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1.
J Cell Mol Med ; 28(15): e18544, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39098996

RESUMO

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue-engineered PLCL/SF/NGF@TA-PPy-RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF-loaded conductive TA-PPy-RGD gel. The gel, synthesized from RGD-modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA-PPy-RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA-PPy-RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect.


Assuntos
Hidrogéis , Fator de Crescimento Neural , Regeneração Nervosa , Oligopeptídeos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Nervo Isquiático , Transdução de Sinais , Animais , Regeneração Nervosa/efeitos dos fármacos , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células PC12 , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Hidrogéis/química , Fator de Crescimento Neural/farmacologia , Fator de Crescimento Neural/metabolismo , Ratos Sprague-Dawley , Masculino , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Polímeros/química
2.
FASEB J ; 37(5): e22921, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37052612

RESUMO

The serious clinical challenge of peripheral nerve injury (PNI) is nerve regeneration. Nerve conduit represents a promising strategy to contribute to nerve regeneration by bridging injured nerve gaps. However, due to a unique microenvironment of nerve tissue, autologous nerves have not been substituted by nerve conduit. Nerve regeneration after nerve conduit implantation depends on many factors, such as conductivity and biocompatibility. Therefore, Gelatin (Gel) with biocompatibility and polypyrrole (Ppy) with conductivity is highly concerned. In this paper, Gel-Ppy modified nerve conduit was fabricated with great biocompatibility and conductivity to evaluate its properties of enhancing nerve regeneration in vivo and in vitro. The proliferation of Schwann cells on Gel-Ppy modified nerve conduit was remarkably increased. Consistent with in vitro results, the Gel-Ppy nerve conduit could contribute to the regeneration of Schwann cell in vivo. The axon diameters and myelin sheath thickness were also enhanced, resulting in the amelioration of muscle atrophy, nerve conduction, and motor function recovery. To explain this interesting phenomenon, western blot results indicated that the Gel-Ppy conduit facilitated nerve regeneration via upregulating the Rap1 pathway to induce neurite outgrowth. Therefore, the above results demonstrated that Gel-Ppy modified nerve conduit could provide an acceptable microenvironment for nerve regeneration and be popularized as a novel therapeutic strategy of PNI.


Assuntos
Tecido Nervoso , Traumatismos dos Nervos Periféricos , Ratos , Animais , Polímeros , Gelatina , Ratos Sprague-Dawley , Pirróis , Nervo Isquiático/lesões , Traumatismos dos Nervos Periféricos/cirurgia , Regeneração Nervosa/fisiologia
3.
Molecules ; 29(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38338311

RESUMO

The prevalence of facial nerve injury is substantial, and the restoration of its structure and function remains a significant challenge. Autologous nerve transplantation is a common treatment for severed facial nerve injury; however, it has great limitations. Therefore, there is an urgent need for clinical repair methods that can rival it. Tissue engineering nerve conduits are usually composed of scaffolds, cells and neurofactors. Tissue engineering is regarded as a promising method for facial nerve regeneration. Among different factors, the porous nerve conduit made of organic materials, which has high porosity and biocompatibility, plays an indispensable role. This review introduces facial nerve injury and the existing treatment methods and discusses the necessity of the application of porous nerve conduit. We focus on the application of porous organic polymer materials from production technology and material classification and summarize the necessity and research progress of these in repairing severed facial nerve injury, which is relatively rare in the existing articles. This review provides a theoretical basis for further research into and clinical interventions on facial nerve injury and has certain guiding significance for the development of new materials.


