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1.  Fibrin glue in the treatment of anal fistula: a systematic review 
New sphincter-saving approaches have been applied in the treatment of perianal fistula in order to avoid the risk of fecal incontinence. Among them, the fibrin glue technique is popular because of its simplicity and repeatability. The aim of this review is to compare the fibrin glue application to surgery alone, considering the healing and complication rates.
We performed a systematic review searching for published randomized and controlled clinical trials without any language restriction by using electronic databases. All these studies were assessed as to whether they compared conventional surgical treatment versus fibrin glue treatment in patients with anal fistulas, in order to establish both the efficacy and safety of each treatment. We used Review Manager 5 to conduct the review.
The healing rate is higher in those patients who underwent the conventional surgical treatment (P = 0,68), although the treatment with fibrin glue gives no evidence of anal incontinence (P = 0,08). Furthermore two subgroup analyses were performed: fibrin glue in combination with intra-adhesive antibiotics versus fibrin glue alone and anal fistula plug versus fibrin glue. In the first subgroup there were not differences in healing (P = 0,65). Whereas in the second subgroup analysis the healing rate is statistically significant for the patients who underwent the anal fistula plug treatment instead of the fibrin glue treatment (P = 0,02).
In literature there are only two randomized controlled trials comparing the conventional surgical management versus the fibrin glue treatment in patients with anal fistulas. Although from our statistical analysis we cannot find any statistically significant result, the healing rate remains higher in patients who underwent the conventional surgical treatment (P = 0,68), and the anal incontinence rate is very low in the fibrin glue treatment group (P = 0,08). Anyway the limited collected data do not support the use of fibrin glue. Moreover, in our subgroup analysis the use of fibrin glue in combination with intra-adhesive antibiotics does not improve the healing rate (P = 0.65), whereas the anal fistula plug treatment compared to the fibrin glue treatment shows good results (P = 0,02), although the poor number of patients treated does not lead to any statistically evident conclusion. This systematic review underlines the need of new RCTs upon this issue.
PMCID: PMC2784785  PMID: 19912660
2.  Fibrin glue‐assisted glaucoma drainage device surgery 
The British Journal of Ophthalmology  2006;90(12):1486-1489.
To describe the use of fibrin glue as a suture substitute for portions of glaucoma drainage device (GDD) surgery.
Retrospective non‐randomised case–control study reviewing 28 consecutive cases of GDD implantation using traditional suture material compared with 14 consecutive cases of GDD implantation using Tisseel fibrin glue (Baxter AG, Vienna, Austria) for portions of the procedure. The fibrin glue was used to close the conjunctiva, secure the pericardium patch graft and secure the tube to the sclera. Three‐month follow‐up data for each group as well as data on operating times, postoperative conjunctival inflammation, drugs used for glaucoma and intraocular pressure (IOP) were evaluated. Statistical analysis was carried out using analysis of variance.
The mean (SD) age of the patients in the suture group (17 men and 11 women) was 56.6 (10.5) years and that in the Tisseel‐assisted group (8 men and 6 women) was 54.7 (8.6) years (p = 0.56). No significant differences were observed in IOP levels at any time point between the two groups. No significant differences were found for the need for postoperative glaucoma drops or postoperative complication rates in both groups. Conjunctival inflammation was more pronounced in the suture group (p = 0.002) using a standard scale for comparison. The mean (SD) time of surgery was significantly less for the Tisseel‐assisted group, 15.0 (3.11) min, than for the suture group, 25.93 (4.04) min (p<0.001).
Tisseel fibrin glue seems to be a safe substitute for some of the sutures used in GDD surgery. Use of Tisseel seems to have no effect on IOP control or complications, whereas it considerably improved postoperative conjunctival inflammation and reduced time of surgery. Further studies are needed to better understand the role of fibrin glue in GDD implantation.
PMCID: PMC1857532  PMID: 16916877
3.  Comparison of Fibrin Glue and Sutures for Conjunctival Wound Closure in Strabismus Surgery 
To evaluate and compare the efficacy and tolerance of fibrin glue and sutures for closing conjunctival wounds in strabismus surgery.
In a prospective trial, we performed strabismus surgery using limbal incisions. Conjunctival wounds were closed with fibrin glue in 20 eyes of 20 patients (fibrin group) and 8-0 polyglactin suture in 20 eyes of 20 patients (suture group). Postoperative pain, tearing, and inflammation were compared at 1 day, 1 week, 3 weeks, and 6 weeks after surgery. Conjunctival incision healing was also investigated.
One day and one week post-operatively, pain and tearing scores were lower in the fibrin group (p = 0.000, respectively). Mean surgery time was significantly shorter in the fibrin (48 ± 5 minutes) than the suture group (63 ± 7 minutes) (p = 0.000). Inflammation was significantly more severe in the suture group until 3 weeks postoperative (p = 0.000, respectively), but conjunctival healing did not differ between the groups. Hyperemia appeared more prominent in the fibrin group 3 and 6 weeks after surgery (p = 0.087 and 0.000, respectively). Two eyes in the fibrin group showed conjunctival gaps of more than 2 mm, which closed spontaneously by three weeks after surgery. No allergic reactions or infections developed.
Fibrin glue proved to be as effective as sutures in closing conjunctival wounds. It provides more comfortable early postoperative courses and might be considered as an alternative to sutures in strabismus surgery.
