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Sample records for collagen nerve conduits

  1. Collagen nerve conduits promote enhanced axonal regeneration, schwann cell association, and neovascularization compared to silicone conduits.

    PubMed

    Kemp, Stephen W P; Syed, Shahbaz; Walsh, Walsh; Zochodne, Douglas W; Midha, Rajiv

    2009-08-01

    Peripheral nerve regeneration within guidance conduits involves a critical association between regenerating axons, Schwann cells (SCs), and neovascularization. However, it is currently unknown if there is a greater association between these factors in nonpermeable versus semipermeable nerve guide conduits. We therefore examined this collaboration in both silicone- and collagen-based nerve conduits in both 5- and 10-mm-injury gaps in rat sciatic nerves. Results indicate that collagen conduits promoted enhanced axonal and SC regeneration and association when compared to silicone conduits in the shorter 5-mm-gap model. In addition, collagen tubes displayed enhanced neovascularization over silicone conduits, suggesting that these three factors are intimately related in successful peripheral nerve regeneration. At later time points (1- and 2-month analysis) in a 10-mm-gap model, collagen tubes displayed enhanced axonal regeneration, myelination, and vascularization when compared to silicone-based conduits. Results from these studies suggest that regenerating cables within collagen-based conduits are revascularized earlier and more completely, which in turn enhances peripheral nerve regeneration through these nerve guides as compared to silicone conduits.

  2. Collagen Type I Conduits for the Regeneration of Nerve Defects

    PubMed Central

    Klein, Silvan; Vykoukal, Jody; Felthaus, Oliver; Dienstknecht, Thomas; Prantl, Lukas

    2016-01-01

    To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve repair using a type I collagen nerve conduit. Patients were re-examined at a minimal follow-up of 14.0 months and a mean follow-up of 19.9 months. Regeneration of nerve tissue within the conduits was assessed by nerve conduction velocity (NCV), a static two-point discrimination (S2PD) test, and as disability of arm shoulder and hand (DASH) outcome measure scoring. Quality of life measures including patients’ perceived satisfaction and residual pain were evaluated using a visual analog scale (VAS). No implant-related complications were observed. Seven out of 10 patients reported being free of pain, and the mean VAS was 1.1. The mean DASH score was 17.0. The S2PD was below 6 mm in 40%, between 6 and 10 mm in another 40% and above 10 mm in 20% of the patients. Eight out of 10 patients were satisfied with the procedure and would undergo surgery again. Early treatment correlated with lower DASH score levels. The use of type I collagen in large-diameter gaps in young patients and early treatment presented superior functional outcomes. PMID:28773346

  3. Type I collagen nerve conduits for median nerve repairs in the forearm.

    PubMed

    Dienstknecht, Thomas; Klein, Silvan; Vykoukal, Jody; Gehmert, Sebastian; Koller, Michael; Gosau, Martin; Prantl, Lukas

    2013-06-01

    To evaluate patients with median nerve damage in the distal forearm treated with type 1 collagen nerve conduits. Nine patients with damage to the median nerve in the distal forearm underwent treatment with a type 1 collagen nerve conduit. The nerve gaps ranged between 1 and 2 cm. An independent observer reexamined patients after treatment at a minimal follow-up of 14 months and a mean follow-up of 21 months. Residual pain was evaluated using a visual analog scale. Functional outcome was quantified by assessing static 2-point discrimination, nerve conduction velocity relative to the uninjured limb, and Disabilities of the Arm, Shoulder, and Hand outcome measure scoring. We also recorded quality of life measures including patients' perceived satisfaction with the results and return to work latency. We observed no implant-related complications. Of 9 patients, 7 were free of pain, and the mean visual analog scale was 0.6. The mean Disabilities of the Arm, Shoulder, and Hand score was 6. The static 2-point discrimination was less than 6 mm in 3 patients, between 6 and 10 mm in 4 patients, and over 10 mm in 2 patients. Six patients reached a status of M4 or higher. Eight patients were satisfied with the procedure and would undergo surgery again. This study indicates that purified type 1 bovine collagen conduits are a practical and efficacious method for the repair of median nerves in the distal forearm. Therapeutic IV. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  4. Peripheral facial nerve regeneration using collagen conduit entubulation in a cat model.

    PubMed

    Dresner, Harley S; King, Timothy A; Clark, H Brent; Juhn, Steven K; Levine, Samuel C

    2006-08-01

    Facial nerve (FN) injuries are functionally, psychologically, and financially debilitating. Facial nerve autograft repairs produce significant donor nerve morbidity and functional results that rarely exceed House-Brackmann (HB) grade III over VI. In this study we sought to enhance FN regeneration via collagen conduit entubulation. Five control cats underwent right ("cut-side") FN transection and immediate microsurgical anastomosis repair. Five experimental cats underwent identical repairs plus collagen conduit entubulation of each anastomosis. Postoperative behavioral observations revealed gradual FN functional recovery in all cats, who attained adapted HB grades of II to III over VI after 6 weeks. Electromyographic latencies and amplitudes from the bilateral orbicularis oculi and orbicularis oris muscles indicated restoration of FN continuity in all 10 cats. In comparison with FN repairs without conduits, repairs with conduits significantly enhanced recovery of amplitude in cut-side orbicularis oculi muscles (p = .037) and latency in cut-side orbicularis oris muscles (p = .048). In comparison with intact left ("uncut-side") FN latencies and amplitudes, more statistically significant differences in cut-side FN function were observed in repairs without conduits than in repairs with conduits. Conduits therefore facilitated a more complete return of electrophysiological function. Histologic analyses confirmed FN continuity and revealed more organized FN regenerative architecture in conduit-implanted repairs. The overall results support enhanced FN regeneration with collagen conduit entubulation.

  5. Processed allografts and type I collagen conduits for repair of peripheral nerve gaps.

    PubMed

    Whitlock, Elizabeth L; Tuffaha, Sami H; Luciano, Janina P; Yan, Ying; Hunter, Daniel A; Magill, Christina K; Moore, Amy M; Tong, Alice Y; Mackinnon, Susan E; Borschel, Gregory H

    2009-06-01

    Autografting is the gold standard in the repair of peripheral nerve injuries that are not amenable to end-to-end coaptation. However, because autografts result in donor-site defects and are a limited resource, an effective substitute would be valuable. In a rat model, we compared isografts with Integra NeuraGen (NG) nerve guides, which are a commercially available type I collagen conduit, with processed rat allografts comparable to AxoGen's Avance human decellularized allograft product. In a 14-mm sciatic nerve gap model, isograft was superior to processed allograft, which was in turn superior to NG conduit at 6 weeks postoperatively (P < 0.05 for number of myelinated fibers both at midgraft and distal to the graft). At 12 weeks, these differences were no longer apparent. In a 28-mm graft model, isografts again performed better than processed allografts at both 6 and 22 weeks; regeneration through the NG conduit was often insufficient for analysis in this long graft model. Functional tests confirmed the superiority of isografts, although processed allografts permitted successful reinnervation of distal targets not seen in the NG conduit groups. Processed allografts were inherently non-immunogenic and maintained some internal laminin structure. We conclude that, particularly in a long gap model, nerve graft alternatives fail to confer the regenerative advantages of an isograft. However, AxoGen processed allografts are superior to a currently available conduit-style nerve guide, the Integra NeuraGen. They provide an alternative for reconstruction of short nerve gaps where a conduit might otherwise be used.

  6. Fabrication of seamless electrospun collagen/PLGA conduits whose walls comprise highly longitudinal aligned nanofibers for nerve regeneration.

    PubMed

    Ouyang, Yuanming; Huang, Chen; Zhu, Yi; Fan, Cunyi; Ke, Qinfei

    2013-06-01

    An ideal nerve scaffold should supply structural guidance and trophic support to facilitate nerve regeneration. Aligned electrospun nanofibers have shown considerable promise for the precise guidance of regenerating axons in vitro and in vivo. Therefore, uniaxially aligned three-dimension (3D) nanofiberous scaffolds may allow regenerating axons to traverse large gaps to treat severe nerve injuries. However, the aligned 3D conduit was always rolled by an aligned 2-dimensional (2D) sheet in current fabrication methods, which was inconvenient for transplant due to the discontinuous joint and inconsistent size. We developed a modified one-step electrospinning technique to produce a seamless 3D nanofiberous nerve conduit (NC) with highly longitudinal aligned nanofibers that combines the biocompatibility of natural collagen and the strength of the synthetic polymer poly(lactic-co-glycolic acid) (PLGA). Scanning electron microscopy (SEM) confirmed the parallel alignment of the scaffold fibers. To test the effectiveness of these scaffolds at restoring neuronal connections, they were implanted into adult rats across a 13 mm sciatic nerve defect. Tests of, motor function, nerve conduction, axonal and Schwann cell morphology, and marker expression all revealed that uniaxially aligned seamless 3D electrospun collagen/PLGA NCs were superior to randomly oriented NCs and inferior to autografts for promoting axon regeneration, myelination, action potential propagation, neuromuscular transmission, and functional recovery. These uniaxially aligned seamless 3D electrospun collagen/PLGA nerve guides can also incorporate signaling molecules and additional structural cues to guide nerve growth, and so may be a promising substitute for autogenous nerve grafts.

  7. Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

    PubMed Central

    Zhuang, Hai; Bu, Shoushan; Hua, Lei; Darabi, Mohammad A; Cao, Xiaojian; Xing, Malcolm

    2016-01-01

    In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide®). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group (P>0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable

  8. Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth.

    PubMed

    Zhuang, Hai; Bu, Shoushan; Hua, Lei; Darabi, Mohammad A; Cao, Xiaojian; Xing, Malcolm

    2016-01-01

    In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide(®)). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group (P>0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable

  9. Peripheral nerve conduits: technology update

    PubMed Central

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  10. The influence of nerve conduits diameter in motor nerve recovery after segmental nerve repair.

    PubMed

    Giusti, Guilherme; Shin, Richard H; Lee, Joo-Yup; Mattar, Tiago G; Bishop, Allen T; Shin, Alexander Y

    2014-11-01

    Many conduits have demonstrated potential to substitute nerve autografts; however, the influence of conduit inner diameter (ID) has never been studied as a separate parameter. This experimental study compared motor recovery after segmental nerve repair with two different ID collagen conduits: 1.5 and 2.0 mm. In addition, the conduits were analyzed in vitro to determine the variations of ID before and after hydration. Thirty rats were divided into three groups: 2.0 mm ID, 1.5 mm ID, and a control group autograft. After 12 weeks, the 1.5 mm ID group demonstrated significant increase in force (P < 0.0001) and weight (P < 0.0001) of the tibialis anterior muscle and better histomorphometry results of the peroneal nerve (P < 0.05) compared to 2.0 mm ID group; nevertheless, autograft results outperformed both conduits (P < 0.0001). Conduits ID were somewhat smaller than advertised, measuring 1.59 ± 0.03 mm and 1.25 ± 0.0 mm. Only the larger conduit showed a 6% increase in ID after hydration, changing to 1.69 ± 0.02 mm. Although autografts perform best, an improvement in motor recovery can be achieved with collagen conduits when a better size match conduit is being used. Minimal changes in collagen conduits ID can be expected after implantation.

  11. [The preparation and evaluation of tissue inducible nerve guide conduit].

    PubMed

    Zhao, Hongbin; Liu, Xingyan; Ge, Baofeng; Guo, Chao; Zhen, Ping

    2012-04-01

    The objective of this research was to fabricate a novel tissue inducible nerve guide conduit, and to evaluate its biologic property. The microspheres were prepared with chitosan that encapsulated ligustrazine. The drug release of the chitosan microspheres was detected with application of the controlled release method in vitro. Chitosan microspheres were mixed with collagen to fabricate the tissue inducible nerve conduit, which were crosslinked with 2% genipin for 24h. Mechanical properties of the nerve guide conduit samples, including maximum load and breaking load, were measured using an Instron Series IX Automated Materials Testing System. The flexibility of the nerve guide conduit was determined with the texture evaluation instrument. Different methods, such as scanning electron microscope (SEM), light microscope (LMS) and immunofluorescence were used to analyze the spatial structure of the nerve guide conduit, the distribution of the microspheres, the state of the nerve duct combined with mesenchymal stem cells (MSCs), and the effect of the ligustrazine that released from chitosan microsphere on MSCs differentiation into nerve cells, respectively. The results showed that the chitosan microspheres had better releasing effect. The mechanical properties resultant nerve guide conduit were determined. The maximum load and breaking load of the genipin crosslinked samples were significantly higher than that observed with the non-crosslinkers, increasing to (0.76 +/- 0.15) N and (0.69 +/- 0.17) N from (0.23 +/- 0.09) N and (0.20 +/- 0.12) N for the non-crosslinkers (P < 0.01). The degradation rates of non-crosslinked and crosslinked by genipin were(58.62 +/- 7.59) mg and (9.23 +/- 2.47) mg, respec- tively. This had a statistical significance (P < 0.01). The average linearities in dry and hygrometric state of the nerve guide conduit were (0.597 +/- 0.012) LC and (0.333 +/- 0.015) LC, respectively, which also had statistical significance (P < 0.01). The flexibility in

  12. A novel electrospun nerve conduit enhanced by carbon nanotubes for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Yu, Wenwen; Jiang, Xinquan; Cai, Ming; Zhao, Wen; Ye, Dongxia; Zhou, Yong; Zhu, Chao; Zhang, Xiuli; Lu, Xiaofeng; Zhang, Zhiyuan

    2014-04-01

    For artificial nerve conduits, great improvements have been achieved in mimicking the structures and components of autologous nerves. However, there are still some problems in conduit construction, especially in terms of mechanical properties, biomimetic surface tomography, electrical conductivity and sustained release of neurotrophic factors or cells. In this study, we designed and fabricated a novel electrospun nerve conduit enhanced by multi-walled carbon nanotubes (MWNTs) on the basis of a collagen/poly(ɛ-caprolactone) (collagen/PCL) fibrous scaffold. Our aim was to provide further knowledge about the mechanical effects and efficacy of MWNTs on nerve conduits as well as the biocompatibility and toxicology of MWNTs when applied in vivo. The results showed that as one component, carboxyl MWNTs could greatly alter the composite scaffold’s hydrophilicity, mechanical properties and degradability. The electrospun fibers enhanced by MWNTs could support Schwann cell adhesion and elongation as a substrate in vitro. In vivo animal studies demonstrated that the MWNT-enhanced collagen/PCL conduit could effectively promote nerve regeneration of sciatic nerve defect in rats and prevent muscle atrophy without invoking body rejection or serious chronic inflammation. All of these results showed that this MWNT-enhanced scaffold possesses good biocompatibility and MWNTs might be excellent candidates as engineered nanocarriers for further neurotrophic factor delivery research.

  13. Nanofibrous nerve conduit-enhanced peripheral nerve regeneration.

    PubMed

    Jiang, Xu; Mi, Ruifa; Hoke, Ahmet; Chew, Sing Yian

    2014-05-01

    Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regeneration have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15-mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly (ε-caprolactone) (PCL) microfibers (981 ± 83 nm, Microfiber) or nanofibers (251 ± 32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non-porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93 ± 0.71 × 10(3) vs. 0.98 ± 0.30 × 10(3) in Microfiber, p < 0.01). In addition, the compound muscle action potential (CMAP) amplitudes were higher and distal motor latency values were lower in the Nanofiber conduit group compared to the Microfiber group. This study demonstrated the impact of fibre size on peripheral nerve regeneration. These results could provide useful insights for future nerve guide designs.

  14. Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration.

