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PubMed2005

Neurite extension and in vitro myelination within three-dimensional modified fibrin matrices.

The deposition of fibrin clots in vivo occurs after injury in the peripheral nervous system and their removal correlates with nerve regeneration. Fibrin clots provide a provisional matrix for invading cells, induce wound healing, and become proteolytically removed by regenerating tissue. Here, neurite extension and in vitro myelination were studied within three-dimensional fibrin matrices that were covalently modified with the sixth Ig-like domain of cell adhesion molecules L1 containing N-terminal transglutaminase substrate sequences (TG-L1Ig6) for covalent incorporation into fibrin matrices. TG-L1Ig6 is a specific receptor for alphavbeta3-integrin involved in neurite extension of PC12 cells and dorsal root ganglion neurons (DRGs). Neurite extension of PC12 cells depended on interactions between cell surface alphavbeta3 and RGD-sites provided by TG-L1Ig6. In addition, matrix properties such as fibrin crosslink density and matrix degradation by serine proteases were crucial. No involvement of matrix metalloproteinases was found. DRG neurite extension in native fibrin matrices was retarded as compared to neurite extension within L1Ig6-modified and laminin-1-containing matrices. Moreover, myelinated structures were almost exclusively found in TG-L1Ig6-modified and laminin-1-containing matrices. These results indicate that potential use of three-dimensional matrices in a biomaterials-based healing device to induce and/or help in vivo nerve regeneration requires specific structural and biological signals.

Animals↗
PubMed2002

Fibrin application for preventing lymphocysts after retroperitoneal lymphadenectomy in patients with gynecologic malignancies.

OBJECTIVE: We performed a randomized, prospective trial to assess the impact of fibrin glue on the incidence of lymphocysts after systematic pelvic or pelvic and paraaortic lymphadenectomy in patients with gynecologic malignancies. METHODS: Ninety-three consecutive patients with gynecologic pelvic malignancies who underwent surgery including pelvic or pelvic and paraaortic lymphadenectomy were randomized during surgery to be treated with fibrin glue or not. Serial computed tomography (CT) scans were performed during follow-up. CT findings of a smooth and thin-walled cavity filled with a water-equivalent fluid, sharply demarcated from its surroundings and without signs of infiltration were interpreted as lymphocysts. RESULTS: Forty-seven patients (51%) were treated with fibrin glue and 46 (49%) were not. All 93 patients underwent pelvic lymphadenectomy; 15 patients (32%) of the fibrin group and 12 (26%) of the controls also underwent paraaortic lymphadenectomy. We found no significant differences between patients who received fibrin glue and those who did not. CONCLUSION: Intraoperative application of fibrin glue did not reduce the rate of postoperative lymphocysts after lymphadenectomy and had no impact on any follow-up parameter. Its use seems not to be indicated in systematic gynecologic pelvic or pelvic and paraaortic lymphadenectomy.

Adult↗
PubMed1993

Effect of fibrin glue and opsite on open wounds in DB/DB mice.

Fibrin glue is a hemostatic and adhesive agent that has been used for many years in Europe. It is made by the simultaneous mixing of concentrated fibrinogen complex and bovine thrombin reconstituted in a solution of calcium chloride. Upon mixing, the final stages of the coagulation cascade are mimicked, resulting in formation of a fibrin clot. Fibrin is vital in wound healing because the network formed in the wound acts not only as a hemostatic barrier but also as a scaffold for migrating cells. In this study, fibrin glue (60 mg/ml) was applied on 6-mm-diameter circular full-thickness wounds in homozygous, genetically diabetic mice. Results showed delayed wound closure as compared to paired control wounds. Dilution of the protein concentration of fibrin glue to 1 mg/ml resulted in higher histological scores compared to those for wounds treated with 60 mg/ml fibrin glue. Finally, the application of an adherent semipermeable dressing (Opsite) over the wound per se resulted in delayed wound closure. Delayed closure may be due either to mechanical obstruction to the migration or proliferation of cells that actively participate in the wound healing process, mechanical inhibition of wound contraction, or both.

Animals↗
PubMed2002

The importance of factor XIII as a component of fibrin sealants.

