Shin, Alexander Y.

We report a patient who has been on tacrolimus for bilateral lung transplantation and presented with a brachial plexus injury (BPI), with unusual improvement of lower trunk innervated hand function. The lower trunk injury with resultant left hand paralysis had developed after his sternotomy 18 months ago. He has been treated with tacrolimus as part of his immunosuppression protocol since the surgery, without severe side effects. Physical examination at 18 months demonstrated unusual excellent grip pattern and full opposition of his thumb with slight claw deformity of his ulnar two digits. While the neurotoxic effects of tacrolimus are more emphasised, the neuroregenerative properties have been recently explored. The recovery in this patient is unique and unusual after BPI and is most likely as a result of the low dose tacrolimus treatment.

AbstractPurposeAdipose derived mesenchymal stem cells (MSCs) are hypothesized to supplement tissues with growth factors essential for regeneration and neovascularization. The purpose of this study was to determine the effect of MSCs with respect to neoangiogenesis when seeded onto a decellularized nerve allograft in a rat sciatic nerve defect model.MethodsAllograft nerves were harvested from Sprague–Dawley rats and decellularized. MSCs were obtained from Lewis rats. 10 mm sciatic nerve defects in Lewis rats were reconstructed with reversed autograft nerves, decellularized allografts, decellularized allografts seeded with undifferentiated MSC or decellularized allografts seeded with differentiated MSCs. At 16 weeks, the vascular surface area and volume were evaluated.ResultsThe vascular surface area in normal nerves (34.9 ± 5.7%), autografts (29.5 ± 8.7%), allografts seeded with differentiated (38.9 ± 7.0%) and undifferentiated MSCs (29.2 ± 3.4%) did not significantly differ from each other. Unseeded allografts (21.2 ± 6.2%) had a significantly lower vascular surface area percentage than normal nonoperated nerves (13.7%, p = .001) and allografts seeded with differentiated MSCs (17.8%, p = .001). Although the vascular surface area was significantly correlated to the vascular volume (r = .416; p = .008), no significant differences were found between groups concerning vascular volumes. The vascularization pattern in allografts seeded with MSCs consisted of an extensive nonaligned network of microvessels with a centripetal pattern, while the vessels in autografts and normal nerves were more longitudinally aligned with longitudinal inosculation patterns.ConclusionsNeoangiogenesis of decellularized allograft nerves was enhanced by stem cell seeding, in particular by differentiated MSCs. The pattern of vascularization was different between decellularized allograft nerves seeded with MSCs compared to autograft nerves.

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° or −80°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.

Management of hand and wrist avascular necrosis with osteochondral fragmentation or focal arthritis can be a challenging problem with a variety procedures described for its treatment. Osteochondral autograft transplantation systems have been utilized in various focal defects of the knee, ankle, elbow, and wrist. The same principle for the treatment of focal defects of the proximal scaphoid, proximal capitate as well as metacarpal head as an alternative treatment is described. The main indication for this treatment is to address focal or partial osteochondral defects where the size of the defect is smaller than the isthmus of the involved bone to accommodate a cylindrical osteochondral graft that can be press fit. Larger and complete defects are contraindications to this treatment. We discuss the surgical technique as well as its main indications and expected outcomes

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 vascularization in nerve regeneration, including the key regulation molecules, and mechanisms and patterns of revascularization after nerve injury. Angiogenesis, the maturation of pre-existing vessels into new areas, is stimulated through angiogenic factors such as vascular endothelial growth factor and precedes the repair of damaged nerves. Vascular endothelial growth factor administration to nerves has demonstrated to increase revascularization after injury in basic science research. In the clinical setting, vascularized nerve grafts could be used in the reconstruction of large segmental peripheral nerve injuries. Vascularized nerve grafts are postulated to accelerate revascularization and enhance nerve regeneration by providing an optimal nutritional environment, especially in scarred beds, and decrease fibroblast infiltration. This could improve functional recovery after nerve grafting, however, conclusive evidence of the superiority of vascularized nerve grafts is lacking in human studies. A well-designed randomized controlled trial comparing vascularized nerve grafts to non-vascularized nerve grafts involving patients with similar injuries, nerve graft repair and follow-up times is necessary to demonstrate the efficacy of vascularized nerve grafts. Due to technical challenges, composite transfer of a nerve graft along with its adipose tissue has been proposed to provide a healthy tissue bed. Basic science research has shown that a vascularized fascial flap containing adipose tissue and a vascular bundle improves revascularization through excreted angiogenic factors, provided by the stem cells in the adipose tissue as well as by the blood supply and environmental support. While it was previously believed that revascularization occurred from both nerve ends, recent studies propose that revascularization occurs primarily from the proximal nerve coaptation. Fascial flaps or vascularized nerve grafts have limited applicability and future directions could lead towards off-the-shelf alternatives to autografting, such as biodegradable nerve scaffolds which include capillary-like networks to enable vascularization and avoid graft necrosis and ischemia.

