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Juan et al. (1995) [2525. Juan FC, Thomazini IA, Gianini MJM, Viterbo F, Toscano E, Moraes RA, et al. Reparation of peripheral nerves with fibrin glue prepared from snake venom. Preliminary results. Sao Paulo Med J. 1995 Sep-Oct;113(5):1000-2.] |
To evaluate the efficacy of fibrin sealant in sciatic nerve repair in rats. |
Application of sealant fractions in sciatic nerves of rats. Initially fibrinogen was obtained from human plasma. |
The results obtained were similar to those of conventional glue. |
The fibrin sealant enabled the adhesion and nervous regeneration. |
Lack of data (e.g. number of animals used). |
Sartori Filho et al. (1998) [4040. Sartori Filho R, Prestes NC, Thomazini IA, Mendes-Giannini MJ, Toscano E, Canavessi AMO, et al. Use of fibrin glue derived from snake venom in testicular biopsy of rams. J Venom Anim Toxins. 1998;4(1):23-35. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-79301998000100003.
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] |
Observation of the results obtained with the use of fibrin sealant in sheep testicular biopsy in relation to: hemorrhage control, adhesion prevention, fibrin material effect as a sealing technique. Evaluation of the efficacy of the new fibrin sealant in anastomosis of colon of rats. |
Thirty sheep divided into three groups (n = 10). G1: Fibrin sealant group; G2: suture group; G3: control group (without surgery or biopsy). |
Twenty days after biopsy - G1: adhesion in three testicles (15%) and two testicles in G2 (10%); G3: without abnormality. On hundred days after the biopsy: orchiectomy. G1 and G2: four testicles (20%) in each group with adherence between the tunics. Subcutaneous adhesions: one (5%) in G1 and three (15%) in G2. |
The fibrin sealant proved to be easy to apply, requiring short postoperative monitoring, exhibited fast healing properties and tended to reduce the formation of subcutaneous adherence. |
One animal in G2 presented scrotal subcutaneous hematoma and developed testicular degeneration and diffuse subcutaneous adhesions. |
Leite et al. (2000) [4141. Leite CVS, Naresse LE, Arantes HL, et al. An evaluation by rat colon anastomosis of the efficacy of fibrin glue derived from snake venom. J Venom Anim Toxins. 2000;6(2):180-93. http://www.scielo.br/scielo.php?pid=S0104-79302000000200004&script=sci_abstract.
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] |
To assess the efficacy of the new fibrin sealant on colon anastomosis of rats. |
Eighty rats divided into two groups of 40 animals: G1 (control group): anastomosis with extramucous interrupted suture; and G2: repair suture + fibrin sealant. |
Twenty-one days after surgery: G1 exhibited a perfect coaptation of intestinal segments. G2: macroscopic alterations were more intense. There was no difference in the values of force of rupture between the two groups. |
Fibrin sealant derived from snake venom proved efficient on allowing anastomosis of the colon of rats. |
The use of fibrin sealant in the anastomosis requires further investigation in larger animals to understand the sealant behavior on larger organs. |
Chalhoub et al. (2000) [4242. Chalhoub M, Prestes NC, Lopes MD, Rocha NS, Thomazini-Santos IA, Mendes-Giannini MJ. The use of snake venom derived fibrin glue in hysterorrhaphy of ovine caesarean surgery. J Venom Anim Toxins. 2000;6(2):220-37. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-79302000000200007.
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] |
To evaluate fibrin sealant derived from snake venom as an alternative to conventional uterine suture after ovine cesarean surgery. |
Twenty-eight pregnant sheep divided into four groups of seven animals: six animals were submitted to surgery with fibrin sealant and one animal underwent the conventional hysterorrhaphy. |
The healing of the wound showed good macroscopic appearance 30 days after surgery with the application of the sealant. However, microscopically, the uterus did not return to pre-pregnancy conditions 30 days after the experimental cesarean section. |
Animals submitted to conventional cesarean section showed a better process of wound healing. |
Further studies on the use of this new sealant in hysterorrhaphy after cesarean section in several animal species are required. |
Rahal et al. (2004) [4343. Rahal SC, Amaral MSP, Pai VD, Barraviera SRCS, Caporal EH., Crocci AJ. Effect of fibrin glue derived from snake venom on the viability of autogenous split-thickness skin graft. J Venom Anim Toxins incl Trop Dis. 2004;10(2):161-72. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992004000200006.