Assuntos
Traumatismos do Nervo Facial , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Traumatismos do Nervo Facial/terapia , Porosidade , Próteses e Implantes , Polímeros , Regeneração Nervosa , Alicerces Teciduais
4.
Cell Tissue Res ; 391(3): 505-522, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36562866

RESUMO

In this study, a biological conduit, consisting of an adipocyte-derived mesenchymal stem cell (AdMSCs) sheet and amniotic membrane (AM), was designed for the reconstruction of peripheral nerve defects. To evaluate the effect of the produced conduit on neural regeneration, a 10-mm sciatic nerve defect was created in rats, and experiments were carried out on six groups, i.e., sham control group (SC), negative control group (NC), nerve autograft group (NG), the biological conduit (AdMSCs + AM) group, the commercial PGA tube conduit (PGA) group, and the conduit only consisting of AM (AM) group. The effects of different nerve repair methods on the peripheral nerve and gastrocnemius muscle were evaluated by functional, histological, and immunohistochemical tests. When the number of myelinated axons was compared between the groups of AdMSCs + AM and PGA, it was higher in the AdMSCs + AM group (p < 0.05). The percentage of gastrocnemius collagen bundle area of AdMSCs + AM group was found to be statistically lower than the PGA group (p < 0.05). The muscle fiber diameter of AdMSCs + AM group was lower than that of the NG group, but significantly higher than that of the PGA group and the AM group (p < 0.001). Muscle weight index was significantly higher in the AdMSCs + AM group compared to the PGA group (p < 0.05). It was observed that nerve regeneration was faster in the AdMSCs + AM group, and there was an earlier improvement in pin-prick score and sciatic functional index compared to the PGA group and the AM group. In conclusion, the biological conduit prepared from the AdMSCs sheet and AM is regarded as a new biological conduit that can be used as an alternative treatment method to nerve autograft in clinical applications.


Assuntos
Células-Tronco Mesenquimais , Tecido Nervoso , Humanos , Ratos , Animais , Âmnio , Nervo Isquiático/cirurgia , Nervo Isquiático/transplante , Modelos Animais de Doenças , Regeneração Nervosa/fisiologia
5.
J Mater Sci Mater Med ; 34(7): 35, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37477830

RESUMO

Peripheral nerve injury (PNI) is a common and severe clinical disease worldwide, which leads to a poor prognosis because of the complicated treatments and high morbidity. Autologous nerve grafting as the gold standard still cannot meet the needs of clinical nerve transplantation because of its low availability and limited size. The development of artificial nerve conduits was led to a novel direction for PNI treatment, while most of the currently developed artificial nerve conduits was lack biochemical cues to promote nerve regeneration. In this study, we designed a novel composite neural conduit by inserting decellularized the rat sciatic nerve or kidney in a poly (lactic-co-glycolic acid) (PLGA) grooved conduit. The nerve regeneration effect of all samples was analyzed using rat sciatic nerve defect model, where decellularized tissues and grooved PLGA conduit alone were used as controls. The degree of nerve regeneration was evaluated using the motor function, gastrocnemius recovery, and morphological and histological assessments suggested that the combination of a grooved conduit with decellularized tissues significantly promoted nerve regeneration compared with decellularized tissues and PLGA conduit alone. It is worth to note that the grooved conduits containing decellularized nerves have a promotive effect similar to that of autologous nerve grafting, suggesting that it could be an artificial nerve conduit used for clinical practice in the future.


Assuntos
Ácido Láctico , Traumatismos dos Nervos Periféricos , Ratos , Animais , Ácido Láctico/farmacologia , Nervo Isquiático/fisiologia , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Traumatismos dos Nervos Periféricos/patologia , Próteses e Implantes
6.
J Orthop Sci ; 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37149481

