The Road to Optimized Nerve Reconstruction

Traumatic injuries to the peripheral nerves cause considerable disability and economic burden. It is estimated that 5% of patients admitted to Level I trauma centers have peripheral nerve injury. The reconstruction of peripheral nerve defects remains a clinical challenge. The gold standard for nerve injuries that cannot be directly reconstructed is the use of a bridging autologous nerve graft. The use of autograft nerve is limited by supply, diameter, and length, and has associated donor site morbidity. This has constrained the ability to optimally reconstruct injured nerves of patients with multiple segmental defects and resulted in the prioritization of which nerves to reconstruct. This thesis focuses on reconstruction of peripheral nerve defects and highlights the clinical problem and focuses on the optimization of a decellularized nerve allografts

Ligament reconstruction in thumb carpometacarpal joint instability: A systematic review

Summary: In thumb carpometacarpal (CMC) instability, laxity of the ligaments surrounding the joint leads to pain and weakness in grip and pinch strength, which predisposes the patient to developing CMC joint arthritis. Recent advancements in joint anatomy and kinematics have led to the development of various surgical reconstructive procedures. This systematic review outlines the available ligament reconstruction techniques and their efficacy in treating nontraumatic and nonarthritic CMC instability. Additionally, we aimed to provide evidence which specific ligament reconstruction technique demonstrates the best results. Four databases (Embase, MEDLINE, Web of Science, and Cochrane Central) were searched for studies that reported on surgical techniques and their clinical outcomes in patients with nontraumatic and nonarthritic CMC instability. Twelve studies were analyzed for qualitative review, including nine different surgical ligament reconstruction techniques involving two hundred and thirty thumbs. All but one of the reported techniques improved postoperative pain scores and showed substantial improvement in pinch and grip strength. Complication rates varied between 0% and 25%. The included studies showed that ligament reconstruction effectively alleviated the patients’ complaints regarding pain and instability, resulting in overall high patient satisfaction. Nevertheless, drawing definitive conclusions regarding the superiority of any ligament reconstruction technique remains challenging owing to the limited availability of homogeneous data in the current literature

Functional Outcome after Reconstruction of a Long Nerve Gap in Rabbits Using Optimized Decellularized Nerve Allografts

Contains fulltext : 220188.pdf (Publisher’s version ) (Closed access)BACKGROUND: Processed nerve allografts are a promising alternative to nerve autografts, providing an unlimited, readily available supply and avoiding donor-site morbidity and the need for immunosuppression. Currently, clinically available nerve allografts do not provide satisfactory results for motor reconstruction. This study evaluated motor recovery after reconstruction of a long nerve gap using a processed nerve allograft and the influence of storage techniques. METHODS: Nerve allografts were decellularized using elastase and detergents and stored at either 4 degrees or -80 degrees C. In 36 New Zealand White rabbits, a 3-cm peroneal nerve gap was repaired with either an autograft (group 1, control) or a cold-stored (group 2) or frozen-stored (group 3) processed nerve allograft. Nerve recovery was evaluated using longitudinal ultrasound measurements, electrophysiology (compound muscle action potentials), isometric tetanic force, wet muscle weight, and histomorphometry after 24 weeks. RESULTS: Longitudinal ultrasound measurements showed that the cold-stored allograft provided earlier regeneration than the frozen-stored allograft. Furthermore, ultrasound showed significantly inferior recovery in group 3 than in both other groups (p < 0.05). Muscle weight and isometric tetanic force showed similar outcomes in the autograft and cold-stored allograft groups [p = 0.096 (muscle weight) and p = 0.286 (isometric tetanic force)], and confirmed the inferiority of the frozen-stored allograft to the autograft [p < 0.01 (muscle weight) and p = 0.02 (isometric tetanic force)]. CONCLUSIONS: Frozen storage of the nerve allograft significantly impairs functional recovery and should be avoided. The cold-stored optimized nerve allograft yields functional recovery similar to the gold standard autograft in the reconstruction of a 3-cm motor nerve defect. Future studies should focus on further improvement of the nerve allograft

Outcomes of Single versus Double Fascicular Nerve Transfers for Restoration of Elbow Flexion in Patients with Brachial Plexus Injuries: A Systematic Review and Meta-Analysis