    PubMed

    Evans, Gregory R D; Brandt, Keith; Katz, Steven; Chauvin, Priscilla; Otto, Lisa; Bogle, Melissa; Wang, Bao; Meszlenyi, Rudolph K; Lu, Lichun; Mikos, Antonios G; Patrick, Charles W

    2002-02-01

    This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously tested poly(L-lactic acid) (PLLA) conduits by incorporating them with allogeneic Schwann cells (SCs). The SCs were harvested, cultured to obtain confluent monolayers and two concentrations (1 x 10(4) and 1 x 10(6) SC/ml) were combined with a collagen matrix (Vitrogen) and injected into the PLLA conduits. The conduits were then implanted into a 12 mm right sciatic nerve defect in rats. Three control groups were used: isografts, PLLA conduits filled with collagen alone and empty silicone tubes. The sciatic functional index (SFI) was calculated monthly through four months. At the end of second and fourth months, the gastrocnemius muscle was harvested and weighed for comparison and the graft conduit and distal nerve were harvested for histomorphologic analysis. The mean SFI demonstrated no group differences from isograft control. By four months, there was no significant difference in gastrocnemius muscle weight between the experimental groups compared to isograft controls. At four months, the distal nerve demonstrated a statistically lower number of axons mm2 for the high and low SC density groups and collagen control. The nerve fiber density was significantly lower in all of the groups compared to isograft controls by four months. The development of a "bioactive" nerve conduit using tissue engineering to replace autogenous nerve grafts offers a potential approach to improved patient care. Although equivalent nerve regeneration to autografts was not achieved, this study provides promising results for further investigation.

  15. A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance Conduit for Peripheral Nerve Repair.

    PubMed

    Ryan, Alan J; Lackington, William A; Hibbitts, Alan J; Matheson, Austyn; Alekseeva, Tijna; Stejskalova, Anna; Roche, Phoebe; O'Brien, Fergal J

    2017-10-04

    Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze-drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration.

    PubMed

    Das, Suradip; Sharma, Manav; Saharia, Dhiren; Sarma, Kushal Konwar; Sarma, Monalisa Goswami; Borthakur, Bibhuti Bhusan; Bora, Utpal

    2015-09-01

    We report a novel silk-gold nanocomposite based nerve conduit successfully tested in a neurotmesis grade sciatic nerve injury model in rats over a period of eighteen months. The conduit was fabricated by adsorbing gold nanoparticles onto silk fibres and transforming them into a nanocomposite sheet by electrospinning which is finally given a tubular structure by rolling on a stainless steel mandrel of chosen diameter. The conduits were found to promote adhesion and proliferation of Schwann cells in vitro and did not elicit any toxic or immunogenic responses in vivo. We also report for the first time, the monitoring of muscular regeneration post nerve conduit implantation by recording motor unit potentials (MUPs) through needle electromyogram. Pre-seeding the conduits with Schwann cells enhanced myelination of the regenerated tissue. Histo-morphometric and electrophysiological studies proved that the nanocomposite based conduits pre-seeded with Schwann cells performed best in terms of structural and functional regeneration of severed sciatic nerves. The near normal values of nerve conduction velocity (50 m/sec), compound muscle action potential (29.7 mV) and motor unit potential (133 μV) exhibited by the animals implanted with Schwann cell loaded nerve conduits in the present study are superior to those observed in previous reports with synthetic materials as well as collagen based nerve conduits. Animals in this group were also able to perform complex locomotory activities like stretching and jumping with excellent sciatic function index (SFI) and led a normal life.

  17. Collagen nerve wrap for median nerve scarring.

    PubMed

    Kokkalis, Zinon T; Mavrogenis, Andreas F; Ballas, Efstathios G; Papagelopoulos, Panayiotis J; Soucacos, Panayotis N

    2015-02-01

    Nerve wrapping materials have been manufactured to inhibit nerve tissue adhesions and diminish inflammatory and immunologic reactions in nerve surgery. Collagen nerve wrap is a biodegradable type I collagen material that acts as an interface between the nerve and the surrounding tissues. Its main advantage is that it stays in place during the period of tissue healing and is then gradually absorbed once tissue healing is completed. This article presents a surgical technique that used a collagen nerve wrap for the management of median nerve tissue adhesions in 2 patients with advanced carpal tunnel syndrome due to median nerve scarring and adhesions. At last follow-up, both patients had complete resolution with no recurrence of their symptoms. Complications related to the biodegradable material were not observed. Copyright 2015, SLACK Incorporated.

  18. Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

    PubMed Central

    Zhu, Yiqian; Wang, Aijun; Patel, Shyam; Kurpinski, Kyle; Diao, Edward; Bao, Xuan; Kwong, George; Young, William L.

    2011-01-01

    Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID:21501089

  19. A polylactic acid non-woven nerve conduit for facial nerve regeneration in rats.

    PubMed

    Matsumine, Hajime; Sasaki, Ryo; Yamato, Masayuki; Okano, Teruo; Sakurai, Hiroyuki

    2014-06-01

    This study developed a biodegradable nerve conduit with PLA non-woven fabric and evaluated its nerve regeneration-promoting effect. The buccal branch of the facial nerve of 8 week-old Lewis rats was exposed, and a 7 mm nerve defect was created. A nerve conduit made of either PLA non-woven fabric (mean fibre diameter 460 nm), or silicone tube filled with type I collagen gel, or an autologous nerve, was implanted into the nerve defect, and their nerve regenerative abilities were evaluated 13 weeks after the surgery. The number of myelinated neural fibres in the middle portion of the regenerated nerve was the highest for PLA tubes (mean ± SD, 5051 ± 2335), followed by autologous nerves (4233 ± 590) and silicone tubes (1604 ± 148). Axon diameter was significantly greater in the PLA tube group (5.17 ± 1.69 µm) than in the silicone tube group (4.25 ± 1.60 µm) and no significant difference was found between the PLA tube and autograft (5.53 ± 1.93 µm) groups. Myelin thickness was greatest for the autograft group (0.65 ± 0.24 µm), followed by the PLA tube (0.54 ± 0.18 µm) and silicone tube (0.38 ± 0.12 µm) groups, showing significant differences among the three groups. The PLA non-woven fabric tube, composed of randomly-connected PLA fibres, is porous and has a number of advantages, such as sufficient strength to maintain luminal structure. The tube has demonstrated a comparable ability to induce peripheral nerve regeneration following autologous nerve transplantation. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Induction of rat facial nerve regeneration by functional collagen scaffolds.

    PubMed

    Cao, Jiani; Xiao, Zhifeng; Jin, Wei; Chen, Bing; Meng, Danqing; Ding, Wenyong; Han, Sufang; Hou, Xiaoshan; Zhu, Tiansheng; Yuan, Baoyu; Wang, Jing; Liang, Weibang; Dai, Jianwu

    2013-01-01

    Nerve conduit provides a promising strategy for nerve regeneration, and the proper microenvironment in the lumen could improve the regeneration. Our previous work had demonstrated that linear ordered collagen scaffold (LOCS) could effectively guide the oriented growth of axons. Laminin is known as an important nerve growth promoting factor and can facilitate the growth cone formation. In addition, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) can effectively improve the nerve regeneration after nerve injuries. However, in practice, diffusion caused by the body fluids is the major obstacle in their applications. To retain CNTF or BDNF on the scaffolds, we produced collagen binding CNTF (CBD-CNTF), collagen binding BDNF (CBD-BDNF) and laminin binding CNTF (LBD-CNTF), laminin binding BDNF (LBD-BDNF) respectively. In this work, we developed laminin modified LOCS fibers (L × LOCS) by chemical cross-linking LOCS fibers with laminin. Collagen binding or laminin binding neurotrophic factors were combined with LOCS or L × LOCS, and then filled them into the collagen nerve conduit. They were found to guide the ordered growth of axons, and improve the nerve functional recovery in the rat facial nerve transection model. The combination of CNTF and BDNF greatly enhanced the facial nerve regeneration and functional recovery.

  1. Past, Present, and Future of Nerve Conduits in the Treatment of Peripheral Nerve Injury

    PubMed Central

    Muheremu, Aikeremujiang

    2015-01-01

    With significant advances in the research and application of nerve conduits, they have been used to repair peripheral nerve injury for several decades. Nerve conduits range from biological tubes to synthetic tubes, and from nondegradable tubes to biodegradable tubes. Researchers have explored hollow tubes, tubes filled with scaffolds containing neurotrophic factors, and those seeded with Schwann cells or stem cells. The therapeutic effect of nerve conduits is improving with increasing choice of conduit material, new construction of conduits, and the inclusion of neurotrophic factors and support cells in the conduits. Improvements in functional outcomes are expected when these are optimized for use in clinical practice. PMID:26491662

  2. Regeneration of the Nerves in the Aerial Cavity with an Artificial Nerve Conduit -Reconstruction of Chorda Tympani Nerve Gaps-

    PubMed Central

    Yamanaka, Toshiaki; Hosoi, Hiroshi; Murai, Takayuki; Kobayashi, Takehiko; Inada, Yuji; Nakamura, Tatsuo

    2014-01-01

    Objectives/Hypothesis Due to its anatomical features, the chorda tympani nerve (CTN) is sometimes sacrificed during middle ear surgery, resulting in taste dysfunction. We examined the effect of placing an artificial nerve conduit, a polyglycolic acid (PGA)-collagen tube, across the gap in the section of the resected chorda tympani nerve (CTN) running through the tympanic cavity. Methods The CTN was reconstructed with a PGA-collagen tube in three patients with taste disturbance who underwent CTN resection. To evaluate the effect of the reconstruction procedure on the patients' gustatory function, we measured the patients' electrogustometry (EGM) thresholds. The patients were followed-up for at least two years. Results Gustatory function was completely restored in all of the patients after the reconstruction. The patients' EGM thresholds exhibited early improvements within one to two weeks and had returned to their normal ranges within three months. They subsequently remained stable throughout the two-year follow-up period. In a patient who underwent a second surgical procedure, it was found that the PGA-collagen tube used in the first surgical procedure had been absorbed and replaced by new CTN fibers with blood vessels on their surfaces. Conclusion These results suggest that reconstruction of the CTN with an artificial nerve conduit, a PGA-collagen tube, allows functional and morphological regeneration of the nerve and facilitates the recovery of taste function. PGA-collagen tubes might be useful for repairing CTNs that are resected during middle ear surgery. Further research is required to confirm these preliminary results although this is the first report to describe the successful regeneration of a nerve running through an aerial space. PMID:24691095

  3. Preclinical evaluations of acellular biological conduits for peripheral nerve regeneration

    PubMed Central

    Liao, I-Chien; Wan, Hua; Qi, Shijie; Cui, Cunqi; Patel, Paarun; Sun, Wendell

    2013-01-01

    Various types of natural biological conduits have been investigated as alternatives to the current surgical standard approach for peripheral nerve injuries. Autologous nerve graft, the current gold standard for peripheral nerve damage, is limited by clinical challenges such as donor-site morbidity and limited availability. The purpose of this study was to evaluate the efficacy of using acellular xenographic conduits (nerve, artery, and dermis) for the repair of a 1.2 cm critical size defect of peripheral nerve in a rodent model. Four months post surgery, the animal group receiving acellular artery as a nerve conduit showed excellent physiological outcome in terms of the prevention of muscle atrophy and foot ulcer. Histological assessment of the bridged site revealed excellent axon regeneration, as opposed to the nonrepaired control group or the group receiving dermal conduit. Finally, the study evaluated the potential improvement via the addition of undifferentiated mesenchymal stem cells into the artery conduit during the bridging procedure. The mesenchymal stem cell–dosed artery conduit group resulted in significantly higher concentration of regenerated axons over artery conduit alone, and exhibited accelerated muscle atrophy rescue. Our results demonstrated that xenographic artery conduits promoted excellent axonal regeneration with highly promising clinical relevance. PMID:23532671

  4. Photofabricated gelatin-based nerve conduits: nerve tissue regeneration potentials.

    PubMed

    Gámez, Eduardo; Goto, Yoshinobu; Nagata, Kengo; Iwaki, Toru; Sasaki, Tomio; Matsuda, Takehisa

    2004-01-01

    There is a strong demand for development of nerve guide conduit with prompt nerve regeneration potential for injury-induced nerve defect. Prior to study on nerve tissue engineering using Schwann cells or nerve stem cells, the effectiveness of photofabricated scaffolds based on photocurable gelatin was examined. This study describes the evaluation of in vivo nerve tissue regeneration potentials of three custom-designed and -fabricated prostheses (inner diameter, 1.2 mm; outer diameter, 2.4 mm; wall thickness, 0.60 mm; and length, 15 mm) made of photocured gelatin: a plain photocured gelatin tube (model I), a photocured gelatin tube packed with bioactive substances (laminin, fibronectin, and nerve growth factor) coimmobilized in a photocured gelatin rod (model II), and a photocured gelatin tube packed with bioactive substances coimmobilized in multifilament fibers (model III). These prostheses were implanted between the proximal and distal stumps 10 mm of the dissected right sciatic nerve of 70 adult male Lewis rats for up to 1 year. The highest regenerative potentials were found using the model III prosthesis, followed by the model II prosthesis. Markedly retarded neural regeneration was observed using the model I prosthesis. These were evaluated from the viewpoints of functional recovery, electrophysiological responses, and tissue morphological regeneration. The significance of the synergistic cooperative functions of multifilaments, which serve as a platform that provides contact guidance to direct longitudinal cell movement and tissue ingrowth and as a cell adhesive matrix with high surface area, and immobilized bioactive substances, which enhance nerve regeneration via biological stimulation, is discussed.

  5. Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

    PubMed Central

    Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.

    2013-01-01

    Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. PMID:23659607

  6. A silk sericin/silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve.

    PubMed

    Xie, Hongjian; Yang, Wen; Chen, Jianghai; Zhang, Jinxiang; Lu, Xiaochen; Zhao, Xiaobo; Huang, Kun; Li, Huili; Chang, Panpan; Wang, Zheng; Wang, Lin

    2015-10-28

    Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve.

  7. Neurotrophin releasing single and multiple lumen nerve conduits.

    PubMed

    Yang, Yang; De Laporte, Laura; Rives, Christopher B; Jang, Jae-Hyung; Lin, Wei-Chun; Shull, Kenneth R; Shea, Lonnie D

    2005-06-02

    Tissue engineering strategies for nerve repair employ polymer conduits termed guidance channels and bridges to promote regeneration for peripheral nerve injury and spinal cord injury, respectively. An approach for fabrication of nerve conduits with single and multiple lumens capable of controlled release of neurotrophic factors was developed. These conduits were fabricated from a mixture of poly(lactide-co-glycolide) (PLG) microspheres and porogen (NaCl) that was loaded into a mold and processed by gas foaming. The porosity and mechanical properties of the constructs were regulated by the ratio of porogen to polymer microsphere. The neurotrophin, nerve growth factor (NGF), was incorporated into the conduit by either mixing the protein with microspheres or encapsulating the protein within microspheres prior to gas foaming. A sustained release was observed for at least 42 days, with the release rate controlled by method of incorporation and polymer molecular weight. Released NGF retained its bioactivity, as demonstrated by its ability to stimulate neurite outgrowth from primary dorsal root ganglion (DRG). In vivo results indicate that conduits retain their original architecture, and allow for cellular infiltration into the channels. Polymer conduits with controllable lumen diameters and protein release may enhance nerve regeneration by guiding and stimulating neurite outgrowth.

  8. A novel bioactive nerve conduit for the repair of peripheral nerve injury

    PubMed Central

    Li, Bin-bin; Yin, Yi-xia; Yan, Qiong-jiao; Wang, Xin-yu; Li, Shi-pu

    2016-01-01

    The use of a nerve conduit provides an opportunity to regulate cytokines, growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects. We constructed a poly-D-L-lactide (PDLLA)-based nerve conduit that was modified using poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} and β-tricalcium phosphate. The effectiveness of this bioactive PDLLA-based nerve conduit was compared to that of PDLLA-only conduit in the nerve regeneration following a 10-mm sciatic nerve injury in rats. We observed the nerve morphology in the early period of regeneration, 35 days post injury, using hematoxylin-eosin and methylene blue staining. Compared with the PDLLA conduit, the nerve fibers in the PDLLA-based bioactive nerve conduit were thicker and more regular in size. Muscle fibers in the soleus muscle had greater diameters in the PDLLA bioactive group than in the PDLLA only group. The PDLLA-based bioactive nerve conduit is a promising strategy for repair after sciatic nerve injury. PMID:26981105

  9. Effect of an Epineurial-Like Biohybrid Nerve Conduit on Nerve Regeneration.

    PubMed

    Hsieh, Shu-Chih; Chang, Chen-Jung; Cheng, Wen-Tung; Tseng, Ting-Chen; Hsu, Shan-hui

    2016-01-01

    A novel approach of making a biomimetic nerve conduit was established by seeding adipose-derived adult stem cells (ADSCs) on the external wall of porous poly(d,l-lactic acid) (PLA) nerve conduits. The PLA conduits were fabricated using gas foaming salt and solvent-nonsolvent phase conversion. We examined the effect of two different porous structures (GS and GL) on ADSC growth and proliferation. The GS conduits had better structural stability, permeability, and porosity, as well as better cell viability at 4, 7, and 10 days. The epineurial-like tissue was grown from ADSC-seeded conduits cultured for 7 days in vitro and then implanted into 10-mm rat sciatic nerve defects for evaluation. The regeneration capacity and functional recovery were evaluated by histological staining, electrophysiology, walking track, and functional gait analysis after 6 weeks of implantation. Experimental data indicated that the autograft and ADSC-seeded GS conduits had better functional recovery than the blank conduits and ADSC-seeded GL conduits. The area of regenerated nerve and number of myelinated axons quantified based on the histology also indicated that the autograft and AGS groups performed better than the other two groups. We suggested that ADSCs may interact with endogenous Schwann cells and release neurotrophic factors to promote peripheral nerve regeneration. The design of the conduit may be critical for producing a biohybrid nerve conduit and to provide an epineurial-like support.

