Acellular Nerve Research Articles

Dynamic seeding versus microinjection of mesenchymal stem cells for acellular nerve allograft: an in vitro comparison

Mesenchymal stem cell (MSC)-supplemented acellular nerve allografts (ANA) are a potential strategy to improve the treatment of segmental nerve defects. Prior to clinical translation, optimal cell delivery methods must be defined. While two techniques, dynamic seeding and microinjection, have been described, the seeding efficiency, cell viability, and distribution of MSCs in ANAs are yet to be compared. Sciatic nerve segments of Sprague-Dawley rats were decellularized, and MSCs were harvested from the adipose tissue of Lewis rats. Cell viability was evaluated after injection of MSCs through a 27-gauge needle at different flow rates (10, 5, and 1 µL/min). MSCs were dynamically seeded or longitudinally injected into ANAs. Cell viability, seeding efficiency, and distribution were evaluated using LIVE/DEAD and MTS assays, scanning electron microscopy, and Hoechst staining. No statistically significant difference in cell viability after injection at different flow rates was seen. After cell delivery, 84.1±3.7% and 87.8±2.8% of MSCs remained viable in the dynamic seeding and microinjection group, respectively (p=0.41). The seeding efficiency of microinjection (100.4%±5.6) was significantly higher than dynamic seeding (48.1%±8.6) on day 1 (p=0.001). Dynamic seeding demonstrated a significantly more uniform cell distribution over the course of the ANA compared to microinjection (p=0.02). MSCs remain viable after both dynamic seeding and microinjection in ANAs. Higher seeding efficiency was observed with microinjection, but dynamic seeding resulted in a more uniform distribution. In vivo studies are required to assess the effect on gene expression profiles and functional motor outcomes.

Effect of acellular nerve scaffold containing human umbilical cord-derived mesenchymal stem cells on nerve repair and regeneration in rats with sciatic nerve defect.

BackgroundThe aim of the present study was to investigate the effect of acellular nerve scaffold (ANS) containing human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on nerve repair and regeneration in rats with sciatic nerve defect.MethodsSciatic nerve trunks were removed from 6 female Sprague-Dawley (SD) rats, and ANS was prepared by lyophilization + enzymatic method and divided into A, B, C, D and E groups according to different treatment times. hUC-MSCs were isolated from the collected umbilical cords and cultured, and then ANS-hUC-MSCs complexes were made. The other 24 adult female SD rats were randomly divided into the control, autograft, ANS, and ANS-hUC-MSCs groups, and a rat model of sciatic nerve defect was established. Hematoxylin-eosin (HE) staining, Luxol fast blue (LFB) staining, Masson staining, and scanning electron microscopy were used to observe the morphology and tissue structure of ANS. The performance of ANS was evaluated by mechanical detection, and hydroxyproline (HYP) content was evaluated using a biochemical kit. Flow cytometry was adopted to detect the levels of hUC-MSCs surface antigens CD29, CD44, and CD34, as well as electrophysiological detection and muscle wet weight recovery rate for measuring rat muscle performance.ResultsANS was prepared according to group A method and had good mechanical properties, with less residues of cells and myelin, and higher HYP content, indicating that this scaffold had the best performance. ANS-hUC-MSCs significantly reduced myelin injury in the sciatic nerve, and increased axonal regeneration, effectively improving sciatic nerve injury in rats. In addition, ANS-hUC-MSCs significantly increased compound muscle action potential (CMAP), nerve conduction velocity (NCV), and muscle wet weight, and reduced muscle atrophy.ConclusionsANS containing hUC-MSCs can promote nerve repair and regeneration in rats with sciatic nerve defects.

Acellular nerve xenografts based on supercritical extraction technology for repairing long-distance sciatic nerve defects in rats.

