A comparative high-resolution physicochemical analysis of commercially available fibrin sealants: Impact of sealant osmolality on biological performance.

Fibrin sealants are well-established components of the surgical toolbox, especially in procedures that harbor a high risk of perioperative bleeding. Their widespread use as hemostats, sealants or tissue-adhesives in various surgical settings has shown that the choice of the appropriate sealant system affects the clinical outcome. While many studies have compared the hemostatic efficiency of fibrin sealants to that of other natural or synthetic sealants, there is still limited data on how subtle differences in fibrin sealant formulations relate to their biological performance. Here, we performed an in-depth physicochemical and biological characterization of the two most commonly used fibrin sealants in the US and Europe: TISSEEL™ ("FS") and VISTASEAL™/VERASEAL™ ("FS+Osm"). Our chemical analyses demonstrated differences between the two sealants, with lower fibrinogen concentrations and supraphysiological osmolality in the FS+Osm formulation. Rheological testing revealed FS clots have greater clot stiffness, which strongly correlated with network density. Ultrastructural analysis by scanning electron microscopy revealed differences between FS and FS+Osm fibrin networks, the latter characterized by a largely amorphous hydrogel structure in contrast to the physiological fibrillar network of FS. Cytocompatibility experiments with human fibroblasts seeded on FS and FS+Osm fibrin networks, or cultured in presence of sealant extracts, revealed that FS+Osm induced apoptosis, which was not observed with FS. Although differential sealant osmolality and amounts of fibrinogen, as well as the presence of Factor XIII or additives such as antifibrinolytics, may explain the mechanical and structural differences observed between the two fibrin sealants, none of these substances are known to cause apoptosis at the respective concentrations in the sealant formulation. We thus conclude that hyper osmolality in the FS+Osm formulation is the primary trigger of apoptosis-a mechanism that should be evaluated in more detail, as it may affect the cellular wound healing response in situ.

Enhancement of withstanding pressure of fibrin sealant by modified mixing ratio of fibrin sealant components for skull base reconstruction: technical note.

A method to enhance the withstanding pressure of fibrin sealant in gasket-seal closure to prevent cerebrospinal fluid (CSF) leakage after extended transsphenoidal surgery (ETSS) was investigated by adjusting the mixing ratio of the components. A plastic chamber (200 ml) was constructed with a lid made of hydroxyapatite with a hole 10 mm in diameter. The chamber could be pressurized via an opening in the side wall. The hole in the hydroxyapatite lid was covered with a Gore-Tex sheet, 15 mm in diameter. The margin of the sheet was free. Solutions A (fibrinogen 80 mg/ml) and B (thrombin 250 units/ml) of fibrin sealant were mixed in volume ratios of 1:1, 2:1, and 5:1, and applied to the Gore-Tex sheet, then water was introduced to cover the fibrin sealant. The pressure was measured at which air leakage occurred from the side of the Gore-Tex sheet. The pressure values for A/B ratios of 1:1, 2:1, and 5:1 were 117 ± 23.8 mmH(2)O (mean ± standard error) (n = 5), 234 ± 38.8 mmH(2)O (n = 5), and 345 ± 36.4 mmH(2)O (n = 5), respectively, in the acute phase (5 minutes after application of fibrin sealant). Pressures were increased after 24 hours, and that for 5:1 was the highest (373 ± 40.4 mmH(2)O, n = 5). The use of devices such as syringes specially designed to mix solutions A and B in the ratio of 5:1 can easily enhance the preventive effect of fibrin sealant against CSF leakage in ETSS.

