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1.
Eur J Obstet Gynecol Reprod Biol ; 250: 9-16, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32361342

RESUMO

A 31-year-old female patient presented with complaints of cyclic low abdominal wall pain and palpable abdominal mass for more than 4 years. Physical examination revealed a painful mass measuring 7 cm × 5 cm within the abdominal wall. Her surgical history included surgery for congenital lymphatic haemangioma twice and caesarean section delivery twice. Results of abdominal wall ultrasonography, magnetic resonance imaging, and enhanced computed tomography revealed a soft tissue mass within the abdominal wall, indicating abdominal wall endometriosis. Pathologic examination with fine-needle aspiration of the abdominal wall mass showed endometrial glands and stroma. A multidisciplinary treatment team was established at admission, and surgical excision of the abdominal wall endometriosis mass was recommended. Surgery was performed by our multidisciplinary treatment team. Intraoperatively, the abdominal wall muscle, symphysis pubis, and anterior bladder wall were found to be infiltrated by abdominal wall endometriosis tissue. The abdominal wall endometriosis mass was completely resected with part of the bladder wall, symphysis pubis periosteum, and abdominal wall muscle and fascia (measuring 9 cm × 8 cm × 6 cm). The abdominal wall defect could not be sutured in a routine manner; thus, autologous reconstruction of the abdominal wall defect with left anterolateral thigh musculocutaneous flap was performed. The patient recovered without complications, and follow-up was uneventful. The successful treatment in our case suggests that adequate preoperative examinations and multidisciplinary treatment team collaboration are crucial to the treatment of patients with large abdominal wall endometriosis mass. Anterolateral thigh musculocutaneous flap reconstruction may serve as an optional treatment for abdominal wall defects during surgical excision of abdominal wall endometriosis mass.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32336045

RESUMO

Nerve defects are challenging to address clinically without satisfactory treatments. As a reliable alternative to autografts, decellularized nerve matrix scaffolds (DNM-Ss) have been widely used in clinics for surgical nerve repair. However, DNM-Ss remain inferior to autografts in their ability to support nerve regeneration for long nerve defects. In this study, we systematically and clearly presented the nano-architecture of nerve-specific structures, including the endoneurium, basement membrane and perineurium/epineurium in DNM-Ss. Furthermore, we modified the DNM-Ss by supplementing decellularized nerve matrix hydrogel (DNMG) and glial-derived neurotrophic factor (GDNF) and then bridged a 50-mm sciatic nerve defect in a beagle model. Fifteen beagles were randomly divided into three groups (5 per group): an autograft group, DNM-S group and GDNF-DNMG-modified DNM-S (DNM-S/GDNF@DNMG) group. DNM-S/GDNF@DNMGs, as optimized nerve grafts, were used to bridge nerve defects in the same manner as in the DNM-S group. The repair outcome was evaluated by behavioural observations, electrophysiological assessments, regenerated nerve tissue histology and reinnervated target muscle examinations. Compared with the DNM-S group, limb function, electrophysiological responses and histological findings were improved in the DNM-S/GDNF@DNMG group 6 months after grafting, reflecting a narrower gap between the effects of DNM-Ss and autografts. In conclusion, modification of DNM-Ss with DNMG and GDNF enhanced nerve regeneration and functional recovery, indicating that noncellular modification of DNM-Ss is a promising method for treating long nerve defects.

3.
Ann Plast Surg ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31913901

RESUMO

BACKGROUND: Rectus femoris necrosis is a rare but severe complication after anterolateral thigh flap (ALTF) harvesting. It has been previously reported that the blood supply of the rectus femoris (RF) often arises from the same source artery as the ALTF; however, precise descriptions of the relationship remain limited. This article revisits the blood supply of the RF based on computed tomography angiography (CTA) and analyzes the possible influence of the blood supply on the RF during ALTF harvesting. METHODS: Between December 2017 and June 2018, CTA images of the bilateral lower extremities of 25 patients were studied. The RF length, number, and diameter of branches at the entry point into muscle, location, and overall branch vessel origins were recorded. RESULTS: The average ± SD RF length was 384.73 ± 19.28 mm. There were 170 branches (mean ± SD, 3.4 ± 0.96 branches per thigh), mainly arising from the lateral circumflex femoral artery. The average ± SD diameter was 1.90 ± 0.51 mm. The first branch was located at 1/5 of the proximal site of the RF, and 91% of all branches were located above the midpoint. The RF vascularity can be classified into 2 types: type 1 (36% of sides) has branches that arise from a single artery (descending lateral circumflex femoral artery or femoral artery), whereas type 2 (64% of sides) has branches at the 1/5 proximal and 4/5 distal parts, which arise from different arteries. CONCLUSIONS: Preoperative CTA can provide anatomic information about the RF's nutrient vessel(s) and helps to optimize ALTF design.