Compared to conventional artificial nerve guide conduits (NGCs) prepared using natural polymers or synthetic polymers, acellular nerve grafts (ACNGs) derived from natural nerves with eliminated immune components have natural bionic advantages in composition and structure that polymer materials do not have. To further optimize the repair effect of ACNGs, in this study, we used a composite technology based on supercritical carbon dioxide (scCO2) extraction to process the peripheral nerve of a large mammal, the Yorkshire pig, and obtained an innovative Acellular nerve xenografts (ANXs, namely, CD + scCO2 NG). After scCO2 extraction, the fat and DNA content in CD + scCO2 NG has been removed to the greatest extent, which can better supported cell adhesion and proliferation, inducing an extremely weak inflammatory response. Interestingly, the protein in the CD + scCO2 NG was primarily involved in signaling pathways related to axon guidance. Moreover, compared with the pure chemical decellularized nerve graft (CD NG), the DRG axons grew naturally on the CD + scCO2 NG membrane and extended long distances. In vivo studies further revealed that the regenerated nerve axons had basically crossed the CD + scCO2 NG 3 weeks after surgery. 12 weeks after surgery, CD + scCO2 NG was similar to autologous nerves in improving the quality of nerve regeneration, target muscle morphology and motor function recovery and was significantly better than hollow NGCs and CD NG. Therefore, we believe that the fully decellularized and fat-free porcine ACNGs may be the most promising “bridge” for repairing human nerve defects at this stage and for some time to come.

Evaluation of anatomical and histological characteristics of human peripheral nerves: as an effort to develop an efficient allogeneic nerve graft.

Management of peripheral nerve defects is a complicated problem in clinical contexts. Autologous nerve grafting, a gold standard for surgical treatment, has been well known to have several limitations, such as donor site morbidity, a limited amount of available donor tissue, and size mismatches. Acellular nerve allografts (ANAs) have been developed as an alternative and have been applied clinically with favorable outcomes. However, because of the limited availability of commercialized ANAs due to supplier-related issues and high costs, efforts continue to produce alternative sources for ANAs. The present study evaluated the anatomical and histological characteristics of human peripheral nerves using 25 donated human cadavers. The length, diameter, and branching points of various peripheral nerves (median, ulnar, tibial, lateral femoral cutaneous, saphenous, and sural nerves) in both the upper and lower extremities were evaluated. The cross-sectional area (CSA), ratio of fascicular area, and numbers of fascicles were also evaluated via histologic analysis. CSA, the ratio of fascicular area, and the number of fascicles were analyzed statistically in correlation with demographic data (age, sex, height, weight, BMI). The mean length of all evaluated nerves ranged from 17.1 to 41.4cm, and the mean diameter of all evaluated nerves ranged from 1.2 to 4.9mm. Multiple regression analysis revealed correlations between the ratio of fascicular area and sex (p = 0.005) and BMI (p = 0.024) (R2 = 0.051). The results of the present study will be helpful in selecting necessary nerve allograft sources while considering the characteristics of each nerve in the upper and lower extremities during ANAs production.

The effect of mesenchymal stem cells and surgical angiogenesis on immune response and revascularization of acellular nerve allografts in a rat sciatic defect model

Increasing evidence demonstrates an interplay between neoangiogenesis and immune cells. We investigated the immune response and revascularization of acellular nerve allografts (ANA) after combined stem cell delivery and surgical angiogenesis in a rat model. Unilateral sciatic nerve defects in 60 Lewis rats were repaired with (I) autografts, (II) ANAs, and (III) ANAs wrapped within a pedicled superficial inferior epigastric artery fascial flap to induce surgical angiogenesis, combined with seeding of either (IV) undifferentiated mesenchymal stem cells (uMSCs) or (V) MSCs differentiated into Schwann cell-like cells. Immune cell phenotyping was performed on days 7 and 14. The vascular volume of nerves was measured by microcomputed tomography at 12 and 16 weeks. On day 7, helper T cells (CD4+) were significantly increased in groups IV and V compared to group I. Regulatory T cells (CD4+CD25+) were significantly higher in groups III-IV, and cytotoxic T cells (CD8+) were significantly reduced in groups IV and V compared to group II, respectively. Group II demonstrated the highest levels of natural killer cells (CD161+) compared to groups III-V. On day 14, group IV demonstrated the highest CD4/CD8 ratio. Vascular volume was significantly higher in groups III-V compared to group II at 12 weeks and groups IV and V compared to group II at 16 weeks. The CD4/CD8 ratio demonstrated a positive correlation to vascular volumes at 12 weeks. Early favorable immune responses were observed in ANAs treated with surgical angiogenesis with or without stem cell delivery and demonstrated improved vascularity at longer follow-up.

