Human Fibrin Sealant Research Articles

Fibrin Sealant (Tisseel) for Hiatal Mesh Fixation in an Experimental Model in Pigs

This study was designed to assess the efficacy of the fibrin sealant fixation of titanized polypropylene mesh in experimental hiatal mesh closure in pigs. Prosthetic hiatal closure is recommended for the repair of large hiatal/paraesophageal hernias as well as for antireflux surgery. However, only limited data exist on the favorable choice of meshes and fixation devices. Migration of the implant and trauma to neighboring organs due to perforating devices, such as sutures or tacks, present potentially lethal complications. In this study, we propose the fixation of titanized polypropylene meshes (TS) specifically developed for hiatal closure (TISure; GfE Medizintechnik GmbH, Nuremberg, Germany) with human fibrin sealant (FS, Tisseel; Baxter Biosciences, Vienna, Austria). A laparotomy was carried out in 7 mini-pigs (27-30 kg bodyweight) under general anaesthesia, and a TS was implanted after precise dissection of the right and left crura and the crural commissure. The key hole of the TS was placed around the esophagus at the gastroesophageal junction. One mL of FS was applied with the Easy Spray system (Baxter Biosciences, Vienna, Austria) for circular and three dimensional mesh fixation onto the diaphragm. Due to the lack of accepted gold standards of hiatal mesh reinforcement, no control group was used. Animals were sacrificed after 4 wk, and meshes were explanted after macroscopical assessment of the correct position and tissue integration. Histology was performed. All meshes showed excellent tissue integration and no signs of migration or dislocation. FS was completely degraded and replaced by well vascularized fibroblastic tissue. Titanized polypropylene mesh with FS fixation was found to be a safe and efficient combination for reinforcement of the hiatal closure in this preliminary experimental model.

Fixation of Tissue-Engineered Human Neocartilage Constructs with Human Fibrin in a Caprine Model

The primary objective of this study was to determine the retention rate of neocartilage constructs in caprine full-thickness cartilage defects by fibrin sealant alone. Two defects, one each on the trochlea and the medial femoral condyle, were created in the stifle joint in 12 goats. Eight goats (16 defects) were treated with neocartilage constructs and 4 goats (8 defects) with fibrin glue alone. Postoperative activity was protected weight bearing for 6 weeks and then unrestricted for 18 weeks. At 24-week procurement, 4 neocartilage constructs were retained in 8 medial femoral defects and 4 in 8 trochlear defects. In gross comparison, the defects that retained the construct had a mean grade significantly higher than defects treated with fibrin glue alone. The mean histological score of defects with retained constructs was also higher than those treated with fibrin sealant alone. There was no appreciable immunologic reaction to the human neocartilage xenograft or human fibrin sealant.

Revascularization of rat fasciocutaneous flap using CROSSEAL® with VEGF protein or plasmid DNA expressing VEGF

Fasciocutaneous tissue transfer is a common reconstructive procedure. Revascularization of flap tissue is an important component of tissue healing. Gene therapy offers an avenue through which the period of pedicle vascular dependency can be reduced. Rat fasciocutaneous flaps were elevated and a two-hour ischemic time induced. Polycation complex (jet PEI) and human fibrin sealant CROSSEAL was applied between flap and underlying abdominal tissues. Group 1 (six rats) was the control; Group 2 (seven rats) had vascular endothelial growth factor (VEGF) protein applied; Group 3 (seven rats) had plasmid DNA expressing VEGF applied. Vascular pedicles were ligated on postoperative day 5, percentage flap survival evaluated on day 7. All flaps survived initial ischemia. Mean +/- SD percentage area of the flap that survived was 28.1 +/- 12.4 (Group 1), 71.6 +/- 16.2 (Group 2), and 77.5 +/- 12.7 (Group 3) (P < 0.001, Group 1-3, 2-3). No differences were observed between Groups 2 and 3. Locally administered VEGF protein or plasmid DNA expressing VEGF enhanced survival of fasciocutaneous flaps.

AEROSTASIS WITH HUMAN FIBRIN SEALANT (EVICEL) IN PATIENTS UNDERGOING PULMONARY RESECTION

PURPOSE: Air leak following pulmonary resection accounts for higher morbidity, and is the most important cause of delayed hospital discharge. It has been proposed that successful aerostasis will result in increased patient comfort, lower rate of complications and decreased hospitalization and cost. In a preliminary study we studied the use of human fibrin sealant (Evicel) in attaining aerostasis following pulmonary resection. This retrospective study was performed as a pilot for a larger multi-institutional prospective randamized trial.