PMCID: PMC3102821  PMID: 21655043
Conjunctival wound closure; Fibrin tissue adhesive; Polyglactin suture; Strabismus surgery
4.  The Effect of Platelet Rich Plasma from Bone Marrow Aspirate with Added Bone Morphogenetic Protein-2 on the Achilles Tendon-Bone Junction in Rabbits 
Clinics in Orthopedic Surgery  2011;3(4):325-331.
To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period.
A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks.
Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p < 0.05) at 8 weeks after surgery.
Bone marrow derived PRP and BMP-2 in fibrin glue accelerated healing in a rabbit model of tendon-bone junction injury.
PMCID: PMC3232361  PMID: 22162796
Bone-tendon junction; Achilles tendon; Bone marrow derived platelet rich plasma; Bone morphogenetic protein
5.  Fibrin Glue Used as an Adhesive Agent in CNS Tissues 
One of the limitations of many bridging experiments in neural transplantation is that the CNS tissues cannot be sutured. Fibrin glue is a two-component system derived from whole blood which, when mixed, reproduces the final stage of blood coagulation and solidifies. Many experimental studies of humans and animals show that fibrin glue repair of peripheral nerves is almost equivalent to microsurgical sutures. In this study, we attempted to extend its use to CNS tissues and transplants. Two techniques were tried: (1) Bilateral parietal knife cuts were performed by stereotaxic technique in six rats. Fibrin glue was applied in the right-side cortical lesion. Immunohistochemistry using antisera to tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), laminin and neurofilament (NF) was essentially similar between the control and treatment groups. The immunoreactivity of each marker revealed no significant differences between the two groups on days 1, 7 and 30. There was no difference in terms of gliosis or microvascular proliferation. (2) Embryonic day 16 fetal locus coeruleus was grafted together with E16 cortex to the anterior chamber of sympathectomized eyes. In the six eyes of the glue treatment group, the parietal cortical piece and the locus coeruleus piece were joined together before grafting by immersing them in the solution of fibrin glue. In the eight eyes of the control group, pieces of parietal cortex and locus coeruleus were introduced individually and approximated by gently pressing the cornea. The sizes of double grafts showed no significant difference between groups during six weeks postgrafting. The immunohistochemical pictures using antisera against TH, GFAP and laminin were similar in both groups. Catecholaminergic fibers from the grafted locus coeruleus were found bridging over into the parietal cortical piece in both the control and treatment groups. There was no significant difference in TH-positive nerve fiber density between tissue glue joined and control double intraocular grafts. In conclusion, fibrin glue can be used as an adhesive agent in CNS tissues without hampering the outgrowth of neurites or causing adverse tissue reactions in fetal or adult nervous tissues.
PMCID: PMC2565293  PMID: 7578439
6.  Scalded Skin of Rat Treated by Using Fibrin Glue Combined with Allogeneic Bone Marrow Mesenchymal Stem Cells 
Annals of Dermatology  2014;26(3):289-295.
It is difficult to achieve satisfactory results with the traditional treatment of large-area skin defects and deep burns.
To test the treatment effect of an active dressing film made of a mixture of fibrin glue and bone marrow mesenchymal stem cells (BMSCs) for repairing burn wounds on the skin of rats.
Two scald wounds were made on the back of each rat. A total of 30 scald wounds were randomly divided into 3 groups, with 10 wounds in each group. In the experimental treatment group, the scald wounds were covered with the fibrin glue and BMSC mixture. The wounds of the experimental control group were covered with fibrin glue only. No intervention was administered to the blank control group. Thirty days after treatment, pathological sections were cut from the scalded local tissues of all rats from the 3 groups and observed with a microscope.
The speed of scald wound healing in the experimental treatment group was faster than the other 2 groups. In the experimental treatment group, histopathological analysis revealed that the sebaceous glands showed obviously proliferous at the edge of the new tissue and gradually extended to the deep dermal layer of the new tissue.
BMSCs may have an active role in promoting skin tissue repair and generating skin appendages. Allogeneic BMSCs mixed with fibrin glue can contribute to the quick formation of a film-like gel over the scald wounds, which might be of significance for emergency treatment and skin-grafting operations.
PMCID: PMC4069637  PMID: 24966626
Artificial skin; Burns; Fibrin tissue adhesive; Mesenchyma stromal cells; Tissue engineering
7.  Local Application of BMP-2 Specific Plasmids in Fibrin Glue does not Promote Implant Fixation 
BMP-2 is known to accelerate fracture healing and might also enhance osseointegration and implant fixation. Application of recombinant BMP-2 has a time-limited effect. Therefore, a gene transfer approach with a steady production of BMP-2 appears to be attractive. The aim of this study was to examine the effect of locally applied BMP-2 plasmids on the bone-implant integration in a non-weight bearing rabbit tibia model using a comparatively new non-viral copolymer-protected gene vector (COPROG).
Sixty rabbits were divided into 4 groups. All of them received nailing of both tibiae. The verum group had the nails inserted with the COPROG vector and BMP-2 plasmids using fibrin glue as a carrier. Controls were a group with fibrin glue only and a blank group. After 28 and 56 days, these three groups were sacrificed and one tibia was randomly chosen for biomechanical testing, while the other tibia underwent histomorphometrical examination. In a fourth group, a reporter-gene was incorporated in the fibrin glue instead of the BMP-2 formula to prove that transfection was successful.
