Surgical management of acute combined injuries of the ipsilateral wrist and elbow joints.

Background: Combined injuries of ipsilateral wrist and elbow joints are rare in clinical practice, characterized by multiple joint dislocations or/and fractures and varying manifestations. As there are still no clinical guidelines and no consensus on the standard treatment, this study aimed to explore the surgical intervention and complications of this kind of combined injuries. Methods: This retrospective study was conducted in a single center. A total of 13 patients with acute combined injuries of the ipsilateral wrist and elbow joints receiving surgical treatment from August 2013 to May 2016 were retrospectively analyzed. The fracture and joint instability and structural damages were repaired and reconstructed. Results: All 13 patients were followed up for a mean duration of 17 months (range: 14 to 22 months). The X-ray films showed good fracture reduction and joint alignment, no fixation failure, re-displacement, bone nonunion, or ischemic necrosis in all cases. According to the Mayo Elbow Performance Score (MEPS), the excellent and good rate of joint function was 84.6%. According to the Mayo Modified Wrist Score (MMWS), the excellent and good rate of joint function was 76.9%. There were no significant restrictions on elbow and wrist movements. The disabilities of the arm, shoulder, and hand (DASH) score was excellent, with an average of 18.5 points. Conclusions: The key to intervention of combined injuries of the wrist and elbow is to identify the types of injuries and conduct an overall assessment to determine the appropriate surgical methods. Early surgical intervention and rehabilitation exercise are the main principles for the treatment.

Various changes in cryopreserved acellular nerve allografts at -80°C.

The experimental design evaluated histological, mechanical, and biological properties of allogeneic decellularized nerves after cryopreservation in a multi-angle, multi-directional manner to provide evidence for long-term preservation. Acellular nerve allografts from human and rats were cryopreserved in a cryoprotectant (10% fetal bovine serum, 10% dimethyl sulfoxide, and 5% sucrose in RPMI1640 medium) at -80°C for 1 year, followed by thawing at 40°C or 37°C for 8 minutes. The breaking force of acellular nerve allografts was measured using a tensile test. Cell survival was determined using L-929 cell suspensions. Acellular nerve allografts were transplanted into a rat model with loss of a 15-mm segment of the left sciatic nerve. Immunohistochemistry staining was used to measure neurofilament 200 expression. Hematoxylin-eosin staining was utilized to detect relative muscle area in gastrocnemius muscle. Electron microscopy was applied to observe changes in allograft ultrastructure. There was no obvious change in morphological appearance or ultrastructure, breaking force, or cytotoxicity of human acellular nerve allografts after cryopreservation at -80°C. Moreover, there was no remarkable change in neurofilament 200 expression, myelin sheath thickness, or muscle atrophy when fresh or cryopreserved rat acellular nerve allografts were applied to repair nerve injury in rats. These results suggest that cryopreservation can greatly extend the storage duration of acellular nerve tissue allografts without concomitant alteration of the physiochemical and biological properties of the engineered tissue to be used for transplantation.

Evaluation of sensory function and recovery after replantation of fingertips at Zone I in children.

Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few studies have focused on recovery of finger sensory function after replantation. This study retrospectively assessed data of eight patients who had undergone nine Zone I replantations of the fingertips in the First Affiliated Hospital of Sun Yat-sen University of China from July 2014 to January 2016. Variations in the extent of damage, with the residual vessels or nerves in some fingers being too short or even missing, prevented tension-free suture repair in some patients. Thus, repair of four of the nine fingertips included arteriovenous anastomosis, the remaining five undergoing arterial anastomosis during replantation of the amputated fingers. Three patients underwent nerve repair, whereas the remaining six cases did not. Fingertip replantations were successful in all eight patients. Compared with the patients without vascular anastomosis, no obvious atrophy was visible in the fingertips of patients who did undergo vascular anastomosis during replantation and their sensory function did recover. Fingertip replantation provides good sensory function and cosmetic outcomes when good artery and vein anastomoses have been created, even when digital nerves have not been repaired.

Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro.