RESUMO

BACKGROUND: Biodegradable synthetic nerve conduits have become widely used for peripheral nerve injuries. Recently, bioabsorbable collagen conduits filled with collagen fibers (Renerve®) are commercially available in Japan. We investigated the clinical efficacy and safety of Renerve® conduits for digital nerve repair. PATIENTS AND METHODS: We retrospectively reviewed data of patients who underwent digital nerve repair using Renerve® conduits between August 2017 and February 2022 at our hospital and were followed up for at least 12 months. Seventeen patients (20 nerves) with a median age of 46.5 years (interquartile rage: 26-48 years) were included in the analysis. We analyzed sensory nerve function recovery and residual pain or uncomfortable tingling, as well as safety outcomes. The relationship between nerve defect length and sensory function data was assessed using Spearman's rank correlation. RESULTS: Sensory nerve function at 12 months postoperatively was excellent in six, good in 10, and poor in four nerves, and that at the final follow-up (median period, 24 months; range, 12-30 months) was excellent in nine, good in 10, and poor in one nerve. All nerves with a defect length of <12 mm had excellent or good sensory outcomes. At 12 months postoperatively, the correlation coefficients between nerve defect length and Semmes-Weinstein monofilament test results, static two-point discrimination, and dynamic two-point discrimination were 0.35 (p = 0.131), 0.397 (p = 0.0827), and 0.451 (p = 0.0461), respectively. Residual pain or tingling sensation were observed in four nerves at the final follow-up. No postoperative complications were observed in any of the patients. CONCLUSIONS: This study demonstrated the clinical efficacy and safety of Renerve® conduits for digital nerve repair. Our results will be useful in clinical practice because of the scarcity of real-world data on the use of Renerve® conduits for digital nerve repair.

7.
J Artif Organs ; 25(4): 289-297, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35970971

RESUMO

Autologous nerve grafting is the gold standard method for peripheral nerve injury with defects. Artificial nerve conduits have been developed to prevent morbidity at the harvest site. However, the artificial conduit regeneration capacity is not sufficient. A Bio 3D printer is technology that creates three-dimensional tissue using only cells. Using this technology, a three-dimensional nerve conduit (Bio 3D nerve conduit) was created from several cell spheroids. We reported the first application of the Bio 3D nerve conduit for peripheral nerve injury. A Bio 3D nerve conduit that was created from several cells promotes peripheral nerve regeneration. The Bio 3D nerve conduit may be useful clinically to treat peripheral nerve defects.


Assuntos
Traumatismos dos Nervos Periféricos , Humanos , Traumatismos dos Nervos Periféricos/cirurgia , Regeneração Nervosa/fisiologia , Nervos Periféricos/cirurgia , Próteses e Implantes , Autoenxertos , Alicerces Teciduais
8.
J Mater Sci Mater Med ; 33(6): 50, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35639181

RESUMO

Multichannel structures in the design of nerve conduits offer potential advantages for regeneration of damaged nerves. However, lack of biochemical cues and electrical stimulation could hamper satisfactory nerve regeneration. The aim of this study was to simultaneously evaluate the effects of topographical, biological, and electrical cues on sciatic nerve regeneration. Accordingly, a series of multichannel nerve conduit was made using longitudinally-aligned laminin-coated poly (lactic-co-glycolic acid) (PLGA)/carbon nanotubes (CNT) nanofibers (NF, mean diameter: 455 ± 362 nm) in the lumen and randomly-oriented polycaprolactone (PCL) NF (mean diameter: 340 ± 200 nm) on the outer surface. In vitro studies revealed that the materials were nontoxic and able to promote cell attachment and proliferation on nanofibers and on fibrin gel. To determine the influence of laminin as biological and CNT as electrical cues on nerve regeneration, either of hollow PCL conduits, PLGA NF-embedded, PLGA/CNT NF-embedded or laminin-coated PLGA/CNT NF-embedded PCL conduits were implanted in rats. A new surgery method was utilized and results were compared with an autograft. The results of motor and sensory tests in addition to histopathological examination of the regenerated nerves demonstrated the formation of nerve fibers in laminin-coated PLGA/CNT NF-embedded PCL conduits. Results suggested that these conduits have the potential to improve sciatic nerve regeneration. Graphical abstract.


