RESUMEN
BACKGROUND: The treatment of painful neuroma remains challenging. Recently, a nerve-end capping technique using a bioabsorbable nerve conduit was newly introduced to treat amputation neuroma. A collagen-coated polyglycolic acid (PGA) conduit has been commercially available for the reconstruction of peripheral nerve defects, yielding successful clinical outcomes. However, no experimental research has been conducted using this PGA nerve conduit as capping device for treating amputation neuroma. The purpose of this study was to investigate nerve-end capping treatment with the PGA conduit in the rat sciatic nerve amputation model, focusing on histological scar formation and neuroinflammation. METHODS: Forty-seven rats were divided into two groups: no capping (transected nerve stump without capping; n = 25) and capping (nerve-end capping with collagen-coated PGA nerve conduit; n = 22). Twelve weeks after sciatic neurectomy, neuropathic pain was evaluated using the autotomy score. Stump neuromas were histologically evaluated or perineural scar and neuroinflammation. RESULTS: While autotomy scores gradually exacerbated in both groups, they were consistently lower in the capping group at 4, 8, and 12 weeks postprocedure. Twelve weeks after surgery, the transected nerve stumps in the no-capping group had formed macroscopic bulbous neuromas strongly adhering to surrounding tissues, whereas they remained wrapped with the PGA nerve conduits loosely adhering to surrounding tissues in the capping group. Histologically, distal axonal fibers were expanded radially and formed neuromas in the no-capping group, while they were terminated within the PGA conduit in the capping group. Perineural scars and neuroinflammation were widely found surrounding the randomly sprouting nerve end in the no-capping group. In capped counterparts, scars and inflammation were limited to closely around the terminated nerve end. CONCLUSION: Nerve-end capping with a collagen-coated PGA conduit after rat sciatic neurectomy might prevent neuroma formation by suppressing perineural scar formation and neuroinflammation around the nerve stump, potentially relieving neuropathic pain.
Asunto(s)
Neuralgia , Neuroma , Animales , Ratas , Cicatriz/patología , Colágeno , Regeneración Nerviosa/fisiología , Neuroma/cirugía , Ácido Poliglicólico , Nervio Ciático/cirugía , Nervio Ciático/patologíaRESUMEN
BACKGROUND: The development of drug delivery systems has enabled the release of multiple bioactive molecules. The efficacy of nerve conduits coated with dual controlled release of stromal cell-derived factor-1 (SDF-1) and basic fibroblast growth factor (bFGF) for peripheral nerve regeneration was investigated. MATERIALS AND METHODS: Sixty-two C57BL6 mice were used for peripheral nerve regeneration with a nerve conduit (inner diameter, 1 mm, and length, 7 mm) and an autograft. The mice were randomized into five groups based on the different repairs of nerve defects. In the group of repair with conduits alone (n = 9), a 5-mm sciatic nerve defect was repaired by the nerve conduit. In the group of repair with conduits coated with bFGF (n = 10), SDF-1 (n = 10), and SDF-1/bFGF (n = 10), it was repaired by the nerve conduit with bFGF gelatin, SDF-1 gelatin, and SDF-1/bFGF gelatin, respectively. In the group of repair with autografts (n = 10), it was repaired by the resected nerve itself. The functional recovery, nerve regeneration, angiogenesis, and TGF-ß1 gene expression were assessed. RESULTS: In the conduits coated with SDF-1/bFGF group, the mean sciatic functional index value (-88.68 ± 10.64, p = .034) and the axon number (218.8 ± 111.1, p = .049) were significantly higher than the conduit alone group, followed by the autograft group; in addition, numerous CD34-positive cells and micro vessels were observed. TGF-ß1 gene expression relative values in the conduits with SDF-1/bFGF group at 3 days (7.99 ± 5.14, p = .049) significantly increased more than the conduits alone group. CONCLUSION: Nerve conduits coated with dual controlled release of SDF-1 and bFGF promoted peripheral nerve regeneration.