BACKGROUND: The need for factor XIII (FXIII) in fibrin sealant is subject to discussions. Some commercially available fibrin sealants (FS) contain high levels of FXIII (up to 70-80 U/mL) while others contain low levels or none. The objective of the present studies was to investigate the need for FXIII in FS. MATERIALS AND METHODS: Beriplast P, a commercial FS containing 40-80 U/mL FXIII, was compared with FS with different concentrations of FXIII or FXIII depleted FS. In Study 1, Beriplast P or FS with 4 U/mL FXIII was allowed to cross-link for 0.25, 1, and 2 min and the resulting fibrin gamma- and beta-chains as well as gamma-gamma-chain dimers were analyzed by SDS-PAGE and densitometry. In Study 2, a series of six FS was prepared from fibrinogen containing 0 (FS-FXIII), 17.5, 35, 70, 140, and 280 U/mL FXIII. The intrasealant strength was determined using a biomechanical test (twin-bottle test). In Study 3, 18 rabbits underwent bilateral partial kidney resection (acute model); right (n = 18) and left (n = 18) kidneys were treated with Beriplast P or FS with 4 U/mL FXIII (FS + 4U FXIII). In Study 4, rabbits were randomly assigned to receive FXIII depleted FS (FS-FXIII) (n = 15); FS + 3 U/mL FXIII (n = 10); FS + 10 U/mL FXIII (n = 10); or Beriplast P (n = 15), after partial rabbit kidney resection (chronic model). The primary endpoint for Studies 3 and 4 was hemostasis. RESULTS: In Study 1, Beriplast P produced significantly more fibrin gamma-chain cross-linking in the observed period than FS with 4 U/mL FXIII. In Study 2, fibrin clot strength increased as a function of FXIII concentration with a maximum of 70 U/mL. In Study 3, significantly more animals achieved hemostasis in the Beriplast P treated group than in the FS + 4U FXIII group (P = 0.03 at 15 s; P < 0.001 at 1 and 2 min). In Study 4, FS containing FXIII (all concentrations) achieved more efficient hemostasis and reduced the need for respray compared with FS-FXIII. Beriplast P was associated with a lower incidence of postoperative adhesions compared with the other treatment groups. At autopsy, the majority of clots formed from FXIII containing FS exhibited mild to moderate clot lysis, whereas the majority of clots in the FS-FXIII group showed severe lysis. CONCLUSIONS: FXIII, when added to fibrinogen concentrate in FS, improved fibrin cross-linking and clot strength. FXIII containing FS achieved more effective hemostasis than FXIII depleted FS. FXIII is an essential component of commercial FS and should be present in FS at an optimal concentration of about 40-80 U/mL.

Animals↗
PubMed1983

Fibrin as a component of the tumor stroma: origins and biological significance.

An association between cancer and the coagulation system was suggested by Trousseau more than a century ago and initial reports of fibrin deposition in the stroma of solid tumors date back some 25 years. However, the validity and generality of these observations have only quite recently been established, and their implications for an understanding of tumor biology, metastasis, and therapy are only now coming to be appreciated by investigators in the mainstream of cancer research. This article reviews the current status of fibrin's role in the biology of tumor growth, considering in turn: (1) the evidence that fibrin is present in tumors, the nature of such fibrin, and its relation to plasma fibronectin; (2) the mechanisms by which fibrin may come to be deposited in tumors; and (3) the potential biological and medical significance of tumor-associated fibrin deposition and degradation. Among the last are such important possibilities as a barrier function to the immune response and possible roles in angiogenesis, desmoplasia, and metastasis.

Animals↗
PubMed1995

Sutured or fibrin-glued laparoscopic choledochojejunostomy.

