Fibrin glue as a stabilization strategy in peripheral nerve repair when using porous nerve guidance conduits

Abstract

Porous conduits provide a protected pathway for nerve regeneration, while still allowing exchange of nutrients and wastes. However, pore sizes >30 µm may permit fibrous tissue infiltration into the conduit, which may impede axonal regeneration. Coating the conduit with Fibrin Glue (FG) is one option for controlling the conduit’s porosity. FG is extensively used in clinical peripheral nerve repair, as a tissue sealant, filler and drug-delivery matrix. Here, we compared the performance of FG to an alternative, hyaluronic acid (HA) as a coating for porous conduits, using uncoated porous conduits and reverse autografts as control groups. The uncoated conduit walls had pores with a diameter of 60 to 70 µm that were uniformly covered by either FG or HA coatings. In vitro, FG coatings degraded twice as fast as HA coatings. In vivo studies in a 1 cm rat sciatic nerve model showed FG coating resulted in poor axonal density (993 ± 854 #/mm2), negligible fascicular area (0.03 ± 0.04 mm2), minimal percent wet muscle mass recovery (16 ± 1 in gastrocnemius and 15 ± 5 in tibialis anterior) and G-ratio (0.73 ± 0.01). Histology of FG-coated conduits showed excessive fibrous tissue infiltration inside the lumen, and fibrin capsule formation around the conduit. Although FG has been shown to promote nerve regeneration in non-porous conduits, we found that as a coating for porous conduits in vivo, FG encourages scar tissue infiltration that impedes nerve regeneration. This is a significant finding considering the widespread use of FG in peripheral nerve repair.Graphical Abstract

Nöroanastomoz Sonrası Stromal Vasküler Fraksiyonun Nörorejeneratif Etkisinin Histolojik ve Elektromiyografik Değerlendirilmesi

“…In addition, Sta et al [38] , has been stated that the electrophysiologic evaluation is very sensitive in early stage nerve regeneration. Amplitudes, an indicator of regenerated axon count [7,9,19,32] , increased gradually in all groups at PO 8 th weeks. As informed by Martins et al [39] , the highest amplitude was determined in fibrin glue group (GRIII) at PO 8 th week.…”

“…Among these methods, micro suture technique is frequently preferred [3,5,8,31] . Epineural and perineural techniques provide better contact between nerve segments in nerve repair and cause nerve fibers to deteriorate and become more traumatized [8,9,11,31,32] . However, fibrin glue is an atraumatic technique that does not have foreign body effects on the nerve [31,32] and also reduces inflammation and fibrosis [8,10,32] .…”

“…However, fibrin glue is an atraumatic technique that does not have foreign body effects on the nerve [31,32] and also reduces inflammation and fibrosis [8,10,32] . Fibers in fibrin glue-repaired nerves generally extend parallel to the axis, whereas suture-repaired nerves are known to interfere with axonal growth during regeneration [9,10,32] . In addition, suturing can prevent blood circulation by compressing the fascicles [11,32] .…”

“…It is also reported that regenerated axons heal faster and myelinated fibers have larger diameters [17] . Local neuroprotective effect of SVF was reported in diabetic rats [9] . In a nerve graft study, regeneration is better in SVF filled vein grafts and these grafts can be used in peripheral nerve regeneration instead of autologous nerve graft [15] .…”

“…Fibrosis, adhesion neuroma and glioma formation after neurorrhaphy has a negative effect on nerve healing [1,4,5] . Because of the negative effects of neurorrhaphy on healing, tissue adhesives have been developed as an alternative [1,2,8] and fibrin glue, which is used for neural anastomosis, reduces local inflammation and fibrosis and provides neurotropic factors [2,6,[9][10][11] . However, fibrin glue has been shown to inhibit local axonal regeneration by increasing local scar tissue formation and thus its usage has been limited [6,9] .…”