Nerve Gap Research Articles

An Updated Evaluation of the Management of Nerve Gaps: Autografts, Allografts, and Nerve Transfers.

Within the past decade, there have been multiple innovations in the field of nerve surgery. In this review, we highlight critical changes and innovations that have helped advance the field and present opportunities for further study. This includes the modification and clarification of the classification schema for nerve injuries which informs prognosis and treatment, and a refined understanding and application of electrodiagnostic studies to guide patient selection. We provide indications for operative intervention based on this nerve injury classification and propose strategies best contoured for varying injury presentations at differing time points. Lastly, we discuss new developments in surgical techniques and approaches based on these advancements.

Feasibility of a cross-face reconstruction of the mental nerve—A cadaveric simulation study with histomorphometric analysis

IntroductionThe inevitable sacrifice of the inferior alveolar nerve (IAN) during oncologic resections results in substantial sensory impairment, impacting crucial functions such as speech, saliva retention, and mastication. This study investigates the feasibility of sensory restoration through cross-face reconstruction of the mental nerve via a contralateral mental nerve branch. MethodsThe cross-face reconstruction procedure was simulated in five formalin-fixed cadavers for both sides to evaluate the anatomic fundamentals and the nerve gap between the mental nerve main trunk and the transferred contralateral mental nerve branch. Furthermore, a histomorphometric analysis was performed to assess cross-sectional area and axon counts. ResultsThe mean gap distance between the main mental nerve trunk and the transferred contralateral branch was 15.3mm. End-to-end coaptation was achieved in 9 out of 10 simulations. The mean cross-sectional area was 0.996 mm2 at the main mental nerve trunk and 0.253mm2 at the coaptation site of the nerve branch. The mean donor-to-recipient axon ratio was found to be 0.3:1. ConclusionThe cadaveric simulation demonstrates the feasibility of a cross-face reconstruction of the mental nerve with only minimal gapping. Advantages of the proposed technique include the use of shorter nerve grafts, minimizing donor site morbidity and enabling fast reinnervation. This technique may offer a promising method for enhancing the quality of life for a patient group with increasing survival rates and life expectancy.

PMMA-induced biofilm promotes Schwann cells migration and proliferation mediated by EGF/Tnc/FN1 to improve sciatic nerve defect

ObjectiveThe purpose of this study is to investigate the role of PMMA-induced biofilm in nerve regeneration compared with silicone-induced biofilm involved in the mechanism. MethodsPMMA or silicon rods were placed next to the sciatic nerve to induce a biological membrane which was assayed by PCR, Western blot, immunohistochemistry, immunofluorescence and proteomics. A 10 mm sciatic nerve gaps were repaired with the autologous nerve wrapped in an induced biological membrane. The repair effects were observed through general observation, functional evaluation of nerve regeneration, ultrasound examination, neural electrophysiology, the wet weight ratio of bilateral pretibial muscle and histological evaluation. Cell proliferation and migration of Schwann cells co-cultured with EGF-treated fibroblasts combined with siRNA were investigated. ResultsThe results indicated that expression of GDNF, NGF and VEGF along with neovascularization was similar in the silicone and PMMA group and as the highest at 6 weeks after operation. Nerve injury repair mediated by toluidine blue and S100β/NF200 expression, the sensory and motor function evaluation, ultrasound, target organ muscle wet-weight ratio, percentage of collagen fiber, electromyography and histochemical staining were not different between the two groups and better than blank group. EGF-treated fibroblasts promoted proliferation and migration may be Tnc expression dependently. ConclusionOur study suggested that PMMA similar to silicon induced biofilm may promote autogenous nerve transplantation to repair nerve defects through EGF/Tnc/FN1 to increase Schwann cells proliferation and migration.

Skeletal Muscle-Derived Stem Cell Transplantation Accelerates the Recovery of Peripheral Nerve Gap Injury under 50% and 100% Allogeneic Compatibility with the Swine Leucocyte Antigen.

