burn Severity Index. sGPVI levels positively correlated with levels of D-dimer (a fibrin degradation product) in ICU patients and patients with thermal injury. sGPVI levels in ICU patients at admission were significantly associated with 28- and 90-day mortality independent of platelet count. sGPVI levels in patients with thermal injury were associated with 28-day mortality at days 1, 14, and 21 when adjusting for platelet count. In both cohorts, sGPVI associations with mortality were stronger than D-dimer levels. Mechanistically, release of GPVI was triggered by exposure of platelets to polymerized fibrin, but not by engagement of G protein-coupled receptors by thrombin, adenosine 5'-diphosphate, or thromboxane mimetics. Enhanced fibrin production in these patients may therefore contribute to the observed elevated sGPVI levels. sGPVI is an important platelet-specific marker for platelet activation that predicts sepsis progression and mortality in injured patients.

Topics: Biomarkers; Burns; Disease Progression; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Inflammation; Inflammatory Bowel Diseases; Mortality; Platelet Activation; Platelet Count; Platelet Membrane Glycoproteins; Predictive Value of Tests; Sepsis; Solubility

Harvesting of autografts results in donor site morbidities and is limited in scenarios such as large total body surface area burns. In these instances, coverage is increased by meshing grafts at the expense of delayed biologic closure. Moreover, graft meshing increases the likelihood of contraction and hypertrophic scarring, limits range of motion, and worsens cosmesis. Many tissue engineering technologies have touted the promise of adipose-derived stem cells (ASCs) for burn wounds. The primary objective of the current study was to determine feasibility and efficacy of in situ ASC delivery via PEGylated fibrin (FPEG) hydrogels as adjuncts to meshed split thickness skin grafts in a porcine model. Deep partial thickness burns were created on the dorsum of anesthetized Yorkshire pigs, and subsequently debrided on post-burn day 4. After debridement, wounds were treated with: split thickness skin grafts (STSG); meshed STSG (mSTSG); and mSTSG + FPEG with increasing doses of ASCs. We show that FPEG hydrogels can be delivered in situ to prevent the contraction seen after meshing of STSG. Moreover, ASCs delivered in FPEG dose-dependently increase blood vessel size which significantly correlates with CD31 protein levels. The current study reports a dual-action adjunct therapy to autografting administered in situ, wherein FPEG acts as both scaffolding to prevent contraction, and as a delivery vehicle for ASCs to accelerate angiogenesis. This strategy may be used to incorporate other biologics for generating tissue engineered products aimed at improving wound healing and minimizing donor sites or scarring. Stem Cells Translational Medicine 2018;7:360-372.

Topics: Adipocytes; Animals; Autografts; Biocompatible Materials; Burns; Cicatrix; Debridement; Female; Fibrin; Hydrogels; Polyethylene Glycols; Skin; Skin Transplantation; Stem Cells; Swine; Transplantation, Autologous; Wound Healing

The purpose of this study was to create a fibrin-based human skin substitute in vitro with epidermal and dermal component and to assess its healing potential in deep partial and full thickness burns. Fibrin scaffolds were prepared from commercial fibrin glue kits. Human fibroblasts were cultured in fibrin gel. Human keratinocytes were seeded on the top of the gel. Viability of cells was determined fluorimetrically. Scanning electron microscope and immunocytochemistry analysis of cultured cells were performed. After hydrosurgical preparation of deep burn necrotic tissue, wound bed was prepared for skin substitutes. Progress of healing was documented using visual estimation and photos. Scanning electron microscope images showed good cell attachment and colony spreading of\ keratinocytes and fibroblasts on fibrin scaff old. Immunofluorescent staining of cell cultures on fibrin scaffold showed expression of vimentin, a marker of fibroblast cells, cytokeratin 19, a marker of epithelial stem cells, as well as involucrin, a marker of differentiated keratinocytes. Clinical results clearly showed that appearance of the skin did not differ significantly from the areas of transplanted skin using split-thickness skin graft techniques. In conclusion, using these fibrin-cultured autografts on massive full-thickness burn resulted in good healing.

Topics: Adolescent; Burns; Cell Culture Techniques; Cell Survival; Child, Preschool; Fibrin; Fibroblasts; Humans; Keratinocytes; Male; Skin Transplantation; Skin, Artificial; Tissue Scaffolds; Wound Healing

Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd.