Acellular nerve grafts with bone marrow mesenchymal stem cells/Schwann cells for sciatic nerve regeneration in rats: a meta-analysis.

The aim of this meta-analysis was to evaluate the effects of acellular nerve grafts (ANGs) with bone marrow mesenchymal stem cells (BMSCs) or Schwann cells (SCs) on the treatment of sciatic nerve defect in rats. Electronic databases were accessed to identify eligible targets. ANGs data were extracted for meta-analysis using Review Manager 5.3. The rats subjected to ANGs+BMSCs or ANGs+SCs are characterized by different sciatic nerve function index, nerve conduction, latency, amplitude, myelin sheath thickness, myelinated nerve fibers and gastrocnemius wet weight. accompanied with evidently superior recovery of limb function. These differences are of statistical significance (P<0.05) when compared to that of control group with ANGs only. ANGs with BMSCs or SCs can promote nerve regeneration and functional recovery in peripheral nerve defects.

Repair of ovine peripheral nerve injuries with xenogeneic human acellular sciatic nerves prerecellularized with allogeneic Schwann-like cells-an innovative and promising approach.

IntroductionThe iatrogenic effects of repairing peripheral nerve injuries (PNIs) with autografts (AGTs) encouraged the present study to involve a new approach consisting of grafting xenogeneic prerecellularized allogeneic cells instead of AGTs.MethodsWe compared sheep's AGT regenerative and functional capacity with decellularized human nerves prerecellularized with allogeneic Schwann-like cell xenografts (onwards called xenografts). Mesenchymal stem cells were isolated from ovine adipose tissue and induced in vitro to differentiate into Schwann-like cells (SLCs). Xenografts were grafted in ovine sciatic nerves. Left sciatic nerves (20 mm) were excised from 10 sheep. Then, five sheep were grafted with 20 mm xenografts, and five were reimplanted with their nerve segment rotated 180° (AGT).ResultsAll sheep treated with xenografts or AGT progressively recovered the strength, movement, and coordination of their intervened limb, which was still partial when the study was finished at sixth month postsurgery. At this time, numerous intrafascicular axons were observed in the distal and proximal graft extremes of both xenografts or AGTs, and submaximal nerve electrical conduction was observed. The xenografts and AGT-affected muscles appeared partially stunted.ConclusionsXenografts and AGT were equally efficacious in starting PNI repair and justified further studies using longer observation times. The hallmarks from this study are that human xenogeneic acellular scaffolds were recellularized with allogenic SCL and were not rejected by the nonhuman receptors but were also as functional as AGT within a relatively short time postsurgery. Thus, this innovative approach promises to be more practical and accessible than AGT or allogenic allografts and safer than AGT for PNI repair.

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production.

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.

VP8: Immune Response and Revascularization of Acellular Nerve Allografts Following Mesenchymal Stem Cell Seeding and Surgical Angiogenesis