Implant fixation strength was significantly lower after 28 and 56 days in the verum group. Histomorphometry supported the findings after 28 days, showing less bone-implant contact.
In the fourth group, successful transfection could be confirmed by detection of the reporter-gene in 20 of 22 tibiae. But, also systemic reporter-gene expression was found in heterotopic locations, showing an undesired spreading of the locally applied gene formula.
Our results underline the transfecting capability of this vector and support the idea that BMP-2 might diminish osseointegration. Further studies are necessary to specify the exact mechanisms and the systemic effects.
PMCID: PMC3146913  PMID: 21762501
BMP-2; gene transfer; non viral gene vector; COPROG; implant healing; fibrin glue
8.  Fibrin sealant use for minimising peri-operative allogeneic blood transfusion 
Fibrin sealants (also referred to as biological glue or fibrin tissue adhesives) have gained increasing popularity as interventions to improve peri-operative (intra- and post-operative) haemostasis and diminish the need for allogeneic red cell transfusion (blood from an unrelated donor).
To examine the efficacy of fibrin sealants in reducing peri-operative blood loss and allogeneic red blood cell (RBC) transfusion.
Search methods
We identified studies by searching CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1950 to 2008), EMBASE (1980 to 2008), manufacturer web sites (to March 2008), and bibliographies of relevant published articles.
Selection criteria
Controlled trials in which adult patients scheduled for elective surgery were randomised to fibrin sealant treatment or to a control group which did not receive fibrin sealant treatment. Trials were eligible if they reported data on the number of patients exposed to allogeneic red cell transfusion, the volume of blood transfused, or blood loss (assessed objectively).
Data collection and analysis
The primary outcomes measured were the: number of patients exposed to allogeneic red cells, amount of blood transfused, and blood loss. Other outcomes measured were: re-operation due to bleeding, infection, mortality, thrombotic events, and length of hospital stay. Treatment effects were pooled using a random-effects model.
Main results
Eighteen trials that included a total of 1406 patients reported data on peri-operative exposure to allogeneic RBC transfusion. Fibrin sealant treatment, on average, reduced the rate of exposure to allogeneic RBC transfusion by a relative 37% (relative risk (RR) 0.63, 95% confidence interval (CI) 0.45 to 0.88) and 7% in absolute terms (95% CI 2% to 13%). Fourteen trials, including a total of 853 patients, provided data for post-operative blood loss. In aggregate, fibrin sealant treatment reduced blood loss on average by around 161 ml per patient (95% CI 98.25 to 224.53 ml). In the context of orthopaedic surgery, fibrin sealant treatment reduced post-operative blood loss on average by around 223 ml per patient (95% CI 119.85 to 325.18 ml) and reduced the risk of exposure to allogeneic RBC transfusion by 32% (RR 0.68, 95% CI 0.51 to 0.89). Fibrin sealant treatment was not associated with an increased risk of wound infection (RR 0.61, 95% CI 0.24 to 1.58), any infection (RR 0.93, 95% CI 0.44 to 1.94), haematoma formation (RR 0.46, 95% CI 0.18 to 1.18), or death (RR 0.85, 95% CI 0.38 to 1.89). Hospital length of stay was not reduced in patients treated with fibrin sealant (weighted mean difference (WMD) −0.21 days, 95% CI −0.42 to 0.01 days).
Authors’ conclusions
Overall, the results suggest that fibrin sealants are efficacious in reducing both post-operative blood loss and peri-operative exposure to allogeneic RBC transfusion. Although treatment-effect heterogeneity was observed for these primary efficacy outcomes, heterogeneity was generally in terms of the size of effect rather than the direction of effect. Fibrin sealants appeared to demonstrate their greatest beneficial effects in the context of orthopaedic surgery, where blood loss is often substantial. Trials not involving orthopaedic surgery generally showed a trend toward decreased post-operative blood loss but the observed reductions were not clinically significant. The majority of trials included in this review were small, which raises concerns about the potential effects of publication bias. Funnel plot assessment indicates that there is some evidence of publication bias in the form of a missing population of small negative trials. We believe that large, methodologically rigorous, randomised controlled trials of fibrin sealants are needed.
PMCID: PMC4171968  PMID: 12804501
*Erythrocyte Transfusion; Blood Loss, Surgical [*prevention & control]; Blood Transfusion; Fibrin Tissue Adhesive [*therapeutic use]; Hemostatics [*therapeutic use]; Randomized Controlled Trials as Topic; Surgical Procedures, Elective; Transplantation, Homologous; Adult; Humans
9.  Fibrin Glue Reduces the Duration of Lymphatic Drainage after Lumpectomy and Level II or III Axillary Lymph Node Dissection for Breast Cancer: A Prospective Randomized Trial 
This randomized prospective study investigated the effect of fibrin glue use on drainage duration and overall drain output after lumpectomy and axillary dissection in breast cancer patients. A total of 100 patients undergoing breast lumpectomy and axillary dissection were randomized to a fibrin glue group (N=50; glue sprayed onto the axillary dissection site) or a control group (N=50). Outcome measures were drainage duration, overall drain output, and incidence of seroma. Overall, the fibrin glue and control groups were similar in terms of drainage duration, overall drain output, and incidence of seroma. However, subgroup analysis showed that fibrin glue use resulted in a shorter drainage duration (3.5 vs. 4.7 days; p=0.0006) and overall drain output (196 vs. 278 mL; p=0.0255) in patients undergoing level II or III axillary dissection. Fibrin glue use reduced drainage duration and overall drain output in breast cancer patients undergoing a lumpectomy and level II or III axillary dissection.
