Delayed repair of the facial nerve and its negative impacts on nerve and muscle regeneration

Abstract Background: In this experimental protocol, we evaluated the immediate and delayed repair of the buccal branch of the facial nerve (BBFN) with heterologous fibrin biopolymer (HFB) as a coaptation medium and the use of photobiomodulation (PBM), performing functional and histomorphometric analysis of the BBFN and perioral muscles. Methods: Twenty-eight rats were divided into eight groups using the BBFN bilaterally (the left nerve was used for PBM), namely: G1 - control group, right BBFN (without injury); G2 - control group, left BBFN (without injury + PBM); G3 - Denervated right BBFN (neurotmesis); G4 - Denervated left BBFN (neurotmesis + PBM); G5 - Immediate repair of right BBFN (neurotmesis + HFB); G6 - Immediate repair of left BBFN (neurotmesis + HFB + PBM); G7 - Delayed repair of right BBFN (neurotmesis + HFB); G8 - Delayed repair of left BBFN (neurotmesis + HFB + PBM). Delayed repair occurred after two weeks of denervation. All animals were sacrificed after six weeks postoperatively. Results: In the parameters of the BBFN, we observed inferior results in the groups with delayed repair, in relation to the groups with immediate repair, with a significant difference (p < 0.05) in the diameter of the nerve fiber, the axon, and the thickness of the myelin sheath of the group with immediate repair with PBM compared to the other experimental groups. In measuring the muscle fiber area, groups G7 (826.4 ± 69.90) and G8 (836.7 ± 96.44) were similar to G5 (882.8 ± 70.51). In the functional analysis, the G7 (4.10 ± 0.07) and G8 (4.12 ± 0.08) groups presented normal parameters. Conclusion: We demonstrated that delayed repair of BBFN is possible with HFB, but with worse results compared to immediate repair, and that PBM has a positive influence on nerve regeneration results in immediate repair.

A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy

Abstract Background: The association of scaffolds to repair extensive bone defects can contribute to their evolution and morphophysiological recomposition. The incorporation of particulate biomaterials into three-dimensional fibrin bioproducts together with photobiomodulation therapy (PBM) has potential and can improve regenerative medicine procedures. The objective of this experiment was to evaluate the effects of PBM therapy on critical size defects filled with xenogenic bone substitute associated with fibrin biopolymer. Methods: A critical defect of 8 mm was performed in 36 Wistar male adult rats that were divided into four groups. Groups BC and BC-PBM were defined as controls with defects filled by a clot (without or with PBM, respectively) and groups XS and XS-PBM that comprised those filled with biocomplex Bio-OssTM in association with fibrin biopolymer. PBM was applied immediately after the surgery and three times a week every other day, with the parameters: wavelength of 830 nm, energy density 6.2 J/cm2, output power 30 mW, beam area of 0.116 cm2, irradiance 0.258,62 W/cm2, energy/point 0.72 J, total energy 2.88 J. Fourteen and 42 days after the surgery, animals were euthanatized and subjected to microtomography, qualitative and quantitative histological analysis. Results: The BC-PBM and XS-PBM groups had a similar evolution in the tissue repair process, with a higher density of the volume of new formed bone in relation to the groups without PBM (p = 0.04086; p = 0.07093, respectively). Intense vascular proliferation and bone deposition around the biomaterial particles were observed in the animals of the groups in which biocomplex was applied (XS and XS-PBM). Conclusion: PBM therapy allowed an improvement in the formation of new bone, with a more organized deposition of collagen fibers in the defect area. Biocomplex favored the insertion and permanence of the particulate material in bone defects, creating a favorable microenvironment for accelerate repair process.

A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy

The association of scaffolds to repair extensive bone defects can contribute to their evolution and morphophysiological recomposition. The incorporation of particulate biomaterials into three-dimensional fibrin bioproducts together with photobiomodulation therapy (PBM) has potential and can improve regenerative medicine procedures. The objective of this experiment was to evaluate the effects of PBM therapy on critical size defects filled with xenogenic bone substitute associated with fibrin biopolymer. Methods: A critical defect of 8 mm was performed in 36 Wistar male adult rats that were divided into four groups. Groups BC and BC-PBM were defined as controls with defects filled by a clot (without or with PBM, respectively) and groups XS and XS-PBM that comprised those filled with biocomplex Bio-OssTM in association with fibrin biopolymer. PBM was applied immediately after the surgery and three times a week every other day, with the parameters: wavelength of 830 nm, energy density 6.2 J/cm2, output power 30 mW, beam area of 0.116 cm2, irradiance 0.258,62 W/cm2, energy/point 0.72 J, total energy 2.88 J. Fourteen and 42 days after the surgery, animals were euthanatized and subjected to microtomography, qualitative and quantitative histological analysis. Results: The BC-PBM and XS-PBM groups had a similar evolution in the tissue repair process, with a higher density of the volume of new formed bone in relation to the groups without PBM (p = 0.04086; p = 0.07093, respectively). Intense vascular proliferation and bone deposition around the biomaterial particles were observed in the animals of the groups in which biocomplex was applied (XS and XS-PBM). Conclusion: PBM therapy allowed an improvement in the formation of new bone, with a more organized deposition of collagen fibers in the defect area. Biocomplex favored the insertion and permanence of the particulate material in bone defects, creating a favorable microenvironment for accelerate repair process.(AU)

