fibrin and Peripheral-Nerve-Injuries

Since the last update on nerve conduits and allograft in 2000, investigations have established the efficacy of these alternatives to autograft in the repair of small sensory neural gaps. However, limited insights into the biology of the regenerating nerve continue to preclude intelligent conduit design. Ongoing discoveries in neuroscience and biomaterial engineering hold promise for the eventual development of allograft and conduits with potential of surpassing nerve autografts in clinical efficacy. In this review, we summarize the history, recent advances, and emerging developments in nerve conduits and allograft.

Topics: Allografts; Biocompatible Materials; Cell-Free System; Chitosan; Collagen Type I; Fibrin; Guided Tissue Regeneration; History, 19th Century; History, 20th Century; Humans; Microsurgery; Nerve Regeneration; Neurosurgical Procedures; Peripheral Nerve Injuries; Peripheral Nerves; Polyesters; Polyglycolic Acid; Prostheses and Implants; Tissue Engineering; Tissue Scaffolds; Transplantation, Autologous; Vascular Grafting

Peripheral nerve injuries (PNI) lead to alterations in the Agrin-LRP4-MuSK pathway. This results in disaggregation of AChRs and change from epsilon (mature, innervated) to gamma (immature, denervated) subunit. Tubulization technique has been shown to be effective for PNI repair and it also allows the use of adjuvants, such as fibrin biopolymer (FB). This study evaluated the effect of the association of tubulization with FB after PNI on AChRs and associated proteins. Fifty-two adults male Wistar rats were used, distributed in 4 experimental groups: Sham Control (S), Denervated Control (D); Tubulization (TB) and Tubulization + Fibrin Biopolymer (TB+FB). Catwalk was performed every 15 days. Ninety days after surgery the right soleus muscles and ischiatic nerves were submitted to the following analyses: (a) morphological and morphometric analysis of AChRs by confocal microscopy; (b) morphological and morphometric analysis of the ischiatic nerve; (c) protein quantification of AChRs: alpha, gama, and epsilon, of Schwann cells, agrin, LRP4, MuSK, rapsyn, MMP3, MyoD, myogenin, MURF1 and atrogin-1. The main results were about the NMJs that in the TB+FB group presented morphological and morphometric approximation (compactness index; area of the AChRs and motor plate) to the S group. In addition, there were also an increase of S100 and AChRε protein expression and a decrease of MyoD. These positive association resulted in AChRs stabilization that potentiate the neuromuscular regeneration, which strengthens the use of TB for severe injuries repair and the beneficial effect of FB, along with tubulization technique.

Topics: Agrin; Animals; Fibrin; Male; Neuromuscular Junction; Normal Distribution; Peripheral Nerve Injuries; Rats; Rats, Wistar; Receptors, Cholinergic

Neural tissue engineering has been introduced as a novel therapeutic strategy for trauma-induced sciatic nerve defects. Here, a neuropeptide S (NPS)-crosslinked fibrin scaffolds (NPS@Fg) loaded with an ectomesenchymal stem cell (EMSC) system to bridge an 8-mm sciatic nerve defect in rats are reported. The Schwann cell-like and neural differentiation of the EMSCs on the engineered fibrin scaffolds are also assessed in vitro. These results show that the NPS@Fg promotes the differentiation of EMSCs into neuronal lineage cells, which may also contribute to the therapeutic outcome of the NPS@Fg+EMSCs strategy. After transplantation NPS@Fg+EMSCs into sciatic nerve defects in rats, nerve recovery is assessed up to 12 weeks postinjury. In vivo experiments show that the combination of NPS crosslinked fibrin scaffolds with EMSCs can significantly accelerate nerve healing and improve morphological repair. In the study, NPS@Fg+EMSCs may represent a new potential strategy for peripheral nerve reconstruction.

Topics: Animals; Fibrin; Gels; Nerve Regeneration; Peripheral Nerve Injuries; Rats; Rats, Sprague-Dawley; Schwann Cells; Sciatic Nerve

