Chronic venous ulcers: a review on treatment with fibrin sealant and prognostic advances using proteomic strategies

Venous ulcers are the main causes of chronic lower-limb ulcers. The healing difficulties encourage the research and development of new products in order to achieve better therapeutic results. Fibrin sealant is one of these alternatives. Besides being a validated scaffold and drug delivery system, it possesses excellent healing properties. This review covered the last 25 years of the literature and showed that the fibrin sealant is used in various clinical situations to promote the healing of different types of ulcers, especially chronic ones. These are mostly venous in origin and usually does not respond to conventional treatment. Commercially, only the homologous fibrin sealants obtained from human blood are available, which are highly efficient but very expensive. The heterologous fibrin sealant is a non-commercial experimental low-cost product and easily produced due to the abundance of raw material. The phase I/II clinical trial is already completed and showed that the product is safe and promisingly efficacious for the treatment of chronic venous ulcers. In addition, clinical proteomic strategies to assess disease prognosis have been increasingly used. By analyzing liquid samples from the wounds through proteomic strategies, it is possible to predict before treatment which ulcers will evolve favorably and which ones will be difficult to heal. This prognosis is only possible by evaluating the expression of isolated proteins in exudates and analysis using label-free strategies for shotgun. Multicentric clinical trials will be required to evaluate the efficacy of fibrin sealant to treat chronic ulcers, as well as to validate the proteomic strategies to assess prognosis.(AU)

Neuroprotection and immunomodulation by dimethyl fumarate and a heterologous fibrin biopolymer after ventral root avulsion and reimplantation

Background: Ventral root avulsion (VRA) is an experimental approach in which there is an abrupt separation of the motor roots from the surface of the spinal cord. As a result, most of the axotomized motoneurons degenerate by the second week after injury, and the significant loss of synapses and increased glial reaction triggers a chronic inflammatory state. Pharmacological treatment associated with root reimplantation is thought to overcome the degenerative effects of VRA. Therefore, treatment with dimethyl fumarate (DMF), a drug with neuroprotective and immunomodulatory effects, in combination with a heterologous fibrin sealant/biopolymer (FS), a biological glue, may improve the regenerative response. Methods: Adult female Lewis rats were subjected to VRA of L4-L6 roots followed by reimplantation and daily treatment with DMF for four weeks. Survival times were evaluated 1, 4 or 12 weeks after surgery. Neuronal survival assessed by Nissl staining, glial reactivity (anti-GFAP for astrocytes and anti-Iba-1 for microglia) and synapse preservation (anti-VGLUT1 for glutamatergic inputs and anti-GAD65 for GABAergic inputs) evaluated by immunofluorescence, gene expression (pro- and anti-inflammatory molecules) and motor function recovery were measured. Results: Treatment with DMF at a dose of 15 mg/kg was found to be neuroprotective and immunomodulatory because it preserved motoneurons and synapses and decreased astrogliosis and microglial reactions, as well as downregulated the expression of pro-inflammatory gene transcripts. Conclusion: The pharmacological benefit was further enhanced when associated with root reimplantation with FS, in which animals recovered at least 50% of motor function, showing the efficacy of employing multiple regenerative approaches following spinal cord root injury.(AU)

The effect of fibrin glue in preventing staple-line leak after sleeve gastrectomy. An experimental study in rats

Abstract Purpose To evaluate the effect of fibrin glue on staple-line leak after sleeve gastrectomy. Methods Fourteen adult wistar rats 300 gr were randomized into two groups: Control group (n=7) and study group (n=7). All the rats underwent sleeve gastrectomy using lineer stapler. In the study group, fibrin glue was used to reinforce the staple-line. The rats were sacrificed 7 days after surgery. The stomach was resected, submerged in saline and exposed to excess pressure to obtain a burst pressure value. The gastric staple line was evaluated histopathologically according to the Ehrlich Hunt scale. The results of the two groups were compared. Results The mean Ehrlich-Hunt scores for inflammation, fibroblastic activity and neo-angiogenesis were similar between the groups (p>0.05). Collagen deposition was significantly higher in study group (3.42±0.53) when compared with control group (2.57±0.78) (p=0.035). The mean burst pressure was 137.8±8.5 mmHg for control group and 135.0±8.1 mmHg for study group (p=0.536). Conclusion Reinforcement of the staple-line with fibrin glue has no effect on the burst pressure after sleeve gastrectomy. More studies are needed to evaluate the precautions against leak after sleeve gastrectomy.(AU)