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] |
To assess the effect of snake venom derived from fibrin glue on the viability of split-thickness skin graft in dogs. |
One group of nine dogs: a skin graft was collected from the left lateral thoracic area and fixed using several single sutures. On the right side the fibrin sealant + suture was applied. |
Compared to the sutured graft, the graft fixed with the sealant showed more cells and a greater number of collagen fibers in the papillary layer of the dermis. |
Fibrin sealant increased the survival of the autogenous skin graft, but has moderate adhesive power. |
The fibrin sealant did not have sufficient adhesive strength to fix the graft on its own, especially at the site where the wound was induced. |
Moraes et al. (2004) [4444. Moraes JRE, Correia PHA, Camplesi AC, Moraes FR. Experimental use of fibrin glue derived from snake venom in non-pregnant canine uterus. J Venom Anim Toxins incl Trop Dis. 2004;10(2):133-43. http://www.scielo.br/scielo.php?pid=S1678-91992004000200003&script=sci_abstract.
http://www.scielo.br/scielo.php?pid=S167...
] |
Evaluation of the healing process in canine uterus hysterorrhaphy using fibrin sealant derived from snake venom. |
Twelve adult female dogs divided into three groups (n = 4). G1: double layer suture; G2: only the fibrin sealant; G3: suture + fibrin sealant as reinforcement. |
All groups presented total regeneration of the epithelium, regardless of the treatment. The thickness of healing tissue was higher in G2 than G1 and G3. |
The experimental model was appropriate to achieve the proposed objectives. Fibrin sealant produced less inflammation in the exudative phase and eased the evolution of proliferation and maturation phases. |
The amount of fibrin sealant used in surgery was not reported. |
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Ferraro et al. (2005) [4545. Ferraro G, Moraes JRE, Pereira G, Moraes FR, Bueno de Camargo MH. Clinical and morphological evaluation of snake venom derived fibrin glue on the tendon healing in dogs. J Venom Anim Toxins incl Trop Dis. 2005;11(4):433-46.] |
Assessment of the effect of the fibrin sealant derived from snake venom on the tendon force in the healing process in dogs. |
Left and right thoracic limbs of 15 dogs were used. Members were divided into three groups (n = 10). Each group corresponded to the day of evaluation after the application of the sealant: 7th, 15th and 30th postoperative day. |
There was 62.5% of stump retraction in tendons, and 20.8% moderate to excessive adherence affecting sliding. The group of 30 days showed the best coaptation. |
The sealant allowed a progressive increase of the resistance for the maximum tensile force and permanent deformations. Thus, fibrin sealant derived from snake venom can be used to promote healing in the flexor tendon of dogs. |
None informed. |
Sampaio et al. (2007) [4646. Sampaio RL , Ranzani JJT, Brandão CVS, Thomazini- Santos I A, Barraviera B, Barraviera SRCS. Use of fibrin glue derived from snake venom in the repair of deep corneal ulcers - experimental study in dogs (Canis familiaris, Linnaeus, 1758). J Venom Anim Toxins incl Trop Dis. 2007;13(4):857-73. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992007000400014.
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] |
To elucidate mechanisms related to the repair of corneal ulcers treated with the fibrin sealant derived from snake venom. |
Twenty-one dogs were submitted to lamellar keratectomy divided into seven groups (n = 31). G1 to G6: keratectomized areas with fibrin sealant (collection performed on days 1, 3, 7, 15, 30, 60 after surgery); G7: without sealant. |
The corneas collected at day 60 presented discrete changes compared to day 30 in postoperative group. Inflammatory cells were rare, and fibrosis was moderate. |
The fibrin sealant helped in repair of the site, contributing to healing mechanisms and preventing the formation of edema in the wound. |
Early elimination of fibrin sealant (in three animals) due to the presence of substances in the tear that caused lysis of fibrin. |
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Barbosa et al. (2008) [3030. Barbosa MDS, Stipp AC, Passanezi E, Greghi SLA. Fibrin adhesive derived from snake venom in periodontal surgery. Histological analysis. J Appl Oral Sci. 2008 Sep-Oct;16(5):310-5.] |
To compare and to evaluate histological effects in periodontal surgery, especially in gingival grafts, using the new heterologous fibrin sealant compared with traditional sutures, in humans. |
Fifteen patients - with surgical procedures in two contralateral areas - were divided into control (only traditional suture technique) and experimental group (fibrin sealant). |
At day 14, the experimental group had a more mature epithelial tissue than the control group, but both presented epithelial tissue. At day 45, there were no significant difference between the groups, with an increase in collagen fibers. Epithelium was already mature. |
Despite the limitations of the study, the fibrin sealant tested may represent an alternative to sutures in periodontal surgery. |
Limited number of patients, sample and statistical analyzes. The histological results were not sufficient to achieve a conclusion. |
Gatti et al. (2011) [3838. Gatti MAN, Vieira LM, Barraviera B, Barraviera SRCS. Treatment of venous ulcers with fibrin sealant derived from snake venom. J Venom Anim Toxins incl Trop Dis. 2011;17(2):226-9. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992011000200015.