Peripheral nerve injury (PNI) results in persistent pain, a burning sensation, tingling, or complete loss of sensation. Treating large nerve defects is a major challenge, and the use of autologous nerve grafts (ANGs) cannot overcome this challenge. Hence, substitutes for ANGs that can serve as artificial nerve fibers are urgently needed in the clinical treatment of PNI. To develop such substitutes, we genetically engineered a virus nanofiber (M13 phage) that displays a high density of RGD peptide on its sidewall, producing an RGD-displaying phage (R-phage). In the presence of neural stem cells (NSCs), the resultant negatively charged R-phage nanofibers were electrostatically bound to a complex (with a net positive charge) of negatively charged fibrin and positively charged polyethyleneimine (PEI). The biocompatible injectable fibrin gel (FG) was integrated with R-phage and seeded with NSCs, forming a hydrogel termed R-phage/FG, which is further extruded through a syringe to form a fiber. The developed fiber-shaped hydrogel exhibited the desired excellent physical-chemical properties, and controllable and appropriate mechanical properties (170-240 kPa) similar to native nerve. The R-phage/FG not only promoted NSC adhesion, infiltration, and proliferation, but also induced efficient preferential differentiation of NSCs into neurons in the hydrogels in a non-differentiating medium within only 4 days. After the NSC-seeded R-phage/FG was injected into the long-gap (10 mm) defect of a rat's sciatic nerve, a solid neuron-rich hydrogel fiber was formed as an artificial nerve fiber graft that stimulated neurogenesis in the transplanted area within 60 days for nerve regeneration. These results suggest that the R-phage/FG fiber represents a potential substitute ANG for repairing large nerve injuries. This work demonstrates a new phage-based biomaterial that can be used as a graft for treating PNI through neurogenesis.

Topics: Animals; Cell Differentiation; Fibrin; Hydrogels; Nanofibers; Neurons; Peripheral Nerve Injuries; Rats; Rats, Sprague-Dawley

Promoting regeneration after segmental nerve injury repair is a challenge, but improving angiogenesis could be beneficial. Macrophages facilitate regeneration after injury by promoting angiogenesis. Our aim in this study was to evaluate the feasibility and effects of transplanting exogenous macrophages to a segmental nerve injury.. Bone marrow-derived cells were harvested from donor mice and differentiated to macrophages (BMDM), then suspended within fibrin hydrogels to facilitate BMDM transplantation. BMDM survival was characterized in vitro. The effect of this BMDM fibrin hydrogel construct at a nerve injury site was assessed using a mouse sciatic nerve gap injury. Mice were equally distributed to "fibrin+Mφ" (fibrin hydrogels containing culture medium and BMDM) or "fibrin" hydrogel control (fibrin hydrogels containing culture medium alone) groups. Flow cytometry (n = 3/group/endpoint) and immunohistochemical analysis (n = 5/group/endpoint) of the nerve gap region were performed at days 3, 5, and 7 after repair.. Incorporating macrophage colony-stimulating factor (M-CSF) improved BMDM survival and expansion. Transplanted BMDM survived for at least 7 days in a nerve gap (~40% retained at day 3 and ~15% retained at day 7). From transplantation, macrophage quantities within the nerve gap were elevated when comparing fibrin+Mφ with fibrin control (~25% vs. 3% at day 3 and ~14% vs. 6% at day 7). Endothelial cells increased by about fivefold within the nerve gap, and axonal extension into the nerve gap increased almost twofold for fibrin+Mφ compared with fibrin control.. BMDM suspended within fibrin hydrogels at a nerve gap do not impair regeneration.

Topics: Endothelial Cells; Feasibility Studies; Fibrin; Humans; Hydrogels; Macrophages; Nerve Regeneration; Peripheral Nerve Injuries; Sciatic Nerve

Peripheral nerve injury is a significant clinical problem with a substantial impact on quality of life, for which no optimal treatment has been found. This study aimed to analyze the effect and mechanism of Wnt5a-loaded fibrin hydrogel on a 10-mm rat sciatic nerve defect.. The Wnt5a-loaded fibrin hydrogel was synthesized by mixing a Wnt5a solution with thrombin and fibrinogen solutions. The loading capacity and release profile of Wnt5a-loaded fibrin hydrogel and the effect of Wnt5a on Schwann cells were evaluated in vitro. We also assessed the in vivo repair status via histological analysis of the regenerative nerve and gastrocnemius muscle, electrophysiological examination, gait analysis, and muscle wet weight.. We developed a nerve conduit filled with Wnt5a-loaded fibrin hydrogel (Fn) as a sustained-release system to repair a 10-mm rat sciatic nerve defect. In vitro, Wnt5a could promote SC proliferation and the gene expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and cholinergic neurotrophic factor (CNTF), as well as the protein secretion of VEGF and NGF. In vivo, the Wnt5a/Fn group was superior to the hollow, fibrin hydrogel, and Wnt5a groups in terms of axonal growth, myelination, electrophysiological recovery, target organ innervation, and motor function recovery 12 weeks after the operation.. The Wnt5a/Fn nerve conduit can promote peripheral nerve defect regeneration, with potential clinical applications. The mechanism for this may be the facilitation of multiple neurotrophin secretion, combining vascularization and neurotrophic growth cues.