Effective Approach for the Treatment of Bronchopleural Fistula: Application of Endovascular Metallic Ring-Shaped Coil in Combination With Fibrin Glue

The development of bronchopleural fistula is an important complication after pulmonary resections. Generally, conventional treatment methods are used in patients having bronchopleural fistulas. Recently, there has been an increase in the use of minimally invasive methods yielding better results. In our study, we applied a combination of endovascular metallic ring coil and fibrin glue. We hereby think that such an approach for a combination might be a contribution to improving the already existing minimally invasive treatment methods.

The long-term neurocompatibility of human fibrin sealant and equine collagen as biomatrices in experimental spinal cord injury

Introduction While fibrin sealant (FS) and equine collagen (EC) have been used as scaffold materials in experimental spinal cord injury (SCI), questions concerning neurocompatibility still remain. In this study, we assessed potential adverse effects, as well as functional and histological impact of FS and EC in subtotal hemisection of the thoracic spinal cord (SC) in rats. Methods 124 male rats were randomly assigned to four main groups ( n = 31 ): Sham (SH), Lesion only (L), fibrin sealant (GFS) and equine collagen group (GEC). SH animals received laminectomy only; all other animals underwent subtotal lateral hemisection at T9. Treatment consisted of application of FS or EC into the lesion gap in GFS and GEC, which was left empty in L. GFS, GEC, L and SH were each further divided into 4 subgroups: One subgroup, consisting of 10 rats was subjected to behavioural and reflex testing before surgery and followed up on days 1,7, 14, 21, 28 post op and then sacrificed. Haemalaun or cresyl violet (CV) was used to identify neutrophils in parasagittal cord sections which were obtained on day 1 ( n = 7 ). Sections stained for quantification of microglia/macrophages using ED-1 on day 3 ( n = 7 ), day 7 ( n = 7 ) and day 28 ( n = 7 out of 10). Additionally, neural filament (NF) staining was chosen to detect axonal regeneration and the length of ingrowth into FS and EC, Luxol blue for myelination, Von Willebrand factor for vascularisation, and glial fibrillary acidic protein (GFAP) staining for detection of astrocytes in glial scars on day 28. Results No adverse effects were observed in the treatment groups. Compared to L, GFS and GEC performed significantly better in the Basso, Beattie, Bresnahan (BBB) score and hopping responses. Proprioceptive placing was markedly improved in FS and EC compared to L. Axonal regrowth was found in GFS and GEC – the regrowth in the GFS was accompanied by myelination and vascularisation. Glial scarring occurred in all groups. Discussion Both biomatrices improved functional recovery compared to L and no adverse effects were perceived.

Skin graft fixation by slow clotting fibrin sealant applied as a thin layer

Human fibrin sealant (FS) has been proven effective for skin grafting after severe burn, however no systematic evaluation of application conditions has been performed so far. In order to find the optimal FS amount for fixation of skin grafts to deep defects, we created four full thickness wounds (8 cm × 4 cm) on the dorsum of six male pigs. Wounds were covered with unmeshed split thickness skin grafts and fixed either with a thin layer (0.05 ml/cm 2) or a thick layer (0.15 ml/cm 2) of fibrin sealant (FS) without additional sutures. Sutures served as controls. FS was used as a slow clotting spray (4–5 IU thrombin/ml). Outcome measurements revealed that hematoma formation (day of surgery) was more extensive and occurred more frequently in the suture group as compared to FS 0.05 ml/cm 2 ( p < 0.05). Areas of graft dislocation tended to be larger in the suture group versus the FS 0.05 ml/cm 2. The FS 0.05 ml/cm 2 graft take on day 5 appeared to be enhanced in comparison to the suture group. Excellent outcome was notable on the final observation day (day 21) in the FS 0.05 ml/cm 2 group with a take of 99.7% (IQR 96.1–100%). Corresponding values in the FS 0.15 ml/cm 2 group were 96.9% (IQR 92.2–99%) and 95.9% (IQR 93.2–98%) in the suture group. The results indicate, that the usage of a sprayed thin FS layer (0.05 ml/cm 2) in a slow clotting rate (4–5 IU thrombin/ml) is an appropriate fixation method in split thickness skin transplantation.