Pig skeletal muscle-derived stem cells (SK-MSCs) were transplanted onto the common peroneal nerve with a collagen tube as a preclinical large animal experiment designed to address long nerve gaps. In terms of therapeutic usefulness, a human family case was simulated by adjusting the major histocompatibility complex to 50% and 100% correspondences. Swine leukocyte antigen (SLA) class I haplotypes were analyzed and clarified, as well as cell transplantation. Skeletal muscle-derived CD34+/45- (Sk-34) cells were injected into bridged tubes in two groups (50% and 100%) and with non-cell groups. Therapeutic effects were evaluated using sedentary/general behavior-based functional recovery score, muscle atrophy ratio, and immunohistochemistry. The results indicated that a two-Sk-34-cell-transplantation group showed clearly and significantly favorable functional recovery compared to a non-cell bridging-only group. Supporting functional recovery, the morphological reconstitution of the axons, endoneurium, and perineurium was predominantly evident in the transplanted groups. Thus, Sk-34 cell transplantation is effective for the regeneration of peripheral nerve gap injury. Additionally, 50% and 100% SLA correspondences were therapeutically similar and not problematic, and no adverse reaction was found in the 50% group. Therefore, the immunological response to Sk-MSCs is considered relatively low. The possibility of the Sk-MSC transplantation therapy may extend to the family members beyond the autologous transplantation.

Biohacking Nerve Repair: Novel Biomaterials, Local Drug Delivery, Electrical Stimulation, and Allografts to Aid Surgical Repair.

The regenerative capacity of the peripheral nervous system is limited, and peripheral nerve injuries often result in incomplete healing and poor outcomes even after repair. Transection injuries that induce a nerve gap necessitate microsurgical intervention; however, even the current gold standard of repair, autologous nerve graft, frequently results in poor functional recovery. Several interventions have been developed to augment the surgical repair of peripheral nerves, and the application of functional biomaterials, local delivery of bioactive substances, electrical stimulation, and allografts are among the most promising approaches to enhance innate healing across a nerve gap. Biocompatible polymers with optimized degradation rates, topographic features, and other functions provided by their composition have been incorporated into novel nerve conduits (NCs). Many of these allow for the delivery of drugs, neurotrophic factors, and whole cells locally to nerve repair sites, mitigating adverse effects that limit their systemic use. The electrical stimulation of repaired nerves in the perioperative period has shown benefits to healing and recovery in human trials, and novel biomaterials to enhance these effects show promise in preclinical models. The use of acellular nerve allografts (ANAs) circumvents the morbidity of donor nerve harvest necessitated by the use of autografts, and improvements in tissue-processing techniques may allow for more readily available and cost-effective options. Each of these interventions aid in neural regeneration after repair when applied independently, and their differing forms, benefits, and methods of application present ample opportunity for synergistic effects when applied in combination.

Cost Comparison of Digital Nerve Repair Techniques.

Direct cost comparison of nerve allograft with other techniques for repairing short digital nerve gaps are lacking. This study compares the costs of various techniques for digital nerve repair, anticipating significant cost increases for allograft implants. The State Ambulatory Surgery and Services Database for Florida, New York, and Wisconsin from 2015-2020 was used. Patients with primary repair, short autograft, conduit, and allograft were compared along total, surgical supply, operating room (OR), and anesthesia charges. Among 5,009 patients were 2,967 primary nerve repairs (59.2%), 77 autografts (1.5%), 1,647 conduits (32.9%), and 318 allografts (6.3%). 2,886 patients were male (57.6%) with mean age 40.4 ± 16.3 years. Over the study period, primary repairs decreased (63.9% in 2015 to 56.3% in 2020) while allografts increased significantly (8.8% in 2018 to 12.6% in 2020).Median total charges significantly varied across procedures, with the most expensive being allograft ($35,295), followed by conduit ($25,717), autograft ($24,749), and primary repair ($18,767). On multivariable regression, allograft is significantly more expensive than autograft for total charges by $11,224 (95CI: $4,196-$18,252) and supply charges by $10,484 (95CI: $6,073-$14,896), but not for OR or anesthesia charges. Flexor tendon repair was associated with greater total, OR, and anesthesia charges but similar supply charges. Nerve allograft is the most expensive digital nerve repair technique most likely due to the cost of the implant. To minimize health care expenditure and ensure equitable patient access, surgeons should consider this cost along with clinical factors in choosing digital nerve repair techniques.