  10. Conductive PPY/PDLLA conduit for peripheral nerve regeneration

    PubMed Central

    Xu, Haixing; Holzwarth, Jeremy M.; Yan, Yuhua; Xu, Peihu; Zheng, Hua; Yin, Yixia; Li, Shipu; Ma, Peter X.

    2013-01-01

    The significant drawbacks and lack of success associated with current methods to treat critically sized nerve defects have led to increased interest in neural tissue engineering. Conducting polymers show great promise due to their electrical properties, and in the case of polypyrrole (PPY), its cell compatibility as well. Thus, the goal of this study is to synthesize a conducting composite nerve conduit with PPY and poly(D, L-lactic acid) (PDLLA), assess its ability to support the differentiation of rat pheochromocytoma 12 (PC12) cells in vitro, and determine its ability to promote nerve regeneration in vivo. Different amounts of PPY (5%, 10%, and 15%) are used to synthesize the conduits resulting in different conductivities (5.65, 10.40, and 15.56 ms/cm, respectively). When PC12 cells are seeded on these conduits and stimulated with 100 mV for 2 h, there is a marked increase in both the percentage of neurite-bearing cells and the median neurite length as the content of PPY increased. More importantly, when the PPY/PDLLA nerve conduit was used to repair a rat sciatic nerve defect it performed similarly to the gold standard autologous graft. These promising results illustrate the potential that this PPY/PDLLA conducting composite conduit has for neural tissue engineering. PMID:24138830

  11. Differential expression of GAP-43 and neurofilament during peripheral nerve regeneration through bio-artificial conduits.

    PubMed

    Carriel, Víctor; Garzón, Ingrid; Campos, Antonio; Cornelissen, Maria; Alaminos, Miguel

    2017-02-01

    Nerve conduits are promising alternatives for repairing nerve gaps; they provide a close microenvironment that supports nerve regeneration. In this sense, histological analysis of axonal growth is a determinant to achieve successful nerve regeneration. To evaluate this process, the most-used immunohistochemical markers are neurofilament (NF), β-III tubulin and, infrequently, GAP-43. However, GAP-43 expression in long-term nerve regeneration models is still poorly understood. In this study we analysed GAP-43 expression and its correlation with NF and S-100, using three tissue-engineering approaches with different regeneration profiles. A 10 mm gap was created in the sciatic nerve of 12 rats and repaired using collagen conduits or collagen conduits filled with fibrin-agarose hydrogels or with hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs). After 12 weeks the conduits were harvested for histological analysis. Our results confirm the long-term expression of GAP-43 in all groups. The expression of GAP-43 and NF was significantly higher in the group with ADMSCs. Interestingly, GAP-43 was observed in immature, newly formed axons and NF in thicker and mature axons. These proteins were not co-expressed, demonstrating their differential expression in newly formed nerve fascicles. Our descriptive and quantitative histological analysis of GAP-43 and NFL allowed us to determine, with high accuracy, the heterogenic population of axons at different stages of maturation in three tissue-engineering approaches. Finally, to perform a complete assessment of axonal regeneration, the quantitative immunohistochemical evaluation of both GAP-43 and NF could be a useful quality control in tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Sciatic nerve repair by reinforced nerve conduits made of gelatin-tricalcium phosphate composites.

    PubMed

    Yang, Yi-Chin; Shen, Chiung-Chyi; Cheng, Hsu-Chen; Liu, Bai-Shuan

    2011-02-01

    This study proposes a biodegradable GGT composite nerve guide conduit containing genipin-cross-linked gelatin and tricalcium phosphate (TCP) ceramic particles in peripheral nerve regeneration. The proposed genipin-cross-linked gelatin annexed with TCP ceramic particles (GGT) conduit was dark bluish and round with a rough and compact surface. Water uptake and swelling tests indicated that the hydrated GGT conduit exhibited increased stability with not collapsing or stenosis. The GGT conduit had higher mechanical properties than the genipin-cross-linked gelatin without TCP ceramic particles (GG) conduit and served as a better nerve guide conduit. Cytotoxicity tests revealed that the GGT conduit was not toxic and that it promoted the viability and growth of neural stem cells. The experiments in this study confirmed the effectiveness of the GGT conduit as a guidance channel for repairing a 10-mm gap in rat sciatic nerve. Walking track analysis showed a significantly higher sciatic function index score and better toe spreading development in the GGT group than in the silicone group 8 weeks after implantation. Gross examination revealed that the diameter of the intratubular newly formed nerve fibers in GGT conduits exceeded those in silicone tubes after the implantation period. Histological observations revealed that the morphology and distribution patterns of nerve fibers in the GGT conduits at 8 weeks after implantation were similar to those of normal nerves. The quantitative results indicated the superiority of the conduits over the silicone tubes. Motor functional and histomorphometric assessments demonstrate that the proposed GGT conduit is a suitable candidate for peripheral nerve repair. 2010 Wiley Periodicals, Inc.

  13. Enhancing Peripheral Nerve Regeneration with a Novel Drug Delivering Nerve Conduit

    DTIC Science & Technology

    2014-10-01

    Products 21 7. Participants & Other Collaborating Organizations 22 8. Special Reporting Requirements 23 9. Appendices 24 3... Corning Inc) were also added to the nerve conduit. Figure 2 illustrates the nerve conduit in which the drug (NGF) stored in the orifice between...7525 DLG 7E, Evonik). The PLGA was dissolved in acetone and ethanol and conduits were then formed and emulsified in water. 15µm diffusion holes

  14. Peripheral nerve regeneration with conduits: use of vein tubes

    PubMed Central

    Sabongi, Rodrigo Guerra; Fernandes, Marcela; dos Santos, João Baptista Gomes

    2015-01-01

    Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit. PMID:26170802

  15. Orientated Guidance of Peripheral Nerve Regeneration Using Conduits with a Microtube Array Sheet (MTAS).

    PubMed

    Wang, Yueming; Wang, Wenjin; Wo, Yan; Gui, Ting; Zhu, Hao; Mo, Xiumei; Chen, Chien-Chung; Li, Qingfeng; Ding, Wenlong

    2015-04-29

    Material surface topography has been shown to affect the biological behavior of cells in vitro; however, the in vivo effect on peripheral nerve regeneration has not been explored. Here, we studied the potential of a microtube array sheet (MTAS) with a unique longitudinal surface topography to promote peripheral nerve regeneration efficiency, both in vivo and in vitro. Schwann cells, spinal cord motor neurons, and dorsal root ganglion neurons were seeded on the MTAS to study the effect of the construct on the biological properties and behaviors of neural cells. The MTAS guided the oriented migration of Schwann cells without affecting other critical biological properties, such as proliferation and neurotrophin expression. In addition, the MTAS guided the directed extension of neurites from both types of neurons. Next, we tested the capability of the MTAS to facilitate peripheral nerve regeneration by bridging a 10 mm sciatic nerve defect in rats with a nerve conduit equipped with an MTAS lining. The MTAS significantly promoted peripheral nerve regeneration, as suggested by the greater fiber caliber in the midconduit and the greater abundance of fibers in nerve segment distal to the conduit. Moreover, scanning electron microscopy (SEM) analysis suggested the orientated guidance of nerve regeneration by the MTAS, as indicated by the smaller eccentricity of the nerve fibers and the concordant arrangement of the collagen fiber in both the fibers and the matrix in the MTAS group. Our results collectively suggest that the conduits with the MTAS developed in this study have significant potential for facilitating peripheral nerve regeneration by modifying critical biological behaviors and guiding orientated nerve growth.

  16. Engineering a multimodal nerve conduit for repair of injured peripheral nerve

    NASA Astrophysics Data System (ADS)

    Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

    2013-02-01

    Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

  17. Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve defects

    PubMed Central

    Biazar, Esmaeil; Keshel, Saeed Heidari; Pouya, Majid; Rad, Hadi; Nava, Melody Omrani; Azarbakhsh, Mohammad; Hooshmand, Shirin

    2013-01-01

    It has been confirmed that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson's trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit is suitable for repair of long-segment sciatic nerve defects. PMID:25206536

  18. A biosynthetic nerve guide conduit based on silk/SWNT/fibronectin nanocomposite for peripheral nerve regeneration.

    PubMed

    Mottaghitalab, Fatemeh; Farokhi, Mehdi; Zaminy, Arash; Kokabi, Mehrdad; Soleimani, Masoud; Mirahmadi, Fereshteh; Shokrgozar, Mohammad Ali; Sadeghizadeh, Majid

    2013-01-01

    As a contribution to the functionality of nerve guide conduits (NGCs) in nerve tissue engineering, here we report a conduit processing technique through introduction and evaluation of topographical, physical and chemical cues. Porous structure of NGCs based on freeze-dried silk/single walled carbon nanotubes (SF/SWNTs) has shown a uniform chemical and physical structure with suitable electrical conductivity. Moreover, fibronectin (FN) containing nanofibers within the structure of SF/SWNT conduits produced through electrospinning process have shown aligned fashion with appropriate porosity and diameter. Moreover, fibronectin remained its bioactivity and influenced the adhesion and growth of U373 cell lines. The conduits were then implanted to 10 mm left sciatic nerve defects in rats. The histological assessment has shown that nerve regeneration has taken places in proximal region of implanted nerve after 5 weeks following surgery. Furthermore, nerve conduction velocities (NCV) and more myelinated axons were observed in SF/SWNT and SF/SWNT/FN groups after 5 weeks post implantation, indicating a functional recovery for the injured nerves. With immunohistochemistry, the higher S-100 expression of Schwann cells in SF/SWNT/FN conduits in comparison to other groups was confirmed. In conclusion, an oriented conduit of biocompatible SF/SWNT/FN has been fabricated with acceptable structure that is particularly applicable in nerve grafts.

  19. A Biosynthetic Nerve Guide Conduit Based on Silk/SWNT/Fibronectin Nanocomposite for Peripheral Nerve Regeneration

    PubMed Central

    Mottaghitalab, Fatemeh; Farokhi, Mehdi; Zaminy, Arash; Kokabi, Mehrdad; Soleimani, Masoud; Mirahmadi, Fereshteh

    2013-01-01

    As a contribution to the functionality of nerve guide conduits (NGCs) in nerve tissue engineering, here we report a conduit processing technique through introduction and evaluation of topographical, physical and chemical cues. Porous structure of NGCs based on freeze-dried silk/single walled carbon nanotubes (SF/SWNTs) has shown a uniform chemical and physical structure with suitable electrical conductivity. Moreover, fibronectin (FN) containing nanofibers within the structure of SF/SWNT conduits produced through electrospinning process have shown aligned fashion with appropriate porosity and diameter. Moreover, fibronectin remained its bioactivity and influenced the adhesion and growth of U373 cell lines. The conduits were then implanted to 10 mm left sciatic nerve defects in rats. The histological assessment has shown that nerve regeneration has taken places in proximal region of implanted nerve after 5 weeks following surgery. Furthermore, nerve conduction velocities (NCV) and more myelinated axons were observed in SF/SWNT and SF/SWNT/FN groups after 5 weeks post implantation, indicating a functional recovery for the injured nerves. With immunohistochemistry, the higher S-100 expression of Schwann cells in SF/SWNT/FN conduits in comparison to other groups was confirmed. In conclusion, an oriented conduit of biocompatible SF/SWNT/FN has been fabricated with acceptable structure that is particularly applicable in nerve grafts. PMID:24098649

  20. Design of barrier coatings on kink-resistant peripheral nerve conduits

    PubMed Central

    Clements, Basak Acan; Bushman, Jared; Murthy, N Sanjeeva; Ezra, Mindy; Pastore, Christopher M; Kohn, Joachim

    2016-01-01

    Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1) electrospinning a layer of polymer fibers onto the surface of the conduit and (2) coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery. PMID:26977288

  1. Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth

    NASA Astrophysics Data System (ADS)

    Lin, Keng-Min; Shea, Jill; Gale, Bruce K.; Sant, Himanshu; Larrabee, Patti; Agarwal, Jay

    2016-04-01

    Nerve injury can occur due to penetrating wounds, compression, traumatic stretch, and cold exposure. Despite prompt repair, outcomes are dismal. In an attempt to help resolve this challenge, in this work, a poly-lactic-co-glycolic acid (PLGA) nerve conduit with associated biodegradable drug reservoir was designed, fabricated, and tested. Unlike current nerve conduits, this device is capable of fitting various clinical scenarios by delivering different drugs without reengineering the whole system. To demonstrate the potential of this device for nerve repair, a series of experiments were performed using nerve growth factor (NGF). First, an NGF dosage curve was developed to determine the minimum NGF concentration for optimal axonal outgrowth on chick dorsal root ganglia (DRG) cells. Next, PLGA devices loaded with NGF were evaluated for sustained drug release and axon growth enhancement with the released drug. A 20 d in vitro release test was conducted and the nerve conduit showed the ability to meet and maintain the minimum NGF requirement determined previously. Bioactivity assays of the released NGF showed that drug released from the device between the 15th and 20th day could still promote axon growth (76.6-95.7 μm) in chick DRG cells, which is in the range of maximum growth. These novel drug delivery conduits show the ability to deliver NGF at a dosage that efficiently promotes ex vivo axon growth and have the potential for in vivo application to help bridge peripheral nerve gaps.

  2. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis

    PubMed Central

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min

    2013-01-01

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair. PMID:25206505

  3. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis.

    PubMed

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min

    2013-07-25

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair.

  4. Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits

    PubMed Central

    Anderson, Matthew; Shelke, Namdev B.; Manoukian, Ohan S.; Yu, Xiaojun; McCullough, Louise D.; Kumbar, Sangamesh G.

    2017-01-01

    Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration. PMID:27278739

  5. Laminin-modified and aligned PHBV/PEO nanofibrous nerve conduits promote peripheral nerve regeneration.

    PubMed

    Zhang, Xiao-Feng; Liu, Hai-Xia; Ortiz, Lazarus Santiago; Xiao, Zhong-Dang; Huang, Ning-Ping

    2016-11-12

    Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) has received much attention for its biodegradability and biocompatibility, characteristics which are required in tissue engineering. In this study, polyethylene oxide (PEO)-incorporated PHBV nanofibers with random or aligned orientation were obtained by electrospinning. For further use in vivo, the nanofiber films were made into nerve conduits after treated with NH3 plasma, which could improve the hydrophilicity of inner surfaces of nerve conduits and then facilitate laminin adsorption via electrostatic interaction for promoting cell adhesion and proliferation. Morphology of the surfaces of modified PHBV/PEO nanofibrous scaffolds were examined by scanning electron microscopy. Schwann cell viability assay was conducted and the results confirmed that the functionalized nanofibers were favorable for cell growth. Morphology of Schwann cells cultured on scaffolds showed that aligned nanofibrous scaffolds provided topographical guidance for cell orientation and elongation. Furthermore, 3D PHBV/PEO nerve conduits made from aligned and random-oriented nanofibers were implanted into 12-mm transected sciatic nerve rat model and subsequent analysis were conducted at 1 and 2 months post-surgery. The above functionalized PHBV/PEO scaffolds provide a novel and promising platform for peripheral nerve regeneration.

  6. Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration

    NASA Astrophysics Data System (ADS)

    Rutkowski, Gregory E.; Miller, Cheryl A.; Jeftinija, Srdija; Mallapragada, Surya K.