Fibrin Glue: An Alternative Technique for Nerve Coaptation-Part II. Nerve Regeneration and Histomorphometric Assessment

The results of nerve repair with fibrin glue and microsuture were evaluated in rat nerve transection models. Ninety Wistar-Furth rat median nerves were exposed, transected, and repaired in an end-to-end fashion with one of four substances/techniques: 1) human fibrin sealant (Quixil); 2) autologous graft and human fibrin sealant (Quixil); 3) bovine fibrin sealant (Tissucol); and 4) nylon microsuture, epineurial technique. Histologic analyses were performed at 3-, 6-, and 9-month postoperative intervals, and factors evaluated included: presence of inflammatory cells (i.e., macrophages and T cells); number of Schwann cells at the repair site; number of blood vessels; fibrosis; axonal regeneration; and fiber alignment. An additional group underwent histologic analysis at 3 weeks following repair with Quixil. Surgical time of repair was also measured. Nerve repairs performed with fibrin sealants produced less inflammatory response and fibrosis, and better axonal regeneration and fiber alignment than nerve repairs performed with microsuture. In addition, the fibrin sealant techniques were quicker and easier to use. The authors conclude that fibrin sealant represents a good alternative technique to microsuture for peripheral-nerve repair.

Fibrin Glue: An Alternative Technique for Nerve Coaptation-Part I. Wave Amplitude, Conduction Velocity, and Plantar-Length Factors

The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n = 15) or Quixil fibrin glue (n = 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively. Rats receiving Quixil nerve repair returned to baseline performance on the walking-track analysis significantly faster than those with microsuture repairs (6 and 12 weeks postoperatively; p < 0.0001). Recovery of nerve conduction velocities and wave amplitudes was also significantly better in the nerves repaired with Quixil than in those repaired with microsuture (p's < 0.0001). Quixil human fibrin sealant is a good alternative to traditional microsuture nerve repair techniques.

Biphasic ceramics and fibrin sealant for bone reconstruction in ear surgery.

Bone reconstruction is still a matter of concern in middle ear surgery despite the large number of surgical techniques proposed. A composite made of biphasic calcium phosphate ceramic granules mixed with human fibrin sealant, forming a moldable material that is easy to set for bone reconstruction, has been used with success over a 16-year period for reconstruction of the posterior canal wall or for mastoid obliteration. In a retrospective series of 72 ears with long-term follow-up (average follow-up of 46 months), regular microscopic examination, and computed tomographic controls, we have evaluated this bone reconstruction technique for radical mastoidectomy cavities or the closed technique. The bone reconstruction material provided an immediate anatomic reconstruction that remains stable and is well tolerated over the long term. A slight leakage of granules in the meatus was initially observed in several patients with transient aseptic otorrhea. Fifty-seven ears were followed up for 1 year or more. Satisfactory clinical results with complete regression of the mucous membrane disease were found in 82.4% of the patients, with perfect stability of the material in 65%. We did not observe any cases of recurrent cholesteatoma in or behind the filling material. Eighteen biopsies were performed between 8 and 84 months after surgery during a second surgical step performed for functional purposes or for recurrent cholesteatoma; 17 of the 18 cases showed osteointegration of the filling material. After a 16-year experiment, we consider this technique to be a highly satisfactory procedure that could be extended to other situations of bone reconstruction.

Micro macroporous biphasic ceramics and fibrin sealant as a moldable material for bone reconstruction in chronic otitis media surgery. A 15 years experience.

Bone reconstruction is still a matter of concern in middle ear surgery despite the large number of surgical techniques proposed. Combination of biphasic calcium phosphate bioceramics with human fibrin sealant forms a moldable material easy to apply for bone reconstruction. Since 1986, we have been using this composite for reconstruction of mastoid cavities during chronic otitis media surgery. Granules of ceramic provide immediate mechanical stability and later on, promote osseoinduction when fibrin sealant forms a strong bond between granules enhancing the wound healing process. After checking feasibility, efficacy and tolerance through a controlled study on dogs by filling mastoid cavities, we started a clinical series comprising yet 66 mastoid reconstructions. A retrospective data analysis on 63 patients with an average follow up of 42 months including 12 histological controls confirms the stability of bone reconstruction with a remarkable tolerance of the skin in contact. Biopsies confirmed progressive replacement of material by lamellar newly formed bone. Mastoid cavities have a randomed shape making complex bone reconstruction procedure and their filling by the composite constitutes an easy way and represents a highly satisfactory procedure. The authors considered that this should be explored in other indications of bone surgery.

Evaluation of fibrin sealants in cutaneous wound closure.