Platelet-rich plasma (PRP) contains various growth factors and appears to have the potential to promote peripheral nerve regeneration, but evidence is lacking regarding its biological effect on Schwann cells (SCs). The present study was designed to investigate the effect of PRP concentration on SCs in order to determine the plausibility of using this plasma-derived therapy for peripheral nerve injury. PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and growth factor concentrations. Primary cultures of rat SCs were exposed to various concentrations of PRP (40%, 20%, 10%, 5% and 2.5%). Cell proliferation assays and flow cytometry were performed to study to assess SC proliferation. Quantitative real-time PCR and ELISA analysis were performed to determine the ability of PRP to induce SCs to produce nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). Microchemotaxis assay was used to analyse the cell migration capacity. The results obtained indicated that the platelet concentration and growth factors in our PRP preparations were significantly higher than in whole blood. Cell culture experiments showed that 2.5-20% PRP significantly stimulated SC proliferation and migration compared to untreated controls in a dose-dependent manner. In addition, the expression and secretion of NGF and GDNF were significantly increased. However, the above effects of SCs were suppressed by high PRP concentrations (40%). In conclusion, the appropriate concentration of PRP had the potency to stimulate cell proliferation, induced the synthesis of neurotrophic factors and significantly increased migration of SCs dose-dependently. Copyright © 2013 John Wiley & Sons, Ltd.

Development of Dual Neurotrophins-Encapsulated Electrosupun Nanofibrous Scaffolds for Peripheral Nerve Regeneration.

Nerve growth factor (NGF) is widely used for repairing peripheral nerve injury because of its capability in dominating the survival, migration, proliferation, and differentiation of nerve cells. Monosialoganglioside (GM1), as another kind of nerve growth factor, works for regulating NGF function. In this study, GM1 and NGF were incorporated into the Poly(l-lactic acid-co-ε-caprolactone)/silk fibroin (PLCL/SF) nanofibers by the coaxial electrospinning. The fibers morphology and core­shell structure were characterized by SEM and TEM. The scaffolds demonstrated high tensile stress with good flexibility. In vitro cell viability studies indicated that the scaffolds incorporating both GM1 and NGF played a synergistic effect to enhance Schwann cells (SCs) proliferation and Pheochromocytoma (PC12) cells differentiation, in comparison to the scaffolds only incorporating NGF. Subsequently, the nanofibrous conduit scaffolds (NCSs) were evaluated in vivo in a rabbit sciatic nerve defect model. The NGF/GM1 incorporated NCSs group performed better nerve function recovery than single incorporated group, in consideration of the compound muscle action potential (CMAP) and nerve conduction velocity (NCV) results. Furthermore, hematoxylin and eosin (H&E) staining, toluidine blue (TB) staining, and transmission electron microscope (TEM) analysis displayed better nerve regeneration of NGF/GM1 incorporated NCSs both quantitatively and qualitatively. Therefore, the results indicated the dual neurotrophins-incorporated NCSs had potentials for the application in peripheral nerve repairing.

Improved peripheral nerve regeneration using acellular nerve allografts loaded with platelet-rich plasma.

Acellular nerve allografts (ANAs) behave in a similar manner to autografts in supporting axonal regeneration in the repair of short peripheral nerve defects but fail in larger defects. The objective of this article is to evaluate the effect of ANA supplemented with platelet-rich plasma (PRP) to improve nerve regeneration after surgical repair and to discuss the mechanisms that underlie this approach. Autologous PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and the release of growth factors. Forty-eight Sprague-Dawley rats were randomly divided into 4 groups (12/group), identified as autograft, ANA, ANA loaded with PRP (ANA+PRP), and ANA loaded with platelet-poor plasma (PPP, ANA+PPP). All grafts were implanted to bridge long-gap (15 mm) sciatic nerve defects. We found that PRP with a high platelet concentration exhibited a sustained release of growth factors. Twelve weeks after surgery, the autograft group displayed the highest level of reinnervation, followed by the ANA+PRP group. The ANA+PRP group showed a better electrophysiology response for amplitude and conduction velocity than the ANA and ANA+PPP groups. Based on histological evaluation, the ANA+PRP and autograft groups had higher numbers of regenerating nerve fibers. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that PRP boosted expression of neurotrophins in the regenerated nerves. Moreover, the ANA+PRP and autograft groups showed excellent physiological outcomes in terms of the prevention of muscle atrophy. In conclusion, ANAs loaded with PRP as tissue-engineered scaffolds can enhance nerve regeneration and functional recovery after the repair of large nerve gaps nearly as well as autografts.

A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair.

Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripheral nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration.

Penile erectile dysfunction after brachial plexus root avulsion injury in rats.

Our previous studies have demonstrated that some male patients suffering from brachial plexus injury, particularly brachial plexus root avulsion, show erectile dysfunction to varying degrees. However, the underlying mechanism remains poorly understood. In this study, we evaluated the erectile function after establishing brachial plexus root avulsion models with or without spinal cord injury in rats. After these models were established, we administered apomorphine (via a subcutaneous injection in the neck) to observe changes in erectile function. Rats subjected to simple brachial plexus root avulsion or those subjected to brachial plexus root avulsion combined with spinal cord injury had significantly fewer erections than those subjected to the sham operation. Expression of neuronal nitric oxide synthase did not change in brachial plexus root avulsion rats. However, neuronal nitric oxide synthase expression was significantly decreased in brachial plexus root avulsion + spinal cord injury rats. These findings suggest that a decrease in neuronal nitric oxide synthase expression in the penis may play a role in erectile dysfunction caused by the combination of brachial plexus root avulsion and spinal cord injury.