Minimally invasive techniques for choledochojejunostomy offer theoretical advantages for palliating unresectable periampullary neoplasms. Fibrin glue, a biologic adhesive containing concentrated fibrinogen, may obviate suturing and promote healing without stricture formation. We examined the technical ability to perform laparoscopic choledochojejunostomy (LCJ) and the applicability of thrombin-activated fibrin glue in an animal model of biliary obstruction. Domestic pigs underwent laparoscopic cholecystectomy and ligation of the distal bile duct. Three days later, a side-to-side LCJ was performed by intracorporeal sutured anastomosis (n = 7) or using four stay sutures and homologous fibrin glue (n = 7). Control animals underwent a similar bypass via open laparotomy (n = 7). The postoperative interval to ambulation and oral intake was recorded, and serial serum liver enzymes were measured. The animals were sacrificed at 6 weeks, and tensile strength of the anastomoses was assessed by tensometry. Liver function tests returned to normal values within 7 days following all methods of choledochojejunostomy. In the fibrin glue group, three anastomotic leaks (43%) occurred in the 1st postoperative week. At 6 weeks, all other anastomoses were intact and patent by cholangiogram, but there was moderate stenosis of two open and one fibrin-glue anastomosis. The sutured LCJ, while taking approximately 1 h longer to perform (P < 0.05), resulted in similar efficacy and more rapid recovery (P < 0.05) than open biliary-enteric bypass. Fibrin-glued LCJ was performed rapidly, but had less tensile strength (P < 0.05) and often leaked in the early post-operative interval. We conclude that while there may be a role for laser-activated solders for primary anastomosis, thrombin-activated fibrinogen cannot be advocated as the primary means of creating biliary anastomoses. Using intracorporeal suturing techniques, laparoscopic choledochojejunostomy may be performed safely.

Alanine Transaminase↗
PubMed1994

Potentiation of transforming growth factor (TGF-beta 1) by natural coral and fibrin in a rabbit cranioplasty model.

The association of a biodegradable material and a growth factor could be of clinical value for treating bone defects. We therefore tested the association of transforming growth factor beta (TGF-beta 1) in fibrin glue and coral granules to heal skull defects in rabbits. Adult rabbits underwent a double trepanation symmetrically in both parietal bones. Using histomorphometry, we compared bone repair after 1 month in control animals (n = 5) and in animals treated with either TGF-beta 1 as a single injection of 1 microgram in methylcellulose (n = 5) or in fibrin glue (n = 5), or with coral granules in fibrin glue (n = 4) or with coral granules and TGF-beta 1 1 microgram in fibrin glue (n = 5). We measured the diameter of the remaining defect and the surface of the bone growth. TGF-beta 1 without coral in either methyl cellulose or fibrin induced a partial closure of the defect as assessed by a significant decrease in the defect diameter, compared with the control group. However, the association of TGF-beta 1 in fibrin and coral induced an area of the bone growth higher than in any other groups (P < 0.05). Two months after surgery, this triple association induced a better healing of the defect than coral alone or control group. In each group treated with TGF-beta 1, the mineralization rate was increased not only at the treated side but also in the contralateral defect which was untreated, suggesting a diffusion of the growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The role of fibrin in tumor metastasis.

A volume of data that has accumulated for over a century has suggested that fibrin may facilitate the persistence and progression of malignancy. Techniques that have been developed recently have shown that fibrin is indeed a component of the connective tissue stroma in human malignancy but in only a few tumor types. However, therapeutic intervention studies with drugs that limit thrombin activity or enhance fibrinolysis have shown favorable clinical effects in at least one such tumor type. These favorable findings affirm the concept that cause-and-effect relationships do, in fact, exist between thrombin generation with fibrin formation and tumor progression, and suggest that a rational basis exists for the design of future drug intervention trials that target reactions relevant to specific tumor types. These findings also provide a basis for the design of experiments capable of defining further the role of fibrin in the integrity of these tumor types. Because fibrinogen is found much more commonly than fibrin in the connective tissue of a variety of human malignancies, attention might reassumably be directed to determining the possible contribution of this molecule as well as of fibrin to tumor progression.

Fibrin↗
PubMed1975

[Blood coagulation factor XIII and fibrin stabilization (author's transl)].

Coagulation factor XIII (fibrin stabilizing factor, FSF) is detectable in plasma, platelets, placenta and various tissues. In the activated form FSF has the enzymatic properties of a transglutaminase and is capable of stabilizing fibrin by inducing covalent bondings between fibrin monomers. In patients with congenital factor XIII deficiency or acquired immune inhibitors of fibrin stabilization a severe bleeding tendency is evident. There is not yet enough information available concerning the significance of reduced FSF-activity as cofactor in hemorrhagic diathesis and wound healing disturbances in various disease states. There are some indications from experimental studies that there might be an influence of FSF on tumor growth and metastasis as well as arteriosclerosis. The quantitation of the enzyme by radiological and immunological techniques yield reproducible results. Fibrin in its stabilized or non stabilized form can be discriminated in polyacrylamide gel electrophoresis after reduction of fibrin clots.