Fibrin biopolymer as scaffold candidate to treat bone defects in rats

Background:Bone tissue repair remains a challenge in tissue engineering. Currently, new materials are being applied and often integrated with live cells and biological scaffolds. The fibrin biopolymer (FBP) proposed in this study has hemostatic, sealant, adhesive, scaffolding and drug-delivery properties. The regenerative potential of an association of FBP, biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSCs) was evaluated in defects of rat femurs.Methods:Adult male Wistar rats were submitted to a 5-mm defect in the femur. This was filled with the following materials and/or associations: BPC; FBP and BCP; FBP and MSCs; and BCP, FBP and MSCs. Bone defect without filling was defined as the control group. Thirty and sixty days after the procedure, animals were euthanatized and subjected to computed tomography, scanning electron microscopy and qualitative and quantitative histological analysis.Results:It was shown that FBP is a suitable scaffold for bone defects due to the formation of a stable clot that facilitates the handling and optimizes the surgical procedures, allowing also cell adhesion and proliferation. The association between the materials was biocompatible. Progressive deposition of bone matrix was higher in the group treated with FBP and MSCs. Differentiation of mesenchymal stem cells into osteogenic lineage was not necessary to stimulate bone formation.Conclusions:FBP proved to be an excellent scaffold candidate for bone repair therapies due to application ease and biocompatibility with synthetic calcium-based materials. The satisfactory results obtained by the association of FBP with MSCs may provide a more effective and less costly new approach for bone tissue engineering.(AU)

Comparison of platelet rich plasma versus fibrin glue on colonic anastomoses in rats

Purpose: To compare platelet rich plasma (PRP) and fibrin glue about the effect of anastomotic healing. Methods: Thirty six Wistar-Albino male rats diveded into 3 groups according to control (Group1), PRP (Group 2) and fibrin glue (Tisseel VH) (Group 3). The colon was transected with scissor and subsequently an end to end anastomosis was performed using continuous one layer 6/0 vicryl sutures. Postoperative 7th day effect of anastomotic healing measuring with tissue hydroxyproline (TH) level and anastomotic bursting pressure (ABP); moreover comparison of cytokine (IL-6 and IL-10) and procalcitonin levels on 1st,3rd and 7th days. Results: There was no statistically significant difference of the ABP and hydroxyproline levels between PRP and fibrin glue on the 7th day. There was no statistically significant difference between levels of proinflammatory cytokine (IL-6) (P=0.41), anti-inflammatory cytokine (IL-10) (P=0.35), and procalcitonin levels (P=0.63) on 1, 3 and 7 days. Conclusion: Fibrin glue and platelet rich plasma are shown to be effective in healing intestinal anastomoses without superior to each other. (AU)

Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair

Background Peripheral nerve injury is a worldwide clinical problem, and the preferred surgical method for treating it is the end-to-end neurorrhaphy. When it is not possible due to a large nerve gap, autologous nerve grafting is used. However, these surgical techniques result in nerve regeneration at highly variable degrees. It is thus very important to seek complementary techniques to improve motor and sensory recovery. One promising approach could be cell therapy. Transplantation therapy with human embryonic stem cells (hESCs) is appealing because these cells are pluripotent and can differentiate into specialized cell types and have self-renewal ability. Therefore, the main objective of this study was to find conditions under which functional recovery is improved after sciatic nerve neurorrhaphy. We assumed that hESC, either alone or in combination with heterologous fibrin sealant scaffold, could be used to support regeneration in a mouse model of sciatic nerve injury and repair via autografting with end-to-end neurorrhaphy. Methods Five millimeters of the sciatic nerve of C57BL/6 J mice were transected off and rotated 180 degrees to simulate an injury, and then stumps were sutured. Next, we applied heterologous fibrin sealant and/or human embryonic stem cells genetically altered to overexpress fibroblast growth factor 2 (FGF2) at the site of the injury. The study was designed to include six experimental groups comprising neurorrhaphy (N), neurorrhaphy + heterologous fibrin sealant (N + F), neurorrhaphy + heterologous fibrin sealant + doxycycline (N + F + D), neurorrhaphy + heterologous fibrin sealant + wild-type hESC (N + F + W), neurorrhaphy + heterologous fibrin sealant + hESC off (N + F +T), and neurorrhaphy + heterologous fibrin sealant + hESC on via doxycycline (N + F + D + T). We evaluated the recovery rate using Catwalk and von Frey functional recovery tests, as well as immunohistochemistry analysis. Results The experiments indicated...

Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair

Background Peripheral nerve injury is a worldwide clinical problem, and the preferred surgical method for treating it is the end-to-end neurorrhaphy. When it is not possible due to a large nerve gap, autologous nerve grafting is used. However, these surgical techniques result in nerve regeneration at highly variable degrees. It is thus very important to seek complementary techniques to improve motor and sensory recovery. One promising approach could be cell therapy. Transplantation therapy with human embryonic stem cells (hESCs) is appealing because these cells are pluripotent and can differentiate into specialized cell types and have self-renewal ability. Therefore, the main objective of this study was to find conditions under which functional recovery is improved after sciatic nerve neurorrhaphy. We assumed that hESC, either alone or in combination with heterologous fibrin sealant scaffold, could be used to support regeneration in a mouse model of sciatic nerve injury and repair via autografting with end-to-end neurorrhaphy. Methods Five millimeters of the sciatic nerve of C57BL/6 J mice were transected off and rotated 180 degrees to simulate an injury, and then stumps were sutured. Next, we applied heterologous fibrin sealant and/or human embryonic stem cells genetically altered to overexpress fibroblast growth factor 2 (FGF2) at the site of the injury. The study was designed to include six experimental groups comprising neurorrhaphy (N), neurorrhaphy + heterologous fibrin sealant (N + F), neurorrhaphy + heterologous fibrin sealant + doxycycline (N + F + D), neurorrhaphy + heterologous fibrin sealant + wild-type hESC (N + F + W), neurorrhaphy + heterologous fibrin sealant + hESC off (N + F +T), and neurorrhaphy + heterologous fibrin sealant + hESC on via doxycycline (N + F + D + T). We evaluated the recovery rate using Catwalk and von Frey functional recovery tests, as well as immunohistochemistry analysis. Results The experiments indicated...(AU)

Heterologous fibrin sealant derived from snake venom: from bench to bedside - an overview

Hemostatic and adhesive agents date back to World War II, when homologous fibrin sealant came onto scene. Considering that infectious diseases can be transmitted via human blood, a new heterologous fibrin sealant was standardized in the 1990s. Its components were a serine protease (a thrombin-like enzyme) extracted from the venom of Crotalus durissus terrificus snakes and a fibrinogen-rich cryoprecipitate extracted from the blood of Bubalus bubalis buffaloes. This new bioproduct has been used as a coagulant, sealant, adhesive and recently as a candidate scaffold for mesenchymal stem cells and bone and cartilage repair. This review discusses the composition of a new heterologous fibrin sealant, and cites published articles related to its preclinical applications aiming at repairing nervous system traumas and regenerating bone marrow. Finally, we present an innovative safety trial I/II that found the product to be a safe and clinically promising candidate for treating chronic venous ulcers. A multicenter clinical trial, phase II/III, with a larger number of participants will be performed to prove the efficacy of an innovative biopharmaceutical product derived from animal venom.(AU)

Heterologous fibrin sealant derived from snake venom: from bench to bedside - an overview

Hemostatic and adhesive agents date back to World War II, when homologous fibrin sealant came onto scene. Considering that infectious diseases can be transmitted via human blood, a new heterologous fibrin sealant was standardized in the 1990s. Its components were a serine protease (a thrombin-like enzyme) extracted from the venom of Crotalus durissus terrificus snakes and a fibrinogen-rich cryoprecipitate extracted from the blood of Bubalus bubalis buffaloes. This new bioproduct has been used as a coagulant, sealant, adhesive and recently as a candidate scaffold for mesenchymal stem cells and bone and cartilage repair. This review discusses the composition of a new heterologous fibrin sealant, and cites published articles related to its preclinical applications aiming at repairing nervous system traumas and regenerating bone marrow. Finally, we present an innovative safety trial I/II that found the product to be a safe and clinically promising candidate for treating chronic venous ulcers. A multicenter clinical trial, phase II/III, with a larger number of participants will be performed to prove the efficacy of an innovative biopharmaceutical product derived from animal venom.(AU)

Multiple uses of fibrin sealant for nervous system treatment following injury and disease

Lesions to the nervous system often produce hemorrhage and tissue loss that are difficult, if not impossible, to repair. Therefore, scar formation, inflammation and cavitation take place, expanding the lesion epicenter. This significantly worsens the patient conditions and impairment, increasing neuronal loss and glial reaction, which in turn further decreases the chances of a positive outcome. The possibility of using hemostatic substances that also function as a scaffold, such as the fibrin sealant, reduces surgical time and improve postoperative recovery. To date, several studies have demonstrated that human blood derived fibrin sealant produces positive effects in different interventions, becoming an efficient alternative to suturing. To provide an alternative to homologous fibrin sealants, the Center for the Study of Venoms and Venomous Animals (CEVAP, Brazil) has proposed a new bioproduct composed of certified animal components, including a thrombin-like enzyme obtained from snake venom and bubaline fibrinogen. Thus, the present review brings up to date literature assessment on the use of fibrin sealant for nervous system repair and positions the new heterologous bioproduct from CEVAP as an alternative to the commercial counterparts. In this way, clinical and pre-clinical data are discussed in different topics, ranging from central nervous system to peripheral nervous system applications, specifying positive results as well as future enhancements that are necessary for improving the use of fibrin sealant therapy.(AU)