Experimental study on rabbit lamellar corneal transplantation with double-layer corneal stromal lens attactched by fibrin sealant / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the biocompatibility of double-layer corneal stromal lens attactched by fibrin sealant(FS)<i>in vivo</i>, and to explore the feasibility of using this material for corneal transplantation.<p>METHODS: Fifteen healthy and clean New Zealand white rabbits were selected for a self-control study. The right eye of the rabbit was used as the experimental eye and the left eye was used as the control eye. The experimental eyes used FS adhesived double-layer corneal stromal lens as the material for lamellar keratoplasty, and the control eyes did not undergo manual intervention. At 7,14, and 28d after surgery, a hand-held slit lamp was used to observe the cornea of the rabbits and then score the biocompatibility. The corneas of both eyes were taken for histopathological examination by HE staining to observe the corneal recovery at the same time.<p>RESULTS: Slit lamp observation results showed that by 28d after the operation, the corneal epithelium of the experimental eyes grew well, the degree of corneal transparency was basically restored, the degree of edema was reduced, the growth of neovascularization to the corneal edge was not aggravated, and no rejection reaction such as epithelial and endothelial rejection lines were seen; The control eyes had clear corneas and smooth corneal epithelium. The results of biocompatibility score showed that the degree of corneal implant edema gradually decreased, the transparency gradually recovered, the rejection reaction was less, and the biocompatibility of corneal implants was better in the experimental eyes after corneal transplantation. There were no differences in the degree of corneal transparency, edema and neovascularization growth between the experimental and control eyes at 28d after surgery(<i>P</i>>0.01). The results of histopathological examination showed that by 28d after corneal transplantation, there were 4-5 layers of corneal epithelial cells covering the surface of the implant in the experimental eyes, the corneal collagen was neatly and regularly arranged, no obvious inflammatory cell infiltration was seen in the implant, the boundary between the two lenses disappeared, the interlayer FS was completely absorbed by the organism, the implant was fused with the implant bed, and no obvious demarcation was seen.<p>CONCLUSION:Using FS pasted double-layer corneal stroma lens as a graft for lamellar keratoplasty has better recovery, less rejection and better biocompatibility, and can be used for lamellar keratoplasty.

Efficacy of homologous fibrin sealant in the surgery for pneumothorax

Background: Prolonged air leakage following pneumothorax surgery is a significant issue causing increased hospital stay and morbidity. This study aimed to investigate the cost and efficacy of homologous fibrin sealant in preventing the air leakages.Methods: Among the patients who had undergone bullectomy and subtotal parietal pleurectomy for recurrent primary spontaneous pneumothorax via transaxillary mini thoracotomy between 2010 and 2018, two groups each including 35 cases were conducted as to whether fibrin sealent had been applied. These two patient groups were compared in terms of age, gender, duration of air leakage and cost.Results: Mean age of whole group of patients including 59 males and 11 females was 21.5 years. Mean values of air leakage duration and cost of hospital stay was calculated as 1.94 days and 2777 TL for sealant applied group and 2.97 days and 1200 TL for sealent unapplied group, respectively. The patient groups did not indicate a statistically difference in terms of age and gender whereas duration of air leakage was shorter but cost was higher in the group for whom fibrin sealant had been administered (p<0.001). None of the patients developed mortality but recurrence was present in 4 (5.7%) patients.Conclusions: Although homologous fibrin sealant applied in pneumothorax surgery results in cost increase, it contributes to surgical outcomes by preventing possible additional complications in consideration of shortened duration of air leakage.