    2004-09-01

    This paper describes a novel biodegradable conduit that provides a combination of physical, chemical and biological cues at the cellular level to facilitate peripheral nerve regeneration. The conduit consists of a porous poly(D,L-lactic acid) (PDLLA) tubular support structure with a micropatterned inner lumen. Schwann cells were pre-seeded into the lumen to provide additional trophic support. Conduits with micropatterned inner lumens pre-seeded with Schwann cells (MS) were fabricated and compared with three types of conduits used as controls: M (conduits with micropatterned inner lumens without pre-seeded Schwann cells), NS (conduits without micropatterned inner lumens pre-seeded with Schwann cells) and N (conduits without micropatterned inner lumens, without pre-seeded Schwann cells). The conduits were implanted in rats with 1 cm sciatic nerve transections and the regeneration and functional recovery were compared in the four different cases. The number or size of regenerated axons did not vary significantly among the different conduits. The time of recovery, and the sciatic function index, however, were significantly enhanced using the MS conduits, based on qualitative observations as well as quantitative measurements using walking track analysis. This demonstrates that biodegradable micropatterned conduits pre-seeded with Schwann cells that provide a combination of physical, chemical and biological guidance cues for regenerating axons at the cellular level offer a better alternative for repairing sciatic nerve transactions than conventional biodegradable conduits.

  7. Salicylic acid-based poly(anhydride-ester) nerve guidance conduits: Impact of localized drug release on nerve regeneration.

    PubMed

    Lee, Yong S; Griffin, Jeremy; Masand, Shirley N; Shreiber, David I; Uhrich, Kathryn E

    2016-04-01

    Nerve guidance conduits (NGCs) can serve as physical scaffolds aligning and supporting regenerating cells while preventing scar tissue formation that often interferes with the regeneration process. Numerous studies have focused on functionalizing NGCs with neurotrophic factors, for example, to support nerve regeneration over longer gaps, but few directly incorporate therapeutic agents. Herein, we fabricated NGCs from a polyanhydride comprised of salicylic acid (SA), a nonsteroidal anti-inflammatory drug, then performed in vitro and in vivo assays. In vitro studies included cytotoxicity, anti-inflammatory response, and NGC porosity measurements. To prepare for implantation, type I collagen hydrogels were used as NGC luminal fillers to further enhance the axonal regeneration process. For the in vivo studies, SA-NGCs were implanted in femoral nerves of mice for 16 weeks and evaluated for functional recovery. The SA-based NGCs functioned as both a drug delivery vehicle capable of reducing inflammation and scar tissue formation because of SA release as well as a tissue scaffold that promotes peripheral nerve regeneration and functional recovery.

  8. Fabrication and evaluation of a biodegradable proanthocyanidin-crosslinked gelatin conduit in peripheral nerve repair.

    PubMed

    Liu, Bai-Shuan

    2008-12-15

    This study proposed a novel and biodegradable nerve guide conduit in its applicability to peripheral nerve regeneration. A naturally occurring proanthocyanidin (PA) was selected as a cross-linking reagent in preparing the PA-crosslinked gelatin (PCG) conduit. Experimental results indicate that 5 wt % of PA was optimal in the complete cross-linking reaction in the PCG conduit. The PCG conduit was brownish and round with a rough outer surface whereas its inner lumen was smooth. The cross-linked networks of the PCG conduit resisted enzymatic hydrolysis under in vitro degradation studies. PA and gelatin were released from the soaked PCG conduit. During the release phase, the concentrations of PA, gelatin, and PCG-soaking solutions were not only nontoxic but also promoted the viability and growth of Schwann cells. The PCG conduit more effectively supported cell attachment and growth. The effectiveness of the PCG conduit as a guidance channel was studied when it was used to repair a 10 mm gap in the rat sciatic nerve. Throughout the 8-week experimental period, the peak amplitude and area under the muscle action potential curve both increased with the recovery period. Histological observations revealed that various regenerated nerve fibers crossed through and beyond the gap region. These results suggest that the PCG conduit can be a candidate for peripheral nerve repair. 2008 Wiley Periodicals, Inc.

  9. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

    NASA Astrophysics Data System (ADS)

    Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

    2016-08-01

    Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use.

  10. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

    PubMed Central

    Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

    2016-01-01

    Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use. PMID:27572698

  11. Nerve guidance conduits from aligned nanofibers: improvement of nerve regeneration through longitudinal nanogrooves on a fiber surface.

    PubMed

    Huang, Chen; Ouyang, Yuanming; Niu, Haitao; He, Nanfei; Ke, Qinfei; Jin, Xiangyu; Li, Dawei; Fang, Jun; Liu, Wanjun; Fan, Cunyi; Lin, Tong

    2015-04-08

    A novel fibrous conduit consisting of well-aligned nanofibers with longitudinal nanogrooves on the fiber surface was prepared by electrospinning and was subjected to an in vivo nerve regeneration study on rats using a sciatic nerve injury model. For comparison, a fibrous conduit having a similar fiber alignment structure without surface groove and an autograft were also conducted in the same test. The electrophysiological, walking track, gastrocnemius muscle, triple-immunofluorescence, and immunohistological analyses indicated that grooved fibers effectively improved sciatic nerve regeneration. This is mainly attributed to the highly ordered secondary structure formed by surface grooves and an increase in the specific surface area. Fibrous conduits made of longitudinally aligned nanofibers with longitudinal nanogrooves on the fiber surface may offer a new nerve guidance conduit for peripheral nerve repair and regeneration.

  12. Effect of surface pore structure of nerve guide conduit on peripheral nerve regeneration.

    PubMed

    Oh, Se Heang; Kim, Jin Rae; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang; Lee, Jin Ho

    2013-03-01

    Polycaprolactone (PCL)/Pluronic F127 nerve guide conduits (NGCs) with different surface pore structures (nano-porous inner surface vs. micro-porous inner surface) but similar physical and chemical properties were fabricated by rolling the opposite side of asymmetrically porous PCL/F127 membranes. The effect of the pore structure on peripheral nerve regeneration through the NGCs was investigated using a sciatic nerve defect model of rats. The nerve fibers and tissues were shown to have regenerated along the longitudinal direction through the NGC with a nano-porous inner surface (Nanopore NGC), while they grew toward the porous wall of the NGC with a micro-porous inner surface (Micropore NGC) and, thus, their growth was restricted when compared with the Nanopore NGC, as investigated by immunohistochemical evaluations (by fluorescence microscopy with anti-neurofilament staining and Hoechst staining for growth pattern of nerve fibers), histological evaluations (by light microscopy with Meyer's modified trichrome staining and Toluidine blue staining and transmission electron microscopy for the regeneration of axon and myelin sheath), and FluoroGold retrograde tracing (for reconnection between proximal and distal stumps). The effect of nerve growth factor (NGF) immobilized on the pore surfaces of the NGCs on nerve regeneration was not so significant when compared with NGCs not containing immobilized NGF. The NGC system with different surface pore structures but the same chemical/physical properties seems to be a good tool that is used for elucidating the surface pore effect of NGCs on nerve regeneration.

  13. [Large diameter nerve conduits use in the upper limb: report of four cases and literature review].

    PubMed

    Jardin, E; Huard, S; Chastel, R; Uhring, J; Obert, L

    2011-12-01

    Defects of the median, ulnar or radial nerves in the forearm, can be treated by conventional nerve grafts, or by interposing a synthetic guide such as nerve conduits. Wounds without nerve loss treated with simple suture may be supplemented by sleeving to prevent the nerve irritation symptoms using a nerve conduit or a vein sleeve. We studied the results of nerve conduits in both cases in a single-center retrospective study. Four patients underwent surgery with placement of a nerve conduit in the forearm, between May 2007 and January 2011. All patients were reviewed by the same examiner. Pain, tenderness, motor (Medical Research Council classification, MRC), time to return to work and self-evaluation by the patient were measured. The averages of these data were calculated and compared with results of other studies in the literature, the nerve grafts for defects and the Socket joints for venous ulcers. The decrease is on average 30 months (2 years). The defect never exceeds 40mm and is 22mm on average. According to the classification MRC, sensitivity found after inserting nerve conduits in the forearm after a defect is excellent (S4) for two of three patients and good (S3) for the third. Motor results were very good (M4 and M3 for one patient) andM2 for the other. As for the insertion of a nerve conduit as a sleeve, the result is good in terms of sensitivity (S3) and excellent in terms of motor (M5) for our case in the study. For our small group of patients with neuroma we obtained, results similar to those published in the literature with conventional techniques. The nerve conduits seem to give results similar to conventional techniques, in situations of defects or neuromasin the forearm, with a diameter greater than 2mm, but defects of less than 30mm. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  14. Sciatic nerve repair by microgrooved nerve conduits made of chitosan-gold nanocomposites.

    PubMed

    Lin, Yi-Lo; Jen, Jui-Chi; Hsu, Shan-hui; Chiu, Ing-Ming

    2008-12-01

    To better direct the repair of peripheral nerve after injury, an implant consisting of a multicomponent micropatterned conduit seeded with NSC was designed. The mechanical properties of the chi-Au nanocomposites were tested. In vitro, the effect of chi-Au on cell behavior (NSC and glial cell line C6) and the influence of micropattern on cell alignment were evaluated. In vivo, the micropatterned conduits with/without the preseeded NSC were implanted to bridge a 10-mm-long defect of the sciatic nerve in 9 male Sprague-Dawley rats. The repair outcome was investigated 6 weeks after the surgery. Based on the dynamic modulus, chitosan with 50 ppm or more gold was a stronger material than others. In vitro, gold at 25 or 50 ppm led to better cell performance for NSC; and gold at 50 ppm gave better cell performance for C6. On the microgrooved substrate, the NSC had elongated processes oriented parallel to the grooves, whereas the NSC on the nonpatterned surfaces did not exhibit a particular bias in alignment. In vivo, the number of regenerated axons, the regenerated area, and the number of blood vessels were significantly higher in the NSC-preseeded conduit. Modification of the chitosan matrix by gold nanoparticles not only provides the mechanical strength but also affects the cellular response. The preliminary in vivo data demonstrated that the biodegradable micropatterned conduits preseeded with NSC provided a combination of physical and biological guidance cues for regenerating axons at the cellular level and offered a better alternative for repairing sciatic nerve transactions.

  15. A Nerve Conduit Containing a Vascular Bundle and Implanted With Bone Marrow Stromal Cells and Decellularized Allogenic Nerve Matrix.

    PubMed

    Kaizawa, Yukitoshi; Kakinoki, Ryosuke; Ikeguchi, Ryosuke; Ohta, Soichi; Noguchi, Takashi; Takeuchi, Hisataka; Oda, Hiroki; Yurie, Hirofumi; Matsuda, Shuichi

    2017-02-16

    Cells, scaffolds, growth factors, and vascularity are essential for nerve regeneration. Previously, we reported that the insertion of a vascular bundle and the implantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a nerve conduit promoted peripheral nerve regeneration. In this study, the efficacy of nerve conduits containing a vascular bundle, BM-MSCs, and thermally decellularized allogenic nerve matrix (DANM) was investigated using a rat sciatic nerve model with a 20-mm defect. Lewis rats were used as the sciatic nerve model and for the preparation of BM-MSCs, and Dark Agouti rats were used for the preparation of the DANM. The revascularization and the immunogenicity of the DANM were investigated histologically. The regeneration of nerves through nerve conduits containing vessels, BM-MSCs, and DANM (VBD group) was evaluated based on electrophysiological, morphometric, and reinnervated muscle weight measurements and compared with that of vessel-containing conduits that were implanted with BM-MSCs (VB group). The DANM that was implanted into vessel-containing tubes (VCTs) was revascularized by neovascular vessels that originated from the inserted vascular bundle 5-7 days after surgery. The number of CD8+ cells found in the DANM in the VCT was significantly smaller than that detected in the untreated allogenic nerve segment. The regenerated nerve in the VBD group was significantly superior to that in the VB group with regard to the amplitude of the compound muscle action potential detected in the pedal adductor muscle; the number, diameter, and myelin thickness of the myelinated axons; and the tibialis anterior muscle weight at 12 and 24 weeks. The additional implantation of the DANM into the BM-MSC-implanted VCT optimized the axonal regeneration through the conduit. Nerve conduits constructed with vascularity, cells, and scaffolds could be an effective strategy for the treatment of peripheral nerve injuries with significant segmental defects.

  16. A Silk Fibroin/Collagen Nerve Scaffold Seeded with a Co-Culture of Schwann Cells and Adipose-Derived Stem Cells for Sciatic Nerve Regeneration.

    PubMed

    Xu, Yunqiang; Zhang, Zhenhui; Chen, Xuyi; Li, Ruixin; Li, Dong; Feng, Shiqing

    2016-01-01

    As a promising alternative to autologous nerve grafts, tissue-engineered nerve grafts have been extensively studied as a way to bridge peripheral nerve defects and guide nerve regeneration. The main difference between autogenous nerve grafts and tissue-engineered nerve grafts is the regenerative microenvironment formed by the grafts. If an appropriate regenerative microenvironment is provided, the repair of a peripheral nerve is feasible. In this study, to mimic the body's natural regenerative microenvironment closely, we co-cultured Schwann cells (SCs) and adipose-derived stem cells (ADSCs) as seed cells and introduced them into a silk fibroin (SF)/collagen scaffold to construct a tissue-engineered nerve conduit (TENC). Twelve weeks after the three different grafts (plain SF/collagen scaffold, TENC, and autograft) were transplanted to bridge 1-cm long sciatic nerve defects in rats, a series of electrophysiological examinations and morphological analyses were performed to evaluate the effect of the tissue-engineered nerve grafts on peripheral nerve regeneration. The regenerative outcomes showed that the effect of treatment with TENCs was similar to that with autologous nerve grafts but superior to that with plain SF/collagen scaffolds. Meanwhile, no experimental animals had inflammation around the grafts. Based on this evidence, our findings suggest that the TENC we developed could improve the regenerative microenvironment and accelerate nerve regeneration compared to plain SF/collagen and may serve as a promising strategy for peripheral nerve repair.

  17. Can a Small Intestine Segment Be an Alternative Biological Conduit for Peripheral Nerve Regeneration?

    PubMed

    Arda, Mehmet S; Koçman, Emre A; Özkara, Emre; Söztutar, Erdem; Özatik, Orhan; Köse, Aydan; Çetin, Cengiz

    2017-05-05

    Autologous nerve grafts are used to bridge peripheral nerve defects. Limited sources and donor site morbidity are the major problems with peripheral nerve grafts. Although various types of autologous grafts such as arteries, veins and muscles have been recommended, an ideal conduit has not yet been described. To investigate the effectiveness of a small intestinal conduit for peripheral nerve defects. Animal experimentation. Twenty-one rats were divided into three groups (n=7). Following anaesthesia, sciatic nerve exploration was performed in the Sham group. The 10 mm nerve gap was bridged with a 15 mm ileal segment in the small intestinal conduit group and the defect was replaced with orthotopic nerve in autologous nerve graft group. The functional recovery was tested monthly by walking-track analysis and the sciatic functional index. Histological evaluation was performed on the 12th week. Sciatic functional index tests are better in autologous nerve graft group (-55.09±6.35); however, during follow-up, progress in sciatic functional index was demonstrated, along with axonal regeneration and innervation of target muscles in the small intestinal conduit group (-76.36±12.08) (p<0.05). In histologic sections, distinctive sciatic nerve regeneration was examined in the small intestinal conduit group. The expression of S-100 and neurofilament was observed in small intestinal conduit group but was less organised than in the autologous nerve graft group. Although the counted number (7459.79±1833.50 vs. 4226.51±1063.06 mm2), measured diameter [2.19 (2.15-2.88) vs. 1.74 (1.50-2.09) µm] and myelin sheath thickness [1.18 (1.09-1.44) vs. 0.66 (0.40-1.07) µm] of axons is significantly high in the middle sections of autologous nerve graft compared to the small intestinal conduit group, respectively (p<0.05), the peripheral nerve regeneration was also observed in the small intestinal conduit group. Small intestinal conduit should not be considered as an alternative to

  18. Use of nerve conduits for peripheral nerve injury repair: A Web of Science-based literature analysis.

    PubMed

    Nan, Jinniang; Hu, Xuguang; Li, Hongxiu; Zhang, Xiaonong; Piao, Renjing

    2012-12-15

    To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.