4.
Injury ; 50 Suppl 5: S111-S116, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31759618

RESUMO

PURPOSE: Complex injuries of the extremity can be very challenging to treat. In the setting of soft tissue infection and vascular defect, arterial reconstructions are at high risk of failure. Historically, there have not been good options to successfully salvage limbs with these serious injuries. We describe our experience of utilizing a cross limb vessel transfer to salvage the limb. METHODS: Patients were identified retrospectively with complex vascular injuries of the extremity and wound infection, who were treated with a cross limb vessel transfer. Once the infection has successfully been cleared, flow-through flap transfer was performed for definitive reconstruction of the arterial injury. Data collated included patient demographics, injury and operation details, and post-operative outcomes including blood supply of the limb, wound infection and complications. RESULTS: Between April 2014 and January 2017, 3 patients with an average age of 21 years (range, 16-29) were admitted. The median length of hospital stay was 62 days (range, 26-122). The average number of operation was 7.3 times (range, 6-10). Two patients' upper limb had survived with limited movement, relatively minor donor site morbidity and confirmed flow through the vessel reconstruction using CTA, while one patient had lower limb amputation due to severe infection and prolonged ischemia time. CONCLUSIONS: This series of patients demonstrates that cross limb vessel transfer is an invaluable technique to salvage the limb in patients with complex vascular injury and wound infection. However, for lower limb with prolonged ischemia time and severe infection, limb salvage is not recommended.

5.
Neural Regen Res ; 14(12): 2173-2182, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31397357

RESUMO

The intermingling of regenerated nerve fibers inside nerve grafts is the main reason for mismatched nerve fibers. This is one of the key factors affecting limb function recovery after nerve injury. Previous research has shown that the accuracy of axon regeneration can be improved by a bionic structural implant. To this aim, iodine and freeze-drying high-resolution micro-computed tomography was performed to visualize the 3D topography of the New Zealand rabbit sciatic nerve (25 mm). A series of 1-, 2-, 3-, and 4-custom anatomy-based nerve conduits (CANCs) were fabricated based on the anatomical structure of the nerve fascicle. The match index, luminal surface, and mechanical properties of CANCs were evaluated before implanting in a 10-mm gap of the sciatic nerve. Recovery was evaluated by histomorphometric analyses, electrophysiological study, gastrocnemius muscle weight recovery ratio, and behavioral assessments at 12 and 24 weeks postoperatively. The accuracy of nerve regeneration was determined by changes in fluorescence-labeled profile number during simultaneous retrograde tracing. Our results showed that the optimal preprocessing condition for high-resolution micro-computed tomography visualization was treatment of the sciatic nerve with 40% Lugol's solution for 3 days followed by lyophilization for 2 days. In vitro experiments demonstrated that the match index was highest in the 3-CANC group, followed by the 2-, 1-, and 4-CANC groups. The luminal surface was lowest in the 1-CANC group. Mechanical properties (transverse compressive and bending properties) were higher in the 3- and 4-CANC groups than in the 1-CANC group. In vivo experiments demonstrated that the recovery (morphology of regenerated fibers, compound muscle action potential, gastrocnemius muscle weight recovery ratio, pain-related autotomy behaviors, and range of motion) in the 3-CANC group was superior to the other CANC groups, and achieved the same therapeutic effect as the autograft. The simultaneous retrograde tracing results showed that the percentages of double-labeled profiles of the 2-, 3-, and 4-CANC groups were comparatively lower than that of the 1-CANC group, which indicates that regenerated nerve fascicles were less intermingled in the 2-, 3-, and 4-CANC groups. These findings demonstrate that the visualization of the rabbit sciatic nerve can be achieved by iodine and freeze-drying high-resolution micro-computed tomography, and that this method can be used to design CANCs with different channels that are based on the anatomical structure of the nerve. Compared with the 1-CANC, 3-CANC had a higher match index and luminal surface, and improved the accuracy of nerve regeneration by limiting the intermingling of the regenerated fascicles. All procedures were approved by the Animal Care and Use Committee, Xinjiang Medical University, China on April 4, 2017 (ethics approval No. IACUC20170315-02).