Topics: Animals; Burns; Delayed-Action Preparations; Extracellular Matrix; Fibrin; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Swine; Wound Healing

To determine the effectiveness of low-intensity therapeutic ultrasound (LITUS) on wound healing in rats with third-degree burns.. Twenty rats were divided into the Control Group that comprised four rats without third-degree burns that did not undergo LITUS, the Burned Group (BG), comprising eight rats with third-degree burns that did not undergo LITUS, and the Burned with Treatment Group (BTG), comprising eight rats with third-degree burns that were administered LITUS. LITUS began 24 h after injury and involved daily applications for 8 min at 0.1 W/cm2 for 14 days.. The BTG lost less weight than the BG (Q=2.75; p<0.05). No visible differences were apparent among the groups' lesions on day 4. By the end of treatment, wound healing was more evident in the BTG. No statistically significant differences were found between the BG and the BTG in relation to the parameters measured using the histological changes in burn wound healing scoring system.. The LITUS protocol applied to the animals with third-degree burns accelerated the formation of fibrin-leukocyte crusts and significantly reduced weight loss. However, burn wound healing was not accelerated.

Topics: Animals; Burns; Connective Tissue; Fibrin; Hot Temperature; Male; Rats, Wistar; Re-Epithelialization; Ultrasonic Waves; Weight Loss; Wound Healing

Injury due to burning is known to impact on coagulation and haemostasis by disturbing the coagulation cascade and is also associated with impaired fibrinolysis. Also, venous thrombosis, pulmonary embolism and hypercoagulability are common during thermal injury. Using a Wistar albino rat model, we investigated in this study whether burn injury affects the ultrastructure of the fibrin networks. A typical fibrin network will contain mostly major, thick fibres with minor, thin fibres distributed amongst them. We found that the clot architecture changes after burn injury, showing more prominent minor, thin fibres in a netted appearance. Also, the clot showed areas of matted fibrin. We suggest that the thrombotic events associated with burn injury are due to the thickened and netlike areas formed when thrombin activates the coagulation cascade. This is due to impaired fibrinolysis activities, causing the resulting fibrin clots not to be successfully disseminated. Small fragments of these netted, clumped areas may therefore break loose and lead to thrombotic events after burn injuries. The current study therefore provided morphological evidence for thrombotic events associated with burn injury.

Topics: Animals; Blood Coagulation; Burns; Disease Models, Animal; Fibrin; Fibrinolysis; Microscopy, Electron, Scanning; Rats; Rats, Wistar; Thrombosis

A major factor limiting survival following extensive thermal injury is insufficient availability of donor sites to provide enough skin for the required grafting procedures. Limitation of autologous grafting promotes the usage of allograft skin substitutes to promote wound healing. Here, we investigated the wound healing potential of allograft single layered tissue engineered skin which comprises of either keratinocytes (SLTES-K) or fibroblast (SLTES-F) with fibrin as the delivery system. Results from gross and microscopic evaluation showed our single layered tissue engineered skin constructed with keratinocytes or fibroblast after gamma radiation with the dosage of 2Gy could serve as allograft for the treatment of skin loss.

Topics: Animals; Biopsy; Burns; Fibrin; Fibroblasts; Keratinocytes; Models, Animal; Pilot Projects; Sheep, Domestic; Skin Transplantation; Tissue Engineering; Transplantation, Homologous; Wound Healing

The effectiveness of fibrin mat and Tegaderm delivery systems to maintain clonogenic keratinocytes in culture were evaluated using in vitro methods. A fibrin mat was found to provide a culture environment that is conducive for the proliferation of keratinocytes and supporting their ability to form colonies of good growth potential in vitro. This confirms that the fibrin mat is a good delivery system for cultured epithelial autograft (CEA). In our unit, fibrin-CEA is limited only for the treatment of severe burns due to the high cost of fibrin glue. However, this substrate is able to maintain the regenerative properties of the CEA which is crucial for the treatment of extensive and full thickness burns. Tegaderm, a cost-effective polyurethane wound dressing is able to support keratinocyte cell growth but at a slower rate and with fewer colonies formed compared to the fibrin system. This suggests that Tegaderm can be an alternative approach of delivering autologous cells, limited to treat chronic wounds and less extensive burns. The use of simple and relatively inexpensive bench techniques can potentially serve as a quality control to check for keratinocytes cultured and delivered to every patient in the clinical setting.