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] |
To assess the effect of the new fibrin sealant in the repair process of venous ulcers in 24 adult patients. |
Two groups: G1 (control, n = 11) treated with essential fatty acids and Unna’s boot and, G2 (n = 13) treated with essential fatty acids, fibrin sealant and Unna’s boot. Fibrin sealant was applied in the first and fourth week of treatment. |
Fibrin sealant was effective in the healing of chronic venous ulcers, presenting ease of application, preparation of the wound bed, reduction of pain and greater number of discharges after eight weeks. |
The application of fibrin sealant can improve wound healing processes and increase healing levels. |
Preliminary phase I study and major studies with a larger number of patients should be conducted to evaluate the best way to apply the new sealant. |
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Iatecola et al. (2013) [4747. Iatecola A, Barraviera B, Ferreira RS Jr, dos Santos GR, Neves JI, da Cunha MR. Use of a new fibrin sealant and laser irradiation in the repair of skull defects in rats. Braz Dent J. 2013 Sep-Oct;24(5):456-61.] |
Evaluation of the osteogenic capacity of the new fibrin sealant (FS) combined with bone graft and laser irradiation. |
Thirty rats were divided into six groups (n = 5). G1 (control): autogenous graft; G2: graft + laser 5 J/cm²; G3: graft + laser 7 J/cm²; G4: graft + FS; G5: graft + FS + laser 5 J/cm²; and G6: graft + FS + laser 7 J/cm². |
The analyses showed absence of inflammatory infiltrate in the bone defect. Bone neoformation occurred in all groups, more intensely in G6. |
The osteogenic effect of the 7 J/cm2 laser has proved to be very efficient, and its combination with fibrin sealant derived from snake venom can accelerate the regeneration process. |
The combination of laser and sealant becomes a therapeutic resource to be further investigated in bone regeneration research. |
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Barbizan et al. (2013) [4848. Barbizan R, Castro MV, Rodrigues AC, Barraviera B, Ferreira RS, Oliveira ALR. Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom. PLoS One. 2013 May 7;8(5):e63260.] |
To assess the effects of fibrin sealant on functional recovery, neuronal survival, synaptic plasticity and glial reaction of the motor neuron after ventral root reimplantation. |
Thirty rats divided into two groups (n = 15). G1: unilateral avulsion of the lumbar ventral roots L4-L6; and G2: avulsion followed by reimplantation of the injured root, using the fibrin sealant. |
G2 showed no significant changes in the microglial response compared to G1. However, the astroglial reaction was significantly reduced in this group. |
The root reimplantation performed with fibrin sealant increased neuronal survival and improved recovery of motor function, improving the regeneration process. |
It is not clear whether it is the reimplantation site or the sealant that may be responsible for neuronal survival. |
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Benitez et al. (2014) [4949. Benitez SU, Barbizan R, Spejo A, Ferreira Jr RS. Synaptic plasticity and sensory-motor improvement following fibrin sealant dorsal root reimplantation and mononuclear cell therapy. Front Neuroanat. 2014 Sep 8:1-16.] |
Evaluation of motor and sensory functions after dorsal root reimplantation with fibrin sealant associated with mononuclear cells of the bone marrow. Comparison of the local injection of mononuclear cells in the spinal cord with the possibility of homogenizing these cells with the fibrin sealant after avulsion of the ventral root and reimplantation. |
Sixty-five rats divided into three groups. G1: rhizotomy (n = 22); G2: rhizotomy + fibrin sealant (n = 23); G3: rhizotomy + sealant + mononuclear cells of the bone marrow (n = 20). Animals submitted to unilateral avulsion of L4-L6 ventral roots divided into four groups. G1: avulsion only; G2: reimplantation with fibrin sealant; G3: reimplantation with fibrin sealant associated with mononuclear cells; and G4: reimplantation with fibrin sealant and injected mononuclear cells. |
The reimplantation decreased the glial reaction and improved the synaptic plasticity of the afferent entries. Both replanted groups had twice as much motor control compared to the untreated group. After four weeks: G4 obtained G2-like results; in G3, the neuronal rescue was greater. After eight weeks: G4 with increased degeneration, reaching the level of G1 (injection caused late inflammatory response, occurring delay in cell death); in G3 there was functional recovery, resulting in the preservation of the neurons. |