6.
Int J Numer Method Biomed Eng ; 35(10): e3245, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31370097

RESUMO

Biofabricated nanostructured and microstructured scaffolds have exhibited great potential for nerve tissue regeneration and functional restoration, and prevascularization and biotransportation within 3D fascicle structures are critical. Unfortunately, an ideal internal fascicle and microvascular model of human peripheral nerves is lacking. In this study, we used microcomputed tomography (microCT) to acquire high-resolution images of the human sciatic nerve. We propose a novel deep-learning network technique, called ResNetH3D-Unet, to segment fascicles and microvascular structures. We reconstructed 3D intraneural fascicles and microvascular topography to quantify the fascicle volume ratio (FVR), microvascular volume ratio (MVR), microvascular to fascicle volume ratio (MFVR), fascicle surface area to volume ratio (FSAVR), and microvascular surface area to volume ratio (MSAVR) of human samples. The frequency distributions of the fascicle diameter, microvascular diameter, and fascicle-to-microvasculature distance were analyzed. The obtained microCT analysis and reconstruction provided high-resolution microstructures of human peripheral nerves. Our proposed ResNetH3D-Unet method for fascicle and microvasculature segmentation yielded a mean intersection over union (IOU) of 92.1% (approximately 5% higher than the U-net IOU). The 3D reconstructed model showed that the internal microvasculature runs longitudinally within the internal epineurium and connects to the external vasculature at some points. Analysis of the 3D data indicated a 48.2 ± 3% FVR, 23.7 ± 1.8% MVR, 4.9 ± 0.5% MFVR, 7.26 ± 2.58 mm-1 FSAVR, and 1.52 ± 0.52 mm-1 MSAVR. A fascicle diameter of 0.98 mm, microvascular diameter of 0.125 mm, and microvasculature-to-fascicle distance of 0.196 mm were most frequent. This study provides fundamental data and structural references for designing bionic scaffolding constructs with 3D microvascular and fascicle distributions.

7.
Biomed Res Int ; 2019: 9365291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309121

RESUMO

Objective: The aim of this study was to assess muscle injury associated with upper and lower closed limb fracture using ultrasound, and to develop ultrasound classification criteria for muscle injury. Patients and Methods: Thirty patients with limb fracture and muscle injury participated in this study. Ultrasonography was used to assess muscle fibre, hematoma, vascular injury, and diameter growth rate. Injury was classified into three grades according to the ultrasound imaging: scores of less than, equal to, or greater than 9. Results: Of 30 patients, focal fibre rupture was observed in 11 cases; in 9 cases, the injured area exceeded 30% of the muscle area. Six patients had muscle hematoma (the largest reaching 39 mm); in 4 patients, the hematoma showed a honeycombed pattern. Vascular rupture was observed in 6 patients, of which 2 had decreased main arterial diameter and blood flow. The greatest increase in muscle thickness was 17 mm. Of all patients, 11 showed an increase in the diameter growth rate of the muscle exceeding 50%. In addition, among the 30 patients, 11 patients with scores ranging from 4 to 8 received conservative treatment; 9 patients with scores ranging from 10 to 14 received operative treatment; and 10 patients with scores equal to 9 received either conservative or operative treatment. Conclusions: Ultrasonography is useful for diagnosing muscle injury associated with closed limb fracture. The ultrasound classification criteria for muscle injury can be used to assess the severity of injury and guide the decision of treatment.


Assuntos
Extremidades/fisiopatologia , Fraturas Ósseas/complicações , Fraturas Fechadas/complicações , Músculos/lesões , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Adolescente , Adulto , Idoso , Feminino , Consolidação da Fratura/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ruptura/etiologia , Ultrassonografia/métodos , Adulto Jovem
8.
ACS Appl Mater Interfaces ; 11(19): 17167-17176, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31002219

RESUMO

Synergistic intercellular interactions have been widely acknowledged in tuning functional cell behaviors in vivo, and these interactions have inspired the development of a variety of scaffolds for regenerative medicine. In this paper, the promotion of Schwann cell (SC)-neurite interactions through the use of a nerve extracellular matrix-coated nanofiber composite in vitro was demonstrated using a cell culturing platform consisting of either random or aligned electrospun poly(l-lactic acid) nanofibers and decellularized peripheral nerve matrix gel (pDNM gel) from porcine peripheral nervous tissue. The pDNM-coated nanofiber platform served as a superior substrate for dorsal root ganglion culturing. Furthermore, SC migration was facilitated by pDNM gel coating on the nanofibers, accompanied with much faster axonal extension, in comparison with the effect of topographical guidance from the aligned electrospun fibers only. Finally, the decellularized nerve matrix promoted the ability of SCs to wrap around bundled neurites, triggering axonal remyelination toward nerve fiber functionalization.