  19. New nerve regeneration strategy combining laminin-coated chitosan conduits and stem cell therapy.

    PubMed

    Hsu, Sung-Hao; Kuo, Wen-Chun; Chen, Yu-Tzu; Yen, Chen-Tung; Chen, Ying-Fang; Chen, Ko-Shao; Huang, Wen-Cheng; Cheng, Henrich

    2013-05-01

    Nerve regeneration remains a difficult challenge due to the lack of safe and efficient matrix support. We designed a laminin (LN)-modified chitosan multi-walled nerve conduit combined with bone marrow stem cell (BMSC) grating to bridge a 10 mm long gap in the sciatic nerve of Sprague-Dawley rats. The repair outcome was monitored during 16 weeks after surgery. Successful grafting of LN onto the chitosan film, confirmed by immunolocalization, significantly improved cell adhesion. In vivo study showed that newly formed nerve cells covered the interior of the conduit to connect the nerve gap successfully in all groups. The rats implanted with the conduit combined with BMSCs showed the best results, in terms of nerve regrowth, muscle mass of gastrocnemius, function recovery and tract tracing. Neuroanatomical horseradish peroxidase tracer analysis of motor neurons in the lumbar spinal cord indicated that the amount and signal intensity were significantly improved. Furthermore, BMSCs suppressed neuronal cell death and promoted regeneration by suppressing the inflammatory and fibrotic response induced by chitosan after long-term implantation. In summary, this study suggests that LN-modified chitosan multi-walled nerve conduit combined with BMSCs is an efficient and safe conduit matrix for nerve regeneration. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells.

    PubMed

    Jenkins, Phillip M; Laughter, Melissa R; Lee, David J; Lee, Young M; Freed, Curt R; Park, Daewon

    2015-12-01

    Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension.

  1. A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells

    NASA Astrophysics Data System (ADS)

    Jenkins, Phillip M.; Laughter, Melissa R.; Lee, David J.; Lee, Young M.; Freed, Curt R.; Park, Daewon

    2015-06-01

    Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension.

  2. Biodegradable fibrin conduit promotes long-term regeneration after peripheral nerve injury in adult rats.

    PubMed

    Pettersson, Jonas; Kalbermatten, Daniel; McGrath, Aleksandra; Novikova, Liudmila N

    2010-11-01

    Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. Biosynthetic neural conduits could be an alternative treatment strategy in such injuries. The present study investigates the long-term effects of a tubular fibrin conduit on neuronal regeneration, axonal sprouting and recovery of muscle weight following peripheral nerve injury and repair in adult rats. Sciatic axotomy was performed proximally in the thigh to create a 10-mm gap between the nerve stumps. The injury gap was bridged by using a 14-mm-long fibrin glue conduit, entubulating 2 mm of the nerve stump at each end. A reversed autologous nerve graft was used as a control. The regenerative response from sensory and motor neurones was evaluated following retrograde labelling with Fast Blue fluorescent tracer. In control experiments, at 16 weeks following peripheral nerve grafting, 5184 (±574 standard error of mean (SEM)) sensory dorsal root ganglion neurones and 1001 (±37 SEM) spinal motor neurones regenerated across the distal nerve-graft interface. The fibrin conduit promoted regeneration of 60% of sensory neurones and 52% of motor neurones when compared to the control group. The total number of myelinated axons in the distal nerve stump in the fibrin-conduit group reached 86% of the control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89% of the controls, respectively. The present results suggest that a tubular fibrin conduit can be used to promote neuronal regeneration following peripheral nerve injury. Copyright © 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  3. Regenerative effect of adipose tissue-derived stem cells transplantation using nerve conduit therapy on sciatic nerve injury in rats.

    PubMed

    Liu, Bai-Shuan; Yang, Yi-Chin; Shen, Chiung-Chyi

    2014-05-01

    This study proposed a biodegradable GGT nerve conduit containing genipin crosslinked gelatin annexed with tricalcium phosphate (TCP) ceramic particles for the regeneration of peripheral nerves. Cytotoxicity tests revealed that GGT-extracts were non-toxic and promoted proliferation and neuronal differentiation in the induction of stem cells (i-ASCs) derived from adipose tissue. Furthermore, the study confirmed the effectiveness of a GGT/i-ASCs nerve conduit as a guidance channel in the repair of a 10-mm gap in the sciatic nerve of rats. At eight weeks post-implantation, walking track analysis showed a significantly higher sciatic function index (SFI) (P < 0.05) in the GGT/i-ASC group than in the autograft group. Furthermore, the mean recovery index of compound muscle action potential (CMAP) differed significantly between GGT/i-ASCs and autograft groups (P < 0.05), both of which were significantly superior to the GGT group (P < 0.05). No severe inflammatory reaction in the peripheral nerve tissue at the site of implantation was observed in either group. Histological observation and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/i-ASCs nerve conduits were similar to those of the autografts. These promising results achieved through a combination of regenerative cells and GGT nerve conduits suggest the potential value in the future development of clinical applications for the treatment of peripheral nerve injury.

  4. An animal model of peripheral nerve regeneration after the application of a collagen-polyvinyl alcohol scaffold and mesenchymal stem cells.

    PubMed

    Marinescu, Silviu Adrian; Zărnescu, Otilia; Mihai, Ioana Ruxandra; Giuglea, Carmen; Sinescu, Ruxandra Diana

    2014-01-01

    Extensive nerve injuries often leading to nerve gaps can benefit, besides the gold standard represented by autologous nerve grafts, by the inciting field of tissue engineering. To enhance the role of biomaterials in nerve regeneration, the nerve conduits are associated with Schwann or Schwann-like cells. In this study, we evaluated rat sciatic nerve regeneration, by using a biodegradable nerve guide composed of Collagen (COL) and Polyvinyl Alcohol (PVA), associated with mesenchymal stem cells (MSC). After the exposure of the rat sciatic nerve, a nerve gap was created by excising 1 cm of the nerve. Three experimental groups were used for nerve gap bridging: autografts, nerve conduits filled with medium culture and nerve conduits filled with MSC. The methods of sensory and motor assessment consisted of the functional evaluation of sciatic nerve recovery - toe-spread, pinprick tests and gastrocnemius muscle index (GMI). The histological and immunocytochemical analysis of the probes that were harvested from the repair site was performed at 12 weeks. Successful nerve regeneration was noted in all three groups at the end of the 12th week. The functional and immunocytochemical results suggested that COL-PVA tubes supported with mesenchymal stem cells could be considered similar to autologous nerve grafts in peripheral nerve regeneration, without the drawbacks of the last ones. The functional results were better for the autografts and the ultrastructural data were better for the nerve conduits, but there were not noticed any statistical differences.

  5. A new nerve guide conduit material composed of a biodegradable poly(phosphoester).

    PubMed

    Wang, S; Wan, A C; Xu, X; Gao, S; Mao, H Q; Leong, K W; Yu, H

    2001-05-01

    There is a resurgence of interest in the development of degradable and biocompatible polymers for fabrication of nerve guide conduits (NGCs) in recent years. Poly(phosphoester) (PPE) polymers are among the attractive candidates in this context, in view of their high biocompatibility, adjustable biodegradability, flexibility in coupling fragile biomolecules under physiological conditions and a wide variety of physicochemical properties. The feasibility of using a biodegradable PPE, P(BHET-EOP/TC), as a novel NGC material was investigated. Two types of conduits were fabricated by using two batches of P(BHET-EOP/TC) with different weight-average molecular weights (Mw) and polydispersity indexes (PI). The polymers as well as conduits were non-toxic to all six types of cells tested, including primary neurones and neuronally differentiated PC12 cells. After in situ implantation in the sciatic nerve of the rat, two types of conduits triggered a similar tissue response, inducing the formation of a thin tissue capsule composed of approximately eight layers of fibroblasts surrounding the conduits at 3 months. Biological performances of the conduits were examined in the rat sciatic nerve model with a 10 mm gap. Although tube fragmentation, even tube breakage, was observed within less than 5 days post-implantation, successful regeneration through the gap occurred in both types of conduits, with four out of 10 in the Type I conduits (Mw 14,900 and PI 2.57) and 11 out of 12 in the Type II conduits (Mw 18,900 and PI 1.72). The degradation of conduits was further evidenced by increased roughness on the tube surface in vivo under scanning electron microscope and a mass decrease in a time-dependent manner in vitro. The Mw of the polymers dropped 33 and 24% in the Type I and II conduits, respectively, in vitro within 3 months. Among their advantages over other biodegradable NGCs, the PPE conduits showed negligible swelling and no crystallisation after implantation. Thus, these PPE

  6. Enhanced Femoral Nerve Regeneration After Tubulization with a Tyrosine-Derived Polycarbonate Terpolymer: Effects of Protein Adsorption and Independence of Conduit Porosity

    PubMed Central

    Ezra, Mindy; Bushman, Jared; Shreiber, David

    2014-01-01

    Following complete nerve transection, entubulation of the nerve stumps helps guide axons to reconnect distally. In this study, a biodegradable and noncytotoxic tyrosine-derived polycarbonate terpolymer composed of 89.5 mol% desaminotyrosyl tyrosine ethyl ester (DTE), 10 mol% desaminotyrosyl tyrosine (DT), and 0.5 mol% poly(ethylene glycol) (PEG, molecular weight [Mw]=1 kDa) [designated as E10-0.5(1K)] was used to fabricate conduits for peripheral nerve regeneration. These conduits were evaluated against commercially available nonporous polyethylene (PE) tubes. The two materials are characterized in vitro for differences in surface properties, and the conduits are then evaluated in vivo in a critical-sized nerve defect in the mouse femoral nerve model. Conduits were fabricated from E10-0.5(1K) in both porous [P-E10-0.5(1K)] and nonporous [NP-E10-0.5(1K)] configurations. The results illustrate that adsorption of laminin, fibronectin, and collagen type I was enhanced on E10-0.5(1K) compared to PE. In addition, in vivo the E10-0.5(1K) conduits improved functional recovery over PE conduits, producing regenerated nerves with a fivefold increase in the number of axons, and an eightfold increase in the percentage of myelinated axons. These increases were observed for both P-E10-0.5(1K) and NP-E10-0.5(1K) after 15 weeks. When conduits were removed at 7 or 14 days following implantation, an increase in Schwann cell proteins and fibrin matrix formation was observed in E10-0.5(1K) conduits over PE conduits. These results indicate that E10-0.5(1K) is a pro-regenerative material for peripheral nerves and that the porosity of P-E10-0.5(1K) conduits was inconsequential in this model of nerve injury. PMID:24011026

  7. Behavioral evaluation of regenerated rat sciatic nerve by a nanofibrous PHBV conduit filled with Schwann cells as artificial nerve graft.

    PubMed

    Biazar, Esmaeil; Heidari Keshel, Saeed; Pouya, Majid

    2013-10-01

    The aim of this study is to develop a nanofibrous polymeric nerve conduit with Schwann cells (SCs) and to evaluate its efficiency on the promotion of functional and locomotive activities in rats. The conduits were implanted into a 30-mm gap in the sciatic nerves of the rats. Four months after surgery, the rats were monitored and evaluated by behavioral analyses such as toe out angle, toe spreading analysis, walking track analysis, extensor postural thrust, open-field analysis, swimming test and nociceptive function, four months post surgery. Four months post-operatively, the results from behavioral analyses demonstrated that in the grafted groups especially in the grafted group with SCs, the rat sciatic nerve trunk had been reconstructed with functional recovery such as walking, swimming and recovery of nociceptive function. This study proves the feasibility of artificial conduit with SCs for nerve regeneration by bridging a longer defect in the rat model.

  8. Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery

    PubMed Central

    Knipfer, Christian; Hadlock, Tessa

    2016-01-01

    Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration. PMID:27556032

  9. Novel use of biodegradable casein conduits for guided peripheral nerve regeneration.

    PubMed

    Hsiang, Shih-Wei; Tsai, Chin-Chuan; Tsai, Fuu-Jen; Ho, Tin-Yun; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2011-11-07

    Recent advances in nerve repair technology have focused on finding more biocompatible, non-toxic materials to imitate natural peripheral nerve components. In this study, casein protein cross-linked with naturally occurring genipin (genipin-cross-linked casein (GCC)) was used for the first time to make a biodegradable conduit for peripheral nerve repair. The GCC conduit was dark blue in appearance with a concentric and round lumen. Water uptake, contact angle and mechanical tests indicated that the conduit had a high stability in water and did not collapse and cramped with a sufficiently high level of mechanical properties. Cytotoxic testing and terminal deoxynucleotidyl transferase dUTP nick-end labelling assay showed that the GCC was non-toxic and non-apoptotic, which could maintain the survival and outgrowth of Schwann cells. Non-invasive real-time nuclear factor-κB bioluminescence imaging accompanied by histochemical assessment showed that the GCC was highly biocompatible after subcutaneous implantation in transgenic mice. Effectiveness of the GCC conduit as a guidance channel was examined as it was used to repair a 10 mm gap in the rat sciatic nerve. Electrophysiology, labelling of calcitonin gene-related peptide in the lumbar spinal cord, and histology analysis all showed a rapid morphological and functional recovery for the disrupted nerves. Therefore, we conclude that the GCC can offer great nerve regeneration characteristics and can be a promising material for the successful repair of peripheral nerve defects.

  10. Peripheral nerve repair of transplanted undifferentiated adipose tissue-derived stem cells in a biodegradable reinforced nerve conduit.

    PubMed

    Shen, Chiung-Chyi; Yang, Yi-Chin; Liu, Bai-Shuan

    2012-01-01

    This study proposes a biodegradable nerve conduit containing genipin-cross-linked gelatin annexed with tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT) in peripheral nerve regeneration. Firstly, cytotoxicity tests revealed that the GGT-extracts were not toxic, and promoted the proliferation and neuronal differentiation of adipose tissue-derived stem cells (ADSCs). Secondly, the GGT composite film effectively supported ADSCs attachment and growth. Additionally, the GGT substrate was biocompatible with the neonatal rat sciatic nerve and produced a beneficial effect on peripheral nerve repair through in vitro tissue culture. Finally, the experiments in this study confirmed the effectiveness of a GGT/ADSCs nerve conduit as a guidance channel for repairing a 10-mm gap in a rat sciatic nerve. Eight weeks after implantation, the mean recovery index of compound muscle action potentials (CMAPs) was significantly different between the GGT/ADSCs and autografts groups (p < 0.05), both of which were significantly superior to the GGT group (p < 0.05). Furthermore, walking track analysis also showed a significantly higher sciatic function index (SFI) score (p < 0.05) and better toe spreading development in the GGT/ADSCs group than in the autograft group. Histological observations and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/ADSCs nerve conduits were similar to those of the autografts. The GGT nerve conduit offers a better scaffold for the incorporation of seeding undifferentiated ADSCs, and opens a new avenue to replace autologous nerve grafts for the rapid regeneration of damaged peripheral nerve tissues and an improved approach to patient care. Copyright © 2011 Wiley Periodicals, Inc.

  11. Peripheral nerve regeneration within an asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.

    PubMed

    Oh, Se Heang; Kim, Jun Ho; Song, Kyu Sang; Jeon, Byeong Hwa; Yoon, Jin Hwan; Seo, Tae Beom; Namgung, Uk; Lee, Il Woo; Lee, Jin Ho

    2008-04-01

    Asymmetrically porous tubes with selective permeability and hydrophilicity as nerve guide conduits (NGCs) were fabricated using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a modified immersion precipitation method. The inner surface of the tube had nano-size pores ( approximately 50nm) which can effectively prevent from fibrous tissue infiltration but permeate nutrients and retain neurotrophic factors, while the outer surface had micro-size pores ( approximately 50microm) which can allow vascular ingrowth for effective supply of nutrients into the tube. From the animal study using a rat model, the hydrophilized PLGA/F127 (3wt%) tube showed better nerve regeneration behavior than the control silicone or hydrophobic PLGA tubes, as investigated by immunohistochemical observation (by fluorescent microscopy with anti-neurofilament staining), histological observations (by light microscopy with toluidine blue staining and transmission electron microscopy), and electrophysiological evaluation (by compound muscle action potential measurement). This is probably owing to the effective permeation of nutrients and prevention of fibrous scar tissue invasion as well as the good mechanical strength of the tube to maintain a stable support structure for the nerve regeneration.