Multiple uses of fibrin sealant for nervous system treatment following injury and disease

Lesions to the nervous system often produce hemorrhage and tissue loss that are difficult, if not impossible, to repair. Therefore, scar formation, inflammation and cavitation take place, expanding the lesion epicenter. This significantly worsens the patient conditions and impairment, increasing neuronal loss and glial reaction, which in turn further decreases the chances of a positive outcome. The possibility of using hemostatic substances that also function as a scaffold, such as the fibrin sealant, reduces surgical time and improve postoperative recovery. To date, several studies have demonstrated that human blood derived fibrin sealant produces positive effects in different interventions, becoming an efficient alternative to suturing. To provide an alternative to homologous fibrin sealants, the Center for the Study of Venoms and Venomous Animals (CEVAP, Brazil) has proposed a new bioproduct composed of certified animal components, including a thrombin-like enzyme obtained from snake venom and bubaline fibrinogen. Thus, the present review brings up to date literature assessment on the use of fibrin sealant for nervous system repair and positions the new heterologous bioproduct from CEVAP as an alternative to the commercial counterparts. In this way, clinical and pre-clinical data are discussed in different topics, ranging from central nervous system to peripheral nervous system applications, specifying positive results as well as future enhancements that are necessary for improving the use of fibrin sealant therapy.(AU)

End-to-side nerve repair using fibrin glue in rats / Anastomose nervosa término-lateral usando cola de fibrina em ratos

Purpose: To evaluate axonal regeneration after end-to-side nerve repair with fibrin glue in rats. Methods: Forty-five Wistar rats were divided into three groups: group A (n=15), were not submitted to surgery (control group); group B (n=15) were submitted to fibular transection without repair; and group C (n=15), were submitted to fibular transection with end-to-side nerve anastomosis using fibrin glue, in the lateral surface of an intact tibial nerve. The three groups were submitted to walking track (30 and 90 days) and posterior morphometrical analysis (90 days). Results: The functional tests demonstrated that there was no difference in the walking track during the study in group A (p>0.05). The group B had walking pattern impairment in the two tests (p>0.05). The group C had walking pattern impairment in the first test, with important recovery in the second test (p<0.05). The morphometrical assessment revealed significantly higher number of regenerated mielinates axons in group C, compared to group B (p<0.05). Conclusion: The end-to-side nerve repair with fibrin glue shows axonal recovery, demonstrated through functional and morphometrical ways in rats.(AU)

Objetivo: Avaliar a regeneração axonal após anastomose nervosa término-lateral (ATL) usando cola de fibrina em ratos. Métodos: Quarenta e cinco ratos Wistar distribuídos em três grupos: os animais do grupo A (n=15) não foram submetidos à secção nervosa (grupo controle); os animais do grupo B (n=15) foram submetidos apenas à secção do nervo fibular, sem posterior anastomose; e os animais do grupo C (n=15) foram submetidos à secção do nervo fibular e à ATL com cola de fibrina no nervo tibial. Posteriormente, os animais foram submetidos a dois testes de marcha (30 e 90 dias) e à análise morfométrica (90 dias). Resultados: A análise estatística dos testes de marcha demonstrou que o grupo A não apresentou alteração no padrão de caminhada durante o estudo (p>0,05). O grupo B apresentou prejuízo motor no primeiro e no segundo teste (p>0,05). O grupo C apresentou um padrão de atrofia no primeiro teste, com recuperação da marcha no segundo teste (p<0,05). Na análise morfométrica, o grupo C apresentou regeneração axonal significativamente superior ao grupo B (p<0,05). Conclusão: A ATL realizada com cola de fibrina resultou em regeneração axonal no rato, demonstrada tanto histologicamente quanto funcionalmente.(AU)

Ultrastructural evaluation of human keratinocyte growth and differentiation on a fibrin substrate / Avaliação ultraestrutural do crescimento e da diferenciação de queratinócitos sobre um substrato de fibrina

PURPOSE: In order to circumvent several difficulties that have been met in the routine use of the in vitro keratinocyte cultures using the standard procedure described by Rheinwald and Green, and obtain a more resilient and the least possible immunogeneic skin substitute for a future clinical application, this work studied a new keratinocyte culture system, which envisages the utilization of a fibrin substrate in association with high densities of human keratinocytes. METHODS: Through light and transmission electron microscopy and immunohistochemical assays, long-term proliferative and differentiative characteristics of keratinocytes cultured onto a fibrin gel under immerse and air-liquid interface culture conditions were evaluated. RESULTS: Despite the absence of a dermal substitute, the results demonstrated that the proposed composite was constituted of a transparent and elastic fibrin film covered by a well-attached, multistratified epithelium with morphological characteristics that resemble human epidermis, including the neoformation, albeit incomplete, of the basement membrane. CONCLUSIONS: Increased mechanical resistance due to the presence of an easy handling substrate, the delivery of nonclonfluent keratinocytes as well as the removal of animal-derived cells from the culture system suggest its potential use for future transplantation purposes.(AU)