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

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)

Prospective Study on the Impact of the Use of Human Fibrin Sealant free of Clot-Stabilizing Agents in Total Knee Arthroplasty / Estudo prospectivo sobre o impacto do uso do selante de fibrina humano livre de agentes estabilizadores de coágulo na artroplastia total de joelho

Abstract Objective The present study aimed to evaluate the results of the intraoperative topical use of a human fibrin sealant free of clot-stabilizing agents in total knee arthroplasties (TKAs), looking for differences between groups regarding blood loss, transfusion requirement, length of hospital stay, pain perception, range of motion (ROM), and incidence of complications. Methods We have analyzed prospectively an intervention group with 32 patients (Sealant) and a control group with 31 patients (Control) with symptomatic knee osteoarthritis who underwent TKA. Results The results were similar between the groups regarding visible blood loss in the drain in 24 hours (Control, 276.5 mL ± 46.24 versus Sealant, 365.9 mL ± 45.73), total blood loss in 24 hours (Control, 930 mL ± 78 versus Sealant, 890 mL ± 67) and in 60 hours after surgery (Control, 1,250 mL ± 120 versus Sealant, 1,190 mL ± 96), blood transfusion requirement (which occurred only in 1 control patient), length of hospital days stay (Control, 5.61 ± 0.50 versus Sealant, 4.81 ± 0.36), postoperative pain, and ROM. Sealant use was not related to wound healing complications, to infection, or to deep venous thrombosis. Conclusion We have concluded that the hemostatic agent composed of human fibrin was not effective in reducing bleeding volume and blood transfusion requirement, nor it interfered with hospital length of stay, pain perception, and ROM. Its use was not related to any complications.

Resumo Objetivo O objetivo do presente estudo foi avaliar os resultados do uso tópico intraoperatório do selante de fibrina humano livre de agentes estabilizadores de coágulo em pacientes com osteoartrite (OA) submetidos a artroplastia total de joelho (ATJ), buscando diferenças entre os grupos em relação à perda sanguínea, à necessidade transfusional, ao tempo de internação hospitalar, à percepção de dor, à amplitude de movimento e à incidência de complicações. Métodos Foram analisados prospectivamente um grupo de intervenção (Selante) com 32 pacientes e um grupo controle (Controle) com 31 pacientes, com OA sintomática dos joelhos, submetidos a ATJ. Resultados Os resultados foram semelhantes entre os grupos, em relação à perda sanguínea visível no dreno em 24 horas (Controle 276,5 mL ± 46,24 versus Selante 365,9mL ± 45,73), à perda sanguínea total em24 horas (Controle 930 mL ± 78 versus Selante 890 mL ± 67) e em 60 horas de pós-operatório (Controle 1.250 mL ± 120 versus Selante 1.190 mL ± 96), à necessidade de hemotransfusão (ocorreu em apenas 1 controle), ao tempo de dias na permanência hospitalar (Controle 5,61 ± 0,50 [n = 31] versus Selante 4,81 ± 0,36), dor pós-operatória e amplitude de movimento. O uso do agente selante de fibrina não se relacionou à ocorrência de complicações da cicatrização de ferida, de infecção ou de trombose venosa profunda. Conclusão Concluímos que o agente hemostático de fibrina humana não foi eficaz em reduzir o volume de sangramento e a necessidade de hemotransfusão ou em interferir no tempo de internação hospitalar, na percepção de dor e na amplitude de movimento. Seu uso não se relacionou a nenhuma complicação.

Fibrin biopolymer as scaffold candidate to treat bone defects in rats

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)

Unique heterologous fibrin biopolymer with hemostatic, adhesive, sealant, scaffold and drug delivery properties: a systematic review

Fibrin biopolymers, previously referred as "fibrin glue" or "fibrin sealants", are natural biomaterials with diverse applications on health. They have hemostatic, adhesive, sealant, scaffold and drug delivery properties and have become widely used in medical and dental procedures. Historically, these biomaterials are produced from human fibrinogen and human or animal thrombin, and the possibility of transmission of infectious diseases by human blood is not ruled out. In the 1990s, to overcome this problem, a new heterologous biomaterial composed of a thrombin-like enzyme purified from Crotalus durissus terrificus venom and a cryoprecipitate rich in fibrinogen extracted from buffaloes Bubalus bubalis blood has been proposed. Therefore, a systematic review of studies on exclusively heterologous fibrin sealants published between 1989 and 2018 was carried out using the following databases: PubMed, SciELO and Google Scholar. The keyword used was "heterologous fibrin sealant". The search resulted in 35 scientific papers in PubMed, four in SciELO and 674 in Google Scholar. After applying the inclusion/exclusion criteria and complete reading of the articles, 30 studies were selected, which formed the basis of this systematic review. It has been observed that the only completely heterologous sealant is the one produced by CEVAP/UNESP. This heterologous biopolymer is proven effective by several studies published in refereed scientific journals. In addition, clinical trials phase I/II for the treatment of chronic venous ulcers authorized by the Brazilian Health Regulatory Agency (ANVISA) were completed. Preliminary results have indicated a safe and promising effective product. Phase III clinical trials will be proposed and required to validate these preliminary findings.(AU)