Ensaio clínico randonizado e duplo cego de curatios bioativos: cola de fibrina versus gel de papaína® no processo de cicatrização de úlceras crônicas de etiologia venosa / Randomized clinical essay and double-blind bioactive curatives: fibrin glue against papaya gel in the healing process of the chronic ulcers in a venous etiology

A UV traduz um dos estágios mais avançados da doença venosa crônica (DVC), e esta apresenta elevada morbidade pela sua cronificação e recidivas frequentes. Constitui importante problema de saúde pública por alterar a qualidade de vida do indivíduo e elevar o ônus público, já que os tratamentos são longos e dispendiosos. Apesar dos fatores de risco e a etiopatogenia desta doença serem conhecidos, grande parte da população usuária do sistema público de saúde não possui diagnóstico e tratamento precoces da DVC, resultando assim em evolução clínica tormentosa da doença. A dificuldade de avaliação com profissionais especializados predispõe a evolução da UV. Quando manejadas de formas inadequadas, as UVs tendem a tornar crônico o processo de cicatrização e ficam sujeitas a complicações como colonização crítica e infecção de partes moles. Esta revisão procura reunir informações atualizadas sobre a epidemiologia da DVC (enfocando principalmente dados do Brasil). Além disso, serão discutidos os fatores de risco, a etiopatogenia da UV e suas manifestações clínicas. Finalmente será feita uma atualização sobre os métodos auxiliares do processo de cicatrização da UV, expondo os avanços ao conhecimento relacionados a esta área, incluindo o preparo do leito da úlcera. O objetivo é propor mudanças que favoreçam a quebra do ciclo pernicioso da UV.

The VU is one of the most advanced stage` s chronic venous disease (CVD), and it has a high morbidity, because your recidivates are chronics and happens frequently. It is an important public health problem, because it modifies the quality of an individual and put up the public costs, since the medical treatment are longs and expensive. In spite of the risk factors and the studies of this disease are knew, a very part of the population, that use the public health utilities, don`t have diagnosis and CVD`S precocious medical treatment, for this reason the disease evolution is very hard. There is the evolution of the VU, because it is very difficult to evaluate it with an expert professional. The VUs can become chronics in a healing process, when they are badly controlled; they can dominate it and contaminate the soft parts. The objective of this revision is to join current in formations about CVD`s epidemiology (mainly Brazilian documents). Besides, the risk factors, the VU`s path physiology and their clinic manifestations will be discussed Finally, will be done an update about the auxiliary methods of the VU`s healing process, showing the know advances in this area, and how to prepare an ulcer bed. The object is to suggest changes that finish the VU`s pernicious cycle.

Release of bioactive adeno-associated virus from fibrin scaffolds: effects of fibrin glue concentrations.

Fibrin glue (FG) is used in a variety of clinical applications and in the laboratory for localized and sustained release of factors potentially important for tissue engineering. However, the effect of different fibrinogen concentrations on FG scaffold delivery of bioactive adeno-associated viruses (AAVs) has not been established. This study was performed to test the hypothesis that FG concentration alters AAV release profiles, which affect AAV bioavailability. Gene transfer efficiency of AAV-GFP released from FG was measured using HEK-293 cells. Bioactivity of AAV transforming growth factor-beta1 (TGF-ß(1)) released from FG was assessed using the mink lung cell assay, and by measuring induction of cartilage-specific gene expression in human mesenchymal stem cells (hMSCs). Nondiluted FG had longer clotting times, smaller pore sizes, thicker fibers, and slower dissolution rate, resulting in reduced release of AAV. AAV release and gene transfer efficiency was higher with 25% and 50% FG than with the 75% and 100% FG. AAV-TGF-ß(1) released from dilute-FG transduced hMSCs, resulting in higher concentrations of bioactive TGF-ß(1) and greater upregulation of cartilage-specific gene expression compared with hMSC from undiluted FG. This study, showing improved release, transduction efficiency, and chondrogenic effect on hMSC of bioactive AAV-TGF-ß(1) released from diluted FG, provides information important to optimization of this clinically available scaffold for therapeutic gene delivery, both in cartilage regeneration and for other tissue engineering applications.

Platelet-rich fibrin versus albumin in surgical wound repair: a randomized trial with paired design.