Adult↗
PubMed1992

Healing of ischemic colonic anastomosis: fibrin sealant does not improve wound healing.

Fibrin adhesives have been advocated as a protective sealant in high-risk colonic anastomoses to prevent leakage. To assess the effect of fibrin glue sealing on the healing ischemic anastomosis, we compared the healing of sutured colonic anastomoses in the rat, with and without fibrin adhesive (Groups IA and IB), and ischemic anastomoses with and without fibrin adhesive (Groups IIA and IIB). On days two, four, and seven, 10 animals in each group were sacrificed. Adhesion formation was scored, and the in situ bursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was more prominent in Groups IB, IIA, and IIB on day four only; abscesses were noted in the ischemic group in four rats. Anastomotic bursting pressure was significantly lower in sealed (IB) and ischemic anastomoses (IIA) than in normal anastomoses (IA) on day four. Sealing of ischemic anastomoses did not change bursting pressures on days two, four, and seven. The relative decrease of collagen in the sealed anastomoses is significantly higher on day four only. It is concluded that sealing of normal colonic anastomoses in the rat has a negative effect on wound healing. Ischemia at the anastomotic site results in weaker anastomotic strength on day four postoperatively. Also in ischemic anastomoses, fibrin sealant does not improve wound healing during the first seven days. Adhesion formation on ischemic intestinal anastomoses was not prevented by fibrin sealing.

Anastomosis, Surgical↗
PubMed1997

Effect of fibrin glue on irradiated colonic anastomoses.

INTRODUCTION: The present study was planned to research the effects of fibrin glue on irradiated colonic anastomoses. METHOD: The effect of fibrin glue on irradiated colonic anastomoses was investigated in four identical groups of rats. In Group I (control group) colonic anastomoses were performed without radiotherapy; in Group II, colonic anastomoses were performed five days after radiotherapy; in Group III, fibrin glue was applied to anastomotic line without radiotherapy; in Group IV, fibrin glue was applied to anastomotic line with radiotherapy. The healing of left colonic anastomoses was evaluated through the bursting pressure of the anastomotic segment and the hydroxyproline contents of the anastomosis. RESULTS: Measurements done on the fourth postoperative day revealed that anastomotic healing was impaired in rats that underwent radiotherapy (P < 0.001); fibrin glue had no effect on anastomotic healing in groups with or without radiotherapy. CONCLUSION: In the early phases of anastomotic healing, fibrin glue cannot help remove unwanted effects of preoperative radiotherapy.

Anastomosis, Surgical↗
PubMedDate not supplied

Subverting bacterial resistance using high dose, low solubility antibiotics in fibrin.

Antibiotics (ABs) delivered from fibrin were evaluated for control of multi-drug resistant (MDR) Staphylococcus aureus. ABs having low aqueous solubility (< or = 1 mg/ml) were encapsulated by fibrin (composed of fibrinogen, thrombin, Factor XIIIa and calcium chloride) and examined. Electron microscopy revealed fibrin-caged, tetracycline crystals that were 0.26 to 2.8 microns in size and bound within the reticular matrix. Antibiograms documented that S. aureus ATCC 27659 was resistant to erythromycin (ERY), penicillin G (PEN), streptomycin (STR), sulfamethoxazole-trimethoprim (SXT) and tetracycline (TET). However, low solubility formulations of STR (10 mg/ml) or SXT (0.5 mg/ml), delivered from fibrin and evaluated by the agar disk diffusion assay, produced zones of growth inhibition after 18-24 h at 37 degrees C in vitro, indicating renewed susceptibility of S. aureus ATCC 27659 to these ABs. ERY, PEN and TET were unable to overcome resistance at concentrations up to 10 mg/ml. In vivo, intraperitoneal (i.p.) injection of 150 mg/kg STR delivered from fibrin resulted in 100% survival of rats with MDR S. aureus peritonitis as compared with control rats receiving i.p. STR (150 mg/kg) in 0.9% saline. The results demonstrate that some low solubility ABs delivered from fibrin are efficacious in controlling infection mediated by MDR S. aureus.

Animals↗
PubMed1979

Growth characteristics of skin fibroblasts and 3T3 cells entrapped by polymerizing fibrin.