Asunto(s)
Quimiocina CXCL12/administración & dosificación , Materiales Biocompatibles Revestidos , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Regeneración Tisular Dirigida/instrumentación , Regeneración Nerviosa , Nervios Periféricos/cirugía , Andamios del Tejido , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución AleatoriaRESUMEN
BACKGROUND: The ulnar artery perforator (UAP) flap, which is hairless, thin, and pliable, has been used for the reconstruction of soft tissues from the finger to the elbow. Preoperative planning is essential for a perforator flap surgery, and there are some tests to identify perforators. Color Doppler ultrasonography (US) with a high-frequency transducer helps in detecting decreased flow in smaller vessels, such as perforators. The purpose of this study was to determine the anatomical locations and origins of perforators arising from the ulnar artery using color Doppler US in healthy volunteers. METHODS: Forty forearms of 20 healthy volunteers were included in the study. Perforators arising from the ulnar artery, within 100 mm proximal to the pisiform, were investigated using color Doppler US with a high-frequency transducer. RESULTS: A total of 205 perforators were identified. On comparing the locations in each 20 mm section from the pisiform, the largest number of perforators was 58 (28%), within 20 mm proximal to the pisiform. The axial view demonstrated 44 (21%), 64 (31%), 32 (16%), and 65 (32%) perforators in the radial, ulnar, superficial, and deep aspects of the ulnar artery, respectively. Fifty-two and 28 essential perforators were supplied by the UAPs arising from the superficial and ulnar aspect within 20 mm proximal to the pisiform and between 21 and 40 mm proximal to the pisiform, respectively, while elevating the UAP flap. CONCLUSION: This is the first study to assess the UAP using color Doppler US. Identification of UAP using color Doppler US can be used as a preoperative assessment for reliable elevation of a UAP flap.
Asunto(s)
Colgajo Perforante , Arteria Cubital , Antebrazo , Humanos , Arteria Radial/diagnóstico por imagen , Arteria Cubital/diagnóstico por imagen , Ultrasonografía Doppler en ColorRESUMEN
Background The radial artery perforator (RAP) flap has been widely used for covering hand and forearm defects, and real-time accurate perforator mapping is important in planning and elevating the perforator flap. The origins of perforators, especially the superficial and ulnar perforators, arising from the radial artery are very important in the elevation of the RAP flap. Recently, color Doppler ultrasonography (US) using a higher frequency transducer has been developed for high-quality detection of lower flow in smaller vessels. This study aimed to identify the anatomical locations and origins of perforators arising from the radial artery using color Doppler US in healthy volunteers. Methods Twenty forearms of 10 volunteers were examined. Results In total, 120 perforators arising from the radial artery were identified 15 cm proximal to the distal wrist crease, with an average of six perforators per forearm. More than half the perforators (n = 72, 60%) were located within 50 mm proximal to the distal wrist crease. Regarding the perforator origins in the axial view, 40 perforators (33%) were located in the radial aspect of the radial artery, 47 (39%) in the ulnar aspect, 15 (13%) in the superficial aspect, and 18 (15%) in the deep aspect. In total, 62 (52%) perforators were located in the superficial and ulnar areas, which are important in nourishing and elevating the RAP flap. Conclusion We are the first to evaluate RAP using color Doppler US. This noninvasive, convenient, and real-time technique could be useful for preoperative planning and reliably elevating the RAP flaps.
Asunto(s)
Antebrazo/irrigación sanguínea , Colgajo Perforante/irrigación sanguínea , Arteria Radial/diagnóstico por imagen , Ultrasonografía Doppler en Color , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Adulto JovenRESUMEN
Isolated injury to the deep motor branch of the ulnar nerve caused by stabbing is sporadic, with only one reported case in the English-language literature. We report one such case treated successfully using nerve grafting. A 33-year-old patient had sustained a stab wound to the right hypothenar eminence and showed a claw hand deformity. Needle electromyography study revealed denervation potentials with no voluntary motor unit action potentials (MUAPs) in the first dorsal interosseous (FDI) muscles. Nerve exploration revealed a neuroma-in-continuity in the intrinsic motor branch of the ulnar nerve. Intraoperative nerve stimulation confirmed the absence of compound muscle action potentials in the FDI. The damaged scarred nerve was resected, and the 15-mm defects were reconstructed with cable autografting. Two years and 5 months after the surgery, voluntary MUAPs were observed in the FDI. The pinch strengths recovered. Laceration of the deep branch of the ulnar nerve caused by stabbing can sometimes remain hidden as the hand sensation remains intact. Pre- and intraoperative electrophysiological examination is essential to assess the severity of the injured nerve and determine an appropriate surgical option. Even nerve grafting can facilitate satisfactory results as target intrinsic muscles are quite close to the repair site.