OBJECTIVE: To study the effects of autologous platelet-rich fibrin (PRF) versus human albumin on incisional wound breaking strength and subcutaneous collagen deposition in patients undergoing laparoscopic cholecystectomy in a randomized trial. SUMMARY BACKGROUND DATA: Platelet peptidic growth factors may stimulate collagen synthesis and tissue repair. METHODS: One expanded polytetrafluoroethylene (ePTFE) tube was inserted subcutaneously from the edge of each of the two 10-mm trocar incisions in 51 patients. Treatment with PRF prepared from the patient's own blood or human albumin was randomized to respective wound site by concealed allocation. On postoperative day 10, breaking strength of the incisional wounds as well as the collagen concentration, type I procollagen mRNA, type III procollagen mRNA, matrix metalloproteinase-1 mRNA, and fibroblast density in the ePTFE tubes were determined. All analyses were assessor-blinded. The trial was registered in the Current Controlled Trials Registry (ISRCTN34481461). RESULTS: Local PRF had no significant effect on incisional wound-breaking strength. In the ePTFE tubes, PRF treatment decreased collagen concentration by 24% (P=0.046) and type I procollagen mRNA level by 29% (P=0.003), but had no significant impact on type III procollagen mRNA, matrix metalloproteinase-1 mRNA or fibroblast infiltration. The profibrotic transforming growth factor-beta1 level increased (P<0.0001) 2-fold with PRF. Collagen concentration in albumin-treated ePTFE tubes correlated with breaking strength of the skin incisions (rs=0.48, P=0.03). CONCLUSIONS: PRF did not improve wound strength significantly compared with albumin but suppressed subcutaneous collagen synthesis and deposition during early repair of surgical wounds in humans. Furthermore, deposition of reparative collagen in the subcutaneous ePTFE tube model partly predicted the breaking strength of an incisional skin wound.

Fijación con sutura frente a sellante de fibrina en hernioplastia con prótesis reabsorbible (ácido poliglicólico y carbonato trimetileno). Estudio experimental en animales / Mesh fixation with sutures versus fibrin sealant in hernioplasty with re-absorbable prosthesis (polyglycolic acid and trimethylene carbonate). Experimental study in animals

Introducción Dado que estudios actuales han mostrado la validez de la fijación atraumática con cola de fibrina (Tissucol®) frente a las suturas convencionales con malla de polipropileno, en este trabajo se quiere estudiar el comportamiento en las mallas reabsorbibles. Material y métodos Se utilizaron 20 ratas blancas Wistar. Se realizaron 2 defectos herniarios en la pared abdominal, que se repararon de forma preperitoneal con malla reabsorbible de ácido poliglicólico y carbonato trimetileno, en el lado de la derecha la malla se fijó con Tissucol® y en el lado de la izquierda se fijó con sutura convencional fijada a la fascia muscular. Se sacrificaron 10 ratas a los 14 días (serie A) y el resto a los 28 días (serie B). Se emplearon para comprobar la contingencia de la pared abdominal 2 test; el test de presión: neumoperitoneo mayor de 40mmHg mantenido durante 1min, y el test de tracción: dinamometría de la zona afectada mayor de 300g de tracción por cm2. Se analizó la pared abdominal para determinar la integración de la malla de nueva generación. Resultados La fijación de la malla tras los test de presión y de tracción no evidenció alteraciones estadísticamente significativas en los 2 grupos. La integración de la malla fue mayor en los casos de fijación con cola de fibrina, donde se observó un aumento del número de neovasos. Conclusiones La fijación con colas biológicas de fibrina equiparó a la convencional. La malla reabsorbible se integró adecuadamente y se comprobó que tanto la neoformación vascular como la propia integración de la malla es más notable al aplicar el sellante de fibrina que con la sutura convencional. (AU)