Skin fibroblasts as well as 3T3 cells were cultured after entrapping freshly prepared cells in medium containing polymerizing fibrin. In contrast to cells grown on plastic substratum, fibrin-clot-cultured cells became highly elongated forming strands of cells. The strands interconnected by lateral cellular protrusions so that horizontal networks of cells were present throughout the clots. Cell growth as well as stretching were dependent upon the concentrations of fibrin. Highest growth rates were obtained with low fibrin concentrations (0.3 mg fibrinogen per ml). As shown by deprivation experiments nutritional limitations appear to be responsible for differences in growth rates observed in fibrin clots of higher density. In this system the fibrin meshwork serves as substratum for adhesion, elongation and multiplication of fibroblasts. The method makes it possible to study single cells in culture and the effects of persistent microenvironmental influences.

Animals↗
PubMed2004

Biocompatibility studies on fibrin glue cultured with bone marrow mesenchymal stem cells in vitro.

By culturing bone marrow mesenchymal stem cells of rabbits with fibrin glue in vitro, the biocompatibility of fibrin glue was investigated to study whether this material can be used as scaffolds in bone tissue engineering. After 2-months old New Zealand rabbits had been anesthetized, about 4-6 ml of bone marrow were aspirated from rabbit femoral trochanter. The monocytes suspension was aspirated after bone marrow was centrifuged with lymphocyte separating medium and cultured primarily. Then the cells were divided into two groups: one was cultured with complete medium and the other with induced medium. The cells of the two groups were collected and inoculated to the culture plate containing fibrin glue. In the control group, cells were inoculated without fibrin glue. The implanted cells and materials were observed at different stages under a phase-contrast microscope and scanning electron microscope. MTT and alkaline phosphatase (ALP) were measured. Bone marrow mesenchymal stem cells grew on the surface of fibrin glue and adhered to it gradually. Cells light absorption value (A value) and the ALP content showed no significant difference. Fibrin glue had no inhibitory effect on cell morphology, growth, proliferation and differentiation. It has good biocompatibility and can be used as scaffold materials for bone marrow mesenchymal stem cells in bone tissue engineering.

Animals↗
PubMed2003

Does fibrin glue reduce lymph leakage (pleural effusion) after extended esophagectomy? Prospective randomized clinical trial.

Fibrin glue has been shown to be effective in improving postoperative chylothorax following various thoracic procedures and in reducing lymphorrhea after axillary dissection. It is unknown, however, whether fibrin glue is effective in reducing lymph leakage (pleural effusion) after esophagectomy. A series of 43 consecutive patients with thoracic esophageal cancer who underwent extended esophagectomy were prospectively randomized to two groups: group A (n = 21), in whom 3 ml of fibrin glue was applied to the dissected mediastinum; and group B (n = 22), in whom fibrin glue was not applied. The time of drain removal and the volume of the thoracic drainage were compared. All data were expressed as the mean +/- standard deviation. There were no significant differences in the clinicopathologic characteristics between the two groups. None of the patients developed chylothorax or died during their hospital stay. The daily volume from the thoracic drain (457 +/- 273 ml) was significantly (p < 0.05) larger on postoperative day (POD) 1 in group A than in group B (298 +/- 158 ml) and tended to be larger (p < 0.10) on PODs 4 and 6 in group A than in group B. The cumulative drainage volume was significantly (p < 0.05) larger on PODs 4 to 6 and POD 9, and it tended to be larger (p < 0.10) on PODs 1, 3, 7, 8, 10, and 11 in group A than in group B, suggesting that the cumulative drainage volume in group A was consistently larger than that in group B. The cumulative numbers of patients with a drain remaining in place were not significantly different for the two groups (p = 0.4683). Three patients in group A, however, had prolonged insertion (> 20 days) of the chest tube. There were no significant differences in the incidence of postoperative chest-related complications. No patients in group A developed viral infectious disease during the long-term follow-up. Application of fibrin glue to the dissected mediastinum seems to induce postoperative lymph leakage and thus be responsible for prolonged chest tube insertion in some patients. Hence the use of fibrin glue cannot be recommended for reducing lymph leakage after esophagectomy.

Adult↗
PubMed1996

[Intraocular rt-PA injection in fibrin formation after combined glaucoma and cataract operation].