OBJETIVO: Com o intuito de contornar diversas dificuldades encontradas no uso rotineiro de queratinócitos cultivados in vitro pela técnica descrita por Rheinwald e Green, e obter um substituto cutâneo mais resistente e o menos imunogênico possível para futuras aplicações clínicas, este trabalho avaliou um novo sistema de cultura de queratinócitos que prevê a utilização de um substrato de fibrina em associação com queratinócitos humanos em alta densidade. MÉTODOS: Através de microscopia óptica e eletrônica e análise imunohistoquímica, foram avaliadas as características proliferativas e de diferenciação em longo prazo de queratinócitos cultivados em condição imersa e na interface ar-líquido. RESULTADOS: Apesar da ausência de um substituto dérmico, foi demonstrado que o composto proposto constituiu-se de um substrato de fibrina transparente e elástico coberto por epitélio multi-estratificado, bem aderido, com características morfológicas semelhantes à epiderme humana, incluindo a neo-formação, embora incompleta, da membrana basal. CONCLUSÕES: A maior resistência mecânica com a presença de um substrato de fácil manuseio, a possível liberação de queratinócitos não-confluentes, e a remoção de células com origem animal dos sistemas de cultura sugerem que o composto proposto neste estudo apresenta grande potencial para uso clínico futuro.(AU)

Fibrin adhesive and the vaginal vault synthesis on female rabbits abdominal hysterectomies / Adesivo de fibrina e a síntese da cúpula vaginal após histerectomia abdominal em coelhos fêmeas

PURPOSE: To investigate the effectiveness of fibrin glue in comparison with polyglycolic acid suture to promote the closure of rabbit's vaginal vault, after abdominal hysterectomy. METHODS: Twenty female, adults, New Zealand rabbits, were submitted to abdominal hysterectomy and randomly distributed to polyglycolic acid suture (G-PA / n=10) or fibrin glue closure of vaginal vault (G-FG / n=10). Radiograph study allowed identifying vault vaginal suture disrupter or fistulas to urinary bladder or rectum. Videovaginoscopy study allowed identifying the presence of cellulites, abscess formation, tissue granulation or granuloma. Vaginal cuff burst test allowed to identify by the escape of air bubbles and rupture pression record. Histological sections stained with Picrosirius red allowed the measure of fibrous tissue healing. RESULTS: The videovaginoscopy identified a significant difference (Fisher Test p<0.3142) of granulation tissue in the animals of G-PA (40 percent) in comparison with the G-FG (20 percent). The gross inspection showed the same relation in the granulation tissue occurrence (Fisher test p< 0.1749) with G-PA (50 percent) and G-FB (20 percent). The visceral adhesion to the vaginal vault wound was statistical significant (Fisher test p< 0.1749) with G-PA (50 percent) and G-FG (20 percent). The pressure of rupture (mm Hg) of the burst test was similar (p<0.0421) in the animals of G-PA (61.5±19.3) and G-FG (72.5±21.9). The collagen matrix of vault wound healing was similar (p< 0.0231) between the G-PA (31.63±15) and the G-FG (23.2±13.2). CONCLUSION: The vaginal vault closure using the fibrin glue is a safe and reliable procedure after abdominal hysterectomy in female rabbit model.(AU)

OBJETIVO: Investigar a eficácia da cola de fibrina e da sutura usando fio de ácido poliglicólico para promover o fechamento da cúpula vaginal de coelhas, após histerectomia abdominal. MÉTODOS: Vinte coelhos fêmeas, New Zealand, adultas foram submetidas à histerectomia abdominal e distribuídas para sutura da cúpula vaginal com fio de ácido poliglicólico (G-PA / n=10) ou cola de fibrina (G-FG / n=10). Estudo radiológico foi realizado para identificar deiscências ou fístulas vesicais ou retais. Videovaginoscopia foi realizada para identificar a presença de secreções, abscessos, tecido de granulação ou granuloma tipo corpo estranho. Teste in vitro de pressão de rompimento sob selo d'água foi realizado para identificar a perviedade da sutura. O tecido de cicatrização foi estudado pela coloração com picrosirius red para mensuração do tecido fibrótico. RESULTADOS: A videovaginoscopia mostrou uma diferença significante (Teste de Fisher p<0,3142) no tecido de granulação do grupo G-PA (40 por cento) em comparação com o grupo G-FG (20 por cento). A análise macroscópica mostrou a mesma relação com o tecido de granulação (Teste de Fisher p< 0.1749) com G-PA (50 por cento) e G-FB (20 por cento). A aderência visceral à cúpula vaginal foi estatisticamente significativa (Teste de Fisher p< 0.1749) com o G-PA (50 por cento) e G-FG (20 por cento). A pressão de rompimento (mmHg) foi similar (p<0.0421) nos animais do grupo G-PA (61.5±19.3) e G-FG (72.5±21.9). A matriz colagenosa do tecido de cicatrização teve resultados semelhantes (p< 0.0231) entre G-PA (31.63±15) e G-FG (23.2±13.2). CONCLUSÃO: O fechamento da cúpula vaginal usando cola de fibrina é um procedimento seguro e confiável após histerectomia abdominal em coelhos fêmeas.(AU)