  12. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects.

    PubMed

    Wang, Yang; Li, Zheng-Wei; Luo, Min; Li, Ya-Jun; Zhang, Ke-Qiang

    2015-06-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was

  13. Use of natural neural scaffolds consisting of engineered vascular endothelial growth factor immobilized on ordered collagen fibers filled in a collagen tube for peripheral nerve regeneration in rats.

    PubMed

    Ma, Fukai; Xiao, Zhifeng; Meng, Danqing; Hou, Xianglin; Zhu, Jianhong; Dai, Jianwu; Xu, Ruxiang

    2014-10-15

    The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF) plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD) to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices.

  14. Characteristics and biocompatibility of a biodegradable genipin-cross-linked gelatin/β-tricalcium phosphate reinforced nerve guide conduit.

    PubMed

    Yang, Yi-Chin; Shen, Chiung-Chyi; Huang, Tsung-Bin; Chang, Shun-Hsung; Cheng, Hsu-Chen; Liu, Bai-Shuan

    2010-10-01

    To modulate the mechanical properties of nerve guide conduit for surgical manipulation, this study develops a biodegradable composite containing genipin cross-linked gelatin annexed with β-tricalcium phosphate ceramic particles as a nerve guide material. The conduit was dark bluish and round with a rough and compact outer surface compared to the genipin cross-linked gelatin conduit (without β-tricalcium phosphate). Water uptake and swelling tests indicate that the conduit noticeably increases the stability in water, and the hydrated conduit does not collapse and stenose. The conduit has a sufficiently high level of mechanical properties to serve as a nerve guide. After subcutaneous implantation on the dorsal side of a rat, the degraded conduit only evokes a mild tissue response, and the formation of a very thin fibrous capsule surrounds the conduit. This paper assesses the effectiveness of the conduit as a guidance channel when we use it to repair a 10 mm gap in the rat's sciatic nerve. The experimental results show no gross inflammatory reactions of the peripheral nerve tissues at the implantation site in either group. In overall gross examination, the diameter of the intratubular and newly formed nerve fibers in the conduits exceeds that of the silicone tubes during the implantation period. The quantitative results indicate the superiority of the conduits over the silicone tubes. This study microscopically observes the nerve regeneration in the tissue section at the middle region of all implanted conduits. Therefore, the histomorphometric assessment demonstrates that the conduit could be a candidate for peripheral nerve repair.

  15. The behavior of neuronal cells on tendon-derived collagen sheets as potential substrates for nerve regeneration.

    PubMed

    Alberti, Kyle A; Hopkins, Amy M; Tang-Schomer, Min D; Kaplan, David L; Xu, Qiaobing

    2014-04-01

    Peripheral nervous system injuries result in a decreased quality of life, and generally require surgical intervention for repair. Currently, the gold standard of nerve autografting, based on the use of host tissue such as sensory nerves is suboptimal as it results in donor-site loss of function and requires a secondary surgery. Nerve guidance conduits fabricated from natural polymers such as collagen are a common alternative to bridge nerve defects. In the present work, tendon sections derived through a process named bioskiving were studied for their potential for use as a substrate to fabricate nerve guidance conduits. We show that cells such as rat Schwann cells adhere, proliferate, and align along the fibrous tendon substrate which has been shown to result in a more mature phenotype. Additionally we demonstrate that chick dorsal root ganglia explants cultured on the tendon grow to similar lengths compared to dorsal root ganglia cultured on collagen gels, but also grow in a more oriented manner on the tendon sections. These results show that tendon sections produced through bioskiving can support directional nerve growth and may be of use as a substrate for the fabrication of nerve guidance conduits. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Repairing nerve gaps by vein conduits filled with lipoaspirate-derived entire adipose tissue hinders nerve regeneration.

    PubMed

    Papalia, Igor; Raimondo, Stefania; Ronchi, Giulia; Magaudda, Ludovico; Giacobini-Robecchi, Maria G; Geuna, Stefano

    2013-05-01

    In spite of great recent advancements, the definition of the optimal strategy for bridging a nerve defect, especially across long gaps, still remains an open issue since the amount of autologous nerve graft material is limited while the outcome after alternative tubulization techniques is often unsatisfactory. The aim of this study was to investigate a new tubulization technique based on the employment of vein conduits filled with whole subcutaneous adipose tissue obtained by lipoaspiration. In adult rats, a 1cm-long defect of the left median nerve was repaired by adipose tissue-vein-combined conduits and compared with fresh skeletal muscle tissue-vein-combined conduits and autologous nerve grafts made by the excised nerve segment rotated by 180°. Throughout the postoperative period, functional recovery was assessed using the grasping test. Regenerated nerve samples were withdrawn at postoperative month-6 and processed for light and electron microscopy and stereology of regenerated nerve fibers. Results showed that functional recovery was significantly slower in the adipose tissue-enriched group in comparison to both control groups. Light and electron microscopy showed that a large amount of adipose tissue was still present inside the vein conduits at postoperative month-6. Stereology showed that all quantitative morphological predictors analyzed performed significantly worse in the adipose tissue-enriched group in comparison to the two control groups. On the basis of this experimental study in the rat, the use of whole adipose tissue for tissue engineering of peripheral nerves should be discouraged. Pre-treatment of adipose tissue aimed at isolating stromal vascular fraction and/or adipose derived stem/precursor cells should be considered a fundamental requisite for nerve repair. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. A Review of Bioactive Release from Nerve Conduits as a Neurotherapeutic Strategy for Neuronal Growth in Peripheral Nerve Injury

    PubMed Central

    Choonara, Yahya E.; Bijukumar, Divya; du Toit, Lisa C.

    2014-01-01

    Peripheral nerve regeneration strategies employ the use of polymeric engineered nerve conduits encompassed with components of a delivery system. This allows for the controlled and sustained release of neurotrophic growth factors for the enhancement of the innate regenerative capacity of the injured nerves. This review article focuses on the delivery of neurotrophic factors (NTFs) and the importance of the parameters that control release kinetics in the delivery of optimal quantities of NTFs for improved therapeutic effect and prevention of dose dumping. Studies utilizing various controlled-release strategies, in attempt to obtain ideal release kinetics, have been reviewed in this paper. Release strategies discussed include affinity-based models, crosslinking techniques, and layer-by-layer technologies. Currently available synthetic hollow nerve conduits, an alternative to the nerve autografts, have proven to be successful in the bridging and regeneration of primarily the short transected nerve gaps in several patient cases. However, current research emphasizes on the development of more advanced nerve conduits able to simulate the effectiveness of the autograft which includes, in particular, the ability to deliver growth factors. PMID:25143934

  18. Fibrin Glue Increases the Tensile Strength of Conduit-Assisted Primary Digital Nerve Repair.

    PubMed

    Childe, Jessica R; Regal, Steven; Schimoler, Patrick; Kharlamov, Alexander; Miller, Mark C; Tang, Peter

    2017-02-01

    An ideal peripheral nerve repair construct does not currently exist. Our primary goal was to determine whether fibrin glue adds to the tensile strength of conduit-assisted primary digital nerve repairs. Our secondary goal was to evaluate the impact of varying suture number and location on the tensile strength. Ninety cadaveric digital nerves were harvested and divided equally into the following repair groups: A (4/4), B (2/2), C (0/2), D (0/1), and E (0/0) with the first number referring to the number of sutures at the coaptation and the second number referring to the number of sutures at each proximal and distal end of the nerve-conduit junction. When fibrin glue was added, the group was labeled prime. The nerve specimens were transected and then repaired with 8-0 nylon suture and conduit. The tensile strength of the repairs was tested, and maximum failure load was determined. The results were analyzed with a 2-way analysis of variance. The Tukey post hoc test compared repair groups if the 2-way analysis of variance showed significance. Both suture group and glue presence significantly affected the maximum failure load. Increasing the number of sutures increased the maximum failure load, and the presence of fibrin glue also increased the failure load. Fibrin glue was found to increase the strength of conduit-assisted primary digital nerve repairs. Furthermore, the number of sutures correlated to the strength of the repair. Fibrin glue may be added to a conduit-assisted primary digital nerve repair to maintain strength and allow fewer sutures at the primary coaptation site.

  19. Aligned bacterial PHBV nanofibrous conduit for peripheral nerve regeneration.

    PubMed

    Demirbilek, Murat; Sakar, Mustafa; Karahaliloğlu, Zeynep; Erdal, Ebru; Yalçın, Eda; Bozkurt, Gökhan; Korkusuz, Petek; Bilgiç, Elif; Temuçin, Çağrı Mesut; Denkbaş, Emir Baki

    2015-01-01

    The conventional method of peripheral nerve gap treatment is autografting. This method is limited. In this study, an aligned nanofibrous graft was formed using microbial polyester, Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The regenerative effect of the graft was compared with that of autografting in vivo. To determine the regenerative effect, rats were assessed with sciatic nerve functional index, electromyographic evaluation, and histological evaluation. Results found in this study include PHBV grafts stimulated progressive nerve regeneration, although regeneration was not comparable with that of autografting. We conclude that the study results were promising for aligned bacterial polymeric grafts for peripheral nerve regeneration.

  20. In Vivo Evaluation of Nerve Guidance Conduits Comprised of a Salicylic Acid-based Poly(anhydride-ester) Blend

    NASA Astrophysics Data System (ADS)

    Lee, Yong Soo

    Unlike the central nervous system, peripheral nervous system can regenerate from injury. However, without surgical intervention, the results are often poor. Autologous nerve grafting is the golden standard for repairing peripheral nerve injury; but limited donor availability and donor site morbidity led researchers to seek alternative methods. Among the many alternative treatment options, synthetic nerve guidance conduits (NGCs) have been most actively developed. The goal of NGCs is to serve as a physical scaffold that aids the axonal regeneration process while preventing scar tissue formation that interferes with regeneration. Biocompatible and biodegradable NGCs would provide additional benefits: minimize foreign body reaction and avoid secondary surgeries to remove NGCs. We developed a unique NGC that incorporated the characteristics described above and can release an anti-inflammatory drug, salicylic acid. In this work, in vivo assays were performed to evaluate NGCs fabricated from a poly(anhydride-ester) blend. To further assist in the regeneration process, bovine native collagen type I hydrogel were inserted into the NGCs lumen which was then implanted in femoral nerve of mice for up to 16 weeks. These studies demonstrated in vivo biodegradability, biocompatibility, and axonal regeneration following an injury to the peripheral nerve. These studies provide greater insights into the importance of designing NGCs and how they aid in regeneration and functional recovery of subjects.

  1. Linear Ordered Collagen Scaffolds Loaded with Collagen-Binding Basic Fibroblast Growth Factor Facilitate Recovery of Sciatic Nerve Injury in Rats

    PubMed Central

    Ma, Fukai; Xiao, Zhifeng; Chen, Bing; Hou, Xianglin

    2014-01-01

    Natural biological functional scaffolds, consisting of biological materials filled with promoting elements, provide a promising strategy for the regeneration of peripheral nerve defects. Collagen conduits have been used widely due to their excellent biological properties. Linear ordered collagen scaffold (LOCS) fibers are good lumen fillers that can guide nerve regeneration in an ordered direction. In addition, basic fibroblast growth factor (bFGF) is important in the recovery of nerve injury. However, the traditional method for delivering bFGF to the lesion site has no long-term effect because of its short half-life and rapid diffusion. Therefore, we fused a specific collagen-binding domain (CBD) peptide to the N-terminal of native basic fibroblast growth factor (NAT-bFGF) to retain bFGF on the collagen scaffolds. In this study, a natural biological functional scaffold was constructed using collagen tubes filled with collagen-binding bFGF (CBD-bFGF)-loaded LOCS to promote regeneration in a 5-mm rat sciatic nerve transection model. Functional evaluation, histological investigation, and morphometric analysis indicated that the natural biological functional scaffold retained more bFGF at the injury site, guided axon growth, and promoted nerve regeneration as well as functional restoration. PMID:24188561

  2. An in vivo study of tricalcium phosphate and glutaraldehyde crosslinking gelatin conduits in peripheral nerve repair.

    PubMed

    Chen, Ming-Hong; Chen, Pei-Ru; Chen, Mei-Hsiu; Hsieh, Sung-Tsang; Huang, Jing-Shan; Lin, Feng-Huei

    2006-04-01

    In order to modulate the mechanical properties of gelatin, we previously developed a biodegradable composite composed by tricalcium phosphate and glutaraldehyde crosslinking gelatin (GTG) feasible for surgical manipulation. In this study, we evaluated the in vivo applications of GTG conduit for peripheral nerve repair. The effect of sciatic nerve reconstruction was compared between resorbable permeable GTG conduits and durable impermeable silicone tubes. Traditional methods of assessing nerve recovery following peripheral nerve repair including histomorphometric and electrophysiologic features were conducted in our study. In addition, autotomy score and sciatic function index (SFI) in walking tract analysis were used as additional parameters for assessing the return of nerve function. Twenty-four weeks after sciatic nerve repair, the GTG conduits were harvested. Microscopically, regeneration of nerves was observed in the cross-section at the mid portion of all implanted GTG conduits. The cross-sectional area of regenerated nerve of the GTG group was significant larger than that of the silicone group. In the compound muscle action potentials (CMAP), the mean recovery index of CMAP amplitude was 0.24 +/- 0.02 for the silicone group, 0.41 +/- 0.07 for the GTG group. The mean SFI increased with time in the GTG group during the evaluation period until 24 weeks. Walking tract analysis showed a higher SFI score in the GTG group at both 12 and 24 weeks. The difference reached a significant level at 24 weeks. Thus, the histomorphometric, electrophysiologic, and functional assessments demonstrate that GTG can be a candidate for peripheral nerve repair.

  3. PRGD/PDLLA conduit potentiates rat sciatic nerve regeneration and the underlying molecular mechanism.

    PubMed

    Li, Binbin; Qiu, Tong; Iyer, K Swaminathan; Yan, Qiongjiao; Yin, Yixia; Xie, Lijuan; Wang, Xinyu; Li, Shipu

    2015-07-01

    Peripheral nerve injury requires optimal conditions in both macro-environment and micro-environment for reestablishment. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the micro-environment provided by nerve conduit remains unclear. In this study, the rat sciatic nerve of 10 mm defect was made and bridged by PRGD/PDLLA nerve conduit. We investigated the process of nerve regeneration using histological, functional and real time PCR analyses after implantation from 7 to 35 days. Our data demonstrated that the ciliary neurotrophic factor highly expressed and up-regulated the downstream signaling pathways, in the case of activated signals, the expressions of axon sprout relative proteins, such as tubulin and growth-associated protein-43, were strongly augmented. Taken together, these data suggest a possible mechanism of axon regeneration promoted by PRGD/PDLLA conduit, which created a micro-environment for enhancement of diffusion of neurotrophic factors secreted by the injured nerve stumps, and activation of molecular signal transduction involved in growth cone, to potentiate the nerve recovery.