Dorsal root reimplantation with fibrin sealant associated with mononuclear cells of the bone marrow significantly improved motor and sensory function. |
The lack of sensory information caused significant motor changes in G1. |
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Barbizan et al. (2014) [3265. Barbizan R, Vidigal M., Ferreira Junior RS, Barraviera B, Oliveira ALR. Long-term spinal ventral root reimplantation, but not bone marrow mononuclear cell treatment, positively influences ultrastructural synapse recovery and motor axonal regrowth. Int J Mol Sci. 2014 Nov;15(11):19535-51.] |
To compare the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion and reimplantation. |
Animals submitted to unilateral avulsion of L4-L6 ventral roots and divided into four groups. G1: avulsion only; G2: reimplantation with fibrin sealant; G3: reimplantation with fibrin sealant associated with mononuclear cells; and G4: reimplantation with fibrin sealant and injection of mononuclear cells. |
After four weeks: G4 obtained results similar to G2; in G3, the neuronal rescue was greater. After eight weeks: G4 had increased degeneration, reaching the level of G1 (injection caused late inflammatory response, occurring delay in cell death); G3 had functional recovery, resulting in the preservation of the neurons. |
The use of the fibrin sealant homogenized with mononuclear cells technique provided the best and most long-lasting results for neuroprotection compared with intra-spinal injection. |
The relatively poor clinical outcome requires more attention. |
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Cunha et al. (2015) [3434. Cunha MR, Menezes FA, Santos GR, Pinto CAL, Barraviera B, Martins VCAM, et al. Hydroxyapatite and a new fibrin sealant derived from snake venom as scaffold to treatment of cranial defects in rats. Mat Res. 2015 Jan-Feb;18(1):196-203.] |
Evaluation of the osteogenic potential of a combination of hydroxyapatite (Ha) and the new fibrin sealant (FS) in the improvement of bone regeneration. |
Forty rats were divided into four groups (n = 10). Control group: parietal bone defect without treatment; Ha group: bone defect + 8 mg Ha; FS group: bone defect + 8 mL fibrin sealant; and Ha + FS group: bone defect + 8 mg Ha + 8 mL fibrin sealant. |
Six weeks after surgery: there was bone growth from the original bone, surrounding several particles of hydroxyapatite, without interposition of the connective tissue. Osteogenesis at the bone defect site was higher in the Ha + FS group. |
Hydroxyapatite in combination with the new fibrin sealant accelerated bone repair. |
Six weeks were not sufficient for complete repair of the bone defect, requiring more time for skull regeneration. |
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Buchaim et al. (2015) [3333. Buchaim RL, Andreo JC, Barraviera B, Ferreira Jr RS, Buchaim DV, Rosa Jr GM, et al. Effect of low-level laser therapy (LLLT) on peripheral nerve regeneration using fibrin glue derived from snake venom. Injury. 2015 Apr;46(4):655-60.] |
To assess if the fibrin sealant allows the collateral regeneration of axons from vagus nerve into the interior of a sural nerve graft and if the laser therapy aids in the regeneration. |
Thirty-two rats divided into three groups. CG: intact sural nerve (n = 8); EG: one end of the sural nerve graft coapted to the vagus nerve with the sealant (n = 12), and EGL: procedure equal to EG, with addition of low-level laser therapy LLLT (n = 12). |
Axonal regeneration observed in EG and EGL. CG: all measured dimensions were larger and with a significant difference in relation to EG and EGL, except for the area and thickness of the myelin sheath, with a significant difference in relation to the EG. |
Fibrin sealant was feasible for axonal regeneration, and is an efficient method for recovering injured peripheral nerves. The use of low-level laser therapy has increased nerve regeneration. |
In relation to low-level laser therapy, future studies are required to lead to a better understanding of its efficacy. |
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Machado et al. (2015) [3535. Machado EG, Issa JPM, Figueiredo FA, Santos GR, Galdeano EA, Alves MC, et al. A new heterologous fibrin sealant as scaffold to recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins for the repair of tibial bone defects. Acta Histochem. 2015 Apr;117(3):288-96.] |