PMCID: PMC2650992  PMID: 19270819
Fibrin Tissue Adhesive; Axillary Lymph Node Excision; Lymphatic Drainage; Breast Neoplasms
10.  Management of an extrasphincteric fistula in an HIV-positive patient by using fibrin glue: a case report with tips and tricks 
BMC Gastroenterology  2010;10:18.
Individuals with impaired immunity are at higher risk of perianal diseases. Concerning complex anal fistulas impaired healing and complication rates are also higher. Definitive treatment of a fistula aims controlling the purulent discharge and prevents its recurrence. It depends mainly on the trajectory of the fistula and the underlying disease.
We present a case of a HIV-positive patient with a complex extrasphincteric anal fistula who was treated successfully with fibrin glue application. We further, discuss tips and tricks when applying fibrin glue as plugging material in complex anal fistulas.
Case presentation
A sixty-one-year-old HIV-positive male referred to us for warts and extrasphincteric fistula. Because of the patients' immunological status, we opted against surgery and recommended fibrin glue plugging. The patient was discharged the same day. A follow-up examination was performed 5 days after the initial fibrin glue application showing that the fistula canal was obstructed. Three months and a year post-intervention the fistula tract remains closed.
The best treatment for a disease gives at least the same result with the other treatments with minimised risk for the life of the patient and minimal application effort. Conservative closure of fistula with fibrin plugging is simple, safe and with less morbidity than surgery. Our patient was successfully treated without endangering his life despite his precarious medical state. Not everybody believes in the effectiveness of fibrin glue application, however we consider this solution in cases of complex fistulas at least as primary procedure in special populations such as the immunosupressed.
PMCID: PMC2829488  PMID: 20152052
11.  Pro-osteogenic effects of fibrin glue in treatment of avascular necrosis of the femoral head in vivo by hepatocyte growth factor-transgenic mesenchymal stem cells 
Autologous transplantation of modified mesenchymal stem cells (MSCs) is a promising candidate for the treatment of the refractory clinical disease, avascular necrosis of the femoral head (ANFH). Our previous attempts by compounding MSCs with medical fibrin glue to treat ANFH in animal model have achieved excellent effects. However, the underlying molecular mechanism is unclear, especially on the transgenic gene expression.
Rabbit MSCs were isolated and compounded with fibrin glue. Following degrading of fibrin glue, proliferation, viability, expression of transgenic hepatocyte growth factor gene as well as osteogenic differentiation of MSCs were evaluated together with that of uncompounded MSCs. Fibrin glue-compounded MSCs were transplanted into the lesion of ANFH model, and the therapeutic efficacy was compared with uncompounded MSCs. One-Way ANOVA was used to determine the statistical significance among treatment groups.
Fibrin glue compounding will not affect molecular activities of MSCs, including hepatocyte growth factor (HGF) secretion, cell proliferation and viability, and osteogenic differentiation in vitro. When applying fibrin glue-compounded MSCs for the therapy of ANFH in vivo, fibrin glue functioned as a drug delivery system and provided a sustaining microenvironment for MSCs which helped the relatively long-term secretion of HGF in the femoral head lesion and resulted in improved therapeutic efficacy when compared with uncompounded MSCs as indicated by hematoxylin-eosin staining and immunohistochemistry of osteocalcin, CD105 and HGF.
Transplantation of fibrin glue-compounding MSCs is a promising novel method for ANFH therapy.
PMCID: PMC4036493  PMID: 24885252
Avascular necrosis of the femoral head; Mesenchymal stem cell; Fibrin glue; Proliferation; Differentiation; Osteogenic regeneration
12.  Anterior Cruciate Ligament deficiency leads to early instability of scaffold for cartilage regeneration: a controlled laboratory ex-vivo study 
International Orthopaedics  2011;36(6):1315-1320.
The affect of anterior cruciate ligament (ACL) integrity on the early postoperative stability of a collagen type-I gel scaffold was investigated. The value of fibrin glue for graft fixation in ACL deficient porcine knees over a simulated early postoperative period was also studied.
Full-thickness articular cartilage defects (11 × 6 mm) were created on the medial femoral condyle of 80 porcine knees. The ACL was left intact or completely transected in each of 40 knees. Gel plugs were tested in each group: press-fitting only in 20 specimens and press-fitting plus fibrin glue in 20 specimens. Each knee underwent 2,000 cycles in a validated ex-vivo continuous passive motion model.
Press-fit-only fixation grafts in knee specimens with an intact ACL showed significantly superior stability than that in ACL deficient knees (p = 0.01). In ACL deficient knees, grafts fixed with press-fitting plus fibrin glue showed significantly superior stability than those using press-fit only fixation (p = 0.01). Press-fitting plus fibrin glue fixation showed no significant differences in worn surface area between knee specimens with intact and deficient ACL.