INTRODUCTION: Increasing evidence demonstrates an interplay between neoangiogenesis and immune cells. We investigated the immune response and revascularization of acellular nerve allografts (ANA) after combined stem cell delivery and surgical angiogenesis in a rat model. MATERIALS AND METHODS: Unilateral sciatic nerve defects in 60 Lewis rats were repaired with (I) autografts, (II) ANAs, (III) ANAs wrapped within a pedicled superficial inferior epigastric artery fascia flap to induce surgical angiogenesis, combined with seeding of either (IV) undifferentiated mesenchymal stem cells (MSCs) or (V) MSCs differentiated into Schwann cell-like cells. Immune cell phenotyping was performed on day 7 and 14. The vascular volume of nerves were measured by microcomputed tomography at 12 and16 weeks. RESULTS: On day 7, helper T cells (CD4+) were significantly increased in groups IV and V compared to group I. Regulatory T cells (CD4+CD25+) were significantly higher in groups III-IV and cytotoxic T cells (CD8+) were significantly reduced in groups IV and V compared to group II, respectively. Group II demonstrated the highest levels of natural killer cells (CD161+) compared to groups III-V. On day 14, group IV demonstrated the highest CD4/CD8 ratio. Vascular volume was significantly higher in groups III-V compared to group II at 12 weeks and in groups IV and V compared to group II at 16 weeks. The CD4/CD8 ratio demonstrated a positive correlation to vascular volumes at 12 weeks. CONCLUSION: Early favorable immune responses were observed in ANAs treated with surgical angiogenesis with or without stem cell delivery and demonstrated improved vascularity at longer follow-up.

VP7: In Vitro Comparison of Dynamic Seeding Versus Microinjection of Mesenchymal Stem Cells for Acellular Nerve Allograft

INTRODUCTION: Mesenchymal stem cell (MSC) supplemented acellular nerve allografts (ANA) are a potential strategy to improve treatment of segmental nerve defects. Prior to clinical translation optimal cell delivery methods must be defined. While two techniques, dynamic seeding and microinjection have been described, the seeding efficiency, cell viability, and distribution of MSCs in ANAs of the techniques have yet to be compared. MATERIALS AND METHODS: Sciatic nerve segments of Sprague-Dawley rats were decellularized and MSCs were harvested from the adipose tissue of Lewis rats. Cell viability was evaluated after injection of MSCs through a 27-gauge needle at different flow rates (10, 5, and 1 μL/min). MSCs were dynamically seeded or longitudinally injected in ANAs. Cell viability, seeding efficiency, and distribution were evaluated using Live/Dead and MTS assays, scanning electron microscopy, and Hoechst staining. RESULTS: No statistically significant difference in cell viability after injection at different flow rates was seen. After cell delivery, 84.07% ± 3.68 and 87.75% ± 2.07 of MSCs remained viable in the dynamic seeding and microinjection group, respectively (p=0.41). The seeding efficiency of microinjection (100.4%±5.6) was significantly higher than dynamic seeding (48.1%±8.6) on day 1 (p=0.001). Dynamic seeding demonstrated a significantly more uniform cell distribution over the course of the ANA compared to microinjection (p= 0.02). CONCLUSION: MSCs remain viable after both dynamic seeding and microinjection in ANAs. Higher seeding efficiency was observed with microinjection, but dynamic seeding resulted in more uniform distribution. In vivo studies are required to assess the effect on gene expression profiles and functional motor outcomes.

Chemically Extracted Acellular Nerve Allograft Seeded with SDNF and Autogenic ADSCs for Peripheral Nerve Repairment in a Beagle Model

Peripheral nerve repair is a major challenge in clinical practice. Nerve grafting is required to treat severe peripheral nerve defects caused by injuries. Available nerve sources for autologous transplantation are limited. Stem cells offer promise for peripheral nerve repair and regeneration. However, the current lack of Schwann cell phenotype, high costs, and major trauma limit the production of Schwann cells from stem cell differentiation.

Acellular nerve grafts supplemented with induced pluripotent stem cell-derived exosomes promote peripheral nerve reconstruction and motor function recovery

Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability. Herein, we selected induced pluripotent stem cells (iPSCs) derived exosomes to supplement acellular nerve grafts (ANGs) with the aim of restoring long-distance peripheral nerve defects. Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4, Sox2, Klf4, and c-Myc. The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4, SSEA4, Nanog, Sox2, which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells (SCs) in vitro. After isolation and biological characteristics of iPSCs-derived exosomes, we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination. After that, we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats. Owing to the promotion of iPSCs-derived exosomes, satisfactory regenerative outcomes were achieved including gait behavior analysis, electrophysiological assessment, and morphological analysis of regenerated nerves. Especially, motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers. Taken together, our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects, and thus represents a cell-free strategy for future clinical applications.