Abstract Background An adipofascial flap in the rat may provide new options for adding vascularization to scarred or nonvascularized beds for a variety of research studies. Current literature lacks sufficient description for a simple reproducible flap model for a vascularized pedicled flap in rats, in particular for neovascularization of allograft nerves for the reconstruction of sciatic nerve defects. The purpose of this study was to describe a surgical technique and determine long-term survivability for the pedicled superficial inferior epigastric artery fascial (SIEF) flap in the rat to meet requirement for a tunneled adipofascial flap to add vascularization to the sciatic nerve area. Methods The technique and use of a 4 × 3-cm SIEF flap are described. Twenty Lewis rats underwent the technique to determine feasibility. The flap was wrapped around processed allograft nerve reconstructions and viability of the flap was evaluated after 12 and 16 weeks. To visualize vessels, nerve grafts were harvested at 12 weeks and stained with hematoxylin-eosin and an antibody against microvessels (CD-34). Results All flaps remained viable after survival of 12 and 16 weeks. Complications included one hematoma formation and two lymphocele formations that did not have any impact on the flap. Immunohistochemistry confirmed an increase in microvessels and Schwann cell nuclei in the SIEF group compared with nerve samples from the unoperated, contralateral side. Conclusion A pedicled adipofascial flap model in the rat to provide a vascular bed for sciatic nerve reconstruction is detailed with long-term survivability evaluation of the flap. This flap is technically simple to be harvested and is suitable for revascularization procedures of various tissues in the lower abdomen, genital area, thigh, or upper limb of the rat.

Background: The purpose of this study was to evaluate the molecular mechanisms underlying nerve repair by a decellularized nerve allograft seeded with adipose-derived mesenchymal stromal cells (MSCs) and compare it to the unseeded allograft and autograft nerve. Methods: Undifferentiated MSCs were seeded onto decellularized nerve allografts and used to reconstruct a 10 mm gap in a rat sciatic nerve model. Gene expression profiles of genes essential for nerve regeneration and immunohistochemical staining (IHC) for PGP9.5, NGF, RECA-1, and S100 were obtained 2 weeks postoperatively. Results: Semi-quantitative RT-PCR analysis showed that the angiogenic molecule VEGFA was significantly increased in seeded allografts, and transcription factor SOX2 was downregulated in seeded allografts. Seeded grafts showed a significant increase in immunohistochemical markers NGF and RECA-1, when compared with unseeded allografts. Conclusions: MSCs contributed to the secretion of trophic factors. A beneficial effect of the MSCs on angiogenesis was found when compared with the unseeded nerve allograft, but implanted MSCs did not show evidence of differentiation into Schwann cell-like cells.

Background: This study assessed the risk and factors of complications after volar locking plate fixation of distal radius fractures. Methods: A single-institution retrospective review of patients undergoing volar locking plate fixation of distal radius fractures between May of 2000 and May of 2015 was undertaken. Demographic data, major complications, minor complications, and radiographic parameters were evaluated. Results: Six hundred forty-seven distal radius fractures managed with volar plate fixation in 636 patients were reviewed. Mean follow-up was 9.1 months. Mean age was 56.5 years. Mean body mass index was 28.0, and 14.6 percent of patients had a body mass index greater than 35. Fractures were classified as Arbeitsgemeinschaft für Osteosynthesefragen class 23-C (67.2 percent), 23-A (26.6 percent), and 23-B (6.2 percent). The incidence of major and minor complications was 13.8 percent and 17.5 percent, respectively. The most common complication was transient paresthesia (9.7 percent). The incidence of tendon rupture or irritation was 0.5 percent or 2.5 percent, respectively. Hardware removal for painful/symptomatic hardware occurred in 6.2 percent at an average of 427.8 days after surgery. Major complications and minor complications were increased 2.2- and 1.9-fold, respectively, in patients with a body mass index greater than 35. Major complications were also increased 3.19 times in patients with residual intraarticular step-off. Hardware removal was 3.3 times more likely in patients with Soong grade 2 plate prominence and 2.9 times more likely in patients with a history of diabetes mellitus. Conclusions: Volar plate osteosynthesis of distal radius fractures is associated with an overall low complication rate. Patient factors, including diabetes mellitus and obesity, and intraoperative factors, including intraarticular fracture alignment and plate prominence, were associated with a higher rate of complications or revision surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.