Assuntos
Neurogênese/genética , Medicina Regenerativa , Células de Schwann/efeitos dos fármacos , Engenharia Tecidual , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/genética , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/crescimento & desenvolvimento , Humanos , Ácido Láctico/química , Nanofibras/química , Tecido Nervoso/efeitos dos fármacos , Tecido Nervoso/crescimento & desenvolvimento , Neurogênese/efeitos dos fármacos , Polímeros , Suínos , Tecidos Suporte/química
9.
Neural Regen Res ; 14(1): 51-58, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30531070

RESUMO

Peripheral nerve injury is a common clinical problem and affects the quality of life of patients. Traditional restoration methods are not satisfactory. Researchers increasingly focus on the field of tissue engineering. The three key points in establishing a tissue engineering material are the biological scaffold material, the seed cells and various growth factors. Understanding the type of nerve injury, the construction of scaffold and the process of repair are necessary to solve peripheral nerve injury and promote its regeneration. This review describes the categories of peripheral nerve injury, fundamental research of peripheral nervous tissue engineering and clinical research on peripheral nerve scaffold material, and paves a way for related research and the use of conduits in clinical practice.

10.
Acta Biomater ; 86: 194-206, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30586646

RESUMO

Multi-channel nerve conduits have shown significant advantages in guidance of axonal growth and functional restoration after spinal cord injury (SCI). It was realized that the micro/nano-architectures of these implanted conduits can effectively tune the lesion-induced biological responses, including inflammation and scar formation. In this work, two PLLA multi-channel conduits were fabricated with ladder-like porous channel wall (labelled as LNCs) and nano-fibrous channel wall (labelled as NNCs), respectively, and transferred into complete spinal cord transected injury model in rats. The implantation of such two scaffolds significantly alleviated the infiltration of macrophages/microglia and accumulation of astrocyte and collagen scar, especially in the NNCs group. Meanwhile, recruitment of endogenous stem cells and axonal growth was observed in both of the multi-channel conduits. Compared to the LNCs, the extracellular matrix (ECM) - mimicry nanostructures in the NNCs promoted directional nerve fiber growth within the channels. Moreover, a relatively denser nano-architecture in the channel wall confined the nerve fiber extension within the channels. These results from in vivo evaluations suggested that the NNCs implants possess a great potential in future application for SCI treatment and nerve regeneration. STATEMENTS OF SIGNIFICANCE: The implantation of biocompatible and degradable polymeric scaffolds holds great potential in clinical treatment and tissue regeneration after spinal cord injury (SCI). In this work, the ladder-like nerve conduits (LNCs) and nano-fibrous nerve conduits (NNCs) were fabricated and implanted into completely spinal cord transected rats, respectively. In vivo characteristics showed significant reduction in post-injury inflammation and scar formation, with elevated nerve stem cells (NSCs) recruitment and nerve fiber growth, hence both conduits resulted in significant functional restoration after implantation. Remarkably, we noticed that not only the multi-channels in the conduits can guide nerve fiber regeneration, their micro-/nano-structured walls also played a critical role in modulating the post-implantation biological responses.