Validity of microporous polysaccharide hemispheres as a hemostatic agent in hepatic injuries: an experimental study in rats / Validade de hemosferas microporosas de polissacarídeos como agente hemostático em ferimentos hepáticos: estudo experimental em ratos

INTRODUCTION: In the treatment of hepatic injuries, there is not always adequate and secure hemostasis. A hepatic biopsy is indispensable in the evolution of focal or diffuse liver cell disease, being necessary for candidates for liver transplant and post-transplant treatment. Many patients suffer blood clotting that increases the risk of bleeding. For this reason, it is necessary to seek for substances capable of bringing about hemostasis quickly and effectively. PURPOSE: The aim of this study was to recognize the validity of the use of microporous polysaccharide hemispheres (MPH) as a hemostatic agent for hepatic injuries. METHODS: Thirty Wistar rats were used, split into three groups. Under anaesthetic, a laparoptomy was done and resulted in a standard liver injury that was treated in Group A with MPH, in Group B with n-butyl-2-cyanoacrylate and in Group C with fibrin adhesive. Immediate hemostasis, delayed bleeding and histological evolution were timed. RESULTS: The MPH took on average six minutes to promote hemostasis and also resulted in re-bleeding, which required reapplication; the n-butyl-2-cyanoacrylate took twenty seconds and the fibrin adhesive took one minute. The cyanoacrylate resulted in more intense adherence. The three adhesives mainly showed a chronic inflammatory reaction. The injuries treated with cyanoacrylate showed a larger area of injury (p=0,0164). The density of the collagen was similar in all groups. CONCLUSION: The MPH, despite achieving hemostasis, proved to be no more favorable than n-butyl-cyanoacrylate and the fibrin adhesive, the latter resulting in the lowest tissue reaction.(AU)

INTRODUÇÃO: No tratamento de lesões hepáticas nem sempre se tem hemostasia adequada e segura. Biópsia hepática é indispensável na evolução de doença hepato-celular difusa ou focal sendo necessária para candidatos à transplante hepático e para acompanhamento pós-transplante. Muitos doentes apresentam coagulopatias que aumentam os riscos de sangramento. Daí a necessidade de se procurar substâncias capazes de promover a hemostasia de forma rápida e efetiva. OBJETIVO: O objetivo deste estudo foi reconhecer a validade do uso de hemosferas microporosas de polissacarídeos (MPH) como agente hemostático para lesões hepáticas. MÉTODOS: Utilizaram-se 30 ratos Wistar distribuídos em três grupos. Sob anestesia, fez-se uma laparotomia e produziu-se um ferimento hepático padrão que foi tratado no grupo A com MPH, no grupo B, com n-butil-2-cianoacrilato e no grupo C com adesivo de fibrina. Cronometrou-se o tempo para a obtenção da hemostasia imediata, a existência de sangramento tardio e a evolução histológica. RESULTADOS: O MPH levou, em média, seis minutos para promover a hemostasia e apresentou re-sangramento exigindo reaplicação, o n-butil-2-cianoacrlato, 20 segundos e o adesivo de fibrina, um minuto. O cianoacrilato promoveu aderências mais intensas. Os três adesivos determinaram principalmente reação inflamatória do tipo crônico. As feridas tratadas com cianoacrilato apresentaram maior área de lesão (p=0,0164). A densidade do colágeno foi semelhante entre os grupos. CONCLUSÃO: O MPH, embora tenha conseguido hemostasia, não se mostrou mais favorável do que o n-butil-2-cianoacrilato e o adesivo de fibrina sendo que este último promoveu a menor reação tecidual.(AU)

The role of biological adhesive and suture material on rabbit hepatic injury / O papel da cola biológica e do fio de sutura na lesão hepática em coelhos