BACKGROUND: The fibrinolytic drug rt-PA, which has been successfully used systemically to treat arterial and venous occlusions, is now available for local, intraocular injection. rt-PA converts plasminogen to plasmin, which in turn is able to lyse fibrin and fibrin clots. Intraocular surgery, trauma and inflammation may lead to intraocular accumulation of fibrin. Treatment of this type of complication with high-dose corticosteroids is protracted and often unsuccessful. PATIENTS: Eight patients (age 59-75 years) with fibrin formation following phacoemulsification and IOL implantation combined with trabeculectomy were treated by intraocular injection of 10 micrograms rt-PA. The intraocular status following the local fibrinolytic therapy was documented by biomicroscopy, photography and laser-flare Tyndallometry on days 1, 2 and 8. RESULTS: In all patients the fibrin clots dissolved completely. Neither relapses nor adverse affects were noted. CONCLUSIONS: The intraocular application of rt-PA results in an efficient fibrinolytic effect, which prohibits potential complications of combined glaucoma and cataract surgery due to fibrin formation.

Aged↗
PubMed2006

The use of fibrin glue in the treatment of fistula-in-ano: a prospective study.

PURPOSE: This prospective study was done to analyze the efficacy of commercial fibrin glue application in the healing of patients with fistulas-in-ano. METHODS: This clinical trial of 36 patients was performed during the period from November 2003 to May 2004. Thirty men and six women were treated for a fistula-in-ano with commercial fibrin glue application. None of the patients had undergone prior attempts to correct fistulas-in-ano surgically. All patients received preoperative mechanical bowel preparation and prophylactic intravenous antibiotics. In the operating room, the patients underwent an anorectal examination under spinal anesthesia. The external and internal fistula tract openings were then identified. The fistula tract was curetted. Fibrin glue was injected into the external fistula opening until fibrin glue could be seen coming from the internal opening. No dressing was applied over the external opening. Thereafter, the patient was discharged. A 1-week course of oral antibiotics was prescribed. The patients were followed up for 70 weeks with a mean of 54 weeks (range 40-70 weeks). RESULTS: The cause of the fistula-in-ano was cryptoglandular in all patients. The overall initial success rate was 77.8% (28/36). No complications were encountered related to the application. Two patients underwent a reapplication with fibrin glue and the fistulas of these patients were all closed. The overall success rate was 83.3% (30/36). CONCLUSION: Fibrin glue application was thus found to be an easy, safe, effective, and useful alternative treatment in the management of fistulas-in-ano. However, our findings need substantiation by increasing the number of patients and prolonging the follow-up duration, as well as carrying out comparative studies.

Adolescent↗
PubMed1999

The effect of fibrin adhesive (Tisseel) on interbody allograft fusion: an experimental study with cats.

Fibrin glue has been promoted for use in many neuro- and orthopaedic surgical procedures. At present, some surgeons make routine use of the adhesive in augmentation of bone grafting operations. However, there is controversy about its effectiveness in augmenting bone graft healing. This study investigated the use of two-component fibrin sealant (Tisseel, Immuno AG, Vienna, Austria) as an adjunct to graft material in fusion surgery. Twenty-four cats were fused with corticocancellous bone graft, which was taken from a separate cat, across the disc space in the anterior cervical region. In the present experiment, the authors carried out cervical interbody fusions in 24 cats, divided into two groups, to test the usefulness of fibrin glue in fixation of allograft fusions. At surgery, a piece of corticocancellous allograft was placed into the intervertebral disc space at the C5-C6 region, either untreated or locally treated with fibrin adhesive (Tisseel). Fusion mass formation was examined 6 months after the experimental fusion procedure by radiography and computed tomography (CT) scanning and the new bone formed was evaluated histologically. The authors observed that the allograft fusion mass area is more voluminous in the untreated animals in Group I than in the ones augmented with Tisseel, as illustrated by CT measurement (section area and bone density) (p = 0.038). Accordingly, histopathological studies demonstrated a reduced vascularization of the graft as well as diminished new bone formation in the animals treated with Tisseel in Group II. The present investigation demonstrates that local fibrin sealing significantly retards the osteogenic fusion in a model of corticocancellous bone grafting in cats. In view of our results it seems that fibrin sealant is not suitable for fixation of bone fragments in anterior cervical fusion.

Animals↗