Human fibrin sealant (HFS) and bovine fibrin sealant (BFS) were delivered as preformulated fibrinogen-thrombin mixtures that are light activated. These formulations were evaluated in the healing of incised cutaneous wounds in beagle dogs. Four groups were differentiated by sealant type and study duration with group: BFS for 10 days, HFS for 10 days, BFS for 30 days, and HFS for 30 days. Healing was evaluated by noting incidences of open wounds, laser Doppler perfusion imaging (LDPI), planimetry, breaking strength, and histopathology. In the absence of tension, both sealants tended to hold wound edges together; however, HFS tended to be better than its controls and BFS. Both sealants augmented suture closure, necessitating fewer sutures for wound closure. At 5 and 30 days BFS wounds had more perfusion than HFS wounds, indicating more inflammation. At 10 and 30 days BFS wounds had larger scar areas than their controls, while scar areas of HFS wounds were smaller than either BFS wounds or controls. Breaking strengths indicated that HFS wounds were stronger than their controls and BFS wounds. Histologically, mild to moderate chronic-active inflammation was observed in wounds receiving either sealant, and this persisted longer in BFS wounds. Overall, HFS had positive qualities, thus showing potential for functional and cosmetic wound closure.

98. Characterization of fully recombinant human fibrin sealant

98. Characterization of fully recombinant human fibrin sealant

Haptotactic and growth stimulatory effects of fibrin(ogen) and thrombin on cultured fibroblasts

We tested the ability of purified, ultraviolet C virally inactivated components of human fibrin sealant (FS) to modulate the chemotaxis, adherence, and proliferation of cultured cells. A fibrin clot formed on a near-confluent layer of human fibroblasts (HFs) recruited cells from the surrounding area. Thrombin (Thr) enhanced HF proliferation by a factor of 1.5 to 1.8, whereas fibrinogen (Fib) exerted only a minimal proliferative effect. We developed a new cell haptotactic/attachment assay by using Thr and Fib covalently bound to Sepharose beads (SBs). The kinetics of cell binding were approximately equivalent for beads coated with either protein. Uncoated SBs or fibrinogen-bound SBs (Fib-SB) pretreated with plasmin did not attract HFs. γThr-SB induced a positive migratory response that was not affected by blocking its proteolytic site, whereas γThr-SB elicited no response. X irradiation of HFs at a dose of 6 Gy showed that the migratory response of HF is independent of proliferation, as confirmed by a bromodeoxyuridine uptake assay. Several types of cultured cells (murine fibroblasts, smooth muscle cells, aortic endothelial cells, and murine mammary carcinoma cells) also attached to Fib-SB. By contrast, human keratinocytes, human ovarian carcinoma cells, murine macrophage-like cells, leukemic cells, and murine mast cells did not attach. Our results provide some mechanistic insights into the haptotactic and proliferative effects of Fib and Thr on different cells.

Hemostatic efficacy of a fibrin sealant-based topical agent in a femoral artery injury model: a randomized, blinded, placebo-controlled study.

The efficacy of currently available topical hemostatic agents requires the formation of fibrin generated from circulating blood. Fibrin sealant, which is prepared from high concentrations of thrombin and fibrinogen, has been used in liquid form to promote hemostasis during vascular surgery. In a blinded, randomized, placebo-controlled fashion, we evaluated a dry dressing of purified, viral-inactivated human fibrinogen and human thrombin in a large animal model of arterial injury. Dressings were prepared by application of a layer of lyophilized human fibrin sealant or immunoglobulin G (IgG, control) to a silicone backing material. Six anesthetized female Yorkshire pigs (16 to 27 kg) received bilateral, 4 mm longitudinal femoral arteriotomies after surgical exposure of the arteries. The arteriotomies were not closed. In each animal a fibrin sealant dressing was applied to one artery and a control dressing to the other. Each dressing was secured on the arteriotomy by a mechanical device. After application of the dressings, blood flow was restored to each limb for 1 hour. The compressive device was released for 5 seconds at intervals of 15 minutes to assess hemostasis. Blood flow was measured distal to each arteriotomy with a dual-channel flowmeter to adjust equal bilateral compression. Blood loss (mean +/- SEM) was significantly less from the arteriotomy treated with the fibrin-based dressing compared with the control dressing (4.9 +/- 4.0 ml versus 82.3 +/- 11.1 ml; p = 0.0005). Complete hemostasis was achieved at the first 15-minute interval in five of six arteriotomies treated with fibrin sealant and in none of the six control arteriotomies during 1 hour of assessment (p = 0.03). Blood flow through each femoral artery at baseline was the same in both treatment and control arteries (fibrin sealant, 114.2 +/- 17.4 ml/min; control, 106.7 +/- 16.5 ml/min; p = 0.24) and was not significantly different throughout the experiment. Fibrin-based dressings provide effective hemostasis in a large animal model of arterial injury. Further development of these dressings will address optimal formulation and configuration for clinical use. Our results suggest that fibrin-based dressings will be effective in promotion of hemostasis in arterial bleeding, without compromising blood flow.