To analyze the combination between fibrin sealant (FS) and rhBMP-2 or P1 in the repair of bone defects in rats. |
Sixty rats were divided into six groups (n = 10). Control: unfilled bone defect, G2: defect filled with 5 μg of rhBMP-2, G3: 5 μg of P-1, G4: 8 μg of FS, G5: 8 μg of FS and 5 μg of rhBMP-2, G6: 8 μg of FS and 5 μg of P-1. |
There was a statistically significant difference (p < 0.05) in all groups after six weeks in relation to the volume of newly formed bones in the surgical area. |
The new fibrin sealant proved to be biocompatible and the combination with rhBMP-2 showed greater osteogenic and osteoconductive capacity for bone healing. |
The role of fibrin sealants in healing and osteogenesis remains not fully understood. |
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Cartarozzi et al. (2015) [5050. Cartarozzi LP, Spejo AB, Ferreira RS Jr, Barraviera B, Duek E, Carvalho JL, et al. Mesenchymal stem cells engrafted in a fibrin scaffold stimulate Schwann cell reactivity and axonal regeneration following sciatic nerve tubulization. Brain Res Bull. 2015 Mar;112:14-24.] |
To investigate the effectiveness of mesenchymal stem cells associated with fibrin sealant in the peripheral regenerative process after sciatic nerve tubulization. |
Fifteen Lewis rats divided into three groups (n = 5). G1: unilateral sciatic nerve transection followed by implantation of polycaprolactone tubular prosthesis; G2: tube filled with fibrin sealant, and G3: tube filled with fibrin sealant and mesenchymal stem cells. |
Sixty days after tubulization, the group with mesenchymal stem cells had a higher myelinated axon counting, more compact fibers and a tendency to increase the thickness of the myelin sheath. Cell treated animals also had better motor function. |
The study confirms the efficiency of mesenchymal stem cell treatments after nerve tubulization. In addition, the use of fibrin sealant increases cell reactivity, leading to better compaction of myelinated axons and improving motor recovery. |
Although sensory and motor recovery could be detected by stimulating the toes, recovery through gait recovery could not be recorded. |
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de Barros et al. (2016) [5151. de Barros CN, Miluzzi Yamada AL, Junior RSF, Barraviera B, Hussni CA, de Souza JB, et al. A new heterologous fibrin sealant as a scaffold to cartilage repair-Experimental study and preliminary results. Exp Biol Med. 2016 Jul;241(13):1410-5.] |
To analyze the safety, durability and stability of heterologous fibrin sealant in ovine cartilage repair. |
For the implantation of the sealant arthrotomy, chondral defects were induced in eight sheep and divided into two groups (n = 4). G1: euthanasia after seven days, and G2: euthanasia after 15 days. |
Seven days after implantation (G1), the sealant was present at the lesion site and stably attached to healthy cartilage. Fifteen days after the procedure (G2), only the lesion site without the fibrin gel was observed. |
The applicability of the fibrin sealant was excellent and did not trigger undesirable effects, such as inflammation, allowing a normal repair process in this study. |
Further studies are needed, including the use of cell cultures and in vivo comparison with other types of biological sealants. |
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de Oliveira Gonçalves et al. (2016) [3636. de Oliveira Gonçalves JB, Buchaim DV, de Souza Bueno CR, Pomini KT, Barraviera B, Júnior RSF, et al. Effects of low-level laser therapy on autogenous bone graft stabilized with a new heterologous fibrin sealant. J Photochem Photobiol B. 2016 Sep;162:663-8.] |
Assessment of the effects of low-level laser therapy (LLLT) in stabilized bone graft integration process with a new heterologous fibrin sealant. |
Forty rats divided into two groups (n = 20). AFG: osteotomy in the right parietal bone. An extracted fragment was adhered to the left side with the sealant. AFGL: same process, with addition of LLLT. |
The AFGL group showed a more evident bone neoformation when compared to the AFG group. |
Low-level laser therapy stimulated bone regeneration and accelerated the integration process of autogenous bone grafts. |
Fibrin sealant has not yet demonstrated fixing capacity like screws. |