Topics: Burns; Cell Culture Techniques; Cell Proliferation; Fibrin; Humans; Keratinocytes; Microscopy, Electron, Scanning; Occlusive Dressings; Polyurethanes; Reverse Transcriptase Polymerase Chain Reaction; Wound Healing

Burn wounds are characterised by central necrosis surrounded by an area of stasis with compromised perfusion. Secondary aggravation of the burn wound due to ischaemia in the zone of stasis can also result in necrosis. This study aims to improve circulation in the zone of stasis by reducing microthrombus formation and thereby to reduce secondary aggravation.. Recombinant nematode anticoagulant protein (rNAPc2) was administered to Wistar rats at 3 or 30 microg/kg as a single or daily dose. A comb pattern burn was induced on the dorsum of these rats and its evolution monitored by serial photography, planimetry, laser doppler flowmetry and immunohistochemistry.. In the 30 microg/kg daily group, extension of the burn wound was curbed, limiting the burn area to 1.99+/-0.67 cm(2) on day 28, compared to 3.51+/-0.37 cm(2) in the control group (p=0.015). Laser doppler evaluation showed a significant (p<0.001) increase in circulation in the first day post-burn. Significantly less (p<0.001) microvascular fibrin formation was observed by immunohistochemistry.. Anticoagulation with rNAPc2 improved perfusion of the burn wound. The resultant reduction in the area of the burn led to earlier healing and less scar contracture.

Topics: Animals; Anticoagulants; Burns; Cicatrix; Contracture; Fibrin; Flow Cytometry; Helminth Proteins; Male; Random Allocation; Rats; Rats, Wistar; Recombinant Proteins; Regional Blood Flow

There are a variety of approaches for the delivery of autologous keratinocytes to restore epithelial coverage of burns wounds that include utilizing cultured keratinocyte sheets, transfer of cultured keratinocytes using a membrane and more recently aerosol spraying of a keratinocyte suspension. The purpose of this study was to compare the effectiveness of direct aerosol delivery of a keratinocyte suspension with a fibrin transfer system to an in vitro wound model consisting of organotypical deepidermalized dermis (DED). A comparison was made between the number of keratinocytes delivered to DED with time, either by transfer from a fibrin membrane or using an aerosol. Additionally, the effect of application time of fibrin membranes to DED, on the number of keratinocytes delivered was investigated and compared with keratinocytes delivered by aerosol at the same time points. After 2 days culture little transfer of keratinocytes had occurred from the fibrin membrane to the DED, whereas 20% more cells were present on the DED than were initially delivered by aerosol spraying. After 7 days, aerosol-delivered cells were found to express cytokeratin K6, indicating a proliferative phenotype. The results from this study show that preconfluent keratinocytes can be delivered by aerosol, and thus may well find application clinically.

Topics: Aerosols; Burns; Cell Division; Cell Survival; Cells, Cultured; Fibrin; Humans; Keratinocytes; Skin, Artificial; Wound Healing

Integra, a dermal replacement, is used as an immediate and temporary coverage for acute wounds, after which, autograft is used to reconstitute permanently the epidermal coverage. The fibrin sheet-cultured epithelium autograft (FS-CEA) could provide an effective alternative to the surgical procedure. To evaluate this hypothesis, we compared the association of Integra/FS-CE to Integra/control-cultured epithelium (control-CE). Their respective abilities: (1) to produce dermal-epidermal construct in vitro; (2) to generate skin replacement when grafted onto athymic mice were studied. We have shown that: (1) 83% of the FS-CE attached to the artificial dermis in vitro compared to only 33% for control-CE; (2) retraction of the grafted area was significantly lower 2 weeks after grafted with FS-CE than with the control-CE (P < 0.05); (3) 83% of the mice grafted with FS-CE showed the presence of a differentiated human epidermis 21 days after grafting, while such an epidermis was absent in all the animals of the control-CE group. We found that the use of FS-CE greatly improved adhesion, development of the epithelium and graft take onto the artificial dermis. We believe this technology should significantly improve the performance of dermal-epidermal skin replacement for acute wounds.