PURPOSE: To evaluate the performance of fibrin adhesive and absorbable suture thread in the repairing of hepatic injures in rabbits. METHODS: New Zealand albino rabbits (n=16), males and females, from 5 to 6 months old, average weight of 2500 g, were distributed randomly in Group A (n-8) - biological adhesive and Group B (n=8) - suture thread. After anesthesia with acepromazine (1mg/Kg), ketamine (50mg/Kg) and fentanyl EV (0,5ml/Kg), it was performed a supra-umbilical median laparotomy, the median hepatic lobe was isolated and subjected to severe standardized incision. In the group B the incision edges were sutured with simple 4-0 catgut, in separated stitches. It was evaluated the total time of the procedure, the hemostasis time and hemorrhage volume. In the 21st post-operative day it was evaluated the presence of adherences and signs of infection in the abdominal cavity, and it was followed by the resection of the median hepatic lobe for the histological evaluation. RESULTS: The calculated mean and standard deviation showed that the procedure time, hemostasis time and bleeding amount were significantly smaller in the group of animals subjected to the use of fibrin adhesive. The surgical abdominal incision was significantly more extensive in the animals of the suture group (average of 6,8 cm) in relation to the adhesive group (average of 3,8), as well as the number of occurrences of abscesses. The adherence of the intestinal ansas to the sutured incision (group B) occurred in five cases and the major omentum adhesion occurred in all animals. In the group A (adhesive) it occurred adherences of the major omentum in three cases. The microscopy of the hepatic incision repaired with the use of fibrin showed that the inflammatory infection is less intense, not associated with the formulation of secretion in the abscesses, and therefore has a more favorable later cicatricial aspect than a conventional suture with surgical thread. CONCLUSION: In agreement with other...(AU)

OBJETIVO: Avaliar o desempenho do adesivo de fibrina e do fio de sutura absorvível no reparo de lesões hepáticas provocadas em coelhos. MÉTODOS: Coelhos (n=16),Nova Zelândia, albinos, machos e fêmeas, 5 a 6 meses de idade, peso médio de 2500 gramas, foram distribuídos aleatoriamente em Grupo A(n = 8) - adesivo biológico e Grupo B(n=8) - fio de sutura. Após anestesia com acepromazina (1mg/Kg), quetamina (50mg/Kg) e fentanylEV (0,5ml/Kg), realizou-se laparotomia mediana supra-umbilical, o lobo hepático médio foi isolado e submetido a uma lesão padronizada grave. No grupo A foi aplicado o adesivo de fibrina. No grupo B as bordas da lesão foram suturadas com categute 4-0 simples, em pontos separados. Avaliou-se o tempo total de procedimento, tempo de hemostasia e volume da hemorragia. No 21º dia de pós-operatório avaliou-se a presença de aderências e sinais de infecção na cavidade e procedeu-se a ressecção do lobo hepático médio para a avaliação histológica. RESULTADOS: A média e desvio-padrão calculados mostraram que o tempo de procedimento, tempo de hemostasia e quantidade de sangramento foram significantes menores no grupo de animais submetidos ao uso do adesivo de fibrina. A extensão da ferida operatória foi significativamente maior nos animais do grupo sutura (média de 6,8cm) em relação ao grupo adesivo (média de 3,8cm) assim como o número de vezes da ocorrência de abscessos. A aderência de alças intestinais à lesão suturada (grupo B) ocorreu em 5 casos e adesão do omento maior ocorreu em todos os animais. No grupo A (adesivo) foram observadas aderências do omento maior em três casos. A microscopia da lesão hepática reparada com o uso de fibrina mostrou que a reação inflamatória é menos intensa, não está associada à formação de secreção ou abscessos e com isso tem um aspecto cicatricial tardio mais favorável que uma sutura convencional com fio cirúrgico. CONCLUSÃO: Em concordância com outros trabalhos da literatura biomédica, o adesivo de fibrina é uma opção...(AU)

Fixação de enxerto cutâneo em malha de espessura total com sutura ou cola de fibrina / Fixation of full-thickness mesh skin using suture or fibrin glue

Avaliou-se a influência da cola de fibrina, derivada do veneno de serpente, na fixação e integração de enxerto de pele. Foram utilizados nove cães, sem raça definida, com peso médio de 15kg. Foi induzida ferida de 4×4cm de área, na face crânio-proximal dos antebraços direito e esquerdo. Um enxerto de espessura total foi colhido da região torácica e expandido por meio de expansor de pele. No membro direito o enxerto foi estabilizado no leito receptor por meio de pontos isolados simples; no esquerdo foi fixado pela aplicação de cola de fibrina e oito pontos de sutura. O sítio doador foi fechado empregando-se retalho cutâneo bipediculado. As bandagens do leito receptor foram oclusivas e não aderentes e aplicou-se pomada de neomicina com bacitracina. A troca de bandagens ocorreu diariamente até o sétimo dia de pós-operatório e, posteriormente, a cada três dias. A área de sobrevivência do enxerto foi obtida pela subtração das áreas não viáveis e total medidas com fotomicroscópio Nikon conectado a um sistema de análise de imagem KS-300 aos três, sete, 15 e 30 dias de pós-operatório. Para a avaliação microscópica, a área do enxerto foi colhida em três animais aos sete, 15 e 30 dias de pós-operatório. Não houve diferença entre momentos de avaliação e técnicas de fixação quanto à área de enxerto viável. Os enxertos fixados com cola apresentaram estágio de reparação mais avançado em todos os momentos. Concluiu-se que a cola de fibrina derivada do veneno de serpente tem moderado poder adesivo e, pela análise microscópica, favorece a integração do enxerto cutâneo em malha de espessura total.(AU)