Biological conduits based on spider silk for reconstruction of extended nerve defects.

The availability of appropriate conduits remains an obstacle for successful reconstruction of long-distance nerve defects. In previous sheep trials, we were able to bridge 6 cm nerve gaps with nerve conduits based on spider silk fibers with full functional outcomes. Here, we describe the first application of spider silk for nerve repair inhumans. Four patients with extended nerve defects (>20 cm) underwent nerve reconstruction by interposition of conduits that were composed of spider silk fibers contained in autologous veins. The longitudinal luminal fibers (approx.2500 fibers per graft) consisted of drag line silkfrom Trichonephila spiders. All patients were evaluated between 2and 10 years postreconstruction, clinically, and byneurography. In all patients, primary wound healing and no adverse reactions to the implanted spider silk material wereobserved. Patients regained the following relevant functions: protective sensibility, full flexor function with near-normal grasp and powerful function after microvascular gracilis muscle transfer, and key grip function and gross finger flexion after additional tenodesis. One patient with sciatic nerve reconstruction developed protective sensibility of the lower leg, foot, and gait, enabling normal walking and jogging. No neuroma formation or neuropathic or chronic pain occurred in any of the patients. For patients with extended peripheral nerve defects in the extremities, use of conduits based on spider silk fibers offers the possibility of restoring sensory function and protection from neuroma. This kind of nerve bridges provides new perspectives for the reconstruction of complex and long-distance nerve defects.

Comparative Effectiveness Systematic Review and Meta-analysis of Peripheral Nerve Repair Using Direct Repair and Connector-assisted Repair.

This clinical literature systematic review and meta-analysis were performed to assess differences in outcomes between nerves repaired with direct repair (DR) and connector-assisted repair (CAR). A systematic literature review for DR and CAR was performed. Studies from 1980 through August 2023 were included if DR or CAR repairs were performed in upper extremities with nerve gaps less than 5 mm and reported sensory Medical Research Council Classification (MRCC) outcomes or equivalent. Comparative analyses were planned for meaningful recovery (MR) rate (at both S3 and S3+ or better), postsurgical neuroma, cold intolerance, altered sensation, pain, and revision rate. There were significant differences in MR rates for CAR and DR. At the MRCC S3 threshold, 96.1% of CAR and 81.3% of DR achieved MR (P < 0.0001). At the MRCC S3+ threshold, 87.1% of CAR and 54.2% of DR achieved this higher threshold of MR (P < 0.0001). There were no differences in neuroma rate or pain scores in our dataset. Altered sensation (dysesthesia, paresthesia, hyperesthesia, or hypersensitivity) was not discussed in any CAR studies, so no analysis could be performed. The revision rate for both procedures was 0%. The proportion of patients with cold intolerance was 46.2% in the DR studies, which was significantly higher than the 10.7% of patients in the CAR group. Significantly more patients achieved sensory MR and fewer had cold intolerance when the CAR technique, instead of the DR technique, was performed to repair peripheral nerve injuries.

Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.

Stereolithography 3D printing of microgroove master moulds for topography-induced nerve guidance conduits

&amp;nbsp;Patients who have peripheral nerve damage from trauma or disease may suffer lifelong disability. Current interventions such as nerve allografts are inadequate due to limited availability of tissue and donor-site morbidity. Commercial nerve guidance conduits are used to bridge the damaged nerve gap and restore function. Typically, however, they lack cell-instructive guidance cues to promote directed regeneration. Tissue-engineered nerve guidance conduits that utilise micro- and nano-topographical architectures have been demonstrated to direct cell behaviour and contact guidance. This study uses projection micro-stereolithography-based three-dimensional (3D) printing to fabricate microgrooved (10&amp;ndash;30 &amp;mu;m) master moulds to produce polydimethylsiloxane (PDMS) moulds and solvent cast polycaprolactone and polylactic acid films. The polymer microgrooves were successfully fabricated and were able to be formed into tubular nerve guidance conduits. The surface morphology, roughness, wettability, and thermal properties of the films were characterised. The microgroove topography improved proliferation and induced alignment of SH-SY5Y cells. This facile 3D printing approach is promising for the fabrication of nerve guidance conduits with topographical guidance cues as it obviates the need for using photolithographic techniques. Thus, this approach provides an alternative that is simpler, faster, cheaper, and offers greater design freedom.