11.
Biomed Res Int ; 2019: 3845780, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31915690

RESUMO

Objective: The use of a biofabrication nerve scaffold, which mimics the nerve microstructure, as an alternative for autologous nerve transplantation is a promising strategy for treating peripheral nerve defects. This study aimed to design a customized biofabrication scaffold model with the characteristics of human peripheral nerve fascicles. Methods: We used Micro-MRI technique to obtain different nerve fascicles. A full-length 28 cm tibial nerve specimen was obtained and was divided into 14 two-centimetre nerve segments. 3D models of the nerve fascicles were obtained by three-dimensional reconstruction after image segmentation. The central line of the nerve fascicles was fitted, and the aggregation of nerve fascicles was analysed quantitatively. The nerve scaffold was designed by simulating the clinical nerve defect and extracting information from the acquired nerve fascicle data; the scaffold design was displayed by 3D printing to verify the accuracy of the model. Result: The microstructure of the sciatic nerve, tibial nerve, and common peroneal nerve in the nerve fascicles could be obtained by three-dimensional reconstruction. The number of cross fusions of tibial nerve fascicles from proximal end to distal end decreased gradually. By designing the nerve graft in accordance with the microstructure of the nerve fascicles, the 3D printed model demonstrated that the two ends of the nerve defect can be well matched. Conclusion: The microstructure of the nerve fascicles is complicated and changeable, and the spatial position of each nerve fascicle and the long segment of the nerve fascicle aggregation show great changes at different levels. Under the premise of the stability of the existing imaging techniques, a large number of scanning nerve samples can be used to set up a three-dimensional database of the peripheral nerve fascicle microstructure, integrating the gross imaging information, and provide a template for the design of the downstream nerve graft model.

12.
Neural Regen Res ; 13(11): 1953-1960, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30233069

RESUMO

The most common methods for three-dimensional reconstruction of peripheral nerve fascicles include histological and radiology techniques. Histological techniques have many drawbacks including an enormous manual workload and poor image registration. Micro-magnetic resonance imaging (Micro-MRI), an emerging radiology technique, has been used to report results in the brain, liver and tumor tissues. However, micro-MRI usage for obtaining intraneural structures has not been reported. The aim of this study was to present a new imaging method for three-dimensional reconstruction of peripheral nerve fascicles by 1T micro-MRI. Freshly harvested sciatic nerve samples from an amputated limb were divided into four groups. Two different scanning conditions (Mannerist Solution/GD-DTPA contrast agent, distilled water) were selected, and both T1 and T2 phases programmed for each scanning condition. Three clinical surgeons evaluated the quality of the images via a standardized scale. Moreover, to analyze deformation of the two-dimensional image, the nerve diameter and total area of the micro-MRI images were compared after hematoxylin-eosin staining. The results show that rapid micro-MRI imaging method can be used for three-dimensional reconstruction of the fascicle structure. Nerve sample immersed in contrast agent (Mannerist Solution/GD-DTPA) and scanned in the T1 phase was the best. Moreover, the nerve sample was scanned freshly and can be recycled for other procedures. MRI images show better stability and smaller deformation compared with histological images. In conclusion, micro-MRI provides a feasible and rapid method for three-dimensional reconstruction of peripheral nerve fascicles, which can clearly show the internal structure of the peripheral nerve.

13.
Neural Regen Res ; 13(9): 1643-1649, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30127127

RESUMO

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.

14.
Exp Neurol ; 307: 37-44, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29852179

RESUMO

CSPGs are components of the extracellular matrix in the nervous system, where they serve as cues for axon guidance during development. After a peripheral nerve injury, CSPGs switch roles and become axon inhibitors and become diffusely distributed at the injury site. To investigate whether the spatial distribution of CSPGs affects their role, we combined in vitro DRG cultures with CSPG stripe or coverage assays to simulate the effect of a patterned substrate or dispersive distribution of CSPGs on growing neurites. We observed neurite steering at linear CSPG interfaces and neurite inhibition when diffused CSPGs covered the distal but not the proximal segment of the neurite. The repellent and inhibitory effects of CSPGs on neurite outgrowth were associated with the disappearance of focal actin filaments on growth cones. The application of an actin polymerization inducer, jasplakinolide, allowed neurites to break through the CSPG boundary and grow on CSPG-coated surfaces. The results of our study collectively reveal a novel mechanism that explains how the spatial distribution of CSPGs determines whether they act as a cue for axon guidance or as an axon-inhibiting factor. Increasing our understanding of this issue may promote the development of novel therapeutic strategies that regulate the spatial distributions of CSPGs to use them as an axon guidance cue.


Assuntos
Citoesqueleto de Actina/fisiologia , Proteoglicanas de Sulfatos de Condroitina/fisiologia , Gânglios Espinais/fisiologia , Regeneração Nervosa/fisiologia , Transdução de Sinais/fisiologia , Citoesqueleto de Actina/efeitos dos fármacos , Animais , Células Cultivadas , Depsipeptídeos/farmacologia , Relação Dose-Resposta a Droga , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Neurosci Lett ; 676: 78-84, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29649487

RESUMO

Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury.