Topics: Animals; Fibrin; Hydrogels; Nerve Growth Factor; Nerve Regeneration; Peripheral Nerve Injuries; Rats; Rats, Sprague-Dawley; Recovery of Function; Schwann Cells; Sciatic Nerve; Vascular Endothelial Growth Factor A; Wnt-5a Protein

Denervation leads to severe atrophy of neuromuscular junction (NMJ) structure including decrease of the expression of fundamental proteins. Up to now, conventional suture has been the gold standard method used to correct this injury. Fibrin sealant is one of the alternatives proposed to optimize this method. This study verified if the association of fibrin sealant - Heterologous Fibrin Biopolymer (HFB) and a single suture stitch promotes return of morphology and NMJ structure to mature pattern after peripheral nerve injury. Forty Wistar rats were distributed into 4 groups: Sham-Control (SC), Denervated-Control (DC), Suture-Lesion (SL) and Suture-Lesion + HFB (SFS). In SC group only the right sciatic nerve identification was done. In DC, SL and SFS groups fixation of nerve stumps on musculature immediately after neurotmesis was performed. After seven days, stump reconnection with 3 stitches in SL and a single stitch associated with HFB in SFS were done. After sixty days right soleus muscles were prepared for nicotinic acetylcholine receptors (nAChRs) and nerve terminal confocal analyses, and for nAChRs (α1, ε e γ), S100, Agrin, LRP-4, MMP-3, Rapsyn western blotting analyses. SC group presented normal morphology. In DC group it was observed flattening of NMJ, fragmentation of nAChRs and tangled nerve terminals. The majority of the parameters of SL and SFS groups presented values in between SC and DC groups. There was an increase of relative planar area in these groups (SL and SFS) highlighting that there was less nAChRs fragmentation and the values of protein expression showed return of nAChRs to mature pattern. Use of HFB associated with a single suture stitch decreased surgical time, minimized suture injuries, did not alter nerve regeneration and presented potential to reestablish the NMJ apparatus. These consolidated results encourage surgeons to develop future clinical trials to install definitively this new approach both for reconstructive surgery and neurosurgery.

Topics: Animals; Biopolymers; Fibrin; Nerve Regeneration; Neuromuscular Junction; Peripheral Nerve Injuries; Rats; Rats, Wistar; Sutures

Nerve wrapping improves neurorrhaphy outcomes in case of peripheral nerve injuries (PNIs). The aim of this preclinical study was to assess the efficacy of two novel biodegradable wraps made of a synthetic 1% oxidized polyvinyl alcohol (OxPVA) and a natural leukocyte-fibrin-platelet membrane (LFPm) versus the commercial product NeuraWrap. After rats sciatic nerve transection and neurorrhaphy, the wraps were implanted and compared for functional outcome, by sciatic function index assessment; structural characteristics, by histological/immunohistochemical analysis; ultrastructural features, by transmission electron microscopy. Moreover, a morphometric study was also performed and collagen distribution was observed by Second Harmonic Generation microscopy. After 12 weeks from implantation, all wraps assured nerve function recovery; no scar tissue/neuromas were visible at dissection. LFPm wraps were completely resorbed, while residues of OxPVA and NeuraWrap were observed. In all groups, biocompatibility was confirmed by the absence of significant inflammatory infiltrate. According to histological/immunohistochemical analysis and morphometric findings, OxPVA and LFPm wraps were both effective in preserving nerve integrity. These results assess that bioengineered OxPVA and LFPm wraps successfully guarantee favorable lesion recovery after PNI/neurorrhaphy and, in future, may be considered an interesting alternative to the commercial NeuraWrap.