Obturator to Femoral Nerve Transfer: 2-Dimensional Operative Video.

Injury to the femoral nerve can cause femoral nerve palsy,1 resulting in severe ambulation difficulties and loss of sensory function in the anteromedial thigh and medial calf.2,3 Treatment options focus on nerve repair by direct coaptation, nerve grafting, or nerve transfer.3 If the proximal nerve stump is inaccessible, the location of nerve injury is at a distance from the site of muscle innervation, and/or there is a large nerve gap, nerve transfer may be a promising alternative treatment option.4-6 Nerve transfer uses only one coaptation site and allows for a faster recovery time due to a shorter nerve regeneration distance.2,3 A 32-year-old woman presented with persistent and severe proximal right lower extremity weakness after a right retroperitoneal femoral nerve schwannoma resection at an outside institution. After surgery, she reported that she could not flex her right hip or extend her right knee. MRI demonstrated a right femoral nerve gap defect (7.5 cm) at the schwannoma resection site. A right obturator to femoral nerve transfer was performed (see Video). 1.5-year follow-up visit showed that she had begun to have evidence of active recruitment of the right quadriceps muscle and started walking without a knee brace. 2.5-year follow-up visit showed improving strength (4-) in her right quadriceps muscle, independent walking for longer distances, and participation in sporting activities. The patient consented to the procedure, and the patients and any identifiable individuals consented to publication of his/her image. Institutional Review Board approval was not required for this single case observational surgical video.

Physical cues of scaffolds promote peripheral nerve regeneration

The effective treatment of long-gap peripheral nerve injury (PNI) remains a challenge in clinical settings. The autograft, the gold standard for the long-gap PNI therapy, has several limitations, including a limited supply of donor nerve, size mismatch between the donor and recipient sites, functional loss at the donor site, neuroma formation, and the requirement for two operations. With the increasing abundance of biocompatible materials with adjustable structures and properties, tissue engineering provides a promising avenue for bridging peripheral nerve gaps and addressing the above issues of autograft. The physical cues provided by tissue engineering scaffolds, essential for regulating the neural cell fate and microenvironments, have received considerable research attention. This review elaborates on three major physical cues of tissue engineering scaffolds for peripheral nerve regeneration: topological structure, mechanical support, and electrical stimulation. These three aspects are analogs to Lego bricks, wherein different combinations result in diverse functions. Innovative and more effective bricks, along with multi-level and all-around integration, are expected to provide new advances in tissue engineering for peripheral nerve generation.

Nerve Regeneration after a Nerve Graft in a Rat Model: The Effectiveness of Fibrin Glue.

Simulating the post-traumatic continuity defect of small human peripheral nerves, we compared the effectiveness of fibrin glue with neurorrhaphy for nerve gap restoration. In twenty-four male Wistar rats, a fifteen mm defect in one sciatic nerve only was made and immediately repaired with an inverted polarity autograft. According to the used technique, rats were divided into Group A (Control), using traditional neurorrhaphy, and Group B (Study), using fibrine glue sealing; in total, 50% of rats were sacrificed at 16 weeks and 50% at 21 weeks. Before sacrifice, an assessment of motor function was done through Walking Track Analysis and an electroneurophysiological evaluation. After sacrifice, selected muscle mass indexes and the histology of the regenerated nerves were assessed. All data were evaluated by Student's t test for unpaired data. No significant differences were found between the two groups, with only the exception of a relative improvement in the tibialis anterior muscle's number of motor units in the study group. Despite the fact that the use of fibrin glue as a nerve sealant is not superior in terms of functional recovery, its effectiveness is comparable to that of microsurgical repair. Hence, the faster and technically easier glueing technique could deserve broader clinical application.