Failed Acellular Nerve Allografts: A Critical Review.

Acellular nerve allograft (ANA) occupies an increasingly prominent role in the treatment of peripheral nerve reconstruction. There is demonstrable efficacy; however, some grafts fail to support axonal regrowth and the reasons for this are unclear. This study examines the ANA experience in a specialized peripheral nerve surgery department to discuss the clinical and histological findings in failed cases. Failed ANA grafts were identified from a prospective database using Medical Research Council Classification (MRCC) S3 and M3 as thresholds for success. Cases in which ANA grafting was indicated for nerve related pain and dysesthesia but where no subjective improvement in symptoms occurred were also included. Patients requiring revision surgery after ANA grafting were also considered failures. Cases were then examined in conjunction with a literature review to identify possible mechanisms of failure, including detailed histological analysis in 2 cases. Eight failed procedures were identified from a database of 99 separate allograft records on 74 patients. This included procedures for 2 tibial nerves, 2 superficial radial nerves, 2 median nerves, 1 digital nerve and a lateral cord brachial plexus injury (male/female, 5:3; age range, 24-54 years). Allograft length range 25 to 120 mm. One postoperative infection was identified. Histological findings in 2 cases included adequate vascularization of allograft material without subsequent axonal regeneration, a reduction of large myelinated fibers proximal to a tibial nerve allograft in the setting of a chronic injury, and a preference for small rather than large fiber regeneration. This article reports instances of ANA graft failure in a variety of contexts, for which the primary reasons for failure remain unclear. The etiology is likely to be multifactorial with both patient, graft and surgeon factors contributing to failure. Further clinical and histological analysis of ANA failures will improve our understanding of the mechanisms of graft failure.

Comparison of mesenchymal stem cell attachment efficiency in acellular neural graft for peripheral nerve regeneration

Decellularized nerve allograft is an alternative to autologous nerve graft for nerve defects but has shown inferior clinical outcomes. Mesenchymal stem cells can play a key role in improving nerve regeneration of decellularized nerve allografts. The purpose of this study was to compare different mesenchymal stem cell seeding methods and to find the most efficient way to attach cells to nerve grafts for peripheral nerve regeneration. Wharton's jelly mesenchymal stem cells were collected from human umbilical cords and were seeded in the acellular nerve graft in five different ways as follows: PBS injection, fibrin glue drop, Matrigel drop, bioreactor, and Matrigel injection. A 6-mm sciatic nerve defect of Sprague–Dawley rats was bridged using mesenchymal stem cells-laden acellular nerve grafts according to the five seeding methods. Two days after implantation, the nerve tissue was biopsied and analyzed by the immunofluorescence staining of nuclei. The number of Wharton's jelly mesenchymal stem cells (+ h Nuclei) was counted in the inside, outside, and the total area of the graft sections under 200X magnification. The highest efficiency of mesenchymal stem cell attachment inside the graft and the highest total number of attached mesenchymal stem cells was observed in the group using Matrigel injection (p < 0.0001). This study showed mesenchymal stem cells can be more effectively attached to decellularized nerve graft using the injection method with Matrigel than other static or dynamic seeding methods in vivo.