Introduction Current studies have shown the validity of the atraumatic fixation with fibrin glue (Tissucol®) compared to conventional sutures in polypropylene mesh fixation. We propose to study the behaviour of absorbable mesh. Material and methods We used 20 Wistar white rats. Two hernia defects were made in the abdominal wall, which were repaired using absorbable PGA-TMC preperitoneal mesh. The right side of the mesh was fixed with Tissucol and left side with conventional suture attached to the muscle fascia. One group of 10 rats were sacrificed at day 14 (Series A) and the other 10 rats at 28 days (Series B). We used two tests to assess the contingency of the abdominal wall; Pressure Test: pneumoperitoneum more than 40mmHg maintained for 1min, Traction Test: dynamometry of the affected area more than 300mg per cm2 of traction. Abdominal wall was analysed to determine the integration of the new generation mesh. Results The fixation of the mesh after the pressure and traction tests showed no statistically significant changes in either group. The integration of the mesh and vessel neoformation was higher in the cases of fixation with fibrin glue. Conclusions Biological fixation with fibrin glue is similar to the conventional. Absorbable mesh was suitably integrated and vascular neoformation and integration of the mesh was also found to be better than conventional sutures when fibrin sealant was applied (AU)

The contribution of platelets in the production of cryoprecipitates for use in a fibrin glue.

BACKGROUND AND OBJECTIVES: Cryoprecipitate has a wide application for use as a fibrin glue. In some situations, platelets are added to the preparation in order to enhance the fibrin glue. MATERIALS AND METHODS: Fresh plasma was collected by apheresis from the same donor to produce 250 ml of platelet-rich plasma (PRP) or platelet-poor plasma (PPP) (n = 12 each). Cryoprecipitate was then produced following the standards of the American Association of Blood Banks and resuspended to a total volume of 8 ml, from which aliquots were removed and assayed. Clot formation was measured using the thromboelastogram. RESULTS: The protein content of the two preparations was identical for PRP and PPP. Results for fibrinogen (PPP 475 +/- 220 mg; PRP 399 +/- 215 mg), Factor VIII (PPP 186 +/- 67 IU; PRP 175 +/- 70 IU) and von Willebrand Factor (PPP 260 +/- 104 IU; PRP 221 +/- 88 IU) were not significantly different. The concentration of platelet-derived growth factor was markedly higher (a 100-fold increase at 3778 +/- 1036 ng) when platelets were added to the plasma. There was a small, but not statistically significant, difference in the rate of clot formation (R = 2.3 for PPP and 3.8 for PRP) and clot strength (MA = 63.4 for PPP and 56.6 for PRP) between PPP and PRP cryoprecipitates when measured using the thromboelastogram. CONCLUSIONS: Platelets do not significantly increase the concentration of the usual constituents of cryoprecipitate; however, the levels of platelet-derived growth factor are markedly enhanced. Therefore, there are advantages for using PRP to enhance the growth of new tissue.

Micro-architecture of calcium phosphate granules and fibrin glue composites for bone tissue engineering.

Calcium phosphate ceramics are currently used as bone graft substitutes in various types of clinical applications. Fibrin glue is also used in surgery due to its haemostatic, chemotactic and mitogenic properties. By combining these two biomaterials, new composite scaffolds were prepared. In this study, we attempt to analyse whether thrombin concentration in the fibrin glue could influence the properties of the composite. The association between fibrin glue and calcium phosphate ceramic granules was characterized at the ultra structural level. Micro and macroporous biphasic calcium phosphate ceramic granules with a diameter of 1-2mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) were associated to fibrin glue. The composites were observed by scanning and transmission electron microscopy and microcomputed tomography. Fibre thickness, porosity and homogeneity of the fibrin clot were modified by increased the thrombin concentration. Mixing fibrin glue with calcium phosphate granules (1:2) did not modify the microstructure of the fibrin clot in the composite. Nevertheless, thrombin interacted with the bioceramic by inducing the nucleation of crystalline precipitate at the ceramic/fibrin glue interface. Combining fibrin sealant and calcium phosphate ceramics could lead to new scaffolds for bone tissue engineering with the synergy of the properties of the two biomaterials.

Biochemical characterization of autologous fibrin sealants produced by CryoSeal and Vivostat in comparison to the homologous fibrin sealant product Tissucol/Tisseel.

