Fibrin sealants (FS) are the most successful tissue adhesives to date. They have many advantages over adhesive technologies such as cyanoacrylates and marine adhesives in terms of biocompatibility, biodegradation and hemostasis. There are several commercial products in Europe but none in the United States due to the current regulatory stance against pooled plasma blood products. Blood banks and interested investigators have implemented single- and patient autologous-donor production methods with some success. This article will review the history of FS research and development and describe the chemistry of fibrin(ogen) and the production of commercial and research products. Fibrin sealant and purified fibrin characterization is compared and contrasted. The material and adhesive properties are described, and a survey of the clinical applications in which FS has been used is included as well.
The adhesive strength of fibrin sealants has not been rigorously evaluated to date. The adhesive strength of six different concentrations of cryoprecipitated fibrinogen as well as the commercially available fibrin tissue adhesive Tissucol was tested under controlled conditions utilizing split-thickness skin grafts as the test adherand. This test configuration permitted the modeling of bonding strength for attachment of skin grafts as well as incorporate established engineering test standards for adhesives. An increase in fibrin concentration corresponded with an increase in shear adhesive strength. No significant increases in adhesive strength were attained after 5 min of bonding for all tested concentrations, except for the commercial adhesive, which attained the adhesive strength of an equivalent concentration of cryoprecipitated adhesive after 90 min. The adhesive strength, however, was an order of magnitude less than reported values of the tensile strength of fibrin material for similar concentrations. Therefore, it is important that the surgeon use a sufficiently high fibrinogen concentration for the specific clinical indication. The method of fibrin sealant preparation and/or the compounding adjuncts appear to have an effect on the development of adhesive strength.
A series of analyses were performed on fibrin-based adhesives to describe their failure characteristics. Two test methods were used: uniaxial, monotonic tensile testing of the bulk material, and blister testing using fresh porcine-source skin graft as the adherend. Two fibrin concentrations, high (HFC), and low (LFC), were used to investigate the effects of the gel matrix density upon mechanical properties. In tensile tests, fibrin gels strain hardened, as functions of percent strain and of strain rate. An increase in modulus of elasticity (E) was seen with increasing strain and strain rate at both tested fibrin concentrations. Mode I failure mechanisms were predominant. Both adhesives appeared to fracture from the outer edge to the interior of the specimen at slower strain rate tests. This trend reversed as strain rate increased, becoming a classic "cup and cone" ductile fracture. Syneresis occurred at both concentrations at lower strain rates, but was more pronounced for the LFC. Ultimate tensile strength and E were greater for the HFC than for the LFC at all strain rates, decreasing with increasing strain rate. In the blister test, the failure locus changed from cohesive to adhesive as the strain rate was increased for the HFC. Failure of fibrin gels likely occurs by percolation of the pressurized saline, displacing the entrapped liquid phase of the gel in regions of relatively low moduli and strength, leading to fracture of the matrix. For LFC, the overall fracture locus remained predominantly cohesive regardless of strain rate. Burst strength and failure energy were higher for HFC than for LFC. It would appear that fibrin acts more as a viscous liquid than a rubberlike/elastic material at lower concentrations because adhesive failures had a higher burst strength and fracture energy (Gc) than did cohesive failures.
Objective: To determine if brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) can be successfully delivered to transected and repaired peripheral nerves by cross-linking the factors to collagen tubules (CTs).Methods: Forty-eight Sprague-Dawley rats underwent left sciatic nerve transection and repair. In the control group, CTs were implanted with no neurotrophic ligand (n = 13). There were 3 experimental groups: CT with BDNF covalently linked to the collagen matrix (CT/BDNF; n = 12), CT with CNTF covalently linked (CT/CNTF; n = 12), and CT with both BDNF and CNTF covalently linked (CT/BDNF/ CNTF; n = 11). Functional outcome of neural regeneration was assessed every 10 days using walking track analysis, which was submitted to a sciatic functional index. Nerve morphometry, electrophysiologic studies, and molecular analysis for neural proteins were performed at the completion of the study at postoperative day 90.Results: Animals in all 3 experimental groups achieved significantly superior maximal functional recovery, larger nerve cross-sectional areas, and a greater number of axons when compared with the control CT group (PϽ.001, PϽ.05, and PϽ.05, respectively). The animals in the CT/ BDNF/CNTF group displayed the best functional recovery and had the largest axon diameters, greatest amplitude, and the fastest nerve conduction velocities. Molecular analysis revealed significant differences in the expression of neurofilament, neural cell adhesion molecule, myelin-associated glycoprotein, and myelin basic protein.
Conclusions:We present the first evidence that CNTF covalently linked to CTs can improve functional recovery compared with CTs alone. We also support the previous finding that BDNF covalently linked to CTs significantly increases the functional recovery of transected and repaired nerves. Finally, we found that cotreatment produced the best functional recovery in our model.
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