RESUMEN
Different approaches to fingertip reconstructions are reported for cases in which microsurgical replantation is impossible. This report presents two cases of bipedicled digital artery perforator adiposal flaps for fingertip reconstruction after traumatic amputations. Adiposal flaps, including the radial and ulnar digital artery perforator vessels proximal to the distal interphalangeal joint, were elevated and turned to cover the fingertip defect. After donor-site skin closure, split-thickness skin was grafted onto the fingertip digital artery perforator adiposal flap. The technique is quick and easy to perform under loupe magnification and achieves good results in terms of healing, hand function, appearance, and patient satisfaction.
RESUMEN
CASE: A 43-year-old woman presented with pain, paresthesia, and coldness of the right upper extremity suggestive of the diagnosis of thoracic outlet syndrome. Three-dimensional computed tomography angiography revealed that the right subclavian artery was constricted because it traveled over an abnormal first rib. After anticoagulation and antithrombotic therapy, the patient underwent resection of the abnormal first rib. Postoperative angiography documented improvement over time of the poststenotic dilatation and recanalization of the subclavian artery capable of delivering almost normal distal flow. CONCLUSION: Arterial reconstruction is not always necessary for the treatment of arterial thoracic outlet syndrome associated with poststenotic dilatation of the subclavian artery.
Asunto(s)
Sinostosis , Síndrome del Desfiladero Torácico , Trombosis , Adulto , Femenino , Humanos , Costillas/diagnóstico por imagen , Costillas/cirugía , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/cirugía , Sinostosis/complicaciones , Síndrome del Desfiladero Torácico/complicaciones , Síndrome del Desfiladero Torácico/diagnóstico por imagen , Trombosis/complicaciones , Trombosis/diagnóstico por imagenRESUMEN
We report a 50-year-old woman who presented with infected delayed union after ulnar shortening osteotomy. She was a chronic smoker. Implants were removed and infected tissue was debrided. Sufficient bony union was obtained after 5 months of treatment with weekly teriparatide and low-intensity pulsed ultrasound during the infection-controlled waiting period.
RESUMEN
CASE: A 32-year-old man with Ehlers-Danlos syndrome (EDS) fell while snowboarding and injured his right elbow. Radiography revealed a posterior dislocation of the elbow and a proximal radioulnar joint dislocation. A diagnosis of transverse divergent dislocation of the elbow was established. Open reduction and repair of the annular ligament, anterior oblique ligament, and capsule was performed with good clinical results. CONCLUSION: This is the first report of divergent dislocation of the elbow in an adult with EDS. Dislocation occurred without a fracture that required open reduction and internal fixation. The presence of soft-tissue fragility, hyperextension, and joint laxity peculiar to EDS are likely contributing factors to this phenomenon.
Asunto(s)
Síndrome de Ehlers-Danlos , Articulación del Codo , Luxaciones Articulares , Inestabilidad de la Articulación , Adulto , Síndrome de Ehlers-Danlos/complicaciones , Codo , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/etiología , Luxaciones Articulares/cirugía , Inestabilidad de la Articulación/cirugía , MasculinoRESUMEN
BACKGROUND AND AIMS: Nerve capping treatment using bioabsorbable nerve conduits has recently been introduced for painful amputation neuroma. However, no clinical or experimental data are available for comparing nerve conduits with open distal ends and closed distal ends. Here, we investigated the nerve conduit with open or closed distal ends as the superior capping device, using a commercially available polyglycolic acid (PGA) nerve conduit in a rat sciatic nerve amputation model. METHODS: Ninety-one rats were assigned to three groups: no-capping (n = 30), capping the resected nerve stump with open ends (n = 31), and closed-end nerve conduits (n = 30). Twelve weeks after sciatic neurectomy, with or without capping, the evaluation of neuropathic pain using the autotomy score was performed. Stump neuromas with perineural scars and neuroinflammation were evaluated histologically. RESULTS: The mean autotomy scores in the closed-end nerve conduit group were significantly lower than those in the no-capping group. However, the difference between the open-end nerve conduit and the closed-end nerve conduit groups was insignificant. Histologically, distal axonal fibers expanded radially and formed neuromas in the no-capping group while they were terminated within the PGA conduit in both capping groups. In particular, the closed-end version of the PGA nerve conduit blocked scarring from intruding through the open end and protected the nerve stump with less neuroinflammation. Nerve capping with the closed-end version of the PGA nerve conduit most effectively suppressed perineural neuroinflammation and scar formation around the resected nerve stump. INTERPRETATION: Nerve capping with the PGA nerve conduit, particularly those with closed ends, after rat sciatic neurectomy prevented amputation neuroma and relieved neuropathic pain.