Different principles for production of "autologous fibrin sealant" have been established, and commercial devices employing these methods are nowadays available and used in clinical routine. Users might anticipate for these autologous fibrin sealants features comparable to commercial homologous fibrin sealants, used in surgical routine for many years. However, only little is known about biochemical properties, formation, cross-linking and stability of fibrin sealant clots produced for autologous use with the aid of commercially available devices. We have investigated protein composition, formation and stability of clots obtained from autologuous fibrin sealants produced with commercially available devices (CryoSeal and Vivostat) and compared these parameters to those of the industrially produced homologous fibrin sealant Tissucol/Tisseel. The CryoSeal product is a mixture of many plasma proteins; the Vivostat product and Tissucol/Tisseel appear as comparatively pure plasma derivatives. The products differ in their protein composition and concentrations, including their concentration in fibrin. Significant fibrin alpha and gamma-chain cross-linking by FXIIIa occurs only in Tissucol/Tisseel clots. In test tubes CryoSeal and Vivostat (tranexamic acid-free formulation) fibrin clots liquefy within 1-2 days, but Vivostat (tranexamic acid containing formulation) clots were stable for 4 days and showed partial liquefaction after 5 days. Tissucol/Tisseel clots, containing the protease inhibitor aprotinin, appeared unchanged over the observation period of 5 days. In an in vitro model mimicking in vivo conditions (diffusion of protease inhibitors and proteolytic digestion) clot liquefaction occurs at day 1 for all autologous fibrin sealants clots, with an observable delay for the tranexamic acid containing Vivostat, and day 5 for Tissucol/Tisseel clots. Characterization of the CryoSeal and Vivostat fibrin sealants and Tissucol/Tisseel and their performance show a clear difference in biochemical properties.

Quality control assessment of ePTFE precoating procedure for in vitro endothelial cell seeding.

Over the past two decades, in vitro autologous endothelial cell (EC) coverage of expanded polytetrafluoroethylene (ePTFE) graft has been developed and clinically applied with success in infrainguinal bypasses. Before endothelialization, the luminal surface of the graft has to be coated with a currently used fibrinolytically inhibited fibrin glue. The aim of this work is to validate the precoating of the ePTFE (4 mm ID) ringed graft with fibrin. Twenty cm-long grafts were precoated with fibrin glue (2 operators) then fixed for microscopy investigations. Grafts were sliced into 3 regions. Thickness analysis was evaluated by image processing. Three grafts have been tested for endothelialization and observed at days 3, 8. Cell-free coated ePTFE were imaged using high-frequency ultrasound modality. Whatever the examined segment an overall homogeneous covering protein is shown. Fibrin thickness after image processing is 8.5+/-0.25 and 4.1+/-0.4 microm for two operators (P < .001). We have evaluated reproducibility and inter- and intra-variability of the operator, assessed quality controls and quality assurance all along the prosthesis and finally endothelialization and subsequent behaviour under shear stress conditions.

A review of bioceramics and fibrin sealant.

This review focuses on bone substitute composites made by mixing ceramic biomaterials with fibrin sealants. Different biomaterials such as coral, bone-derived materials, bioactive glass ceramics, and synthetic calcium phosphate have been mixed with fibrin sealant, resulting in a combination of the biological properties of the two components. This type of association has not produced identical results in all studies. In the past for some, the addition of fibrin sealant to the biomaterial failed to produce any significant, positive effect on osteointegration, whereas others found a positive impact on bone colonization. Despite the negative biological effects reported previously, bioceramic-fibrin composites have been widely used in various types of bone surgery because they are easy to manipulate. In particular, the intra-operative preparation of these composites makes it possible to add bone growth factors or autologous osteoprogenitor cells prior to bone reconstruction. The bone growth factors and autologous osteoprogenitor cells associated with the bioceramic-fibrin composites should provide surgeons with tissue engineered grafts with enhanced osteointegrative properties. This review discusses both the advantages and disadvantages, as well as the future perspectives, of using bioceramic-fibrin composites in various clinical indications.