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

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 that sensory function improved when transgenic hESCs were used. The regeneration of sensory fibers indeed led to increased reflexes, upon stimulation of the paw ipsilateral to the lesion, as seen by von-Frey evaluation, which was supported by immunohistochemistry. Conclusions Overall, the present data demonstrated that transgenic embryonic stem cells, engineered to overexpress FGF-2 in an inducible fashion, could be employed to support regeneration aiming at the recovery of both motor and sensory functions.(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...

Effect observation of human fibrin sealant in the surgery of pterygium / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the efficacy and characteristic of human fibrin sealant in the surgery of pterygium. <p>METHODS: A prospective randomized controlled study was conducted. A total of 148 eyes of 148 patients with pterygium were involved in the study from June 2016 to September 2017. All patients were divided into two groups receiving 10-0 vicryl sutures or human fibrin sealant respectively. Patients were seen on postoperative 1, 3d, 1wk, 1, 3, and 6mo after surgery. The duration of surgery, level of patient discomfort, pterygium recurrence, and complications were retrospectively analyzed between two groups. <p>RESULTS: The duration of surgery in observer group was 15.23±2.26min and 28.22±2.70min in control group, the difference was statistically significant(<i>t</i>=-31.75, <i>P</i><0.01). One week later, the level of patient discomfort at 1, 3 and 7d after surgery were 0.62±0.69, 0.34±0.50, 0.16±0.37 in observation group, and the level of patient discomfort were 1.15±0.92, 0.54±0.60, 0.18±0.38 in control group, and the difference were statistically significant in observer group and control group(<i>P</i><0.01); comparison between any two means in either group was significantly different(<i>P</i><0.01). There were significant difference between the two groups on postoperative 1, 3d after surgery(<i>t</i>=-3.94, -2.22; <i>P</i><0.05), and there was not significant difference between the two groups on postoperative 7d after surgery(<i>t</i>=-0.22, <i>P</i>>0.05). Two eyes(2.7%)were recurrent on postoperative 6mo after surgery in observation group and 4 of 74 eyes(5.4%)in control group, demonstrated no significant differences(<i>χ</i>²=24.2, <i>P</i>>0.05). Five of 74 eyes(6.8%)were with complications in observation group and 6 of 74 eyes(8.1%)in control group, demonstrated no significant differences(<i>χ</i>²=16.32, <i>P</i>>0.05). <p>CONCLUSION: The duration of surgery, patient discomfort level were reduced markedly, as less flap dislocation and postoperative reaction with human fibrin sealant compared with 10-0 vicryl sutures. A good result can be obtained by using the human fibrin sealant in the surgery of pterygium.

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

Abstract 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.

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

Abstract 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.

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)

Study on the Hemostatic Effect of Porcine Fibrin Sealant Patch on Bleeding Wound of Liver in Rats and Gluteus Maximus in Heparinized Rabbits / 中国药房

OBJECTIVE:To study the hemostatic effect of porcine fibrin sealant patch (DBT) on bleeding wound of liver in rats and gluteus maximus in heparinized rabbits. METHODS:48 rats and 24 rabbits were randomly divided into sham operation group,operation control group (gauze hemostasis),medical collagen sponge group and DBT group. Except for sham operation group,animals in other groups were reduced for rat model with liver bleeding or heparinized rabbit model with gluteus maximus bleeding. The hemostatic time was recorded,bleeding amount was calculated;DBT degradation and wound adhesion in liver after 3,13 weeks were observed;re-bleeding rate of heparinized rabbits in medical collagen sponge group and DBT group were investi-gated. RESULTS:Compared with sham operation group,the hemostatic time and bleeding amount of animals in operation control group were significantly increased(P<0.01). Compared with operation control group,the hemostatic time and bleeding amount of animals in DBT group and medical collagen sponge group were significantly reduced (P<0.01). After 3,13 weeks,different de-gree of adhesion appeared in the wound of rats in each group,while the adhesion scores had no statistical significances(P>0.05). After 13 weeks,liver margin of rats in administration groups was slightly blunt,but it basically had been restored to preoperative state,with good healing. DBT can be degraded and absorbed completely. The re-bleeding rate of rabbits in DBT group were33.3%,66.7% in medical collagen sponge group. CONCLU-SIONS:DBT has good hemostatic effect on fragile organs and the body with blood coagulation dysfunction,and can be de-graded and absorbed. Its effect is equivalent to medical colla-gen,while the adhesive strength is slightly better than the latter.