Asunto(s)
Implantes Absorbibles , Amputación Quirúrgica/efectos adversos , Neuralgia/cirugía , Neuroma/cirugía , Neoplasias del Sistema Nervioso Periférico/cirugía , Nervio Ciático/cirugía , Animales , Masculino , Neuralgia/etiología , Neuralgia/patología , Neuroma/etiología , Neuroma/patología , Neoplasias del Sistema Nervioso Periférico/etiología , Neoplasias del Sistema Nervioso Periférico/patología , Ratas , Ratas Sprague-Dawley , Nervio Ciático/patologíaRESUMEN
Peripheral nerve regeneration using nerve conduits has been less effective than autogenous nerve grafts. To overcome this hurdle, we developed a tissue-engineered nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres, for the first time, which accelerated nerve regeneration in mice. We previously demonstrated the long-term efficacy and safety outcomes of this hybrid nerve conduit for mouse peripheral nerve regeneration. In this study, we investigated the therapeutic potential of nerve conduits coated with human iPSC (hiPSC)-derived neurospheres in rat sciatic nerve defects, as a translational preclinical study. The hiPSC-derived quaternary neurospheres containing neural stem/progenitor cells were three-dimensionally cultured within the nerve conduit (poly L-lactide and polycaprolactone copolymer) for 14 days. Complete 5-mm defects were created as a small size peripheral nerve defect in sciatic nerves of athymic nude rats and reconstructed with nerve conduit alone (control group), nerve conduits coated with hiPSC-derived neurospheres (iPS group), and autogenous nerve grafts (autograft group) (n = 8 per group). The survival of the iPSC-derived neurospheres was continuously tracked using in vivo imaging. At 12 weeks postoperatively, motor and sensory function and histological nerve regeneration were evaluated. Before implantation, the hiPSC-derived quaternary neurospheres that three-dimensional coated the nerve conduit were differentiated into Schwann-like cells. The transplanted hiPSC-derived neurospheres survived for at least 56 days after implantation. The iPS group showed non-significance higher sensory regeneration than the autograft group. Although there was no actual motor functional nerve regeneration in the three groups: control, iPS, and autograft groups, the motor function in the iPS group recovered significantly better than that in the control group, but it did not recover to the same level as that in the autograft group. Histologically, the iPS group demonstrated significantly higher axon numbers and areas, and lower G-ratio values than the control group, whereas the autograft group demonstrated the highest axon numbers and areas and the lowest G-ratio values. Nerve conduit three-dimensionally coated with hiPSC-derived neurospheres promoted axonal regeneration and functional recovery in repairing rat sciatic nerve small size defects. Transplantation of hiPSC-derived neurospheres with nerve conduits is a promising clinical iPSC-based cell therapy for the treatment of peripheral nerve defects.
Asunto(s)
Células Madre Pluripotentes Inducidas/citología , Regeneración Nerviosa/efectos de los fármacos , Células-Madre Neurales/citología , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/fisiología , Nervio Ciático/citología , Implantes Absorbibles , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Regeneración Tisular Dirigida/métodos , Humanos , Masculino , Ratones , Tejido Nervioso/fisiología , Poliésteres/administración & dosificación , Ratas , Ratas Desnudas , Recuperación de la Función/fisiología , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Since the advent of induced pluripotent stem cells (iPSCs), clinical trials using iPSC-based cell transplantation therapy have been performed in various fields of regenerative medicine. We previously demonstrated that the transplantation of mouse iPSC-derived neurospheres containing neural stem/progenitor cells with bioabsorbable nerve conduits promoted nerve regeneration in the long term in murine sciatic nerve defect models. However, it remains unclear how long the grafted iPSC-derived neurospheres survived and worked after implantation. In this study, the long-term survival of the transplanted mouse iPSC-derived neurospheres with nerve conduits was evaluated in high-immunosuppressed or non-immunosuppressed mice using in vivo imaging for the development of iPSC-based cell therapy for peripheral nerve injury. Complete 5-mm long defects were created in the sciatic nerves of immunosuppressed and non-immunosuppressed mice and reconstructed using nerve conduits coated with iPSC-derived neurospheres labeled with ffLuc. The survival of mouse iPSC-derived neurospheres on nerve conduits was monitored using in vivo imaging. The transplanted iPSC-derived neurospheres with nerve conduits survived for 365 days after transplantation in the immunosuppressed allograft models, but only survived for at least 14 days in non-immunosuppressed allograft models. This is the first study to find the longest survival rate of stem cells with nerve conduits transplanted into the peripheral nerve defects using in vivo imaging and demonstrates the differences in graft survival rate between the immunosuppressed allograft model and immune responsive allograft model. In the future, if iPSC-derived neurospheres are successfully transplanted into peripheral nerve defects with nerve conduits using iPSC stock cells without eliciting an immune response, axonal regeneration will be induced due to the longstanding supportive effect of grafted cells on direct remyelination and/or secretion of trophic factors.