Item does not contain fulltextBACKGROUND: Elbow flexion after upper brachial plexus injury may be restored by a nerve transfer from the ulnar nerve to the biceps motor branch with an optional nerve transfer from the median nerve to the brachialis motor branch (single and double fascicular nerve transfer). This meta-analysis assesses the effectiveness of both techniques and the added value of additional reinnervation of the brachialis muscle. METHODS: Comprehensive searches were performed identifying studies concerning restoration of elbow flexion through single and double fascicular nerve transfers. Only C5 to C6 lesion patients were included in quantitative analysis to prevent confounding by indication. Primary outcome was the proportion of patients reaching British Medical Research Council elbow flexion grade 3 or greater. Meta-analysis was performed with random effects models. RESULTS: Thirty-five studies were included (n = 688). In quantitative analysis, 29 studies were included (n = 341). After single fascicular nerve transfer, 190 of 207 patients reached Medical Research Council grade 3 or higher (random effects model, 95.6 percent; 95 percent CI, 92.9 to 98.2 percent); and after double fascicular nerve transfer, 128 of 134 patients reached grade 3 or higher (random effects model, 97.5 percent; 95 percent CI, 95.0 to 100 percent; p = 0.301). Significantly more double nerve transfer patients reached grade 4 or greater if preoperative delay was 6 months or less (84 of 101 versus 49 of 51; p = 0.035). CONCLUSIONS: Additional reinnervation of the brachialis muscle did not result in significantly more patients reaching Medical Research Council grade 3 or higher for elbow flexion. Double fascicular nerve transfer may result in more patients reaching grade 4 or higher in patients with a preoperative delay less than 6 months. The median nerve may be preserved or used for another nerve transfer without substantially impairing elbow flexion restoration

A systematic review and meta-analysis on the use of fibrin glue in peripheral nerve repair: Can we just glue it?

BACKGROUND: Within the field of peripheral nerve surgery, the use of fibrin glue as an alternative to conventional microsurgical suture repair is becoming increasingly popular. Advantages of fibrin glue for nerve reconstruction include technical ease of use, less tissue manipulation, and shorter operation times. Although fibrin glue seems a promising alternative to conventional microsurgical repair, further insight into the outcomes of nerve recovery is essential. OBJECTIVE: To summarize the current literature on the use of fibrin glue for peripheral nerve repair and compare these results with outcomes following conventional suture repair. METHODS: A systematic search in Embase, MEDLINE, Web of Science, Cochrane, and Google Scholar databases was performed. The search included animal, cadaveric, and human studies assessing outcomes following peripheral nerve repair using fibrin glue. Data on outcomes were subdivided into functional outcomes, electrophysiology, histopathology, biomechanical outcomes, and operation times. We calculated standardized mean differences and combined these in a random effects model to estimate the overall effect. RESULTS: From a total of 2057 references, 37 animal, two cadaveric, and four human studies were included. Fibrin glue repairs resulted in similar functional and electrophysiology outcomes and shorter operation times than suture repairs. However, fibrin glue alone resulted in lower strength and more dehiscence. No dehiscence was reported when fibrin glue was combined with one or two sutures. Yet, we also found that methodological details were poorly reported in animal studies, resulting in an unclear risk of bias. This should be taken into consideration when interpreting the results. CONCLUSION: The results indicate that nerve regeneration may be similar in fibrin glue repairs and suture repairs. Combining fibrin glue with one or two positional sutures allows for a precise realignment of the nerve fibers and seems to provide sufficient strength to prevent dehiscence

The role of vascularization in nerve regeneration of nerve graft

Vascularization is an important factor in nerve graft survival and function. The specific molecular regulations and patterns of angiogenesis following peripheral nerve injury are in a broad complex of pathways. This review aims to summarize current knowledge on the role of vascularizati

Recipient-derived angiogenesis with short term immunosuppression increases bone remodeling in bone vascularized composite allotransplantation: A pilot study in a swine tibial defect model

Current vascularized composite allotransplantation (VCA) transplantation protocols rely upon life-long immune modulation to maintain tissue perfusion. Alternatively, bone-only VCA viability may be maintained in small animal models using surgical angiogenesis from implanted autogenous vessels to develop a neoangiogenic bone circulation that will not be rejected. This study tests the method's efficacy in a large animal model as a bridge to clinical practice, quantifying the remodeling and mechanical properties of porcine tibial VCAs. A segmental tibial defect was reconstructed in Yucatan miniature swine by transplantation of a matched tibia segment from an immunologically mismatched donor. Microsurgical repair of nutrient vessels was performed in all pigs, with simultaneous intramedullary placement of an autogenous arteriovenous (AV) bundle in Group 2. Group 1 served as a no-angiogenesis control. All received 2 weeks of immunosuppression. After 16 weeks, micro-CT and histomorphometric analyses were used to evaluate healing and remodeling. Axial compression and nanoindentation studies evaluated bone mechanical properties. Micro-CT analysis demonstrated significantly more new bone formation and bone remodeling at the distal allotransplant/recipient junction and on the endosteal surfaces of Group 2 tibias (p = 0.03). Elastic modulus and hardness were not adversely affected by angiogenesis. The combination of 2 weeks of immunosuppression and autogenous AV-bundle implantation within a microsurgically transplanted tibial allotransplant permitted long-term allotransplant survival over the study period of 16 weeks in this large animal model. Angiogenesis increased bone formation and remodeling without adverse mechanical effects. The method may allow future composite-tissue allotransplantation of bone without the risks associated with long-term immunosuppres