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Buchaim et al. (2016) [5252. Buchaim DV, Rodrigues A de C, Buchaim RL. The new heterologous fibrin sealant in combination with low-level laser therapy (LLLT) in the repair of the buccal branch of the facial nerve. Lasers Med Sci. 2016;31(5):965-72.] |
To evaluate the effects of low-level laser therapy (LLLT) on the repair of the buccal branch of the facial nerve with two techniques: end-term epineural suture and coaptation with heterologous fibrin sealant. |
Forty-two rats divided into five groups. CG: collection of the buccal branch of the facial nerve (n = 10); EGS: with suture and EGF: with fibrin (n = 16). Suture made on the right side and the fibrin sealant on the left side. EGSL: with suture and laser and EGFL: with fibrin and laser (n = 16). |
Axonal growth was observed in the distal stump of the facial nerve in all groups. Within ten weeks after surgery, EGSL presented the closest results to CG, in all measured variables, except in the axon area. |
Both surgical techniques analyzed were effective in the treatment of peripheral nerve lesions, in which the use of fibrin sealant allowed the manipulation of nerve stumps without trauma. The LLLT presented satisfactory results in facial nerve regeneration. |
Despite the satisfactory results, additional studies are required to confirm the effects of laser therapy on peripheral nerve repair. |
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Biscola et al. (2016) [5353. Biscola NP, Politti Cartarozzi L, Ferreira Junior RS, Barraviera B, Leite Rodrigues de Oliveira A. Long-standing motor and sensory recovery following acute fibrin sealant based neonatal sciatic nerve repair. Neural Plast. 2016;2016:9028126.] |
To analyze the viability and efficiency of the end-to-end coaptation of the neonatal sciatic nerve, performed with the application of fibrin sealant derived from snake venom. |
Two-day old rats were divided into three groups. AX: sciatic nerve axotomy (SNA) without treatment (n = 30); AX + FS: SNA followed by coaptation with fibrin sealant (n = 30); AX + CFS: SNA followed by coaptation with commercial fibrin sealant (n = 30). |
Four weeks post-injury: microglial reaction decreased in the AX + FS and AX + CFS groups. In relation to axonal regeneration, the coaptation allowed the recovery of a greater number of myelinated fibers, with improved morphometric parameters. |
Both sealants promote neuroprotection and regeneration of motor and sensory axons. The CEVAP fibrin sealant was easy to handle at the time of surgery. |
Because of the small size of rats, combined with the delicate structure of peripheral nerves in the perinatal state, post-transection repair is difficult to perform. |
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Vidigal de Castro et al. (2016) [5454. Vidigal de Castro M, Barbizan R, Ferreira RS Jr, Barraviera B, de Oliveira ALR. Direct spinal ventral root repair following avulsion: effectiveness of a new heterologous fibrin sealant on motoneuron survival and regeneration. Neural Plast. 2016;2016:2932784.] |
To compare two fibrin sealants, one derived from human blood and another derived from animal blood and snake venom, in the treatment of axonal lesions, such as ventral root avulsion (VRA). |
Animals submitted to unilateral avulsion of the ventral root and reimplantation in the lumbar intumescence (L4, L5 and L6 right side, n = 5 per group). G1: VRA; G2: avulsion and reimplantation with fibrin sealant derived from snake venom (6 mL); and G3: avulsion and reimplantation with commercial fibrin sealant. |
Twelve weeks after repair: an improved number of fibers indicating regeneration, regardless of the fibrin sealant used, was observed. Myelin thickness reached values close to normal in the reimplanted groups. |
Both fibrin sealants are equally efficient. However, fibrin sealant derived from snake venom is a safer alternative because it is a biological and biodegradable product and does not contain human blood derivatives. |
The amount of commercial fibrin sealant used in surgery was not reported. |
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Floriano et al. (2016) [5555. Floriano JF, Neto FC, da Mota LSLS, Furtado EL, Ferreira Jr, RS, Barraviera B, et al. Comparative study of bone tissue accelerated regeneration by latex membranes from Hevea brasiliensis and Hancornia speciosa. Biomed Phys Eng Express. 2016 Jul 27;2(4):045007.] |
Evaluation of the osteogenic potential of the rubber latex membranes of the clones RRIM 600 and IAN 873 of Hevea brasiliensis and the Hancornia speciosa latex membranes trough the critical calvarial defect (CSD) model with use of fibrin sealant. |