RESUMEN
BACKGROUND: We previously demonstrated that a bioabsorbable nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres accelerated peripheral nerve regeneration in mice. OBJECTIVE: We examined the fate and utility of iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve gaps in mice. METHODS: Complete 5-mm defects were created in sciatic nerves and reconstructed using nerve conduits that were either uncoated or coated with mouse iPSC-derived neurospheres. The survival of the neurospheres on the nerve conduits was tracked using an in vivo imaging. The localization of the transplanted cells and regenerating axons was examined histologically. The gene expression levels in the nerve conduits were evaluated. RESULTS: The neurospheres survived for at least 14 days, peaking at 4--7 days after implantation. The grafted neurospheres remained as Schwann-like cells within the nerve conduits and migrated into the regenerated axons. The expression levels of ATF3, BDNF, and GDNF in the nerve conduit coated with neurospheres were upregulated. CONCLUSIONS: Mouse iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve defects in mice migrated into regenerating axons, survived as Schwann-like cells, and promoted axonal growth with an elevation in the expression of nerve regeneration-associated trophic factors.
Asunto(s)
Células Madre Pluripotentes Inducidas , Animales , Ratones , Regeneración Nerviosa , Células de Schwann , Nervio CiáticoRESUMEN
Although carpal tunnel syndrome (CTS) is exceedingly rare in children, its prevalence in those with Hunter syndrome, mucopolysaccharidosis type II, is high. With the advent of hematopoietic stem cell transplantation and enzyme replacement therapy, the survival of patients with Hunter syndrome has dramatically improved. With improved longevity in these patients, CTS continues to progress with age. However, most patients with Hunter syndrome with CTS have generally been treated with an open carpal tunnel release (OCTR) only, without considering the severity. Here, we present a mid-term follow-up of a 16-year-old patient with Hunter syndrome associated with severe bilateral CTS successfully treated by the simultaneous opposition tendon transfer with an OCTR to improve the thumb function. Intraoperatively, the median nerve was constricted and flattened with congestion by the transverse carpal ligament. External and internal neurolysis of the scarred median nerve were performed and found epineural fibrosis and tethered epineurium. An intraneural lipoma of the left median nerve was especially resected with epineurotomy. During neurolysis and tendon transfer, the soft tissue was very viscous, a characteristic of mucopolysaccharidoses. Transferring the tension of the palmaris longus tendon to the abductor pollicis brevis for the thumb palmar abduction should be stronger than routine adult patients because the soft tissue such as the tendon excursion is stickier and more contracted in patients with Hunter syndrome. Postoperatively, a thumb spica splint was applied for 3 weeks, and then active motion exercises were cautiously started to prevent joint contracture. Early recognition and surgical intervention for CTS are essential in patients with Hunter syndrome.
RESUMEN
Adhesion neuropathy of the median nerve with persistent pain can be a challenging problem. Currently, coverage of the median nerve with a well-vascularized soft tissue is deemed necessary after secondary neurolysis. Herein, we reviewed the outcomes of seven patients with a persistent median nerve neuropathy after a primary open carpal tunnel release or a median nerve repair, treated with neurolysis and median nerve wrapping with radial artery perforator adipose flaps. During the revision surgery, after a careful and complete neurolysis of the scarred median nerve, the distally based radial artery perforator adipose flap without its fascia was raised and rotated to wrap the median nerve. The mean size of the perforator flap was 1146 mm2, which was enough to wrap the median nerve in all patients. At 26 months postsurgery, both the visual analog scale score for pain with tingling, and the patient-reported outcome measures improved. There was no recurrence of the median nerve adhesion neuropathy and no major complications were noted. Tinel's sign at the palmar wrist completely disappeared in four patients and was relieved in three patients. The median distal motor latency becomes recordable, and closer to a normal compound motor action potential postoperatively in all patients. Secondary neurolysis and median nerve wrapping with a radial artery perforator adipose flap, which was modified to be softer and thinner than the radial artery perforator adipofascial flap, was a successful treatment for the recurrent median nerve neuropathy in terms of both pain relief and restoration of the hand function.