Estudo morfológico da regeneração axonial na síntese terminolateral de nervo periférico de ratos com adesivo de fibrina e micro-sutura / Morphological study of axonal regeneration in mice peripherical nerve terminolateral synthesis with fibrin adhesive and microsuture

Quando um nervo periférico é seccionado, com freqüência, há um intervalo variável entre os cotos. Se esta distância é muito grande ou o leito aonde serão colocados os enxertos nervosos não é adequado, podese usar os reparos terminolaterais. Existe, na literatura médica, uma expressiva quan- tidade de trabalhos experimentais sobre este tipo de reparo que constatam resultados satisfatórios com a utilização de fio de poliamida 9-0 e sem a retirada do epineuro. O objetivo deste trabalho é mostrar as alterações morfológicas do reparo terminolateral comparando o adesivo de fibrina ao fio de poliamida. Criou-se dois grupos (A e B) com 11 ratos em cada um deles. No grupo A foi realizado, de um lado, o reparo terminolateral entre o nervo tibial e o fibular com fio de poliamida. No grupo B, no lado contra-lateral, realizouse o mesmo procedimento com adesivo de fibrina. Os animais operados foram observados até o nonagésimo dia de pós-operatório. Sob microscopia óptica contou-se o número de axônios regenerados e seu diâmetro. Do ponto de vista morfológico não se encontrou nenhuma diferença entre os tipos de sínteses empregados. Pode-se, entretanto, inferir que o adesivo de fibrina diminui o tempo operatório e não causa lesões no nervo doador.

When a peripheral nerve is sectioned there is frequently a gap between the stumps. If the distance between them is too wide or there is a lot of fibrosis, we can use the end-to-side repair. In the medical literature, there are quite a few experimental papers about this kind of repair with good results using nylon 9-0 without epineural removal. The objective of the present paper is to show the morphologic alterations of the end to side repair, comparing the fibrin glue with the nylon. For that purpose, we used two groups (A and B) with 11 rats each. In group A, it was conducted, on one side, an end-to-side repair of the tibial and fibular nerves with nylon. In group B, on the other side, we did the same procedure using fibrin glue. The operated animals were observed until the 90th day after the surgery. With optic microscopy, we counted the axons and their diameter. Morphologically, there was not any statistical difference between the two groups. However, one can infer that the fibrin glue reduces the operative time, and does not cause lesion in the donor nerve.

Characterizing fibrin glue performance as modulated by heparin, aprotinin, and factor XIII.

We describe the performance of fibrin glue (FG) as modulated by heparin, aprotinin, or factor XIII levels. In vitro tests and a rat kidney excision model demonstrated that the hemostatic efficacy of fibrin was not modulated by aprotinin. Overlapping rat skin sections demonstrated that adhesion strength (AS) was proportional to the area of overlap as well as to fibrinogen levels. AS was not modulated by exogenous heparin or aprotinin and was independent of the endogenous factor XIII in fibrinogen. SDS-PAGE developed by Coomassie or Western blots with anti-gamma chain antibody confirmed that normal skin sections contain adequate trans-glutaminase to maximally cross-link normal, as well as XIII-depleted, fibrin. Fibrin glue (FG) sprayed onto rat skin incision wounds with a dual channel spray applicator acted in 2 phases: initially (day 1), compared to wounds stapled without or treated with only thrombin, FG significantly increased breaking strength. In the second phase of wound healing (after day 3), all groups achieved increased but equivalent breaking strength. FG containing aprotinin (to 3000 U/m; Immuno, Behringwerke, Germany) exhibited initial tissue bonding strength equivalent to fibrin without aprotinin, but histological examination showed delayed fibrinolysis and a concomitant slower regeneration of granulation tissue. Thus, our data indicated that aprotinin was not particularly beneficial to wound healing and that the endogenous factor XIII level in the fibrinogen did not contribute significantly to skin bonding. Rather, the tissue supplied adequate trans-glutaminase activity required to crosslink fibrin to itself and to the tissue.

Thromboelastograph assay for measuring the mechanical strength of fibrin sealant clots.