Sixty rabbits divided into two groups, depending on the period of implantation (60 or 90 days), and subdivided into five treatment groups (n = 6). Three groups received natural rubber membrane implants; one was positive control group and one negative control group during each experimental period. |
In the 60-day period, a large amount of new immature bone tissue was present in the three groups that received implants. In the positive control, connective tissue was undergoing abundant ossification, indicating the effective formation of new bone and good quality of the newly formed bone. |
The fibrin sealant acted satisfactorily, being highly recommended as a substitute for cyanoacrylate in this type of application. |
Some membranes were associated with inflammatory reactions in adjacent tissue or were rapidly degraded by the enzymatic activity of macrophages and neutrophils. |
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Rosso et al. (2017) [5656. Rosso MPO, Rosa Júnior GM, Buchaim DV, German IJS, Pomini KT, de Souza RG, et al. Stimulation of morphofunctional repair of the facial nerve with photobiomodulation, using the end-to-side technique or a new heterologous fibrin sealant. J Photochem Photobiol B. 2017 Oct;175:20-8.] |
To evaluate the influence of photobiomodulation therapy (PBMT) on repaired facial nerve lesions through end-to-side suture or coaptation with the new heterologous fibrin sealant. |
Thirty-two rats divided into five groups. CG: collection of the buccal branch of the facial nerve (n = 8); ESG and EFG: right side suture and left side sealant (n = 12); ESLG and EFLG: same procedure as before, associated to PBMT with 6.2 J/cm². |
A significant difference was observed in the fiber area between EFG and EFLG. In the axon area, fiber diameter, area and thickness of myelin sheath presented no significant differences. The recovery of the vibrissae movement was better in ESLG and EFLG, with results close to CG. |
The use of low-level laser photobiomodulation therapy (with suture or fibrin sealant) showed better morphofunctional results. |
Future studies could include comparative analyzes between PBMT with new photodynamic therapies, verification of neurotrophic factors and standardization of protocols for laser application. |
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Buchaim et al. (2017) [5757. Buchaim DV, Andreo JC, Ferreira Junior RS, Barraviera B, Rodrigues AC, Macedo MC, et al. Efficacy of laser photobiomodulation on morphological and functional repair of the facial nerve. Photomed Laser Surg. 2017 Aug;35(8):442-9.] |
To assess the efficacy of low-level laser therapy (LLLT) in qualitative, quantitative and functional aspects in the process of facial nerve regeneration after section of buccal branch and suture with fibrin sealant. |
Forty-two rats divided into: control group (CG; n = 10): facial nerve collection without lesion; suture experimental group (SEG) and fibrin experimental group (FEG): n = 16, suture performed on the right side, and fibrin sealant on the left side; experimental laser suture group (LSEG) and experimental fibrin laser group (LFEG): n = 16, same procedures as SEG and FEG with laser addition at 6.2 J/cm². |
There was a significant increase in the number and density of regenerated axons with laser therapy. In the functional analysis, LSEG and LFEG presented better results in comparison to SEG and FEG. |
LLLT increased axonal regeneration and accelerated functional recovery of vibrissae. In both repair techniques (suture and heterologous fibrin sealant), it allowed the growth of axons. |
Electrophysiological tests may aid in functional evaluation, which may be considered a limitation for this study. |
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Araújo et al. (2017) [5858. Araújo MR, Kyrylenko S, Spejo AB, Castro MV, Ferreira Junior RS, Barraviera B, et al. Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion. Exp Neurol. 2017 Aug;294:45-57.] |
To investigate the neuroprotection provided by human embryonic stem cells modified to overexpress a human fibroblast growth factor (FGF-2), applied with a fibrin scaffold. |
Fifty Lewis rats divided into five groups (n = 10). G1: ventral root avulsion and application of fibrin sealant; G2: fibrin sealant, doxycycline and embryonic stem cells; G3: fibrin sealant and doxycycline; G4: fibrin sealant and embryonic stem cells; G5: fibrin sealant and FGF-2 growth factor |