Topics: Animals; Biocompatible Materials; Burns; Cells, Cultured; Chondroitin Sulfates; Collagen; Epidermis; Epithelium; Fibrin; Graft Survival; Keratinocytes; Mice; Mice, Nude; Skin, Artificial

Cell therapy is an emerging therapeutic strategy aimed at replacing or repairing severely damaged tissues with cultured cells. Epidermal regeneration obtained with autologous cultured keratinocytes (cultured autografts) can be life-saving for patients suffering from massive full-thickness burns. However, the widespread use of cultured autografts has been hampered by poor clinical results that have been consistently reported by different burn units, even when cells were applied on properly prepared wound beds. This might arise from the depletion of epidermal stem cells (holoclones) in culture. Depletion of holoclones can occur because of (i) incorrect culture conditions, (ii) environmental damage of the exposed basal layer of cultured grafts, or (iii) use of new substrates or culture technologies not pretested for holoclone preservation. The aim of this study was to show that, if new keratinocyte culture technologies and/or "delivery systems" are proposed, a careful evaluation of epidermal stem cell preservation is essential for the clinical performance of this life-saving technology.. Fibrin was chosen as a potential substrate for keratinocyte cultivation. Stem cells were monitored by clonal analysis using the culture system originally described by Rheinwald and Green as a reference. Massive full-thickness burns were treated with the composite allodermis/cultured autograft technique.. We show that: (i) the relative percentage of holoclones, meroclones, and paraclones is maintained when keratinocytes are cultivated on fibrin, proving that fibrin does not induce clonal conversion and consequent loss of epidermal stem cells; (ii) the clonogenic ability, growth rate, and long-term proliferative potential are not affected by the new culture system; (iii) when fibrin-cultured autografts bearing stem cells are applied on massive full-thickness burns, the "take" of keratinocytes is high, reproducible, and permanent; and (iv) fibrin allows a significant reduction of the cost of cultured autografts and eliminates problems related to their handling and transportation.. Our data demonstrate that: (i) cultured autografts bearing stem cells can indeed rapidly and permanently cover a large body surface; and (ii) fibrin is a suitable substrate for keratinocyte cultivation and transplantation. These data lend strength to the concept that the success of cell therapy at a clinical level requires cultivation and transplantation of stem cells. We therefore suggest that the proposal of a culture system aimed at the replacement of any severely damaged self-renewing tissue should be preceded by a careful evaluation of its stem cell population.

Topics: Adolescent; Adult; Burns; Cell Transplantation; Cells, Cultured; Child; Child, Preschool; Costs and Cost Analysis; Culture Media; Epidermal Cells; Fibrin; Humans; Infant; Keratinocytes; Microscopy, Electron; Stem Cells; Tissue Preservation; Transplantation, Autologous

Fibrin plate assay revealed that rat serum and wound fluid harvested from seven day subcutaneously implanted wound chambers prevented fibrinolysis. Samples of wound fluid from one to four hour burns displayed greater inhibiting activity than unburned or 24 hour old burns. Ibuprofen, a non-steroid anti-inflammatory drug, reversed the blocking of fibrinolysis in wound fluid, but it had no action on rat serum. The activity of ibuprofen appears unrelated to the synthesis of prostanoids. Fractionation of wound fluid and serum by column chromatography showed differences in elutions of inhibitors of fibrinolysis. Serum fractions having molecular weights greater than 60,000 prevented fibrinolysis and they were unaffected by the addition of ibuprofen. Fractionations of wound fluid produced a number of inhibitors, some of which had molecular weights of approximately 40,000. This inhibitor(s) was not detected in serum and was reversed by adding ibuprofen. Wound fluid has a fibrinolytic inhibitor which differs from that in the circulatory system, and which may be critical to the vascular changes of burn trauma.

Topics: Animals; Antifibrinolytic Agents; Burns; Extracellular Space; Fibrin; Fibrinolysis; Ibuprofen; Male; Methods; Rats; Rats, Inbred Strains; Wound Healing

Predictable vascular responses to burn injury can occur where blood vessels are occluded in and just beneath the site of trauma. The loss of vascular patency is linked to the development of ischemia in the surrounding skin. Several mechanisms may be responsible for this occlusion, and their identification will provide a logical means for prevention or reversal of the occlusion. The role of fibrin deposition was investigated here using a rat burn model. If an intravascular fibrin clot is a primary cause of early occlusion, the depletion of circulating fibrinogen should prevent its deposition. Ancrod, a pit viper venom trypsin-like proteinase, when given systemically, converts fibrinogen into a soluble product which does not clot. In studies here, the host is depleted of fibrinogen by intravenous injections of ancrod for 3 days before standard burn trauma. Burn injury in defibrinogenized rats resulted in greatly reduced local vascular occlusion. These results support the idea that vascular occlusion caused by burn injury is dependent on the deposition of fibrin. It is conjectured that the vascular occlusion of burn injury can be reversed by preventing or breaking down intravascular fibrin clots.