Assuntos
Regeneração Nervosa , PTEN Fosfo-Hidrolase/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Nervos Periféricos/embriologia , Nervos Periféricos/metabolismo , Animais , Gânglios Espinais/metabolismo , Compressão Nervosa , Ratos , Nervo Isquiático/lesões , Nervo Isquiático/fisiopatologia
16.
Acta Biomater ; 73: 326-338, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29649641

RESUMO

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. STATEMENT OF SIGNIFICANCE: Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy of decellularized nerve allograft for nerve regeneration, with limited success. Xenogeneic decellularized tissue matrices or hydrogels have been widely used for surgical applications owing to their ease of harvesting and low immunogenicity. Moreover, decellularized tissue matrix hydrogels show good biocompatibility and are highly tunable. In this study, we prepared a porcine decellularized nerve matrix (pDNM-G) and evaluated its potential for promoting nerve regeneration. Our results demonstrate that pDNM-G can support Schwann cell proliferation and peripheral nerve regeneration by means of residual primary extracellular matrix components and nano-fibrous structure features.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Nervos Periféricos/patologia , Animais , Proliferação de Células , Colágeno/química , Matriz Extracelular/química , Fibronectinas/química , Gelatina/química , Glicosaminoglicanos/química , Sistema Imunitário , Macrófagos/metabolismo , Masculino , Nanofibras , Sistema Nervoso Periférico , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/patologia , Suínos , Porco Miniatura , Engenharia Tecidual/métodos , Tecidos Suporte/química
17.
Mater Sci Eng C Mater Biol Appl ; 83: 130-142, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29208270

RESUMO

We recently fabricated multi-channel PLLA nerve conduits (NCs, conduits diameter: ~3mm, channels diameter: ~200µm) with nano-fibrous microstructure (NNCs) and ladder-like microstructure (LNCs), and found the nanofibers in the NNCs promote differentiation of nerve stem cells (NSCs) into neurons. In the present study, we evaluated the degradation profile of NNCs and LNCs, and observed that NNCs degraded too fast to implant. To delay the degradation and retain the nano-scale effect of NNCs, we used gelatin to wrap (2% w/v gelatin) or embed (8% w/v gelatin) NNCs and LNCs via vacuum infusion and chemical cross-linking with genipin. NNCs-wrapped maintained their original nano-fibrous microstructure, but NNCs-embedded presented a porous morphology without nanofibers appearing. Incorporation of gelatin did not change their compressive moduli, but increased the creep recovery ratios of LNCs and NNCs. In vitro degradation revealed that integrity was maintained and the mass loss was <5% for NNCs-wrapped after 10weeks, in comparison with 15% mass loss and collapsed structure of the pure NNCs after 4weeks. Meanwhile, there were no obvious changes in the degradation of LNCs with modification. Nerve stem cells (NSCs) were then seeded onto the six NCs represented as: NNCs, NNCs-wrapped, NNCs-embedded, LNCs, LNCs-wrapped, and LNCs-embedded. Immunocytochemistry analysis demonstrated that gelatin coating enhanced the adhesion and proliferation of NSCs, and the NNCs-wrapped scaffold promoted the differentiation proportion of NSCs into neurons from 25.8% (on pure NNCs) to 53.4% after 14days of seeding. On the other hand, only 14.3% of neurons were derived from the differentiation of the seeded NSCs on the NNCs-embedded. NNCs-wrapped would be a good choice for future studies in nerve injury repair in vivo due to its appropriate degradation rate, flexibility, and nano-scale effect.


Assuntos
Gelatina/química , Nanofibras/química , Células-Tronco Neurais/citologia , Poliésteres/química , Engenharia Tecidual/métodos
18.
Muscle Nerve ; 57(5): 821-828, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29211920

RESUMO

INTRODUCTION: Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. METHODS: Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. RESULTS: Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. DISCUSSION: Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018.