The upper brachial plexus defect model in rhesus monkeys: a cadaveric feasibility study.

To establish a model for nerve grafts and determine the anatomic characteristics of the brachial plexus in rhesus monkeys. Ten specimens of the brachial plexus were obtained from five rhesus monkey cadavers. Anatomic dissection of the brachial plexus was systemically performed. The length of each root, trunk, and each division was measured using a Vernier caliper proximodistally. The anatomic distributions of the suprascapular, axillary, and musculocutaneous nerve were documented. The brachial plexus of rhesus monkeys included the spinal nerves or roots of C5, C6, C7, C8, and T1 (80%, 8/10), with a small contribution from the C4 root (20%, 2/10) occasionally. The upper trunk was not measurable because of their irregular structures. The lower trunk had a mean length of 1.62 (range, 0.96-2.1 mm) and a mean diameter of 2.29 (range, 1.9-2.94 mm). For the upper trunk, the C5 and C6 roots either divided into two very short divisions or sent out very long divisions before they joined together. For the middle trunk, the C7 root had a straight course after leaving the foramen and blended imperceptibly into the middle trunk before dividing into the anterior and posterior divisions. The lower trunk was noted in almost all the specimens (80%, 8/10), which was formed by C8 and T1. The brachial plexus in rhesus monkeys varies from that of humans, and defects can be made at the level of C5 and C6 roots and the C7 root should also be cut off and ligated.

[Study on immune response after repair of nerve defect with acellular nerve xenograft laden with allogenic adipose-derived stem cells in rhesus monkey].

OBJECTIVE: To observe the systemic and local immune response after repair of nerve defect with acellular nerve xenograft laden with allogenic adipose-derived stem cells (ADSCs) in rhesus monkey so as to evaluate the safety of the proposed material for nerve reconstruction. METHODS: Bilateral tibial nerves were taken from a healthy adult male landrace (weighing 48 kg) to prepare acellular nerve xenograft by chemical extraction. ADSCs were isolated from a healthy adult male rhesus monkey (weighing 4.5 kg), and were seeded into the acellular nerve grafts. The radial nerve defect models with 25 mm in length were established in 10 healthy adult female rhesus monkeys (weighing 3-5 kg), and they were divided into cell-laden group (n = 5) and non-cell-laden group (n = 5) randomly. Defect was repaired with acellular nerve xenograft laden with allogenic ADSCs in cell-laden group, with acellular nerve xenograft only in non-cell-laden group. The blood samples were taken from peripheral vein preoperatively and at 14, 60, and 90 days after operation for lymphocyte analysis; at 5 months after operation, the grafts were harvested to perform histological examination for local immune response and nerve regeneration. The nerve autograft in rhesus monkey was used as control. RESULTS: In cell-laden group and non-cell-laden group, no significant difference was found in the count of lymphocytes and T lymphocytes, the percentage ofT lymphocytes, CD8+ T lymphocytes, as well as the ratio of CD4+ T lymphocytes to CD8+ T lymphocytes between pre- and post-operation (P > 0.05); in cell-laden group, the percentage of CD4+ T lymphocytes at 14 days was significantly lower than that at 60 and 90 days postoperatively (P < 0.05). The percentage of CD4+ T lymphocytes in cell-laden group was significantly lower than that in non-cell-laden group at 14 days (P < 0.05), but no significant difference was found in the other indexes at the other time between 2 groups (P > 0.05). At 5 months after operation, mild adhesion was found on the surface of nerve xenografts; the epineurium of nerve xenografts was thicker than that of nerve autografts; and neither necrosis nor fibrosis was found. CD3+, CD4+, CD8+, CD68+, and CD163+ T lymphocytes were scattered within the grafts, in which regenerative axons were revealed. CD3+, CD4+, CD8+, CD68+, and CD163+ T lymphocytes were comparable in cell-laden group, non-cell-laden group, and autograft group. CONCLUSION: Repair of nerve defect with acellular nerve xenograft elicits neither systemic nor local immune response in rhesus monkeys. Implantation of allogenic ADSCs might result in transient depression of CD4+ T lymphocytes proliferation early after surgery, no immune response can be found.