Fabrication of Artificial Nerve Conduits Used in a Long Nerve Gap: Current Reviews and Future Studies.

There are many commercially available artificial nerve conduits, used mostly to repair short gaps in sensory nerves. The stages of nerve regeneration in a nerve conduit are fibrin matrix formation between the nerve stumps joined to the conduit, capillary extension and Schwann cell migration from both nerve stumps, and, finally, axon extension from the proximal nerve stump. Artificial nerves connecting transected nerve stumps with a long interstump gap should be biodegradable, soft and pliable; have the ability to maintain an intrachamber fibrin matrix structure that allows capillary invasion of the tubular lumen, inhibition of scar tissue invasion and leakage of intratubular neurochemical factors from the chamber; and be able to accommodate cells that produce neurochemical factors that promote nerve regeneration. Here, we describe current progress in the development of artificial nerve conduits and the future studies needed to create nerve conduits, the nerve regeneration of which is compatible with that of an autologous nerve graft transplanted over a long nerve gap.

Enhancing sciatic nerve regeneration with osteopontin-loaded acellular nerve allografts in rats: Effects on macrophage polarization

Osteopontin (OPN) is a multifunctional matrix glycoprotein with neuroprotective and immunomodulatory properties. This study explored the potential of OPN-loaded acellular nerve allografts (ANAs) to repair sciatic nerves in male Wistar rats. The research also delved into the impact of OPN on macrophage phenotypes. We reconstructed a 10 mm nerve gap with ANAs containing OPN at 2 nM and 4 nM. The sciatic functional index (SFI) and paw withdrawal reflex latency (WRL) showed the significant efficacy of ANA/OPN (2 nM) in enhancement of target organ reinnervation and subsequent sensorimotor recovery compared to other groups. Electrophysiological and histomorphometric analyses further supported the regenerative properties of ANA/OPN (2 nM). Additionally, ANA/OPN (2 nM) promoted macrophage polarization towards an M2 phenotype and reduced proinflammatory cytokines at the injury site. In conclusion, the study suggested that ANA loaded with 2 nM OPN effectively repaired transected sciatic nerves in rats, potentially through enhancing axonal sprouting and exerting anti-inflammatory effects.

The role of kinases in peripheral nerve regeneration: mechanisms and implications.

Peripheral nerve injury disease is a prevalent traumatic condition in current medical practice. Despite the present treatment approaches, encompassing surgical sutures, autologous nerve or allograft nerve transplantation, tissue engineering techniques, and others, an effective clinical treatment method still needs to be discovered. Exploring novel treatment methods to improve peripheral nerve regeneration requires more effort in investigating the cellular and molecular mechanisms involved. Many factors are associated with the regeneration of injured peripheral nerves, including the cross-sectional area of the injured nerve, the length of the nerve gap defect, and various cellular and molecular factors such as Schwann cells, inflammation factors, kinases, and growth factors. As crucial mediators of cellular communication, kinases exert regulatory control over numerous signaling cascades, thereby participating in various vital biological processes, including peripheral nerve regeneration after nerve injury. In this review, we examined diverse kinase classifications, distinct nerve injury types, and the intricate mechanisms involved in peripheral nerve regeneration. Then we stressed the significance of kinases in regulating autophagy, inflammatory response, apoptosis, cell cycle, oxidative processes, and other aspects in establishing conductive microenvironments for nerve tissue regeneration. Finally, we briefly discussed the functional roles of kinases in different types of cells involved in peripheral nerve regeneration.

Current perspectives on peripheral nerve repair and management of the nerve gap.

From the first surgical repair of a nerve in the 6th century, progress in the field of peripheral nerve surgery has marched on; at first slowly but today at great pace. Whether performing primary neurorrhaphy or managing multiple large nerve defects, the modern nerve surgeon has an extensive range of tools, techniques and choices available to them. Continuous innovation in surgical equipment and technique has enabled the maturation of autografting as a gold standard for reconstruction and welcomed the era of nerve transfer techniques all while bioengineers have continued to add to our armamentarium with implantable devices, such as conduits and acellular allografts. We provide the reader a concise and up-to-date summary of the techniques available to them, and the evidence base for their use when managing nerve transection including current use and applicability of nerve transfer procedures.