Topics: Absorbable Implants; Animals; Blood Platelets; Cell Membrane; Drug Evaluation, Preclinical; Fibrin; Leukocytes; Nerve Regeneration; Nerve Tissue; Neurosurgical Procedures; Peripheral Nerve Injuries; Polyvinyl Alcohol; Rats; Rats, Sprague-Dawley; Recovery of Function

The standard treatment for nerve defects is nerve autograft. There is no conduit available that provides the same regenerative capacity of nerve autograft. This study evaluated the histological and functional recovery of nerve defects treated with fibrin conduit in comparison to the nerve autograft, in a rat model.. A sciatic nerve injury model (10-mm defect) was performed in 20 Wistar rats, nerve defect was reconstructed using a fibrin conduit (n = 10). A nerve autograft was used as control (n = 10). The walking behavior was measured by footprint analysis at 4, 8, and 12 weeks and sciatic function index was determined. After 12 weeks, histological analysis was performed to evaluate the regenerated nerve and measured axonal density. The triceps surae muscle weight was also evaluated.. The fibrin conduit group showed less improvement in walking behavior compared to nerve autograft (-53 ± 2 vs. -36 ± 2; P < 0.001 at 12 weeks). The fibrin conduit group presented axonal density of 40.0 axons/10.995μm2 and the nerve autograft group had 67.2 axons/10.995μm2 (P < 0.001). The triceps surae muscle weight ratio of the fibrin conduit group was 41 ± 3% versus 71 ± 4% of the nerve autograft group (P < 0.001).. The fibrin conduit could be used for nerve reconstruction following peripheral nerve injury in the rat model. However, the functional recovery in the fibrin conduit repair group was worse than that in nerve autograft group and the nerve repair with the fibrin conduit has less myelinated fibers when compared to the repair with nerve autograft.

Topics: Animals; Autografts; Fibrin; Male; Neurosurgical Procedures; Peripheral Nerve Injuries; Rats; Rats, Wistar; Recovery of Function; Treatment Outcome

This study aimed to evaluate the effect of platelet-rich fibrin (PRF) on peripheral nerve regeneration on the sciatic nerve of rats by using functional, histopathologic, and electrophysiologic analyses.. Thirty female Wistar rats were divided randomly into 3 experimental groups. In group 1 (G1), which was the control group, the sciatic nerve was transected and sutured (n = 10). In group 2 (G2), the sciatic nerve was transected, sutured, and then covered with PRF as a membrane (n = 10). In group 3 (G3), the sciatic nerve was transected, sutured by leaving a 5-mm gap, and then covered by PRF as a nerve guide (n = 10). Functional, histopathologic, and electrophysiologic analyses were performed.. The total histopathologic semiquantitative score was significantly higher in G1 compared to G2 and G3 (P < 0.05). Myelin thickness and capillaries were significantly lower in G3 compared to G1 (P < 0.05). There was no statistically significant difference between the groups with regard to the functional and electrophysiologic results.. The study results suggest that PRF decreases functional recovery in sciatic nerve injury. Further studies are required to determine the efficacy of PRF on peripheral nerve regeneration.

Topics: Animals; Blood Platelets; Disease Models, Animal; Female; Fibrin; Nerve Regeneration; Peripheral Nerve Injuries; Rats; Rats, Wistar; Recovery of Function; Sciatic Nerve

Traumatic nerve injuries are a major clinical challenge. Tissue engineering using a combination of nerve conduits and cell-based therapies represents a promising approach to nerve repair. The aim of this study was to examine the regeneration potential of human adipose-derived stem cells (hASCs) after transplantation in a nonautogenous setting and to compare them with autogenous rat ASCs (rASCs) for early peripheral nerve regeneration. Furthermore, the use of MRI to assess the continuous process of nerve regeneration was elaborated. The sciatic nerve injury model in female Sprague-Dawley rats was applied, and a 10-mm gap created by using a fibrin conduit seeded with the following cell types: rASCs, Schwann cell (SC)-like cells from rASC, rat SCs (rSCs), hASCs from the superficial and deep abdominal layer, as well as human stromal vascular fraction (1 × 10(6) cells). As a negative control group, culture medium only was used. After 2 weeks, nerve regeneration was assessed by immunocytochemistry. Furthermore, MRI was performed after 2 and 4 weeks to monitor nerve regeneration. Autogenous ASCs and SC-like cells led to accelerated peripheral nerve regeneration, whereas the human stem cell groups displayed inferior results. Nevertheless, positive trends could be observed for hASCs from the deep abdominal layer. By using a clinical 3T MRI scanner, we were able to visualize the graft as a small black outline and small hyperintensity indicating the regenerating axon front. Furthermore, a strong correlation was found between the length of the regenerating axon front measured by MRI and the length measured by immunocytochemistry (r = 0.74, p = 0.09). We successfully transplanted and compared human and autologous stem cells for peripheral nerve regeneration in a rat sciatic nerve injury model. Furthermore, we were able to implement the clinical 3T MRI scanner to monitor the efficacy of cellular therapy over time.