Evaluation of the Induced Membrane for Neurotrophic Factors

Despite gaining popularity as a bridge for small and moderate nerve gaps, an acellular nerve allograft (ANA) lacks many of the neurotrophic characteristics of a nerve autograft. Pseudomembranes induced to form around temporary skeletal spacers are rich in growth factors. Induced membranes may have beneficial neurotrophic factors which could support ANA. Twenty-two male Sprague-Dawley rats underwent resection of 2 cm of the sciatic nerve. A silicone rod was inset in the defect of 11 experimental rats, and marking sutures only were placed in the nerve stumps of the remaining 11 control rats. After allowing 4 weeks for tissue maturation, tissue samples harvested from the induced membrane (experimental group) and the tissue bed (control group) were analyzed using Luminex multiplex assay to quantify differences in detectable levels of the following neurotrophic factors: nerve growth factor, glial-derived nerve factor, vascular endothelial growth factor, and transforming growth factor ß (TGF-ß) 1, 2, and 3, interleukin-1ß, and monocyte chemoattractant protein1. No difference was detected between the control and experimental groups in levels of vascular endothelial growth factor. Higher levels of TGF-ß1, TGF-ß2, TGF-ß3, glial-derived nerve factor, nerve growth factor, monocyte chemoattractant protein 1, and interleukin-1ß were detected in the experimental group. In the setting of peripheral nerve injury, an induced membrane has higher levels of several neurotrophic factors that may support nerve regeneration compared to wound bed cicatrix. This investigation provides impetus for further study examining the utility of using a staged induced membrane technique in conjunction with delayed nerve grafting in reconstruction of some peripheral nerve defects.

BMSC-derived extracellular matrix better optimizes the microenvironment to support nerve regeneration

A favorable microenvironment plays an important role in nerve regeneration. Extracellular matrix (ECM) derived from cultured cells or natural tissues can facilitate nerve regeneration in the presence of various microenvironmental cues, including biochemical, spatial, and biomechanical factors. This study, through proteomics and three-dimensional image analysis, determines that the components and spatial organization of the ECM secreted by bone marrow mesenchymal cells (BMSCs) are more similar to acellular nerves than those of the ECMs derived from Schwann cells (SCs), skin-derived precursor Schwann cells (SKP–SCs), or fibroblasts (FBs). ECM-modified nerve grafts (ECM-NGs) are engineered by co-cultivating BMSCs, SCs, FBs, SKP-SCs with well-designed nerve grafts used to bridge nerve defects. BMSC-ECM-NGs exhibit the most promising nerve repair properties based on the histology, neurophysiology, and behavioral analyses. The regeneration microenvironment formed by the ECM-NGs is also characterized by proteomics, and the advantages of BMSC-ECM-NGs are evidenced by the enhanced expression of factors related to neural regeneration and reduced immune response. Together, these findings indicate that BMSC-derived ECMs create a more superior microenvironment for nerve regeneration than that by the other ECMs and may, therefore, represent a potential alternative for the clinical repair of peripheral nerve defects.

Preparation of decellularized optic nerve grafts.

Decellularized tissues based on well-conserved extracellular matrices (ECMs) are a common area of research in tissue engineering. Although several decellularization protocols have been suggested for several types of tissues, studies on the optic nerve have been limited. We report decellularization protocol with different detergent for the preparation of acellular optic nerve and tissues were examined. DNA, glycosaminoglycan (GAG), and collagen content of the groups were evaluated with biochemical analyses and examined with histological staining. Mechanical properties, chemical components as well as cytotoxic properties of tissues were compared. According to the results, it was determined that TX-100 (Triton X-100) was insufficient in decellularization when used alone. In addition, it was noticed that 85% of GAG content was preserved by using TX-100 and TX-100-SD (sodium deoxycholate), while this ratio was calculated as 30% for SDS. In contrast, the effect of the decellularization protocols on ECM structure of the tissues was evaluated by scanning and transmission electron microscopy (SEM and TEM) and determined their mechanical properties. Cytotoxicity analyses were exhibited minimum 95% cell viability for all groups, suggesting that there are no cytotoxic properties of the methods on L929 mouse fibroblast cells. The combination of TX-100-SD and TX-100-SDS (sodium dodecyl sulfate) were was determined as the most effective methods to the literature for optic nerve decellularization.

Clinical Outcome of Nerve Decompression Surgery for Migraine Improves with Nerve Wrap.