  4. Cellulose/soy protein composite-based nerve guidance conduits with designed microstructure for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Gan, Li; Zhao, Lei; Zhao, Yanteng; Li, Ke; Tong, Zan; Yi, Li; Wang, Xiong; Li, Yinping; Tian, Weiqun; He, Xiaohua; Zhao, Min; Li, Yan; Chen, Yun

    2016-10-01

    Objective. The objective of this work was to develop nerve guidance conduits from natural polymers, cellulose and soy protein isolate (SPI), by evaluating the effects of cellulose/SPI film-based conduit (CSFC) and cellulose/SPI sponge-based conduit (CSSC) on regeneration of nerve defects in rats. Approach. CSFC and CSSC with the same chemical components were fabricated from cellulose and SPI. Effects of CSSC and CSFC on regeneration of the defective nerve were comparatively investigated in rats with a 10 mm long gap in sciatic nerve. The outcomes of peripheral nerve repair were evaluated by a combination of electrophysiological assessment, Fluoro-Gold retrograde tracing, double NF200/S100 immunofluorescence analysis, toluidine blue staining, and electron microscopy. The probable molecular mechanism was investigated using quantitative real-time PCR (qPCR) analysis. Main results. Compared with CSFC, CSSC had 2.69 times higher porosity and 5.07 times higher water absorption, thus ensuring much higher permeability. The nerve defects were successfully bridged and repaired by CSSC and CSFC. Three months after surgery, the CSSC group had a higher compound muscle action potential amplitude ratio, a higher percentage of positive NF200 and S100 staining, and a higher axon diameter and myelin sheath thickness than the CSFC group, showing the repair efficiency of CSSC was higher than that of CSFC. qPCR analysis indicated the mRNA levels of nerve growth factor, IL-10, IL-6, and growth-associated protein 43 (GAP-43) were higher in the CSSC group. This also indicated that there was better nerve repair with CSSC due to the higher porosity and permeability of CSSC providing a more favourable microenvironment for nerve regeneration than CSFC. Significance. A promising nerve guidance conduit was developed from cellulose/SPI sponge that showed potential for application in the repair of nerve defect. This work also suggests that nerve guidance conduits with better repair efficiency

  5. Chitosan nerve conduits seeded with autologous bone marrow mononuclear cells for 30 mm goat peroneal nerve defect

    PubMed Central

    Muheremu, Aikeremujiang; Chen, Lin; Wang, Xiyuan; Wei, Yujun; Gong, Kai; Ao, Qiang

    2017-01-01

    In the current research, to find if the combination of chitosan nerve conduits seeded with autologous bone marrow mononuclear cells (BM-MNCs) can be used to bridge 30 mm long peroneal nerve defects in goats, 15 animals were separated into BM-MNC group (n = 5), vehicle group (n = 5), and autologous nerve graft group (n = 5). 12 months after the surgery, animals were evaluated by behavioral observation, magnetic resonance imaging tests, histomorphological and electrophysiological analysis. Results revealed that animals in BM-MNC group and autologous nerve graft group achieved fine functional recovery; magnetic resonance imaging tests and histomorphometry analysis showed that the nerve defect was bridged by myelinated nerve axons in those animals. No significant difference was found between the two groups concerning myelinated axon density, axon diameter, myelin sheath thickness and peroneal nerve action potential. Animals in vehicle group failed to achieve significant functional recovery. The results indicated that chitosan nerve conduits seeded with autologous bone marrow mononuclear cells have strong potential in bridging long peripheral nerve defects and could be applied in future clinical trials. PMID:28287100

  6. Chitosan nerve conduits seeded with autologous bone marrow mononuclear cells for 30 mm goat peroneal nerve defect.

    PubMed

    Muheremu, Aikeremujiang; Chen, Lin; Wang, Xiyuan; Wei, Yujun; Gong, Kai; Ao, Qiang

    2017-03-13

    In the current research, to find if the combination of chitosan nerve conduits seeded with autologous bone marrow mononuclear cells (BM-MNCs) can be used to bridge 30 mm long peroneal nerve defects in goats, 15 animals were separated into BM-MNC group (n = 5), vehicle group (n = 5), and autologous nerve graft group (n = 5). 12 months after the surgery, animals were evaluated by behavioral observation, magnetic resonance imaging tests, histomorphological and electrophysiological analysis. Results revealed that animals in BM-MNC group and autologous nerve graft group achieved fine functional recovery; magnetic resonance imaging tests and histomorphometry analysis showed that the nerve defect was bridged by myelinated nerve axons in those animals. No significant difference was found between the two groups concerning myelinated axon density, axon diameter, myelin sheath thickness and peroneal nerve action potential. Animals in vehicle group failed to achieve significant functional recovery. The results indicated that chitosan nerve conduits seeded with autologous bone marrow mononuclear cells have strong potential in bridging long peripheral nerve defects and could be applied in future clinical trials.

  7. Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit

    PubMed Central

    Allmeling, Christina; Jokuszies, Andreas; Reimers, Kerstin; Kall, Susanne; Vogt, Peter M

    2006-01-01

    Defects of peripheral nerves still represent a challenge for surgical nerve reconstruction. Recent studies concentrated on replacement by artificial nerve conduits from different synthetic or biological materials. In our study, we describe for the first time the use of spider silk fibres as a new material in nerve tissue engineering. Schwann cells (SC) were cultivated on spider silk fibres. Cells adhered quickly on the fibres compared to polydioxanone monofilaments (PDS). SC survival and proliferation was normal in Live/Dead assays. The silk fibres were ensheathed completely with cells. We developed composite nerve grafts of acellularized veins, spider silk fibres and SC diluted in matrigel. These artificial nerve grafts could be cultivated in vitro for one week. Histological analysis showed that the cells were vital and formed distinct columns along the silk fibres. In conclusion, our results show that artificial nerve grafts can be constructed successfully from spider silk, acellularized veins and SC mixed with matrigel. PMID:16989736

  8. Natural Occurring Silks and Their Analogues as Materials for Nerve Conduits.

    PubMed

    Radtke, Christine

    2016-10-20

    Spider silk and its synthetic derivatives have a light weight in combination with good strength and elasticity. Their high cytocompatibility and low immunogenicity make them well suited for biomaterial products such as nerve conduits. Silk proteins slowly degrade enzymatically in vivo, thus allowing for an initial therapeutic effect such as in nerve scaffolding to facilitate endogenous repair processes, and then are removed. Silks are biopolymers naturally produced by many species of arthropods including spiders, caterpillars and mites. The silk fibers are secreted by the labial gland of the larvae of some orders of Holometabola (insects with pupa) or the spinnerets of spiders. The majority of studies using silks for biomedical applications use materials from silkworms or spiders, mostly of the genus Nephila clavipes. Silk is one of the most promising biomaterials with effects not only in nerve regeneration, but in a number of regenerative applications. The development of silks for human biomedical applications is of high scientific and clinical interest. Biomaterials in use for biomedical applications have to meet a number of requirements such as biocompatibility and elicitation of no more than a minor inflammatory response, biodegradability in a reasonable time and specific structural properties. Here we present the current status in the field of silk-based conduit development for nerve repair and discuss current advances with regard to potential clinical transfer of an implantable nerve conduit for enhancement of nerve regeneration.

  9. Natural Occurring Silks and Their Analogues as Materials for Nerve Conduits

    PubMed Central

    Radtke, Christine

    2016-01-01

    Spider silk and its synthetic derivatives have a light weight in combination with good strength and elasticity. Their high cytocompatibility and low immunogenicity make them well suited for biomaterial products such as nerve conduits. Silk proteins slowly degrade enzymatically in vivo, thus allowing for an initial therapeutic effect such as in nerve scaffolding to facilitate endogenous repair processes, and then are removed. Silks are biopolymers naturally produced by many species of arthropods including spiders, caterpillars and mites. The silk fibers are secreted by the labial gland of the larvae of some orders of Holometabola (insects with pupa) or the spinnerets of spiders. The majority of studies using silks for biomedical applications use materials from silkworms or spiders, mostly of the genus Nephila clavipes. Silk is one of the most promising biomaterials with effects not only in nerve regeneration, but in a number of regenerative applications. The development of silks for human biomedical applications is of high scientific and clinical interest. Biomaterials in use for biomedical applications have to meet a number of requirements such as biocompatibility and elicitation of no more than a minor inflammatory response, biodegradability in a reasonable time and specific structural properties. Here we present the current status in the field of silk-based conduit development for nerve repair and discuss current advances with regard to potential clinical transfer of an implantable nerve conduit for enhancement of nerve regeneration. PMID:27775616

  10. Recurrent laryngeal nerve regeneration using an oriented collagen scaffold containing Schwann cells.

    PubMed

    Chitose, Shun-Ichi; Sato, Kiminori; Fukahori, Mioko; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito

    2017-07-01

    Regeneration of the recurrent laryngeal nerve (RLN), which innervates the intrinsic laryngeal muscles such that they can perform complex functions, is particularly difficult to achieve. Synkinesis after RLN neogenesis leads to uncoordinated movement of laryngeal muscles. Recently, some basic research studies have used cultured Schwann cells (SCs) to repair peripheral nerve injuries. This study aimed to regenerate the RLN using an oriented collagen scaffold containing cultured SCs. Preliminary animal experiment. A 10-mm-long autologous canine cervical ansa was harvested. The nerve tissue was scattered and subcultured on oriented collagen sheets in reduced serum medium. After verifying that the smaller cultivated cells with high nucleus-cytoplasm ratios were SCs, collagen sheets with longitudinally oriented cells were rolled and inserted into a 20-mm collagen conduit. The fabricated scaffolds containing SCs were autotransplanted to a 20-mm deficient RLN, and vocal fold movements and histological characteristics were observed. Scaffolds containing cultured SCs were successfully fabricated. Immunocytochemical examination revealed that these isolated and cultured cells, identified as SCs, expressed S-100 protein and GFAP but not vimentin. The orientation of SCs matched that of the oriented collagen sheet. Two months after successful transplantation, laryngeal endoscopy revealed coordinated movement of the bilateral vocal folds by external stimulation under light general anesthesia. Hematoxylin and eosin staining showed that the regenerated RLN lacked epineurium surrounding the nerve fibers and was interspersed with collagen fibers. Myelin protein zero was expressed around many axons. Partial regeneration of RLN was achieved through the use of oriented collagen scaffolding. NA Laryngoscope, 127:1622-1627, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Nerve growth factor combined with an epineural conduit for bridging a short nerve gap (10 mm). A study in rabbits.

    PubMed

    Barmpitsioti, Antonia; Konofaos, Petros; Ignatiadis, Ioannis; Papalois, Apostolos; Zoubos, Aristides B; Soucacos, Panagiotis N

    2011-10-01

    The purpose of this study was to evaluate the effect of direct administration of nerve growth factor (NGF) into an epineural conduit across a short nerve gap (10 mm) in a rabbit sciatic nerve model. The animals were divided into two groups. In group 1, n = 6, a 10-mm defect was created in the sciatic nerve and bridged with an epineural flap. A dose of 1 μg of NGF was locally administered daily for the first 21 days. NGF administration was made inside the epineural flap using a silicone reservoir connected to a silicone tube. In group 2, n = 6, the 10-mm defect was bridged with a nerve graft. This group did not receive any further treatment. At 13 weeks, all animals, before euthanasia, underwent electromyography (EMG) studies and then specimen sent for histology morphometric analysis. NGF administration ensured a significantly increased average number of myelinated axons per μm(2) (P = 0.028) and promoted fiber maturation (P = 0.031) and better EMG results (P = 0.046 for latency P = 0.048 for amplitude), compared with the control group. Although nerve grafts remain the gold standard for peripheral nerve repair, NGF-treated epineural conduits represent a good alternative, particularly when an unfavorable environment for nerve grafts is present.

  12. A polymer foam conduit seeded with Schwann cells promotes guided peripheral nerve regeneration.

    PubMed

    Hadlock, T; Sundback, C; Hunter, D; Cheney, M; Vacanti, J P

    2000-04-01

    Alternatives to autografts have long been sought for use in bridging neural gaps. Many entubulation materials have been studied, although with generally disappointing results in comparison with autografts. The purpose of this study was to design a more effective neural guidance conduit, to introduce Schwann cells into the conduit, and to determine regenerative capability through it in an in vivo model. A novel, fully biodegradable polymer conduit was designed and fabricated for use in peripheral nerve repair, which approximates the macro- and microarchitecture of native peripheral nerves. It comprised a series of longitudinally aligned channels, with diameters ranging from 60 to 550 microns. The lumenal surfaces promoted the adherence of Schwann cells, whose presence is known to play a key role in nerve regeneration. This unique channel architecture increased the surface area available for Schwann cell adherence up to five-fold over that available through a simple hollow conduit. The conduit was composed of a high-molecular-weight copolymer of lactic and glycolic acids (PLGA) (MW 130,000) in an 85:15 monomer ratio. A novel foam-processing technique, employing low-pressure injection molding, was used to create highly porous conduits (approximately 90% pore volume) with continuous longitudinal channels. Using this technique, conduits were constructed containing 1, 5, 16, 45, or more longitudinally aligned channels. Prior to cellular seeding of these conduits, the foams were prewet with 50% ethanol, flushed with physiologic saline, and coated with laminin solution (10 microg/mL). A Schwann cell suspension was dynamically introduced into these processed foams at a concentration of 5 X 10(5) cells/mL, using a simple bioreactor flow loop. In vivo regeneration studies were carried out in which cell-laden five-channel polymer conduits (individual channel ID 500 microm, total conduit OD 2.3 mm) were implanted across a 7-mm gap in the rat sciatic nerve (n = 4), and midgraft

  13. Increased axonal regeneration through a biodegradable amnionic tube nerve conduit: effect of local delivery and incorporation of nerve growth factor/hyaluronic acid media.

    PubMed

    Mohammad, J A; Warnke, P H; Pan, Y C; Shenaq, S

    2000-01-01

    The authors emphasize the possible pharmacological enhancement of axonal regeneration using a specific growth factor/ extracellular media incorporated in a biodegradable nonneural nerve conduit material. They investigated the early effects on nerve regeneration of continuous local delivery of nerve growth factor (NGF) and the local incorporation of hyaluronic acid (HA) inside a newly manufactured nerve conduit material from fresh human amnionic membrane. Human amnionic membrane contains important biochemical factors that play a major neurotrophic role in the nerve regeneration process. The process of manufacturing a nerve conduit from fresh human amnionic membrane is described. This nerve conduit system was used in rabbits to bridge a 25-mm nerve gap over 3 months. NGF was released locally, over 28 days, at the distal end of the tube via a system of slow release, and HA was incorporated inside the lumen of the tube at the time of surgery. NGF/HA treatment promoted axonal regeneration across the amnionic tube nerve conduit (8,962 +/- 383 myelinated axons) 45% better than the nontreated amnionic tube group (6,180 +/- 353 myelinated axons). The authors demonstrate that NGF/HA media enhances additional axonal regeneration in the amnionic tube nerve conduit. This result is secondary to the effect of the amnion promoting biochemical factors, in combination with the NGF/HA effect on facilitating early events in the nerve regeneration process.

  14. Evaluation of a multi-layer microbraided polylactic acid fiber-reinforced conduit for peripheral nerve regeneration.

    PubMed

    Lu, Ming-Chin; Huang, Yen-Ting; Lin, Jia-Horng; Yao, Chun-Hsu; Lou, Ching-Wen; Tsai, Chin-Chuan; Chen, Yueh-Sheng

    2009-05-01

    We evaluated peripheral nerve regeneration using a biodegradable multi-layer microbraided polylactic acid (PLA) fiber-reinforced conduit. Biodegradability of the PLA conduit and its effectiveness as a guidance channel were examined as it was used to repair a 10 mm gap in the rat sciatic nerve. As a result, tube fragmentation was not obvious and successful regeneration through the gap occurred in all the conduits at 8 weeks after operation. These results indicate the superiority of the PLA materials and suggest that the multi-layer microbraided PLA fiber-reinforced conduits provide a promising tool for neuro-regeneration.

  15. Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

    PubMed Central

    Shim, Sun Woo; Kwon, Doo Yeon; Lee, Bit Na; Kwon, Jin Seon; Park, Ji Hoon; Lee, Jun Hee; Kim, Jae Ho; Lee, Il Woo; Shin, Jung-Woog; Lee, Hai Bang; Kim, Wan-Doo

    2015-01-01

    The present study employed nerve guidance conduits (NGCs) only, which were made of small intestine submucosa (SIS) and poly(caprolactone-co-lactide) (PCLA) to promote nerve regeneration in a peripheral nerve injury (PNI) model with nerve defects of 15 mm. The SIS- and PCLA-NGCs were easily prepared by rolling of a SIS sheet and a bioplotter using PCLA, respectively. The prepared SIS- and PCLA-NGCs fulfilled the general requirement for use as artificial peripheral NGCs such as easy fabrication, reproducibility for mass production, suturability, sterilizability, wettability, and proper mechanical properties to resist collapsing when applied to in vivo implantation. The SIS- and PCLA-NGCs appeared to be well integrated into the host sciatic nerve without causing dislocations and serious inflammation. All NGCs stably maintained their NGC shape for 8 weeks without collapsing, which matched well with the nerve regeneration rate. Staining of the NGCs in the longitudinal direction showed that the regenerated nerves grew successfully from the SIS- and PCLA-NGCs through the sciatic nerve-injured gap and connected from the proximal to distal direction along the NGC axis. SIS-NGCs exhibited a higher nerve regeneration rate than PCLA-NGCs. Collectively, our results indicate that SIS- and PCLA-NGCs induced nerve regeneration in a PNI model, a finding that has significant implications in the future with regard to the feasibility of clinical nerve regeneration with SIS- and PCLA-NGCs prepared through an easy fabrication method using promising biomaterials. PMID:25435200

  16. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

    SciTech Connect

    Luo, Lihua; Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan; Wang, Xiong; Huselstein, Celine; Chen, Yun

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  17. Characterization and Schwann Cell Seeding of up to 15.0 cm Long Spider Silk Nerve Conduits for Reconstruction of Peripheral Nerve Defects.