Topics: Adipose Tissue; Animals; Disease Models, Animal; Female; Fibrin; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Nerve Regeneration; Peripheral Nerve Injuries; Radiography; Rats; Rats, Sprague-Dawley; Schwann Cells; Sciatic Nerve; Stem Cell Transplantation; Stem Cells; Tissue Engineering; Transplantation, Autologous; Transplantation, Heterologous

Tissue engineering is a popular topic in peripheral nerve repair. Combining a nerve conduit with supporting adipose-derived cells could offer an opportunity to prevent time-consuming Schwann cell culture or the use of an autograft with its donor site morbidity and eventually improve clinical outcome. The aim of this study was to provide a broad overview over promising transplantable cells under equal experimental conditions over a long-term period. A 10-mm gap in the sciatic nerve of female Sprague-Dawley rats (7 groups of 7 animals, 8 weeks old) was bridged through a biodegradable fibrin conduit filled with rat adipose-derived stem cells (rASCs), differentiated rASCs (drASCs), human (h)ASCs from the superficial and deep abdominal layer, human stromal vascular fraction (SVF), or rat Schwann cells, respectively. As a control, we resutured a nerve segment as an autograft. Long-term evaluation was carried out after 12 weeks comprising walking track, morphometric, and MRI analyses. The sciatic functional index was calculated. Cross sections of the nerve, proximal, distal, and in between the two sutures, were analyzed for re-/myelination and axon count. Gastrocnemius muscle weights were compared. MRI proved biodegradation of the conduit. Differentiated rat ASCs performed significantly better than undifferentiated rASCs with less muscle atrophy and superior functional results. Superficial hASCs supported regeneration better than deep hASCs, in line with published in vitro data. The best regeneration potential was achieved by the drASC group when compared with other adipose tissue-derived cells. Considering the ease of procedure from harvesting to transplanting, we conclude that comparison of promising cells for nerve regeneration revealed that particularly differentiated ASCs could be a clinically translatable route toward new methods to enhance peripheral nerve repair.

Topics: Absorbable Implants; Adipocytes; Adipose Tissue; Animals; Cell- and Tissue-Based Therapy; Cells, Cultured; Female; Fibrin; Models, Animal; Muscle, Skeletal; Nerve Regeneration; Neurogenesis; Peripheral Nerve Injuries; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Stem Cell Transplantation; Stem Cells; Tissue Engineering

Tissue-engineering nerve conduits have been studied for a long time in bridging large nerve defects. However, the low oxygen availability within the nerve conduits, which results in death of migratory Schwann cells (SC) or loss of the newly formed tissue's function, is still an obstacle for axonal regeneration. Thus, it was hypothesized that an oxygen-enriched conduit would enhance axonal regeneration and functional recovery in vivo. To address this issue, perfluorotributylamine (PFTBA) enriched fibrin hydrogel was prepared and injected into collagen-chitosan conduits. The conduit containing PFTBA-enriched fibrin hydrogel was then used to bridge a 12-mm sciatic nerve defect in rats. The control rats were bridged with collagen-chitosan conduits filled with fibrin matrices without PFTBA. It was found that axonal regeneration and functional recovery in the combined PFTBA group were significantly higher than those in the control group without PFTBA. Further investigations showed that the mRNA and protein levels of S-100, brain-derived neurotrophic factor and nerve growth factor were enhanced by PFTBA at 1 and 3weeks after surgery. However, the mRNA and protein levels of vascular endothelial growth factor were in a similar range between the combined PFTBA group and the control group without PFTBA. In addition, immunohistochemical results showed that the morphological appearances of regenerated nerve and survival of SC were enhanced by PFTBA at 4 and 12weeks after surgery. In conclusion, PFTBA-enriched nerve conduit is capable of enhancing axonal regeneration, which provides a new avenue for achieving better functional recovery in the treatment of nerve defect.