ACL deficiency led to early scaffold instability in an ex-vivo porcine knee model. Fibrin glue in ACL deficient knees led to additional graft stability. These findings indicated that cartilage regenerative techniques may give optimum results in ACL intact knees.
PMCID: PMC3353066  PMID: 22143317
13.  Efficiency and safety of mesh fixation in laparoscopic inguinal hernia repair using n-butyl cyanoacrylate: long-term biocompatibility in over 1,300 mesh fixations 
Hernia  2011;16(2):153-162.
In adult patients, most inguinal hernias are treated by implanting a prosthetic mesh. To prevent mesh dislocation and thus recurrence, different types of fixation have been proposed. In contrast to penetrating fixation known to cause acute chronic pain, adhesive fixation is becoming increasingly popular as it reduces markedly the risk of injury and chronic pain. Apart from the biological sealants (e.g., fibrin glue), surgical adhesives include a group of synthetic glues and genetically engineered protein glues. For example, cyanoacrylate is used in various medical and veterinary indications due to its fast action, excellent bonding strength and low price.
The main objective of this paper was to communicate positive results obtained using n-butyl-cyanoacrylate glue to fix prosthetic meshes in over 1,300 TAPP repairs of primary and recurrent inguinal hernias. The secondary objective was to highlight the rationale (e.g., safety) for using non-fibrin based glue in this type of procedure.
We present the in vitro and in vivo data necessary for the approval of n-butyl cyanoacrylate Histoacryl® glue. We use an equivalent glue, Glubran-2®, to fix prosthetic meshes in 1,336 laparoscopic TAPP repairs.
Standardized tests to detect sensitization, irritation, genotoxicity or systemic toxicity demonstrated the safety and biocompatibility of Histoacryl®, which met all requirements, including those of ISO 10993. Histological long-term studies in rabbits yielded results comparable to routine suture fixations, with full integration of the mesh into the abdominal wall. The clinical results showed the following advantages: fast application of the glue, reduced postoperative pain, 0.0% infection rate, continuously low recurrence rate and shorter hospital stay. No adverse effects and no complaints were recorded.
The experimental and clinical data demonstrate the safe use and the excellent cost-benefit ratio of n-butyl cyanoacrylate compared with other techniques of mesh fixation.
PMCID: PMC3315639  PMID: 22015810
Laparoscopic hernia repair; Mesh fixation; Glue fixation; Cyanoacrylate
14.  A comparison between fibrin sealant and sutures for attaching conjunctival autograft after pterygium excision 
Use of conjunctival autograft following excision of primary pterygium has reduced the recurrence rate. This study evaluates the efficiency of fibrin glue as compared to sutures in attaching the conjunctival autograft with reference to surgical time, post operative comfort and recurrence during follow up.
60 patients with primary pterygium were included and divided into two groups. In the first group autograft was secured in place with help of 10-0 polyamide monofilament suture while in second group fibrin glue was used. Both the groups were compared in terms of operative time, post op comfort and recurrence.
The average surgical time taken was 50.93 ± 4.96 min with suture group and 34.43 ± 4.94 min with fibrin glue group. Pain and foreign body sensation was markedly less with fibrin glue group. At the end of final follow up at 6 months, 3 cases (10%) from suture group and 1 case (3.33%) from fibrin group had recurrence.
Fibrin glue is effective and safe for attaching conjunctival autograft during pterygium surgery. Although more number of recurrences were observed in suture group as compared to fibrin glue group the difference was not statistically significant (p 0.612).
PMCID: PMC3862656  PMID: 24600089
Pterygium; Conjunctival autograft; Fibrin glue
15.  Efficacy of Fibrin Glue on Seroma Formation after Breast Surgery 
Background and Objectives. This study was designed to determine the effectiveness of fibrin glue plus conventional drain placement versus conventional drain placement in the prevention of seromas after breast procedures. Among methods employed to reduce seroma magnitude and duration, fibrin glue has been proposed in numerous studies, with controversial results. Design and Setting. A prospective, randomized, controlled study of subjects who were randomized into control and experimental groups was conducted. Methods. Collected data included age, surgeon, medical and surgical history, comorbidities, procedure performed, number of axillary nodes, number of positive axillary nodes collected, final pathologic diagnosis, cancer stage, hospital stay, postoperative day of drain removal, complications, incidence of seroma formation, interval to seroma resolution, and number of postoperative visits. Results. Analysis of 60 patients showed similarly matched groups. Seroma formation rate was 24.1% in the control group and 16.1% in the fibrin glue group. The rate of wound complications was similar. Conclusions. Although use of fibrin sealant resulted in a nonsignificant decrease in seroma formation rate compared with that of drain placement, the higher cost and cumbersome technique tend to indicate that there is no advantage to using fibrin glue over drain placement with the technique described.
PMCID: PMC3447350  PMID: 23008776
16.  Polyglycolic acid sheet with fibrin glue potentiates the effect of a fibrin-based haemostat in cardiac surgery 
Hemorrhage from the left ventricle can be critical and sutureless repair using a fibrin-based haemostat (TachoComb) is one effective option. When active hemorrhage is not controlled by the haemostat, we have used a polyglycolic acid (PGA) sheet and fibrin glue in addition. Here we investigated whether the PGA sheet and fibrin glue combined with TachoComb had stronger adhesive properties than TachoComb alone in two experimental models.