456 Arm Flexion to Overcome Gaps for Primary Radial Nerve Repair: An Anatomic Study

INTRODUCTION: It is now well known that direct nerve repairs fare better than grafted nerve repairs. There is currently renewed interest in direct repair of nerves achieved by limb flexion followed by serial distraction as it is the least morbid and most easily implemented surgical technique to provide extra nerve excursion. This is especially simple in the upper extremity, which can be easily immobilized post-operatively in a sling. METHODS: Four fresh and 11 fixed cadaver arms with shoulder intact were dissected to determine the relationship between degrees of EF (ranged from 0-90 degrees EF) and nerve gap length overcome with proximal excursion of the distal nerve. Additional excursion from brachialis branch neurectomy was also assessed. RESULTS: We found an approximately linear relationship between EF and RN excursion. Compliance of fresh cadaveric nerves more closely approximated that of surgical tissue. In fresh cadavers, there was 3mm of RN excursion per 10 degrees EF in the proximal half of the arm, and 4 mm excursion per 10 degrees EF with neurectomy. CONCLUSIONS: Elbow flexion can significantly augment the ability to achieve an end-to-end repair of the RN. To simplify our findings, 90-degree EF should readily overcome a RN gap of 3.5 cm, and additional brachialis neurectomy allows for total RN excursion of 4.7 cm on average in the proximal arm with 90-degrees EF. Given nerve regeneration rates of 1-2 mm/day, we recommend 14-27 days prior to full elbow extension from a RN repair performed with 90-degree EF without neurectomy, and 18-36 days for repair at 90-degree EF with neurectomy.

Gal - T Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.

Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout (GalT-KO) pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. In this study, we compare outcomes between autografts and cold preserved xenografts in a rat sciatic model of nerve gap repair. Fifty male Lewis rats had a 1 cm sciatic nerve defect repaired using either: autograft and suture (n=10); 1-week or 4-week cold preserved xenograft and suture (n=10 per group); 1-week or 4-week cold preserved xenograft and photochemical tissue bonding using a human amnion wrap (PTB/HAM) (n=10 per group). Rats with xenografts were given tacrolimus until 4 months post-operatively. At 4 and 7 months, rats were euthanized and nerve sections harvested. Monthly sciatic functional index (SFI) scores were calculated. All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the 1-week cold preserved PTB/HAM group. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold preserved groups had significantly lower scores than the 4-week cold preserved suture group. Our results in the rat sciatic model suggest that GalT-KO nerve xenografts may be viable alternatives to autografts and demonstrate the need for further studies of long-gap repair and comparison with acellular nerve allografts. This proof-of-concept study in the rat sciatic model demonstrates that cold preserved GalT-KO porcine xenografts support axonal regeneration, as well as axonal viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.

Nerve Reconstruction Using ActiGraft Blood Clot in Rabbit Acute Peripheral Injury Model: Preliminary Study.

This preliminary study aimed to investigate an ActiGraft blood clot implant (RedDress Ltd., Pardes-Hanna, Israel) attempting to treat and induce the regeneration of a completely injured peripheral nerve with a massive loss defect. The tibial portion of the sciatic nerve in 11 rabbits was transected, and a 25 mm nerve gap was reconnected using a collagen tube. A comparison was performed between the treatment group (eight rabbits; reconnection using a tube filled with ActiGraft blood clot) and the control group (three rabbits; gap reconnection using an empty tube). The post-operative follow-up period lasted 18 weeks and included electrophysiological and histochemical assessments. The pathological severity score was high in the tube cross sections of the control group (1.33) compared to the ActiGraft blood clot treatment group (0.63). Morphometric analysis showed a higher percentage of the positive myelin basic protein (MBP) stained area in the ActiGraft blood clot group (19.57%) versus the control group (3.67%). These differences were not statistically significant due to the small group sizes and the large intra-group variability. The results of this preliminary study suggest that the application of an ActiGraft blood clot (into the collagen tube) can enable nerve recovery. However, a future study using a larger animal group is required to achieve objective statistical results.