Assuntos
Nanofibras , Nanotubos de Carbono , Animais , Laminina/química , Nanofibras/química , Nanotubos de Carbono/química , Regeneração Nervosa , Ratos , Nervo Isquiático/fisiologia
9.
Cell Tissue Bank ; 23(4): 909-922, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35503142

RESUMO

Treatment of peripheral nerve injuries (PNIs) remains a challenge. Interposing a graft delivers better regenerative outcomes. Autografts present major drawbacks which have given rise to the development of alternatives such as artificial scaffolds, some of which are very promising. This study was designed to investigate the potential use of an inverted human umbilical cord artery (iHUA) as a 3D scaffold nerve chamber, for nerve regeneration after transection of the sciatic nerve (SN) in rats. Rats underwent surgical SN transection in their right hindlimb, followed by suture of the device at the resected stumps. Local tolerance, insert biodegradability and nerve reconstruction over time were thoroughly studied by histopathological and morphometric analysis, completed by functional test assessment of sensitivity and motricity recovery. We have demonstrated that nerve reconstruction in the presence of an iHUA insert is effective. The device is well tolerated and highly biodegraded. Although the regenerated nerve is still immature at the end of our study, signs of sensitivity and partial functional recovery were witnessed, confirming our histological findings. Our results support the potential clinical use of iHUA as a 3D scaffold to bridge nerve discontinuity and guide axonal regrowth in selected cases of PNIs.


Assuntos
Nervo Isquiático , Artérias Umbilicais , Humanos , Ratos , Animais , Regeneração Nervosa , Axônios , Autoenxertos
10.
Int J Mol Sci ; 23(14)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35886987

RESUMO

(1) Objective: In order to evaluate the effect of a pre-induced mesenchymal stem cell (MSC)-coated cellulose/collagen nanofibrous nerve conduit on facial nerve regeneration in a rat model both in vitro and in vivo. (2) Methods: After fabrication of the cellulose/collagen nanofibrous conduit, its lumen was coated with either MSCs or pre-induced MSCs. The nerve conduit was then applied to the defective main trunk of the facial nerve. Rats were randomly divided into three treatment groups (n = 10 in each): cellulose/collagen nanofiber (control group), cellulose/collagen nanofiber/MSCs (group I), and cellulose/collagen nanofiber/pre-induced MSCs (group II). (3) Results Fibrillation of the vibrissae of each group was observed, and action potential threshold was compared 8 weeks post-surgery. Histopathological changes were also observed. Groups I and II showed better recovery of vibrissa fibrillation than the control group. (4) Conclusions: Group II, treated with the pre-induced MSC-coated cellulose/collagen nanofibrous nerve conduit, showed the highest degree of recovery based on functional and histological evaluations.


Assuntos
Celulose , Colágeno , Nervo Facial , Células-Tronco Mesenquimais , Nanofibras , Regeneração Nervosa , Animais , Celulose/farmacologia , Materiais Revestidos Biocompatíveis , Colágeno/farmacologia , Modelos Animais de Doenças , Nervo Facial/efeitos dos fármacos , Nervo Facial/fisiologia , Regeneração Tecidual Guiada , Células-Tronco Mesenquimais/fisiologia , Nanofibras/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Ratos , Nervo Isquiático/patologia , Alicerces Teciduais
11.
Molecules ; 27(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36558171

RESUMO

Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.


Assuntos
Quitosana , Ratos , Animais , Quitosana/farmacologia , Nervo Isquiático , Regeneração Nervosa , Células de Schwann , Próteses e Implantes
12.
J Obstet Gynaecol Res ; 47(11): 4118-4121, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34263495

RESUMO

Obturator nerve injury is an uncommon complication frequently associated with pelvic gynecologic or urologic cancer surgery. It can lead to disability or adversely affect quality of life. Large segmental defects are particularly difficult to manage as the limited mobility of the nerve prevents tension-free direct end-to-end anastomosis. A 36-year-old woman with cervical cancer underwent sentinel lymph node biopsy, laparoscopic radical hysterectomy, and bilateral adnexectomy. During the procedure, the sentinel lymph node (right obturator node) adherent to the obturator nerve was resected together with the nerve segment leaving a 3 cm defect. Immediate laparoscopic obturator nerve repair was performed using an artificial nerve conduit leading to successful recovery. We report this unique case due to rarity of large segmental obturator nerve defects and present laparoscopic nerve repair with artificial nerve conduits as a useful treatment alternative of these important injuries, without nerve donor site morbidity.


Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Adulto , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Nervo Obturador/cirurgia , Qualidade de Vida , Neoplasias do Colo do Útero/cirurgia
13.
Eur Arch Otorhinolaryngol ; 278(12): 4967-4976, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33948682

RESUMO

OBJECTIVE: To introduce the application of venous nerve conduit in the immediate repair and reconstruction of facial nerve in parotid gland tumor. METHODS: Three patients with parotid gland tumor in Sichuan Provincial Cancer Hospital were reviewed. All patients were found that the tumor encased and invaded the facial nerve which was difficult to be separated during the operation when all patients were treated with facial nerve repair and reconstruction with the venous nerve conduit trapping technique. RESULTS: After 1-year follow-up, all patients recovered well in facial nerve function. CONCLUSION: The venous nerve conduit trapping technique is an effective attempt in the immediate repair and reconstruction of facial nerve in parotid gland tumor, but it needs to be further confirmed by multiple studies.


Assuntos
Neoplasias Parotídeas , Procedimentos de Cirurgia Plástica , Nervo Facial/cirurgia , Humanos , Procedimentos Neurocirúrgicos , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia
14.
Int J Mol Sci ; 22(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34768804

RESUMO

Polyvinylidene fluoride (PVDF) and its copolymer with trifluoroethylene (P(VDF-TrFE)) are considered as promising biomaterials for supporting nerve regeneration because of their proven biocompatibility and piezoelectric properties that could stimulate cell ingrowth due to their electrical activity upon mechanical deformation. For the first time, this study reports on the comparative analysis of PVDF and P(VDF-TrFE) electrospun scaffolds in terms of structural and piezoelectric properties as well as their in vitro performance. A dynamic impact test machine was developed, validated, and utilised, to evaluate the generation of an electrical voltage upon the application of an impact load (varying load magnitude and frequency) onto the electrospun PVDF (15-20 wt%) and P(VDF-TrFE) (10-20 wt%) scaffolds. The cytotoxicity and in vitro performance of the scaffolds was evaluated with neonatal rat (nrSCs) and adult human Schwann cells (ahSCs). The neurite outgrowth behaviour from sensory rat dorsal root ganglion neurons cultured on the scaffolds was analysed qualitatively. The results showed (i) a significant increase of the ß-phase content in the PVDF after electrospinning as well as a zeta potential similar to P(VDF-TrFE), (ii) a non-constant behaviour of the longitudinal piezoelectric strain constant d33, depending on the load and the load frequency, and (iii) biocompatibility with cultured Schwann cells and guiding properties for sensory neurite outgrowth. In summary, the electrospun PVDF-based scaffolds, representing piezoelectric activity, can be considered as promising materials for the development of artificial nerve conduits for the peripheral nerve injury repair.


Assuntos
Polímeros de Fluorcarboneto/química , Gânglios Espinais/fisiologia , Hidrocarbonetos Fluorados/química , Regeneração Nervosa , Polivinil/química , Células de Schwann/fisiologia , Alicerces Teciduais , Adolescente , Adulto , Animais , Materiais Biocompatíveis , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polímeros , Ratos , Adulto Jovem
15.
Biotechnol Bioeng ; 116(1): 143-154, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30229866

RESUMO

Autologous nerve grafts are the current "gold standard" for repairing large nerve gaps. However, they cause morbidity at the donor nerve site and only a limited amount of nerve can be harvested. Nerve conduits are a promising alternative to autografts and can act as guidance cues for the regenerating axons, without the need to harvest donor nerve. Separately, it has been shown that localized delivery of GDNF can enhance axon growth and motor recovery. FK506, an FDA approved small molecule, has also been shown to enhance peripheral nerve regeneration. This paper describes the design of a novel hole-based drug delivery apparatus integrated with a polytetrafluoroethylene (PTFE) nerve conduit for controlled local delivery of a protein such as GDNF or a small molecule such as FK506. The PTFE devices were tested in a diffusion chamber, and the bioactivity of the released media was evaluated by measuring neurite growth of dorsal root ganglions (DRGs) exposed to the released drugs. The drug delivering nerve guide was able to release bioactive concentrations of FK506 or GDNF. Following these tests, optimized drug releasing nerve conduits were implanted across 10 mm sciatic nerve gaps in a BL6 yellow fluorescent protein (YFP) mouse model, where they demonstrated significant improvement in muscle mass, compound muscle action potential, and axon myelination in vivo as compared with nerve conduits without the drug. The drug delivery nerve guide could release drug for extended periods of time and enhance axon growth in vitro and in vivo.