Experiment 1. An airtight circuit that included rabbit skin with holes covered by each type of sealant was gradually pressurized and the burst pressure was recorded automatically (n = 10). Experiment 2. A suture loop was attached to a porcine heart by each sealant, and the peel-off pressure was measured (n = 12).
The PGA sheet and fibrin glue combined with TachoComb showed significantly higher adhesive strength than TachoComb alone in both experiments (p < 0.05).
Adding a PGA sheet and fibrin glue increased the adhesive strength of TachoComb in two experimental models, suggesting that this method might be effective for achieving haemostasis in difficult clinical situations.
PMCID: PMC4105156  PMID: 25002331
Polyglycolic acid sheet; TachoComb; Hemorrhage; Left ventricle
17.  Collagen fleeces do not improve colonic anastomotic strength but increase bowel obstructions in an experimental rat model 
To investigate whether a collagen fleece kept in place by fibrin glue might seal off a colorectal anastomosis, provide reinforcement, and subsequently improve anastomotic healing.
Wistar rats underwent a 1-cm left-sided colonic resection followed by a 4-suture end-to-end anastomosis. They were then randomly assigned to one of three treatment groups: no additional intervention (control, n = 20), the anastomosis covered with fibrin glue (fibrin glue, n = 20), the anastomosis covered with a collagen fleece, kept in place with fibrin glue (collagen fleece, n = 21). At either 3 or 7 days follow-up, anastomotic bursting pressure was measured and tissue was obtained for histology and collagen content assessment after which animals were sacrificed.
Three rats in the control (15%), three in the fibrin glue (15%), and one in the collagen group (4.8%) died due to anastomotic complications (P = 0.497). Anastomotic bursting pressures were not significantly different between groups at 3 and 7 days follow-up (P = 0.659 and P = 0.427, respectively). However, bowel obstructions occurred significantly more often in the collagen group compared to the control group (14/21 vs. 3/20, P = 0.003). Collagen contents were not different between groups, but histology showed a more severe inflammation in the collagen group compared to the other groups at both 3 and 7 days follow-up.
A collagen fleece kept in place by fibrin glue does not improve healing of colonic anastomoses in rats. Moreover, this technique induces significantly more bowel obstructions in rats, warranting further study before being translated to a clinical setting.
PMCID: PMC3098973  PMID: 21344301
Anastomotic dehiscence; Rat; Fibrin glue; Collagen fleece; Bursting pressure
18.  A Comparative Study of the Effect of Fibrin Glue versus Sutures on Clinical Outcome in Patients Undergoing Pterygium Excision and Conjunctival Autografts 
To compare the effect of using fibrin glue or 10-0 nylon sutures on the clinical outcome of patients undergoing pterygium excision and conjunctival autografting.
We retrospectively reviewed the medical records of 52 eyes from 46 patients who underwent pterygium excision and conjunctival autografting and were followed up for more than 3 months. The operation duration, postoperative inflammation, complications, and recurrence rates were compared between groups of 20 patients (22 eyes) for whom fibrin glue was used (fibrin glue group) and 26 patients (30 eyes) for whom suturing was performed with 10-0 nylon (suture group) in pterygium excision and conjunctival autografting.
The operation duration was 27.71 (5.22) minutes in the fibrin glue group and 43.30 (8.18) minutes in the suture group (p = 0.000). Seven days after the operation, the fibrin glue group showed milder conjunctival inflammation than the suture group (p = 0.000). Postoperative complications and corneal recurrence rates were not statistically different between the two groups.
The use of fibrin glue in pterygium excision with conjunctival autografting is likely to be a more effective, safer procedure than suturing.
PMCID: PMC3506813  PMID: 23204794
Conjunctival autograft; Fibrin glue; Pterygium excision
19.  The effect of fibrin glue on the early healing phase of intestinal anastomoses in the rat 
Protecting the anastomotic integrity using suture or staple line reinforcement remains an important goal for ongoing research. The present comprehensive study aims to establish the effects of fibrin glue on the early phase of anastomotic healing in the rat intestine.
One hundred and eight young adult male Wistar rats underwent resection and anastomosis of both the ileum and colon. In half, fibrin glue was applied around the anastomoses. Parameters for repair included wound strength, both bursting pressure and breaking strength at days 1, 3, and 5 after operation; hydroxyproline content; and histology, the latter also after 7 days.
A transient colonic ileus was observed in the experimental group. Anastomotic breaking strength was always similar in both the control and fibrin glue groups. Anastomotic bursting pressures remained low at days 1 and 3, without any differences between the groups. In both groups, the bursting pressure increased sharply (p < 0.001) between days 3 and 5. At day 5, the bursting pressure in the fibrin glue group remained below than that in the controls, although only significantly (p = 0.0138) so in the ileum. At day 5, but not at day 7, the wounds in the fibrin glue group contained less collagen. Other aspects of microscopic wound architecture appeared to be the same.
There is no justification for using fibrin glue on patent anastomoses constructed under low-risk conditions. Its potential benefit under conditions where chances for anastomotic leakage are enhanced needs further investigation.
PMCID: PMC3401510  PMID: 22398458
Anastomoses; Intestine; Fibrin glue; Rat; Seal
20.  Effect of intracameral injection of fibrin tissue sealant on the rabbit anterior segment 
Molecular Vision  2010;16:1087-1097.