Topics: Ancrod; Animals; Arterial Occlusive Diseases; Burns; Fibrin; Ischemia; Male; Models, Cardiovascular; Rats; Rats, Inbred Strains; Skin; Vascular Patency

Pulmonary megakaryocytes and fibrin microthrombi were counted in lung sections from 22 patients dying from extensive burns. There was a significant correlation between numbers of megakaryocytes and fibrin microthrombi, supporting a relationship between disseminated intravascular coagulation (DIC) and numbers of pulmonary megakaryocytes. No correlation was found between antemortem platelet counts and either fibrin microthrombi or megakaryocytes. Possible explanations for this are forwarded and the nature of pulmonary megakaryocytes discussed.

Topics: Adult; Aged; Burns; Cell Count; Disseminated Intravascular Coagulation; Fibrin; Humans; Lung; Megakaryocytes; Middle Aged; Pulmonary Embolism; Respiratory Distress Syndrome

Two series of wounds made by excision were included in this experiment and both healed well with the application of Bioplast. This result encouraged the authors to recommend it for the treatment of other skin defects and burns as well. An excessive degree of epithelization was often found over the granulation tissue, and in these cases a definitive wound cover was provided with Bioplast, which needed only minor aftercare.

Topics: Animals; Biocompatible Materials; Burns; Collagen; Drug Evaluation, Preclinical; Fibrin; Occlusive Dressings; Rats; Skin; Wound Healing

Fibrin is shown to be the agent responsible for the adherence of biological dressings and of autografts to wounds. Its presence is associated with graft success, and its absence with graft failure. The results suggest that the deposition of fibrin provides the basis for the anti-bacterial actions of biological dressings and for the sterilization of the wound under adherent autografts. The total number of bacteria per gram of tissue in the wound, though important, is not critical to the result of skin grafting. The mechanism by which different organisms cause grafts to fail is by the production of plasmin and proteolytic enzymes which dissolve the important fibrin scaffold--thus ensuring their own survival. Thus, it is the levels of these (and the numbers of organisms efficient in producing them) which cause success or failure of applied skin grafts.

Topics: Aged; Biological Dressings; Burns; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Graft Rejection; Humans; Leg Ulcer; Male; Middle Aged; Peptide Hydrolases; Skin Transplantation; Transplantation, Autologous; Transplantation, Heterologous; Wound Healing; Wound Infection

Topics: Adolescent; Burns; Child; Cicatrix; Cytoplasm; Fibrin; Fibroblasts; Granulation Tissue; Humans; Hypertrophy; Infant

Topics: Animals; Burns; Fibrin; Fibrinolysis; Hydrocortisone; Lung; Male; Pulmonary Artery; Rats; Thrombin

Utilizing a 40 percent flame-burned canine model, serial aliquots of burn-wound edema and simultaneous plasma samples were collected for 26 hours after burn, following the injection of 100 muc of 125I-tagged fibrinogen. Both edema fluid and plasma samples were analyzed for radioactivity. In addition, radioactivity in the supernatant was reassayed after sequential in vitro addition of thrombin, protamine sulfate (PS), and trichloroacetic acid (TCA) to each sample. Plasma and edema fibrinogen and fibrin split product concentrations were measured directly. PS and TCA precipitable protein concentrations were calculated. Early post-burn edema radioactivity appeared primarily in the fibrinogen fractions where edema fibrinogen concentration was measured at almost 30 percent of the simultaneous plasma concentration. Late post-burn edema radioactivity (24 to 27 hours) was associated with the PS precipitable protein fraction (soluble fibrin monomer). Fibrin split product concentration increased in both plasma and edema during the study period. These observations allowed construction of a hypothesis to explain the post-burn elevation in plasma fibrin split product concentration noted in burned patients and strongly suggested that the abnormally elevated plasma fibrin split concentrations resulted from extravascular plasmin digestion of fibrinogen.