Topics: Animals; Biomimetic Materials; Combined Modality Therapy; Drug Implants; Equipment Design; Equipment Failure Analysis; Extracellular Matrix; Fibrin; Fluorocarbons; Guided Tissue Regeneration; Male; Materials Testing; Nerve Regeneration; Oxygen; Peripheral Nerve Injuries; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Tissue Scaffolds; Treatment Outcome

The aim of this study was to evaluate the effect of Platelet Rich Plasma (PRP) and Platelet Rich Fibrin (PRF) on peripheral nerve repair. Thirty-two Wistar rats were randomly divided into four equal treatments groups: autologous nerve grafts (ANG), silicon tube plus saline solution (SS), silicon tube plus PRP, and silicon tube plus PRF. In ANG group, 10 mm segment from sciatic nerve was excised and reimplanted between the nerve stumps. In the SS, PRP, and PRF groups, 5 mm segment from sciatic nerve was excised and bridged with a 12 mm silicone conduit to create a 10 mm nerve gap. The conduit was filled in accordance with the different treatments. Walking track analysis was performed periodically and on the 90th post-operative day histomorphometric analysis was performed. The ANG, PRF, and PRP groups presented a significant functional improvement in relation to the SS group (P = 0.001) on 90 days after surgery. Histomorphometric analysis demonstrated that the ANG group achieved a larger nerve fiber diameter in proximal stump while comparing with the SS group (P =0.037) and showed larger fiber diameter in median stump in comparison to the PRP group (P = 0.002) and PRF group (P = 0.001). Axonal diameter and myelin sheath thickness showed no statistical significant difference between the groups in the three stumps (P ≥ 0.05). This study suggests that PRP and PRF have positive effects on the functional nerve recovery; however, these groups don't achieve a significant improvement on the histomorphometric analysis.

Topics: Animals; Autografts; Fibrin; Guided Tissue Regeneration; Male; Nerve Regeneration; Peripheral Nerve Injuries; Platelet-Rich Plasma; Random Allocation; Rats; Rats, Wistar; Recovery of Function; Replantation; Sciatic Nerve; Tissue Scaffolds; Treatment Outcome

The aim of this study was to evaluate long-term regenerative capacity over a 15-mm nerve gap of an autologous nerve conduit, the biogenic conduit (BC), 16 weeks after sciatic nerve transection in the rat.. A 19-mm long polyvinyl chloride (PVC) tube was implanted parallely to the sciatic nerve. After implantation, a connective tissue cover developed around the PVC-tube, the so-called BC. After removal of the PVC-tube the BCs filled with fibrin (n = 8) were compared to autologous nerve grafts (n = 8). Sciatic functional index (SFI) was evaluated every 4 weeks, histological evaluation was performed at 16 weeks postimplantation. Regenerating axons were visualized by retrograde labelling.. SFI revealed no significant differences. Nerve area and axon number in the BC group were significantly lower than in the autologous nerve group (P < 0.05; P < 0.01). Analysis of myelin formation showed no significant difference in both groups. Analysis of N-ratio revealed lower values in the BC group (P < 0.001).. This study reveals the suitability of BC for nerve gap bridging over a period of 16 weeks with functional recovery to comparable extent as the autologous nerve graft despite impaired histomorphometric parameters.

Topics: Animals; Device Removal; Female; Fibrin; Guided Tissue Regeneration; Motor Skills; Nerve Regeneration; Nerve Transfer; Peripheral Nerve Injuries; Polyvinyl Chloride; Rats; Recovery of Function; Sciatic Nerve; Tissue Scaffolds; Treatment Outcome

Nerve anastomoses glued with Fibrinkleber are stabilized against the plasminogen-activators of the tissue by natural and synthetical inhibitors of fibrinolysis administered locally and systemically. So the early lysis of the clots is inhibited. The glued nerve anastomoses do not reach the bond strength of sutured nerves, but foreign body reactions are avoided by this method. Glueing nerves with Fibrinkleber combined with inhibition of fibrinolysis seems to be a good method reuniting severed nerves, especially in nerve transplantation, provided too much tension is avoided.

Topics: Antifibrinolytic Agents; Fibrin; Fibrinogen; Humans; Peripheral Nerve Injuries; Peripheral Nerves; Suture Techniques; Thrombin; Tissue Adhesives

Nerve anastomoses glued with "Fribrinkleber" can be protected from tissue plasminogen-activators both by natural and synthetic inhibitors of fibrinolysis whether administered locally or systemically. The glued nerve-anastomoses do not attain the bond strength of sutured nerves, but show less foreign body reaction. Gluing nerves with Fibrinkleber" combined with inhibition of fibrinolysis would seem to be a good method for reuniting severed nerves. It may be especially useful in nerve transplantation if tension is avoided.

Topics: Animals; Factor VIII; Fibrin; Fibrinogen; Foreign-Body Reaction; Peripheral Nerve Injuries; Peripheral Nerves; Rats; Sciatic Nerve; Thrombin; Time Factors; Tissue Adhesives