To investigate the effect of intracameral injection of fibrin tissue sealant on the anterior segment structures in a rabbit model.
One eye of 10 rabbits received an intracameral injection of fibrin tissue sealant with a thrombin concentration of 500 IU (TISSEEL), and the fellow eye received an intracameral injection of balanced salt solution as a control. The rabbits were followed up with serial slit-lamp examinations, photography, high resolution anterior segment optical coherence tomography scans with pachymetry measurement, and intraocular pressure (IOP) monitoring until complete dissolution of the fibrin sealant. Corneal endothelial cell viability was evaluated using live/dead cell assays. Apoptosis of the cornea and trabecular meshwork were evaluated using TUNEL assays. Ultra-structural examinations of the cornea and trabecular meshwork were performed using electron microscopy. Histology of the trabecular meshwork and iris were analyzed using light microscopy.
The quantity of the intracameral fibrin sealant was shown to be significantly correlated with increased IOP and pachymetry post-operatively. Complete dissolution of the fibrin sealant occurred between 15 and 30 days. Live/dead cell assays showed no decrease in viability of the corneal endothelium, and TUNEL assays showed no increase in apoptosis of the corneal epithelium, stroma, endothelium, or trabecular meshwork in the eyes with the fibrin sealant. Light and electron microscopy of the anterior segment structures were unremarkable.
The intracameral use of fibrin glue was associated with a transient increase in IOP and pachymetry. However, there was no evidence of toxicity or structural damage to the corneal endothelium, trabecular meshwork, or iris.
PMCID: PMC2893049  PMID: 20596250
21.  Preliminary investigation of a polyethylene glycol hydrogel "nerve glue" 
Polyethylene glycol (PEG) hydrogel is a biocompatible semi-adherent gel like substance that can potentially augment nerve repair much like a fibrin sealant. Potential advantages of this substance include fast preparation and set up time, as well as adhesion inhibiting properties. The purpose of this study was to perform an initial evaluation of PEG hydrogel in this application.
The sciatic nerves of 29 rats were transected and repaired using two 10-0 nylon sutures and either PEG hydrogel or fibrin glue. After 10 weeks, contraction forces of the reinnervated muscles were evaluated and histological assessment of scar tissue performed.
Muscle strength testing revealed the average ratio of experimental to control sides for the fibrin glue group was 0.75 and for the PEG hydrogel group was 0.72 (no significant difference). Longitudinal sections through the nerve repair site showed no significant difference in nerve diameter but did demonstrate a significant reduction in scar thickness in the PEG hydrogel group (p < 0.01).
Though further study is necessary to fully evaluate, PEG hydrogel results in less scar tissue formation and equivalent muscle recovery as fibrin sealant when applied as a nerve glue in a rodent sciatic nerve repair model.
PMCID: PMC2753617  PMID: 19754963
22.  The origins and insertions of the extraocular muscles: development, histologic features, and clinical significance. 
The tendinous origins and insertions of the extraocular muscles were studied embryologically by macroscopic and microscopic methods. It is concluded from this investigation that these tendons of origin and insertion arise from mesenchymal tissue similar to that of their respective muscles. These tendon-muscle groups have developed from superior and inferior mesenchymal complexes. The origins of the extraocular muscles are attached to the periorbita by an interlocking of the tendinous and muscular fibers, which allows for mobility of the extraocular muscles in all extreme directions of gaze and also results in a strong mechanical mooring for these muscles. Avulsion at the origins of the extraocular muscles following severe traction or trauma is rare. The additional origin of the superior and medial rectus muscles to the dura of the optic nerve explains the pain that may occur on movement of the eye in optic neuritis. Optic nerve compression and thyroid myopathy is explained by mucopolysaccharide and inflammatory cell infiltration of the muscular interdigitations that extend up to the site of origin of the rectus muscles. Findings of this investigation suggest that the association of ptosis and superior rectus muscle underaction may be due to a persistence of fibrous tissue that has endured from embryologic development between the superior rectus and levator palpebrae superioris muscles. Superior oblique tendon sheath syndrome is explained by embryologic strands remaining between the tendon of the superior oblique muscle and the trochlea. The insertions of the rectus muscles extend from the equator of the eye to the limbus early on in development. By processes of differential degeneration between the sclera and the rectus tendon, posterior recession of the tendon from the limbus, and contemporaneous growth of the anterior segment of the eye, these tendons reach their adult location only between the ages of 18 months and 2 years. In strabismus surgery, measurements for muscle adjustments should be assessed from the limbus rather than from the sites of insertion of these tendons. In the series of patients with esotropia, no mechanical abnormalities were noted in relationship to the insertions of the medial or lateral recti muscles. Furthermore, no correlation was found between the site of insertion of the medial rectus muscle and the degree of esotropia.
PMCID: PMC1298748  PMID: 3590478
23.  Effects of Recession versus Tenotomy Surgery without Recession in Adult Rabbit Extraocular Muscle 
The EOMs are particularly adaptive to changes induced by recession and tenotomy surgery, responding with modulations in fiber remodeling and myosin expression and also with changes in antagonist and contralateral muscles. These results suggest the possibility that these processes are manipulated immediately after surgery to improve surgical success rates.