The purpose of this study was to evaluate the efficiency of fibrin glue, derived from snake venom, on fixation and integration of skin graft. Nine crossbred dogs, with average weight of 15kg were used. Wounds measuring 4×4 cm were induced at the cranioproximal aspect of the right and left forelimb. Full-thickness skin grafts were harvested from thoracic area, and meshed with a commercial mesh dermatome. The graft was secured to the recipient bed using several simple interrupted sutures on the right forelimb. On the left forelimb fibrin glue and eight simple interrupted sutures were used. The bed was closed using bipedicle advancement flap. The non-adherent occlusive bandage and neomycin-bacitracin ointment were used on receptor bed. The bandage was changed every day until the seventh day postoperative and every three days afterwards. The graft survival area was obtained by subtraction of total and nonviable areas measured with a Nikon Photomicroscope connected to a KS-300 image analysis system at 3, 7, 15 and 30 days postsurgically. For microscopic evaluation, the skin graft, recipient bed and adjacent surrounding skin were collected at 7, 15 and 30 days postsurgery. No statistical difference was detected for the viable graft area, in each evaluation moment and between fixation methods. However, based on microscopic evaluation, fibrin glue enhanced the tissue repair process in all evaluation moments. It was possible to conclude that fibrin glue derived from snake venom has moderate adhesive capacity, and, based on microscopic examination, improves the integration of full-thickness mesh skin grafts.(AU)

Reparação microcirúrgica de nervo periférico por meio de sutura, cola de fibrina ou bainha de BioFill® em ratos Wistar / Microsurgical repair of peripheral nerve by means of suture, fibrin glue or BioFill® sheath in Wistar rats

Com o objetivo de comparar três técnicas de neuroanastomose, foram utilizados 54 ratos fêmeas, distribuídos em três grupos de 18 animais, cujos nervos ciáticos direitos foram transeccionados e, em seguida, tratados mediante o emprego das seguintes técnicas: três pontos de sutura epineural, um ponto de sutura epineural associado à bainha de BioFill® e um ponto de sutura epineural com cola de fibrina. A presença do material de sutura foi responsável pelo mau direcionamento das fibras nervosas e formação de neuroma na área da anastomose devido à colisão das fibras nervosas em regeneração com a reação granulomatosa ao fio de sutura. Alterações como degeneração Walleriana, formação de neuroma e proliferação de tecido fibroso foram observadas nos três tratamentos, sendo mais evidentes no grupo que recebeu três pontos de sutura epineural. Os resultados histológicos superiores obtidos com o emprego da bainha de BioFill® e da cola de fibrina comprovaram a eficiência dessas duas técnicas na reparação de nervos periféricos lesados. O uso da bainha de BioFill® oferece vantagens como disponibilidade, simplicidade técnica e baixo custo, tornando-a a melhor alternativa na reparação microcirúrgica do nervo periférico.(AU)

Aiming to compare three neuroanastomosis techniques, 54 female rats were divided into three groups of 18 animals each. The right-side ciatic nerves of these animals were trans-sectioned and, immediately, treated by means of the following techniques: three plain epineural suture stitches, one epineural suture stitch together with a BioFill® sheath, and one perineural suture stitch with fibrine glue. Analysis of the results was based on histopathological aspects of the anastomotic area. It was noted that the presence of the suture material was responsible for the poor directioning of the nerve fibers and formation of a neurome in the anastomosis area, due to the collision of the regenerating nervous fibers with the granulomatous reaction to the suture string. Thus, changes such as Wallerian degeneration, formation of a neurome and proliferation of fibrous tissue were noticed in all three treatments, being more evident in the group that received three stitches of epineural suture. Based on histological results obtained from the use of the BioFill® sheath and the fibrine glue, the efficiency of these techniques for repairing damaged peripheral nerves was evident. However, the use of the BioFill® sheath ensures advantages such as availability, technical simplicity and low cost. Therefore, it becomes a better alternative for microsurgical repair of peripheral nerve.(AU)