Asunto(s)
Tejido Adiposo/trasplante , Neuropatía Mediana/cirugía , Bloqueo Nervioso/métodos , Colgajo Perforante/cirugía , Arteria Radial/trasplante , Reoperación/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
OBJECTIVE: Treatment of painful neuroma remains difficult, despite the availability of numerous surgical procedures. Recently, nerve capping treatment for painful neuroma using artificial nerve conduits has been introduced in clinical and basic research. However, the appropriate length of the nerve conduit and the pain relief mechanism have not been determined. In this study the authors aimed to investigate nerve capping treatment with a bioabsorbable nerve conduit using the rat sciatic nerve amputation model. Using histological analysis, the authors focused on the nerve conduit length and pain relief mechanism. METHODS: Sixteen Sprague Dawley rats were evaluated for neuropathic pain using an autotomy (self-amputation) score and gross and histological changes of the nerve stump 2, 4, 8, and 12 weeks after sciatic nerve neurectomy without capping. Forty-five rats were divided into 3 experimental groups, no capping (control; n = 15), capping with a 3-mm nerve conduit (n = 15), and capping with a 6-mm nerve conduit (n = 15). All rats were evaluated using an autotomy score and nerve stump histology 12 weeks after neurectomy. The nerve conduit was approximately 0.5 mm larger than the 1.5-mm diameter of the rat sciatic nerves to prevent nerve constriction. RESULTS: The autotomy scores gradually exacerbated with time. Without capping, a typical bulbous neuroma was formed due to random axonal regeneration 2 weeks after neurectomy. Subsequently, the adhesion surrounding the neuroma expanded over time for 12 weeks, and at the 12-week time point, the highest average autotomy scores were observed in the no-capping (control) group, followed by the 3- and the 6-mm nerve conduit groups. Histologically, the distal axonal fibers became thinner and terminated within the 6-mm nerve conduit, whereas they were elongated and protruded across the 3-mm nerve conduit. Minimal perineural scar formation was present around the terminated axonal fibers in the 6-mm nerve conduit group. Expressions of anti-α smooth muscle actin and anti-sigma-1 receptor antibodies in the nerve stump significantly decreased in the 6-mm nerve conduit group. CONCLUSIONS: In the rat sciatic nerve amputation model, nerve capping treatment with a bioabsorbable nerve conduit provided relief from neuroma-induced neuropathic pain and prevented perineural scar formation and neuroinflammation around the nerve stump. The appropriate nerve conduit length was determined to be more than 4 times the diameter of the original nerve.
RESUMEN
Aging influences peripheral nerve regeneration. Nevertheless, most basic research of bioabsorbable nerve conduits including commercial products have been performed in very young animals. Results from these studies may not provide information about axonal regeneration in aged tissue, because young nerve tissue holds sufficient endogenous potential for axonal regeneration. The clinical target age for nerve conduit application is most likely going to increase with a rapidly growing elderly population. In the present study, we examined axonal regeneration after sciatic nerve defects in aged and young mice. 5-mm sciatic nerve defects in young (6 weeks old) and aged (92 weeks old) mice were reconstructed using nerve conduits (composed of a poly lactide and caprolactone) or autografts. In addition, in aged mice, sciatic nerve defects were reconstructed using nerve conduits coated with mouse induced pluripotent stem cell (iPSc)-derived neurospheres. Using electrophysiological and histological techniques, we demonstrated axonal regeneration was significantly less effective in aged than in young mice both for nerve conduits and for nerve autografts. However, despite the low regenerative capacity of the peripheral nerve in aged mice, axonal regeneration significantly increased when nerve conduits coated with iPSc-derived neurospheres, rather than nerve conduits alone, were used. The present study shows that aging negatively affects peripheral nerve regeneration based on nerve conduits in mice. However, axonal regeneration using nerve conduits was improved when supportive iPSc-derived neurospheres were added in the aged mice. We propose that tissue-engineered bioabsorbable nerve conduits in combination with iPSc-derived neurospheres hold therapeutic potential both in young and elderly patients. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1752-1758, 2018.