Fibrin sealant in laparoscopic adhesion prevention in the rabbit uterine horn model

To assess the effects of fibrin sealant on adhesions after laparoscopic surgery. Standardized surgical trauma was induced in 60 female rabbits. The animals were randomized in three groups for different adhesion prevention treatment. University research laboratory. After standardized trauma was induced, group 1 (n = 20) received no treatment, group 2 animals (n = 20) were injected in the abdominal cavity with 60 mL of Ringer's lactate, and human fibrin sealant was applied on the surgical lesions under laparoscopic vision in group 3 (n = 20). Five weeks after laparoscopy, a laparotomy was performed, and the adhesions were scored. Fourteen of 20 rabbits in the control group (70%) presented postoperative adhesions, 11 of 20 (55%) in the Ringer's group, and 5 of 20 (25%) in the fibrin sealant group. High-score adhesions were seen in 15% of cases in control and Ringer's group and in 5% of cases in the fibrin sealant group. When used during laparoscopic surgery, fibrin sealant has a preventive effect on de novo postsurgical adhesions. To assess the efficacy in reproductive surgery, a trial on recurrent postsurgical adhesions is required.

Delivery and activity of antimicrobial drugs released from human fibrin sealant.

Engraftment and healing of native or cultured skin grafts depend on adherence, vascularization, and control of microbial contamination in the wound bed. Fibrin sealant is a biocompatible polymer that may be used to promote skin engraftment by serving as a delivery vehicle for antimicrobial drugs. Human fibrin sealant (25 mg/ml) was polymerized with antibacterial agents (mupirocin [32 micrograms/ml], nitrofurazone [0.02% wt/vol], polymyxin B [400 U/ml], or norfloxacin [20 micrograms/ml]) on nitrocellulose (nc) backing and was prepared as 6 mm diameter discs with skin punches. Discs (n = 6) were applied in the Wet Disc Assay to clinical isolates of Staphylococcus aureus (mupirocin, nitrofurazone) or Pseudomonas aeruginosa (polymyxin B, norfloxacin). Controls included drug applied to 6 mm paper discs (25 microliter) and nitrocellulose discs submerged in each drug, blotted, and applied to bacterial cultures on agar in petri dishes. Data were expressed as zone of clearing (mm diameter +/- SEM) after overnight incubation at 35 degrees C. Significant differences (ANOVA and Turkey's test, p < 0.05) were found for each drug released from the disc of fibrin sealant compared with other vehicles. Release from filter paper discs compared with nitrocellulose was significant for nitrofurazone and norfloxacin. Serial transfer of fibrin discs to fresh bacterial cultures after 24 hours showed no zones of clearing. The data show that fibrin sealant releases topical drugs with no inhibition of antimicrobial activity on burn organisms. Greater zones of clearing from fibrin sealant may result from passive fluid retention or from active binding to fibrin followed by protease digestion by burn organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Sections récentes des tendons fléchisseurs des doigts et du pouce: Orientations thérapeutiques nouvelles A propos d'une série clinique de 77 lésions tendineuses

In flexor tendon surgery, the main concern of hand surgeons in the last two decades has been to find an effective and reproducible means to avoid post-operative adhesions. For most authors, these adhesions were responsible for the bad results. Since 1960, a constant progress has been achieved with the progress in operative procedures and the better understanding of tendon healing process. Post-operative rehabilitation, especially Kleinert's and Duran's active and passive methods, have radically transformed the prognosis of fresh tendon lesions. In spite of all this progress, zone II tendon injuries are still a difficult problem. In this clinical study, we wanted to introduce two new orientations in order to improve the overall results, the use of human fibrin sealant instead of the epitendinous running suture and an improvement of Duran's technique, developed by the Bichat rehabilitation team since 1987. Seventy-seven tendon lesions treated according to our technique (55 fingers and 22 thumbs) between 1987 and 1991, were reviewed. All the lesions studied were in zone II and T II. The mean follow-up is 14.4 months. The evaluation is based on the International Federation of Hand Surgery score for fingers, and the Tubiana score for thumbs. 74% of fingers and 86% of thumbs were scored as good and excellent.