Assuntos
Inibidores de 14-alfa Desmetilase/uso terapêutico , Miconazol/uso terapêutico , Regeneração Nervosa/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Animais , Contagem de Células , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/ultraestrutura , Condução Nervosa/efeitos dos fármacos , Proteínas de Neurofilamentos/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Sincalida/metabolismo
19.
Int J Surg ; 48: 53-58, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29017862

RESUMO

BACKGROUND/OBJECTIVES: Complex extremity trauma commonly involves both soft tissue and vascular injuries. Traditional two-stage surgical repair may delay rehabilitation and functional recovery, as well as increase the risk of infections. We report a single-stage reconstructive surgical method that repairs soft tissue defects and vascular injuries with flow-through free flaps to improve functional outcomes. METHODS: Between March 2010 and December 2016 in our hospital, 5 patients with severe upper extremity trauma received single-stage reconstructive surgery, in which a flow-through anterolateral thigh free flap was applied to repair soft tissue defects and vascular injuries simultaneously. Cases of injured artery were reconstructed with the distal trunk of the descending branch of the lateral circumflex femoral artery. A segment of adjacent vein was used if there was a second artery injury. Patients were followed to evaluate their functional recoveries, and received computed tomography angiography examinations to assess peripheral circulation. RESULTS: Two patients had post-operative thumb necrosis; one required amputation, and the other was healed after debridement and abdominal pedicle flap repair. The other 3 patients had no major complications (infection, necrosis) to the recipient or donor sites after surgery. All the patients had achieved satisfactory functional recovery by the end of the follow-up period. Computed tomography angiography showed adequate circulation in the peripheral vessels. CONCLUSIONS: The success of these cases shows that one-step reconstructive surgery with flow-through anterolateral thigh free flaps can be a safe and effective treatment option for patients with complex upper extremity trauma with soft tissue defects and vascular injuries.


Assuntos
Retalhos de Tecido Biológico/irrigação sanguínea , Artéria Radial/lesões , Procedimentos Cirúrgicos Reconstrutivos/métodos , Extremidade Superior/lesões , Lesões do Sistema Vascular/cirurgia , Pré-Escolar , Desbridamento , Tratamento de Emergência/métodos , Feminino , Artéria Femoral/cirurgia , Humanos , Artéria Ilíaca/cirurgia , Masculino , Pessoa de Meia-Idade , Necrose/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/cirurgia , Artéria Radial/transplante , Recuperação de Função Fisiológica , Lesões dos Tecidos Moles/etiologia , Lesões dos Tecidos Moles/cirurgia , Coxa da Perna/irrigação sanguínea , Coxa da Perna/cirurgia , Polegar/patologia , Polegar/cirurgia , Resultado do Tratamento , Extremidade Superior/cirurgia , Lesões do Sistema Vascular/etiologia , Adulto Jovem
20.
Neuroreport ; 28(15): 1008-1015, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28914740

RESUMO

Peripheral nerve injury therapy in the clinic remains less than satisfactory. The gold standard of treatment for long peripheral nerve defects is autologous nerve grafts; however, numerous clinical complications are associated with this treatment. As tissue engineering has developed, tissue-engineered nerve grafts (TENGs) have shown potential applications as alternatives to autologous nerve grafts. To verify the important role of the biomimetic pathway of fascicle design in TENGs, we designed an animal model to study the role of the precise matching of fascicles in the effectiveness of nerve function recovery. 24 Sprague-Dawley rats were divided randomly into three groups (eight/group) that corresponded to 100% fascicle matching (100%FM), 50%FM and 0%FM. We selected Sprague-Dawley rat long-gap (15 mm) sciatic nerve defects. In the 6 weeks after surgery, we found that the 100%FM group showed the most effective functional recovery among the three groups. The 100%FM group showed better functional recovery on the basis of the sciatic functional index than the 50%FM and 0%FM groups. According to histological evaluation, the 100%FM group showed more regenerating nerve fibres. Moreover, in terms of the prevention of muscle atrophy, the 100%FM group showed excellent physiological outcomes. The 100%FM as tissue-engineered scaffolds can enhance nerve regeneration and effective functional recovery after the repair of large nerve defects. The results of this study provide a theoretical basis for future TENG designs including biomimetic fascicle pathways for repairing long nerve defects.


Assuntos
Regeneração Nervosa/fisiologia , Procedimentos Neurocirúrgicos , Traumatismos dos Nervos Periféricos/cirurgia , Nervo Isquiático/lesões , Nervo Isquiático/cirurgia , Tecidos Suporte , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Masculino , Atividade Motora/fisiologia , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Bainha de Mielina/patologia , Bainha de Mielina/fisiologia , Procedimentos Neurocirúrgicos/métodos , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Distribuição Aleatória , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia
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