In order to provide sustained hemostasis or tissue sealing, fibrin sealants must generate adhesive clots with mechanical properties capable of resisting forces, such as shear, that might break or tear the clot. Commercial preparations of fibrin sealants should generate clots of adequate and consistent mechanical strength. The mechanical strength of fibrin sealants is often measured as bonding strength in in vivo or ex vivo animal wound models. These tests can be useful predictors of clinical efficacy. However, these, as well as many in vitro tensile strength tests for fibrin sealant, tend to be laboratory specific and require extensive reagent preparation time and analyst training. The thromboelastograph has historically been used to screen for plasma protein and platelet disorders that lead to defective clot formation. The authors have developed a simple in vitro test, using a standard thromboelastograph that can provide reliable, reproducible information on the rheology of clots generated by fibrin sealant preparations. Using this method, the shear strength of fibrin sealant clots was measured and shown to correlate with the fibrinogen, but not the thrombin, concentration in the sealant. Shear strength was also shown to correlate with the sealant concentration of the fibrin cross-linking proenzyme, factor XIII. Sealants containing lysine, which can act as an alternate substrate for factor XIII enzyme and prevent efficient fibrin chain cross-linking, were shown by this method to generate clots of substantially reduced shear strength. The method distinguished between thrombin-catalyzed clot formation and other fibrinogen clotting mechanisms as evidenced by the significantly lower shear strength associated with batroxobin-generated fibrin clots.

Macroporous biphasic calcium phosphate efficiency in mastoid cavity obliteration: experimental and clinical findings.

Following our previous experimental studies on the performance of macroporous biphasic calcium phosphate (MBCP) in canine mastoid cavities, we used this material in patients requiring surgical intervention. Twenty-two cases were selected, and in eight specific cases a biopsy specimen was taken. Histologic, ultrastructural, and microanalysis studies were performed. This study demonstrates the effectiveness of MBCP implants as bone graft substitutes for mastoid cavity obliteration. Clinical evaluation of the series and histologic and ultrastructural results demonstrated the bioactivity and osteo-conduction of this material, with partial transformation of MBCP granules into lamellar bone after several months.

[Autologous fibrin glue--preparation and clinical use]. / Autolog fibrinklaeber--fremstilling og klinisk anvendelse.

Fibrin tissue adhesive is a tissue adhesive in which the two components are fibrinogen concentrate and a thrombin solution, respectively. In autologous fibrin tissue adhesive, the fibrinogen is prepared from the patient's own blood in contrast to the fibrin adhesive available commercially where the fibrinogen is prepared from pooled donor plasma. In 42 heart and lung operations, autologous fibrin tissue adhesive prepared by a new method was employed in which the fibrinogen is separated from the patient's own plasma by precipitation with ethanol. Either 44 or 88 ml blood was employed for concentration of the fibrinogen. This resulted in 2.5 ml and 4.9 ml fibrinogen concentrate which was mixed with 0.3 parts of thrombin solution containing calcium and aprotinin (fibrolysis inhibitor) so that the total volumes of tissue adhesive were 3.3 ml and 6.4 ml. Production of autologous fibrin tissue adhesive is uncomplicated and takes less than 90 minutes. A new method of production of autologous tissue adhesive based on ethanol is described. The fibrin tissue adhesive prepared in this manner has a high concentration of fibrinogen and is effective as a haemostatic and as an adhesive in surgical operations and it has the further advantage that it is not associated with the risk of transmission of viral or for immunological reactions.

Effect of fibrin glues on the mechanical properties of healing wounds.

Tissue glues are important in clinical practice. Fibrin based glues have many advantages over non-biological adhesives. The optimum formulation of these glues measured by their effect on mechanical properties of healing wounds has not been determined. Using a model involving standard dorsal skin incisions in adult male Wistar rats various glue formulations were compared by varying the fibrinogen, thrombin and factor XIII concentrations. Calcium (40 mumol/ml) and aprotinin (3000 kallidinogenase inactivator units, KIu/ml) concentrations were kept constant. Animals were killed at 8 days and wounds excised. Standard strips of these wounds were mechanically tested using an Instron tensiometer and the stress, strain, elasticity and work required to rupture wounds were calculated. Results indicate that a fibrin glue with a fibrinogen concentration of approximately 39 g/l and a thrombin concentration of 200-600 units/ml with no added factor XIII will result in wounds with significantly increased stress, energy absorption and elasticity values.