Study on the Hemostatic Effect of Porcine Fibrin Sealant Patch on Bleeding Wound of Liver in Rats and Gluteus Maximus in Heparinized Rabbits / 中国药房

OBJECTIVE:To study the hemostatic effect of porcine fibrin sealant patch (DBT) on bleeding wound of liver in rats and gluteus maximus in heparinized rabbits. METHODS:48 rats and 24 rabbits were randomly divided into sham operation group,operation control group (gauze hemostasis),medical collagen sponge group and DBT group. Except for sham operation group,animals in other groups were reduced for rat model with liver bleeding or heparinized rabbit model with gluteus maximus bleeding. The hemostatic time was recorded,bleeding amount was calculated;DBT degradation and wound adhesion in liver after 3,13 weeks were observed;re-bleeding rate of heparinized rabbits in medical collagen sponge group and DBT group were investi-gated. RESULTS:Compared with sham operation group,the hemostatic time and bleeding amount of animals in operation control group were significantly increased(P<0.01). Compared with operation control group,the hemostatic time and bleeding amount of animals in DBT group and medical collagen sponge group were significantly reduced (P<0.01). After 3,13 weeks,different de-gree of adhesion appeared in the wound of rats in each group,while the adhesion scores had no statistical significances(P>0.05). After 13 weeks,liver margin of rats in administration groups was slightly blunt,but it basically had been restored to preoperative state,with good healing. DBT can be degraded and absorbed completely. The re-bleeding rate of rabbits in DBT group were33.3%,66.7% in medical collagen sponge group. CONCLU-SIONS:DBT has good hemostatic effect on fragile organs and the body with blood coagulation dysfunction,and can be de-graded and absorbed. Its effect is equivalent to medical colla-gen,while the adhesive strength is slightly better than the latter.

Comparison of effect between tranexamic acid versus fibrin sealant after joint arthroplasty:a Meta-analysis / 重庆医学

Objective To compare the effectiveness and safety of tranexamic acid and fibrin sealant in joint arthroplasty . Methods The literatures on the application of tranexamic acid and fibrin sealant in joint arthroplasty were retrieved from PubMed , Embase ,Cochrane Library ,CNKI and other internet databases .Two reviewers independently screened the literatures according to the inclusion and exclusion standard .The RevMan 5 .2 software was adopted to conduct the statistical analysis on the extracted da‐ta .Results Four randomized controlled trials(RCTs) and 2 retrospective experiments were included ,involving 449 patients .The meta analysis results showed that tranexamic acid and fibrin sealant had no statistically significant difference in total blood loss[MD= -192 .24 ,95% CI(-496 .16 ,111 .69) ,P=0 .22] and hemoglobin loss amount[MD= -0 .49 ,95% CI(-1 .19 ,0 .20) ,P=0 .16] , had statistically significant difference in the blood transfusion rate[OR=0 .30 ,95% CI(0 .18 ,0 .52) ,P<0 .01] ,and had no statisti‐cally significant difference in the postoperative complications[OR=1 .20 ,95% CI(0 .36 ,3 .99) ,P=0 .76] .Conclusion Tranexamic acid is more effective than fibrin sealant of controlling postoperative transfusion rate in joint arthroplasty .

Use of fibrin glue in preventing pseudorecurrence after laparoscopic total extraperitoneal repair of large indirect inguinal hernia

PURPOSE: Seroma is among the most common complications of laparoscopic total extraperitoneal (TEP) for especially large indirect inguinal hernia, and may be regarded as a recurrence by some patients. A potential area localized behind the mesh and extending from the inguinal cord into the scrotum may be one of the major etiological factors of this complication. Our aim is to describe a novel technique in preventing pseudorecurrence by using fibrin sealant to close that potential dead space. METHODS: Forty male patients who underwent laparoscopic TEP for indirect inguinal hernia with at least 100-mL volume were included in this prospective clinical study. While fibrin sealant was used to close the potential dead space in the study group, nothing was used in the control group. The volume of postoperative fluid collection on ultrasound was compared between the groups. RESULTS: Patient characteristics and the volumes of hernia sac were similar between the 2 groups. The mean volume of postoperative fluid collection was found as 120.2 mL in the control group and 53.7 mL in the study group, indicating a statistical significance (P < 0.001). CONCLUSION: Minimizing the potential dead space with a fibrin sealant can reduce the amount of postoperative fluid collection, namely the incidence of pseudorecurrence.