Peripheral Nerve Defects: Repair Using Autogenous Vein Grafts Filled with PRP and Active Nerve Microtissues and Evaluation by Novel Multimodal Ultrasound Techniques

Background: Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair. Methods: In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T+PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects. Results: Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T+PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively. Conclusion: Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.

Reconstruction of Sciatic Nerve Using Bilateral Vascularized Sural Nerve Grafts: A Case Report

Injury of peripheral nerve may require reconstruction for motor and sensory function recovery. However, when the nerve defect is long, especially in the lower extremities, reconstruction with successful function recovery proved to be difficult. We documented a case of bilateral vascularized sural nerve graft repair of a large and long sciatic nerve defect following malignant tumor resection on posterior thigh. Although we were unable to achieve satisfactory outcomes in motor function recovery, we did accomplish some sensory function recovery.

Nerve recovery from treatment with a vascularized nerve graft compared to an autologous non-vascularized nerve graft in animal models: A systematic review and meta-analysis

Background Treatment of nerve injuries proves to be a worldwide clinical challenge. Vascularized nerve grafts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous non-vascularized nerve graft. However, there is no adequate clinical evidence for the beneficial effect of vascularized nerve grafts and they are still disputed in clinical practice. Objective To systematically review whether vascularized nerve grafts give a superior nerve recovery compared to non-vascularized nerve autografts regarding histological and electrophysiological outcomes in animal models. Material and methods PubMed and Embase were systematically searched. The inclusion criteria were as follows: 1) the study was an original full paper which presented unique data; 2) a clear comparison between a vascularized and a non-vascularized autologous nerve transfer was made; 3) the population study were animals of all genders and ages. A standardized mean difference and 95% confidence intervals for each comparison was calculated to estimate the overall effect. Subgroup analyses were conducted on graft length, species and time frames. Results Fourteen articles were included in this review and all were included in the meta-analyses. A vascularized nerve graft resulted in a significantly larger diameter, higher nerve conduction velocity and axonal count compared to an autologous non-vascularized nerve graft. However, during sensitivity analysis the effect on axonal count disappeared. No significant difference was observed in muscle weight. Conclusion Treating a nerve gap with a vascularized graft results in superior nerve recovery compared to non-vascularized nerve autografts in terms of axon count, diameter and nerve conduction velocity. No difference in muscle weight was seen. However, this conclusion needs to be taken with some caution due to the inherent limitations of this meta-analysis. We recommend future studies to be performed under conditions more closely resembling human circumstances and to use long nerve defects.

Anterior Interosseous Nerve to Ulnar Nerve Transfers: A Systematic Review

Background There has been an increasing utilization of end-to-end (ETE) and reverse “supercharged” end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar nerve transfers (NTs) for treatment of high ulnar nerve injury. This study aimed to review the potential indications for, and outcomes of, ETE and SETS AIN–ulnar NT. Methods A literature review was performed, and 10 articles with 156 patients who had sufficient follow-up to evaluate functional outcomes were included. English studies were included if they reported the outcome of patients with ulnar nerve injuries treated with AIN to ulnar motor NT. Outcomes were analyzed based on the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire scores, grip and key pinch strength, and interosseous Medical Research Council–graded motor strength. Comparisons were made using the independent t-test and the chi-square test. No nerve graft control group was required for eligibility. Ulnar nerve injury types varied. Results NT resulted in 77% of patients achieving M3+ recovery, 53.7 ± 19.8 lb grip strength recovery, 61 ± 21% key pinch recovery, and a mean DASH score of 33.4 ± 16. In this diverse group, NT resulted in significantly greater M3+ recovery and grip strength recovery measured in pounds than in the nerve graft/conventional treatment group, and ETE repairs had significantly better outcomes compared with SETS repairs for grip strength, key pinch strength, and DASH scores, but heterogeneity limits interpretation. Conclusion ETE and SETS AIN–ulnar NTs produce significant restoration of ulnar nerve motor function for high ulnar nerve injuries. For ulnar nerve transection injuries at or above the elbow, ETE NT results in superior motor recovery compared with nerve grafting/conventional repair. However, further research is needed to determine the best treatment for other types of ulnar nerve injury and the role of SETS NT.

933 The Glass Half Full? A Case Of Cutaneous Neuroma Formation Post Laceration Of First Web-Space Of The Hand

Introduction neuromas are lesions resulting from abnormal nerve regeneration following a peripheral nerve injury and may cause severe pain. Method we present a case of a 54-year-old female who developed a painful cutaneous lesion over the first web-space of the hand following an untreated glass laceration 3 years previously. Results surgical resection revealed a 100% transection of ulnar digital nerve (UDN) of thumb with regeneration into the skin. A posterior interosseous nerve (PIN) nerve graft was required to bridge the resulting 15mm gap. Histopathology revealed a 12x12mm neuroma extending into dermis. Conclusions cutaneous neuroma is a rare consequence of penetrating trauma. This case highlights the need for prompt assessment of penetrating injuries to reduce risk of neuroma formation.

Bone marrow-derived mesenchymal stem cells transplanted into a vascularized biodegradable tube containing decellularized allogenic nerve basal laminae promoted peripheral nerve regeneration; can it be an alternative of autologous nerve graft?

Previously, we showed silicone nerve conduits containing a vascular bundle and decellularized allogenic basal laminae (DABLs) seeded with bone marrow-derived mesenchymal stem cells (BMSCs) demonstrated successful nerve regeneration. Nerve conduits should be flexible and biodegradable for clinical use. In the current study, we used nerve conduits made of polyglycoric acid (PGA) fiber mesh, which is flexible, biodegradable and capillary-permeable. DABLs were created using chemical surfactants to remove almost all cell debris. In part 1, capillary infiltration capability of the PGA tube was examined. Capillary infiltration into regenerated neural tissue was compared between the PGA tube with blood vessels attached extratubularly (extratubularly vascularized tube) and that containing blood vessels intratubularly (intratubularly vascularized tube). No significant difference was found in capillary formation or nerve regeneration between these two tubes. In part 2, a 20 mm gap created in a rat sciatic nerve model was bridged using the extratubularly vascularized PGA tube containing the DABLs with implantation of isogenic cultured BMSCs (TubeC+ group), that containing the DABLs without implantation of the BMSCs (TubeC- group), and 20 mm-long fresh autologous nerve graft (Auto group). Nerve regeneration in these three groups was assessed electrophysiologically and histomorphometrically. At 24 weeks, there was no significant difference in any electrophysiological parameters between TubeC+ and Auto groups, although all histological parameters in Auto group were significantly greater than those in TubeC+ and TubeC- groups, and TubeC+ group demonstrated significant better nerve regeneration than TubeC- group. The transplanted DABLs showed no signs of immunological rejection and some transplanted BMSCs were differentiated into cells with Schwann cell-like phenotype, which might have promoted nerve regeneration within the conduit. This study indicated that the TubeC+ nerve conduit may become an alternative to nerve autograft.