Assuntos
Portadores de Fármacos/administração & dosagem , Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Traumatismos dos Nervos Periféricos/terapia , Politetrafluoretileno/administração & dosagem , Regeneração , Tacrolimo/administração & dosagem , Alicerces Teciduais , Animais , Modelos Animais de Doenças , Camundongos , Medicina Regenerativa/métodos , Resultado do Tratamento
16.
Eur J Orthop Surg Traumatol ; 29(2): 263-269, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30483968

RESUMO

The injuries of the peripheral nerves are relatively frequent. Some of them may lead to defects which cannot be repaired with direct end-to-end repair without tension. These injuries may cause function loss to the patient, and they consist a challenge for the treating microsurgeon. Autologous nerve grafts remain the gold standard for bridging the peripheral nerve defects. Nevertheless, there are selected cases where alternative types of nerve reconstruction can be performed in order to cover the peripheral nerve defects. In all these types of reconstruction, the basic principles of microsurgery are necessary and the surgeon should be aware of them in order to achieve a successful reconstruction. The purpose of the present review was to present the most current data concerning the surgical options available for bridging such defects.


Assuntos
Traumatismos dos Nervos Periféricos/cirurgia , Nervos Periféricos/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Aloenxertos , Autoenxertos , Humanos , Transferência de Nervo , Traumatismos dos Nervos Periféricos/classificação , Nervos Periféricos/transplante , Técnicas de Sutura
17.
Muscle Nerve ; 58(2): 251-260, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29406624

RESUMO

INTRODUCTION: Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. METHODS: Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. RESULTS: On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. DISCUSSION: Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve 58: 251-260, 2018.


Assuntos
Adipócitos/transplante , Hidrogéis , Regeneração Nervosa/fisiologia , Nervos Periféricos/crescimento & desenvolvimento , Poloxâmero , Transplante de Células-Tronco/métodos , Adulto , Animais , Axônios/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Neurônios Motores , Fibras Musculares Esqueléticas , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/inervação , Ratos , Nervo Isquiático/lesões , Neuropatia Ciática/terapia
18.
Mol Cell Neurosci ; 79: 1-11, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27865767

RESUMO

Regeneration of injured peripheral nerves is a slow, complicated process that could be improved by implantation of neural stem cells (NSCs) or nerve conduit. Implantation of NSCs along with conduits promotes the regeneration of damaged nerve, likely because (i) conduit supports and guides axonal growth from one nerve stump to the other, while preventing fibrous tissue ingrowth and retaining neurotrophic factors; and (ii) implanted NSCs differentiate into Schwann cells and maintain a growth factor enriched microenvironment, which promotes nerve regeneration. In this study, we identified IL12p80 (homodimer of IL12p40) in the cell extracts of implanted nerve conduit combined with NSCs by using protein antibody array and Western blotting. Levels of IL12p80 in these conduits are 1.6-fold higher than those in conduits without NSCs. In the sciatic nerve injury mouse model, implantation of NSCs combined with nerve conduit and IL12p80 improves motor recovery and increases the diameter up to 4.5-fold, at the medial site of the regenerated nerve. In vitro study further revealed that IL12p80 stimulates the Schwann cell differentiation of mouse NSCs through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that IL12p80 can trigger Schwann cell differentiation of mouse NSCs through Stat3 phosphorylation and enhance the functional recovery and the diameter of regenerated nerves in a mouse sciatic nerve injury model.