The group that received the administration of human embryonic stem cells induced to overexpress the FGF-2 factor by means of doxycycline showed the survival of a significant number of motoneurons when compared to other groups. Embryonic stem cells had a neuroprotective effect, which provided viability to the neurons during the acute post-injury phase. |
Transgenic human embryonic stem cells overexpressing FGF-2 in an inducing medium promote neuroprotective effect in the spinal cord after avulsion of the ventral root. |
The use of human embryonic stem cells can cause the formation of teratomas. |
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Orsi et al. (2017) [5959. Orsi PR, Landim-Alvarenga FC, Justulin LA, Kaneno R, de Assis Golilm M, dos Santos DC, et al. A unique heterologous fibrin sealant (HFS) as a candidate biological scaffold for mesenchymal stem cells in osteoporotic rats. Stem Cell Res Ther. 2017 Sep 29;8(1):1-14.] |
To investigate the citotoxicity and scaffold potential of the association of heterologous fibrin sealant (HFS) with mesenchymal stem cells (MSCs) in the treatment of bone defects in osteoporotic rats. |
Twenty rats divided into two groups: non-ovariectomized (NOVX) and ovariectomized (OVX). Four animals from each group were treated with HFS; HFS + MSCs; HFS + MSCs D; four animals were control with lesions; and four control animals without lesions, both without treatment. |
Fourteen days after surgery, HFS + MSCs and HFS + MSCs D presented higher bone cell formation at the site compared to the control group (without treatment). Collagen formation was evidenced through bone neoformation in all treated and control groups. |
Fibrin sealant was non-toxic to MSCs and showed ability to promote the recovery of bone lesions. In addition, it allowed differentiation of MSCs in MSCs D in the group treated with HFS + MSCs. |
It was not possible to observe the total bone repair, since a period of six weeks was not sufficient for the complete recovery of the critical defect in the femur of rats. |
Mozafari et al. (2018) [6060. Mozafari R, Kyrylenko S, Castro MV, Ferreira RS, Barraviera B, Oliveira ALR. Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair. J Venom Anim Toxins incl Trop Dis. 2018 Apr 12;24:11. doi:10.1186/s40409-018-0147-x.
https://doi.org/10.1186/s40409-018-0147-...
] |
To determine the conditions that improve functional recovery after sciatic nerve neurorrhaphy using human embryonic stem cells (hESC) and heterologous fibrin sealant. |
A 5-mm segment of the sciatic nerve of mice was removed and rotated 180 degrees to simulate an injury, and the stumps were sutured. Then, the heterologous fibrin sealant and/or hESC was applied at the lesion site. |
Sensory function improved when hESCs was used. |
The new heterologous fibrin sealant can facilitate nerve repair. |
For enhanced functional recovery and better motor neuron reinnervation, fibrin sealant and cell therapy should be used in combination with neurotrophic factors. |
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Spejo et al. (2018) [6161. Spejo AB, Chiarotto GB, Ferreira ADF, Gomes DA, Ferreira RS Jr, Barraviera B, et al. Neuroprotection and immunomodulation following intraspinal axotomy of motoneurons by treatment with adult mesenchymal stem cells. J Neuroinflammation. 2018 Aug 14;15(1):230.] |
Evaluation of the use of fibrin sealant as a scaffold to fill the gap formed during induced nerve injury and to retain the stem cells applied at the lesion site. |
Group AI (intramedullary axotomy) Group AI + DMEM (intramedullary axotomy + Dulbecco’s modified Eagle’s medium), Group AI + SF (intramedullary axotomy + fibrin sealant), Group AI + CT (intramedullary axotomy + stem cells), Group AI + SF + CT (intramedullary axotomy + fibrin sealant + stem cells). |
The groups AI and AI + DMEM, suffered a huge degeneration of the injured motor neurons. The groups treated with fibrin sealant, stem cells and fibrin sealant + stem cells, obtained high levels of motor neurons surviving the induced lesion. |
The study demonstrates that mesenchymal stem cell therapy has a neuroprotective activity and, when associated with fibrin sealant, provides a better scaffold to retain cells at the lesion site. |
Further studies, including clinical cases, are needed to understand and enhance the recovery of injured complexes. |
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