Topics: Animals; Burns; Capillary Permeability; Disease Models, Animal; Dogs; Edema; Fibrin; Fibrinogen; Iodine Radioisotopes; Time Factors

A burned rat model was developed to examine post-burn alterations in coagulation. Fibrin split product concentration, as measured by the staphylococcal clumping test, was noted to rise significantly within the first 24 hours following injury. Prophylactic in vivo systemic anticoagulation with heparin was ineffective in modifying this response. However, systemic administration of protamine sulfate prevented post-burn elevation of fibrin split products. In vitro fibrin split product concentration in burn sera following the addition of heparin and protamine sulfate, was also analyzed. The results of these experiments elucidated the biochemical effects of protamine sulfate on circulating fibrin degradation products in the rat burn model.

Topics: Animals; Blood Coagulation Tests; Burns; Disease Models, Animal; Disseminated Intravascular Coagulation; Drug Evaluation; Fibrin; Heparin; Protamines; Rats; Staphylococcus

Topics: Animals; Burns; Fibrin; Fractures, Bone; Humans; Hypoxia; Lung; Microcirculation; Pulmonary Edema; Pulmonary Embolism; Wounds and Injuries

Topics: Animals; Burns; Capillaries; Disease Models, Animal; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hematocrit; Iodine Radioisotopes; Kidney; Kidney Glomerulus; Rats; Thrombin; Time Factors

Topics: Animals; Burns; Cyclohexanecarboxylic Acids; Female; Fibrin; Fibrinogen; Hematocrit; Heparin; Iodine Isotopes; Kidney; Liver; Lung; Methylamines; Plasma; Rats; Skin

Topics: Arrhythmias, Cardiac; Burns; Diabetic Coma; Fibrin; Fibrinogen; Heart Failure; Humans; Intensive Care Units; Lung Diseases, Obstructive; Myocardial Infarction; Poisoning; Shock, Cardiogenic; Tetanus

Topics: Adolescent; Adult; Aged; Burns; Child; Child, Preschool; Clot Retraction; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Hemorrhage; Humans; Immunoassay; Length of Stay; Middle Aged; Prothrombin

Topics: Adolescent; Adult; Animals; Antibody Specificity; Blood Proteins; Burns; C-Reactive Protein; Chromatography, Gel; Female; Fibrin; Fibrinogen; Humans; Immune Sera; Immunoelectrophoresis; Male; Middle Aged; Rabbits; Serum Globulins; Sheep; Species Specificity

Topics: Acetylcholine; Biopsy; Bradykinin; Burns; Capillary Permeability; Complement System Proteins; Edema; Epithelium; Fibrin; Fibrinolysis; Fluorescent Antibody Technique; Globulins; Histamine; Histological Techniques; Humans; Hypertrophy; Inflammation; Kallikreins; Leukocytes; Plasminogen; Serotonin; Skin; Time Factors; Urticaria

Topics: Adhesiveness; Animals; Biodegradation, Environmental; Biophysical Phenomena; Biophysics; Burns; Collagen; Dogs; Female; Fibrin; Intestines; Male; Nylons; Polyurethanes; Prostheses and Implants; Rabbits; Rats; Skin; Surface Properties; Textiles; Tissue Adhesives; Urinary Bladder; Wound Healing; Wound Infection

Topics: Blood Coagulation Factors; Burns; Fibrin; Fibrinolysis; Humans; Thrombocytopenia; Time Factors

Topics: Autopsy; Bronchitis; Burns; Embolism, Fat; Fibrin; Humans; Lung; Pneumonia; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Embolism; Pulmonary Veins; Thoracic Injuries

Topics: Burns; Fibrin; Humans; Outpatients

Topics: Burns; Fibrin; Hemostatics; Humans

Topics: Burns; Fibrin; Hemostatics; Humans

Topics: Burns; Fibrin; Humans

Topics: Burns; Cornea; Corneal Diseases; Disease; Fibrin; Humans; Wounds and Injuries

Topics: Burns; Fibrin; Humans

Topics: Burns; Fibrin; Humans; Penicillins; Powders; Thrombin; Thromboangiitis Obliterans

Topics: Bandages; Burns; Fibrin; Humans

Topics: Animals; Blister; Blood; Blood Chemical Analysis; Blood Glucose; Burns; Cholesterol; Dogs; Ethylamines; Fibrin; Gas Poisoning; Hot Temperature; Irritants; Mustard Gas; Plasma; Rats; Sulfides; Turpentine