Surgical recession of an extraocular muscle (EOM) posterior to its original insertion is a common form of strabismus surgery, weakening the rotational force exerted by the muscle on the globe and improving eye alignment. The purpose of this study was to assess myosin heavy chain (MyHC) isoform expression and satellite cell activity as defined by Pax7 expression in recessed EOMs of adult rabbits compared with that in muscles tenotomized but not recessed and with that in normal control muscles.
The scleral insertion of the superior rectus muscle was detached and sutured either 7 mm posterior to its original insertion site (recession surgery) or at the same site (tenotomy). One day before euthanatization, the rabbits received bromodeoxyuridine (BrdU) injections. After 7 and 14 days, selected EOMs from both orbits were examined for changes in fast, slow, neonatal, and developmental MyHC isoform expression, Pax7 expression, and BrdU incorporation.
Recession and tenotomy surgery resulted in similar changes in the surgical EOMs. These included a decreased proportion of fast MyHC myofibers, an increased proportion of slow MyHC myofibers, and increased BrdU-positive satellite cells. Similar changes were seen in the non-operated contralateral superior rectus muscles. The ipsilateral inferior rectus showed reciprocal changes to the surgical superior rectus muscles.
The EOMs are extremely adaptive to changes induced by recession and tenotomy surgery, responding with modulations in fiber remodeling and myosin expression. These adaptive responses could be manipulated to improve surgical success rates.
PMCID: PMC3061502  PMID: 20538996
24.  Adal‐1 bioadhesive for sutureless recession muscle surgery: a clinical trial 
To evaluate the efficacy and biotolerance of the Adal‐1 adhesive for muscle sealing in strabismus surgery.
27 eyes were included in the study: 17 in the control group and 10 in the study group. Surgery was performed on the recession of the horizontal rectus muscles. In the control group the muscle was joined to the sclera by a Vicryl 7/0 suture. In the study group, the Adal‐1 adhesive was used instead. The efficacy of the sealing of the muscle to the sclera and the biotolerance of the surrounding tissues were evaluated.
The muscular recession in the control group was 8.17 (SD 2.38) with displacement of the sealing point of 0.02 (1.7) mm. In the group sealed with adhesive, the muscular recession was 9.09 (3.08) and the displacement was 0.15 (1.56) mm, with no significant differences between the techniques (p<0.05). The inflammation of the surrounding tissues in the immediate postoperative period was greater with the suture technique (p>0.05), but there were no differences in the other postoperative periods (Mann‐Whitney U test).
Adal‐1 was an effective and safe alternative to sutures in muscle recession for strabismus surgery in this study.
PMCID: PMC1860177  PMID: 16424535
bioadhesives; muscle sealing; strabismus surgery
25.  A single-surgeon randomized trial comparing sutures, N-butyl-2-cyanoacrylate and human fibrin glue for mesh fixation during primary inguinal hernia repair 
Canadian Journal of Surgery  2010;53(3):155-160.
We sought to determine the efficacy of sutures, human fibrin glue and N-butyl-2-cyanoacrylate for mesh fixation in patients undergoing the plug and mesh procedure for groin hernia.
A total of 156 patients with 167 inguinal hernias (11 bilateral) underwent a plug and mesh procedure and were randomly assigned to received either sutures (n = 59 hernias), human fibrin glue (n = 52) or N-butyl-2-cyanoacrylate (n = 56) for mesh fixation.
The overall morbidity rate was 38.98% in the suture group, 9.62% in the fibrin glue group and 10.71% in the N-butyl-2-cyanoacrylate group (suture v. fibrin glue, p < 0.001; suture v. N-butyl-2-cyanoacrylate, p < 0.001). There was no significant difference in morbidity between the fibrin glue and N-butyl-2-cyanoacrylate groups. Overall, short-term morbidity was significantly higher in the suture group (27.12%) than in the fibrin glue (9.62%, p = 0.01) or N-butyl-2-cyanoacrylate (8.93%, p = 0.004) groups, but there was no significant difference between the fibrin glue and N-butyl-2-cyanoacrylate groups. There was no significant difference between the groups in terms of mean postoperative stay (32.6 h in the suture group v. 30.8 h in the fibrin glue group v. 32.0 h in the N-butyl-2-cyanoacrylate group) or mean time to return to work (20.4 d in the suture group v. 20.3 d in the fibrin glue group v. 19.8 d in the N-butyl-2-cyanoacrylate group). Overall, long-term morbidity was significantly higher in the suture group (11.86%) than in the fibrin glue (0%, p = 0.001) or N-butyl-2-cyanoacrylate (1.78%, p = 0.03) groups. There was no recurrence in any of the groups. Two cases (3.39%) of chronic groin pain were reported in patients in the suture group. A sensation of extraneous body was reported in 5 (8.47%) patients who received sutures and in 1 (1.78%) patient in the N-butyl-2-cyanoacrylate group; there were no reported cases in the fibrin glue group (suture v. fibrin glue, p = 0.01; suture v. N-butyl-2-cyanoacrylate, p = 0.03; fibrin glue v. N-butyl-2-cyanoacrylate, p = 0.30).
The use of human fibrin glue or N-butyl-2-cyanoacrylate is better tolerated than sutures in tension-free inguinal open repair using the plug and mesh technique in terms of overall immediate results, and there is a better trend in the long-term data.
PMCID: PMC2878998  PMID: 20507786

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