Asunto(s)
Implantes Absorbibles , Células Inmovilizadas/trasplante , Regeneración Tisular Dirigida/métodos , Células Madre Pluripotentes Inducidas/trasplante , Regeneración Nerviosa , Nervio Ciático , Animales , Autoinjertos , Células Inmovilizadas/citología , Células Madre Pluripotentes Inducidas/citología , Masculino , Ratones , Poliésteres/química , Nervio Ciático/lesiones , Nervio Ciático/fisiologíaRESUMEN
OBJECTIVE Peripheral nerve adhesion caused by extraneural and intraneural scar formation after neurolysis leads to nerve dysfunction. The authors previously developed a novel very flexible biodegradable nerve conduit composed of poly(L-lactide) and poly(ε-caprolactone) for use in peripheral nerve regeneration. In the present study, they investigated the effect of protective nerve wrapping on preventing adhesion in a rat sciatic nerve adhesion model. METHODS Rat sciatic nerves were randomly assigned to one of the following four groups: a no-adhesion group, which involved neurolysis alone without an adhesion procedure; an adhesion group, in which the adhesion procedure was performed after neurolysis, but no treatment was subsequently administered; a nerve wrap group, in which the adhesion procedure was performed after neurolysis and protective nerve wrapping was then performed with the nerve conduit; and a hyaluronic acid (HA) group, in which the adhesion procedure was performed after neurolysis and nerve wrapping was then performed with a 1% sodium HA viscous solution. Six weeks postoperatively, the authors evaluated the extent of scar formation using adhesion scores and biomechanical and histological examinations and assessed nerve function with electrophysiological examination and gastrocnemius muscle weight measurement. RESULTS In the adhesion group, prominent scar tissue surrounded the nerve and strongly adhered to the nerve biomechanically and histologically. The motor nerve conduction velocity and gastrocnemius muscle weight were the lowest in this group. Conversely, the adhesion scores were significantly lower, motor nerve conduction velocity was significantly higher, and gastrocnemius muscle weight was significantly higher in the nerve wrap group than in the adhesion group. Additionally, the biomechanical breaking strength was significantly lower in the nerve wrap group than in the adhesion group and HA group. The morphological properties of axons in the nerve wrap group were preserved. Intraneural macrophage invasion, as assessed by the number of CD68- and CCR7-positive cells, was less severe in the nerve wrap group than in the adhesion group. CONCLUSIONS The nerve conduit prevented post-neurolysis peripheral nerves from developing adhesion and allowed them to maintain their nerve function because it effectively blocked scarring and prevented adhesion-related damage in the peripheral nerves.
Asunto(s)
Materiales Biocompatibles , Bloqueo Nervioso/instrumentación , Nervios Periféricos/cirugía , Poliésteres , Adherencias Tisulares/prevención & control , Animales , Cicatriz/patología , Modelos Animales de Enfermedad , Activación de Macrófagos/fisiología , Nervios Periféricos/patología , Ratas , Ratas Endogámicas Lew , Nervio Ciático/patología , Nervio Ciático/cirugíaRESUMEN
Flexor pollicis longus (FPL) tendon rupture is a major complication of volar locking plate fixation for distal radius fractures. The tendon rupture is usually caused by friction between the distal edge of the plate and the FPL tendon, and has been well detected recently with ultrasonography. Rarely, the volar locking plate itself entraps the FPL tendon, leading to its rupture. A 63-year-old man was consistently unable to flex his right thumb after previous surgery for a distal radius fracture at another hospital. Ultrasonography demonstrated loss of tendon gliding and unusual patterns of the FPL tendon. The tendon was sandwiched between the plate and the distal radius, and was penetrated by the distal locking screw, which was comparable to intraoperative findings of complete entrapment and rupture of the FPL tendon from the underlying plate. The tendon defects were repaired using a palmaris longus tendon graft after removing the screws and plate. Finally, he could flex his thumb actively with satisfaction. Unusual patterns of FPL tendon rupture buried under inadequate plate positioning must be recognized, as in this case. Ultrasonographic assessment is routinely recommended to visibly determine any FPL tendon damage after volar locking plate fixation for distal radius fractures.