Background:Chronic migraine headaches affect nearly 30 million Americans every year and are responsible for roughly 1.2 million emergency department visits annually. Many of the standard therapies commonly used to treat migraines are often unsuccessful and may furthermore introduce unwanted side effects. The purpose of this study was to identify independent predictors of clinical improvement in patients undergoing surgical nerve decompression for migraine.Methods:A retrospective chart review between 2010 and 2020 was conducted. The primary endpoint was clinical improvement at 1-year follow-up, defined as an independence from prescription medications. Patients were stratified into two groups: clinical improvement and treatment failure. Backward multivariable logistic regression was used to examine the associations between migraine improvement and different patient characteristics.Results:A total of 153 patients were included. In total, 129 (84.3%) patients improved and 24 (15.7%) did not. Significant associations with clinical improvement at multivariable logistic regression were found with acellular dermal matrix nerve wrap (OR = 10.80, 95%CI: 6.18–16.27), and operation of trigger sites four (OR = 37.96, 95%CI: 2.16–73.10) and five (OR = 159, 95%CI: 10–299).Conclusion:The use of acellular dermal matrix nerve wraps in surgery was significantly associated with clinical migraine improvement, as was operation at trigger sites four and five.

Acellular nerve graft enriched with mesenchymal stem cells in the transfer of the phrenic nerve to the musculocutaneous nerve in a C5-C6 brachial plexus avulsion in a rat model.

Phrenic nerve transfer has been shown to achieve good nerve regeneration in brachial plexus avulsion. Acellular nerve allografts (ANAs) showed inferior results to autografts, which is why its use with mesenchymal stem cells (MSCs) is currently being studied. The aim is to study the effect of BM-MSCs associated with ANAs in a rat model of phrenic nerve transfer to the musculocutaneous nerve in a C5-C6 avulsion. 42 Wistar-Lewis rats underwent a C5-C6 lesion in the right forelimb by excising a 3 mm segment from both roots, followed by a phrenic nerve transfer to the musculocutaneous nerve associated with the interposition of a three types of nerve graft (randomly distributed): control (autograft) group (n=12), ANAs group (n=12), and ANAs + BM-MSCs group (n=18) After 12 weeks, amplitude and latency of the NAP and the compound motor action potential (CMAP) were measured. Biceps muscles were studied by histological analysis and nerve grafts by electron microscopy and fluorescence analysis. Statistically significant reductions were found in latency of the CMAP between groups control (2.48 ± 0.47 ms) and experimental (ANAs: 4.38 ± 0.78 ms, ANAs + BM-MSCs: 4.08 ± 0.85 ms) and increases in the amplitude of the CMAP between groups control (0.04388 ± 0.02 V) and ANAs + BM-MSCs (0.02275 ± 0.02 V), as well as in the thickness of the myelin sheath between groups control (0.81 ± 0.07 μm) and experimental (ANAs: 0.72 ± 0.08 μm, ANAs + BM-MSCs: 0.72 ± 0.07 μm) and in the area of the myelin sheath between groups control (13.09 ± 2.67 μm2 ) and ANAs (10.01 ± 2.97 μm2 ) (p < .05). No statistically significant differences have been found between groups ANAs and ANAs + BM-MSCs. This study presents a model for the study of lesions of the upper trunk and validates the autologous graft as the gold standard.

Direct Neurotization: Past, Present, and Future Considerations.

Direct neurotization is a method that involves direct implantation of nerve fascicles into a target tissue, that is, muscle fibers, skin, cornea, and so on, with the goal of restoring aesthetic, sensation and or functional capacity. This technique has been implemented since the early 1900s, with numerous experimental and clinical reports of success. Applications have included both sensory and motor neurotization of muscle, as well as protective sensory provision for other organs. These techniques have been used to restore corneal sensation, repair brachial plexus injuries, reestablish tongue movement and function through direct tongue neurotization, and reinnervate multiple facial muscles in patients with facial paralysis. Most recently, these methods have even been used in conjunction with acellular cadaveric nerve grafts to directly neurotize skin. Indications for direct neurotization remain limited, including those in which neural coaptation is not feasible (ie, surgical or traumatic damage to neuromuscular junction, severe avulsion injuries of the distal nerve); however, the success and wide-range application of direct neurotization shows its potential to be implemented as an adjunct treatment in contrast to views that it should solely be used as a salvage therapy. The purpose of the following review is to detail the historic and current applications of direct neurotization and describe the future areas of investigation and development of this technique.