Assuntos
Interleucina-12/metabolismo , Regeneração Nervosa , Células-Tronco Neurais/transplante , Neurogênese , Traumatismos dos Nervos Periféricos/terapia , Células de Schwann/citologia , Nervo Isquiático/fisiologia , Animais , Células Cultivadas , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Fator de Transcrição STAT3/metabolismo , Transplante de Células-Tronco
19.
Int J Neurosci ; 128(6): 563-569, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29098916

RESUMO

BACKGROUND: Conduit-based nerve repairs are commonly used for small nerve gaps, whereas primary repair may be performed if there is no tension on nerve endings. We hypothesize that a conduit-based nerve coaptation device will improve nerve repair outcomes by avoiding sutures at the nerve repair site and utilizing the advantages of a conduit-based repair. METHODS: The left sciatic nerves of female Sprague-Dawley rats were transected and repaired using a novel conduit-based device. The conduit-based device group was compared to a control group of rats that underwent a standard end-to-end microsurgical repair of the sciatic nerve. Animals underwent behavioral assessments at weekly intervals post-operatively using the sciatic functional index (SFI) test. Animals were sacrificed at four weeks to obtain motor axon counts from immunohistochemistry. A sub-group of animals were sacrificed immediately post repair to obtain MRI images. RESULTS: SFI scores were superior in rats which received conduit-based repairs compared to the control group. Motor axon counts distal to the injury in the device group at four weeks were statistically superior to the control group. MRI tractography was used to demonstrate repair of two nerves using the novel conduit device. CONCLUSIONS: A conduit-based nerve coaptation device avoids sutures at the nerve repair site and leads to improved outcomes in a rat model. Conduit-based nerve repair devices have the potential to standardize nerve repairs while improving outcomes.


Assuntos
Matriz Extracelular , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/terapia , Nervo Isquiático , Animais , Imagem de Tensor de Difusão , Modelos Animais de Doenças , Feminino , Microcirurgia , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Traumatismos dos Nervos Periféricos/cirurgia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Nervo Isquiático/cirurgia
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(5): 687-692, 2017 Sep.
Artigo em Zh | MEDLINE | ID: mdl-29130658

RESUMO

OBJECTIVE: To evaluate the effectiveness of autologous vein nerve conduit supported by vascular stent in repairing a 10 mm gap peroneal nerve in white New Zealand rabbits. METHODS: 30 New Zealand rabbits were randomly divided into three groups: autologous nerve group (group A),conventional autologous vein nerve conduit group (group B),autologous vein nerve conduit supported by vascular stent group (group C). 10 mm common peroneal nerve was cut off. In groups A,the peroneal nerve was turned 180 ° before suturing. In group B and group C,20 mm long external jugular vein was cut and removed. After dilution of venous retraction,the venous bridge filled the gap of the nerve defect in group B. In group C,a blood vessel stent was placed for accessing the external jugular vein,and then connected to the nerve defect. Ulnar ulcer was observed after operations. Reflex score of left foot toe was recorded. The nerve regeneration and functional recovery was assessed through electrophysiological examinations,comparison of wet mass ratio between the left and right hind limb gastrocnemius,morphological observations,transmission electron microscopy 12 weeks after operations. RESULTS: Group B had the lowest scoring of toespreading reflex,whereas Group A had the highest scoring of toespreading reflex. There was a statistically significant difference in the scoring of toespreading reflex between group A and group C. In terms of the diameter of regenerated nerve fiber and the thickness of regenerated myelin sheath,no statistically significant ( P>0.05) difference was found between group A and group C,whereas the difference was significant ( P<0.05) between groups A/C and group B. The presence of peripheral nerves found in light microscopic examinations revealed normal characteristics of myelinated fibers in all groups. The myelinated axon profile was almost equal between group B and group C under electron microscopic examinations. However,more degenerated axons with disturbed contoursin were found in group B compared with group C. CONCLUSION: Autologous vein nerve conduit supported by vascular stent increases regeneration of nerves.


Assuntos
Regeneração Nervosa , Nervos Periféricos/crescimento & desenvolvimento , Stents , Enxerto Vascular , Animais , Axônios , Coelhos , Distribuição Aleatória , Recuperação de Função Fisiológica
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