    PubMed

    Kornfeld, Tim; Vogt, Peter M; Bucan, Vesna; Peck, Claas-Tido; Reimers, Kerstin; Radtke, Christine

    2016-11-30

    Nerve reconstruction of extended nerve defect injuries still remains challenging with respect to therapeutic options. The gold standard in nerve surgery is the autologous nerve graft. Due to the limitation of adequate donor nerves, surgical alternatives are needed. Nerve grafts made out of either natural or artificial materials represent this alternative. Several biomaterials are being explored and preclinical and clinical applications are ongoing. Unfortunately, nerve conduits with successful enhancement of axonal regeneration for nerve defects measuring over 4.0 cm are sparse and no conduits are available for nerve defects extending to 10.0 cm. In this study, spider silk nerve conduits seeded with Schwann cells were investigated for in vitro regeneration on defects measuring 4.0 cm, 10.0 cm and 15.0 cm in length. Schwann cells (SCs) were isolated, cultured and purified. Cell purity was determined by immunofluorescence. Nerve grafts were constructed out of spider silk from Nephila edulis and decellularized ovine vessels. Finally, spider silk implants were seeded with purified Schwann cells. Cell attachment was observed within the first hour. After 7 and 21 days of culture, immunofluorescence for viability and determination of Schwann cell proliferation and migration throughout the conduits was performed. Analyses revealed that SCs maintained viable (>95%) throughout the conduits independent of construct length. SC proliferation on the spider silk was determined from day 7 to day 21 with a proliferation index of 49.42% arithmetically averaged over all conduits. This indicates that spider silk nerve conduits represent a favorable environment for SC attachment, proliferation and distribution over a distance of least 15.0 cm in vitro. Thus spider silk nerve implants are a highly adequate biomaterial for nerve reconstruction.

  18. Characterization and Schwann Cell Seeding of up to 15.0 cm Long Spider Silk Nerve Conduits for Reconstruction of Peripheral Nerve Defects

    PubMed Central

    Kornfeld, Tim; Vogt, Peter M.; Bucan, Vesna; Peck, Claas-Tido; Reimers, Kerstin; Radtke, Christine

    2016-01-01

    Nerve reconstruction of extended nerve defect injuries still remains challenging with respect to therapeutic options. The gold standard in nerve surgery is the autologous nerve graft. Due to the limitation of adequate donor nerves, surgical alternatives are needed. Nerve grafts made out of either natural or artificial materials represent this alternative. Several biomaterials are being explored and preclinical and clinical applications are ongoing. Unfortunately, nerve conduits with successful enhancement of axonal regeneration for nerve defects measuring over 4.0 cm are sparse and no conduits are available for nerve defects extending to 10.0 cm. In this study, spider silk nerve conduits seeded with Schwann cells were investigated for in vitro regeneration on defects measuring 4.0 cm, 10.0 cm and 15.0 cm in length. Schwann cells (SCs) were isolated, cultured and purified. Cell purity was determined by immunofluorescence. Nerve grafts were constructed out of spider silk from Nephila edulis and decellularized ovine vessels. Finally, spider silk implants were seeded with purified Schwann cells. Cell attachment was observed within the first hour. After 7 and 21 days of culture, immunofluorescence for viability and determination of Schwann cell proliferation and migration throughout the conduits was performed. Analyses revealed that SCs maintained viable (>95%) throughout the conduits independent of construct length. SC proliferation on the spider silk was determined from day 7 to day 21 with a proliferation index of 49.42% arithmetically averaged over all conduits. This indicates that spider silk nerve conduits represent a favorable environment for SC attachment, proliferation and distribution over a distance of least 15.0 cm in vitro. Thus spider silk nerve implants are a highly adequate biomaterial for nerve reconstruction. PMID:27916868

  19. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect.

    PubMed

    Luo, Lihua; Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan; Wang, Xiong; Huselstein, Celine; Chen, Yun

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  20. In vivo evaluation of a biodegradable EDC/NHS-cross-linked gelatin peripheral nerve guide conduit material.

    PubMed

    Chang, Ju-Ying; Lin, Jia-Horng; Yao, Chun-Hsu; Chen, Jiunn-Horng; Lai, Tung-Yuan; Chen, Yueh-Sheng

    2007-04-10

    Peripheral nerve regeneration has been evaluated using a biodegradable nerve conduit, which is made of a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked gelatin. The EDC/NHS crosslinked gelatin (ENG) conduit is brownish in appearance, and is concentric and round with a smooth outer surface and inner lumen. After subcutaneous implantation on the dorsal side of a rat, the degraded ENG conduit only evoked a mild tissue response, with the formation of a thin tissue capsule surrounding the conduit. Biodegradability of the ENG conduit and its effectiveness as a guidance channel has been examined by its use to repair a 10 mm gap in the rat sciatic nerve. As a result, the tubes degraded throughout the implantation period, but still remained circular with a thin round lumen until they were completely integrated with the enclosed nerves. Successful regeneration through the gap occurred in all the conduits over the three experimental periods of 4, 8, and 12 weeks. Histological observation showed that numerous myelinated axons had crossed through the gap region even at the shortest implantation period of 4 weeks. Peak amplitude, area under the muscle action potential curve, and nerve conductive velocity all showed an increase as a function of the recovery period, which indicates that the nerve had undergone adequate regeneration. These results indicate the superiority of the ENG materials and suggest that the novel ENG conduits provide a promising tool for neuro-regeneration.

  1. Influence of spontaneously occurring bursts of muscle sympathetic nerve activity on conduit artery diameter

    PubMed Central

    Fairfax, Seth T.; Padilla, Jaume; Vianna, Lauro C.; Holwerda, Seth H.; Davis, Michael J.

    2013-01-01

    Large increases in muscle sympathetic nerve activity (MSNA) can decrease the diameter of a conduit artery even in the presence of elevated blood pressure, suggesting that MSNA acts to regulate conduit artery tone. Whether this influence can be extrapolated to spontaneously occurring MSNA bursts has not been examined. Therefore, we tested the hypothesis that MSNA bursts decrease conduit artery diameter on a beat-by-beat basis during rest. Conduit artery responses were assessed in the brachial (BA), common femoral (CFA) and popliteal (PA) arteries to account for regional differences in vascular function. In 20 young men, MSNA, mean arterial pressure (MAP), conduit artery diameter, and shear rate (SR) were continuously measured during 20-min periods of supine rest. Spike-triggered averaging was used to characterize beat-by-beat changes in each variable for 15 cardiac cycles following all MSNA bursts, and a peak response was calculated. Diameter increased to a similar peak among the BA (+0.14 ± 0.02%), CFA (+0.17 ± 0.03%), and PA (+0.18 ± 0.03%) following MSNA bursts (all P < 0.05 vs. control). The diameter rise was positively associated with an increase in MAP in relation to increasing amplitude and consecutive numbers of MSNA bursts (P < 0.05). Such relationships were similar between arteries. SR changes following MSNA bursts were heterogeneous between arteries and did not appear to systematically alter diameter responses. Thus, in contrast to our hypothesis, spontaneously occurring MSNA bursts do not directly influence conduit arteries with local vasoconstriction or changes in shear, but rather induce a systemic pressor response that appears to passively increase conduit artery diameter. PMID:23832696

  2. Peripheral Nerve Regeneration Through Hydrogel-Enriched Chitosan Conduits Containing Engineered Schwann Cells for Drug Delivery.

    PubMed

    Meyer, Cora; Wrobel, Sandra; Raimondo, Stefania; Rochkind, Shimon; Heimann, Claudia; Shahar, Abraham; Ziv-Polat, Ofra; Geuna, Stefano; Grothe, Claudia; Haastert-Talini, Kirsten

    2016-01-01

    Critical length nerve defects in the rat sciatic nerve model were reconstructed with chitosan nerve guides filled with Schwann cells (SCs) containing hydrogel. The transplanted SCs were naive or had been genetically modified to overexpress neurotrophic factors, thus providing a cellular neurotrophic factor delivery system. Prior to the assessment in vivo, in vitro studies evaluating the properties of engineered SCs overexpressing glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF-2(18kDa)) demonstrated their neurite outgrowth inductive bioactivity for sympathetic PC-12 cells as well as for dissociated dorsal root ganglion cell drop cultures. SCs within NVR-hydrogel, which is mainly composed of hyaluronic acid and laminin, were delivered into the lumen of chitosan hollow conduits with a 5% degree of acetylation. The viability and neurotrophic factor production by engineered SCs within NVR-Gel inside the chitosan nerve guides was further demonstrated in vitro. In vivo we studied the outcome of peripheral nerve regeneration after reconstruction of 15-mm nerve gaps with either chitosan/NVR-Gel/SCs composite nerve guides or autologous nerve grafts (ANGs). While ANGs did guarantee for functional sensory and motor regeneration in 100% of the animals, delivery of NVR-Gel into the chitosan nerve guides obviously impaired sufficient axonal outgrowth. This obstacle was overcome to a remarkable extent when the NVR-Gel was enriched with FGF-2(18kDa) overexpressing SCs.

  3. Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts.

    PubMed

    Tos, P; Battiston, B; Geuna, S; Giacobini-Robecchi, M G; Hill, M A; Lanzetta, M; Owen, E R

    2000-01-01

    Diffusible factors from the distal stumps of transected peripheral nerves exert a neurotropic effect on regenerating nerves in vivo (specificity). This morphological study was designed to investigate the existence of tissue specificity in peripheral nerve fiber regeneration through a graft of vein filled with fresh skeletal muscle. This tubulization technique demonstrated experimental and clinical results similar to those obtained with traditional autologous nerve grafts. Specifically, we used Y-shaped grafts to assess the orientation pattern of regenerating axons in the distal stump tissue. Animal models were divided into four experimental groups. The proximal part of the Y-shaped conduit was sutured to a severed tibial nerve in all experiments. The two distal stumps were sutured to different targets: group A to two intact nerves (tibial and peroneal), group B to an intact nerve and an unvascularized tendon, group C to an intact nerve and a vascularized tendon, and group D to a nerve graft and an unvascularized tendon. Morphological evaluation by light and electron microscopy was conducted in the distal forks of the Y-shaped tube. Data showed that almost all regenerating nerve fibers spontaneously oriented towards the nerve tissue (attached or not to the peripheral innervation field), showing a good morphological pattern of regeneration in both the early and late phases of regeneration. When the distal choice was represented by a tendon (vascularized or not), very few nerve fibers were detected in the corresponding distal fork of the Y-shaped graft. These results show that, using the muscle-vein-combined grafting technique, regenerating axons are able to correctly grow and orientate within the basement membranes of the graft guided by the neurotropic lure of the distal nerve stump. Copyright 2000 Wiley-Liss, Inc.

  4. Acceleration of peripheral nerve regeneration through asymmetrically porous nerve guide conduit applied with biological/physical stimulation.

    PubMed

    Kim, Jin Rae; Oh, Se Heang; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang; Jeon, Byeong Hwa; Lee, Jin Ho

    2013-12-01

    Sufficient functional restoration of damaged peripheral nerves is a big clinical challenge. In this study, a nerve guide conduit (NGC) with selective permeability was prepared by rolling an asymmetrically porous polycaprolactone/Pluronic F127 membrane fabricated using a novel immersion precipitation method. Dual stimulation (nerve growth factor [NGF] as a biological stimulus and low-intensity pulse ultrasound [US] as a physical stimulus) was adapted to enhance nerve regeneration through an NGC. The animal study revealed that each stimulation (NGF or US) has a positive effect to promote the peripheral nerve regeneration through the NGC, however, the US-stimulated NGC group allowed more accelerated nerve regeneration compared with the NGF-stimulated group. The NGC group that received dual stimulation (NGF and US) showed more effective nerve regeneration behavior than the groups that received a single stimulation (NGF or US). The asymmetrically porous NGC with dual NGF and US stimulation may be a promising strategy for the clinical treatment of delayed and insufficient functional recovery of a peripheral nerve.

  5. Preparation and evaluation of novel nano-bioglass/gelatin conduit for peripheral nerve regeneration.

    PubMed

    Koudehi, Masoumeh Foroutan; Fooladi, Abbas Ali Imani; Mansoori, Kourosh; Jamalpoor, Zahra; Amiri, Afsaneh; Nourani, Mohammad Reza

    2014-02-01

    Peripheral nerves are exposed to physical injuries usually caused by trauma that may lead to a significant loss of sensory or motor functions and is considered as a serious health problem for societies today. This study was designed to develop a novel nano bioglass/gelatin conduit (BGGC) for the peripheral nerve regeneration. The bioglass nanoparticles were prepared by sol-gel technique and characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction analysis. The interfacial bonding interaction between the nano-bioglass and gelatin in the developed conduits was assessed by FTIR. The surface morphology and pore size of the nanocomposite were investigated through scanning electron microscopy with the pore size of the conduits being 10-40 μm. Biocompatibility was assessed by MTT assay which indicated the BGGC to have good cytocompatibility. The guidance channel was examined and used to regenerate a 10 mm gap in the right sciatic nerve of a male Wistar rat. Twenty rats were randomly divided into two experimental groups, one with the BGGC and the other being normal rats. The gastrocnemius muscle contractility was also examined at one, two and three months post-surgery in all groups using electromyography (EMAP). Histological and functional evaluation and the results obtained from electromyography indicated that at three months, nerve regeneration of the BGGC group was statistically equivalent to the normal group (p > 0.05). Our result suggests that the BGGC can be a suitable candidate for peripheral nerve repair.

  6. Nerve guidance conduit with a hybrid structure of a PLGA microfibrous bundle wrapped in a micro/nanostructured membrane.

    PubMed

    Peng, Shih-Wen; Li, Ching-Wen; Chiu, Ing-Ming; Wang, Gou-Jen

    2017-01-01

    Nerve repair in tissue engineering involves the precise construction of a scaffold to guide nerve cell regeneration in the desired direction. However, improvements are needed to facilitate the cell migration/growth rate of nerves in the center of a nerve conduit. In this paper, we propose a nerve guidance conduit with a hybrid structure comprising a microfibrous poly(lactic-co-glycolic acid) (PLGA) bundle wrapped in a micro/nanostructured PLGA membrane. We applied sequential fabrication processes, including photolithography, nano-electroforming, and polydimethylsiloxane casting to manufacture master molds for the repeated production of the PLGA subelements. After demolding it from the master molds, we rolled the microfibrous membrane into a bundle and then wrapped it in the micro/nanostructured membrane to form a nerve-guiding conduit. We used KT98/F1B-GFP cells to estimate the migration rate and guidance ability of the fabricated nerve conduit and found that both elements increased the migration rate 1.6-fold compared with a flat PLGA membrane. We also found that 90% of the cells in the hybrid nano/microstructured membrane grew in the direction of the designed patterns. After 3 days of culturing, the interior of the nerve conduit was filled with cells, and the microfiber bundle was also surrounded by cells. Our conduit cell culture results also demonstrate that the proposed micro/nanohybrid and microfibrous structures can retain their shapes. The proposed hybrid-structured conduit demonstrates a high capability for guiding nerve cells and promoting cell migration, and, as such, is feasible for use in clinical applications.

  7. Nerve guidance conduit with a hybrid structure of a PLGA microfibrous bundle wrapped in a micro/nanostructured membrane

    PubMed Central

    Peng, Shih-Wen; Li, Ching-Wen; Chiu, Ing-Ming; Wang, Gou-Jen

    2017-01-01

    Nerve repair in tissue engineering involves the precise construction of a scaffold to guide nerve cell regeneration in the desired direction. However, improvements are needed to facilitate the cell migration/growth rate of nerves in the center of a nerve conduit. In this paper, we propose a nerve guidance conduit with a hybrid structure comprising a microfibrous poly(lactic-co-glycolic acid) (PLGA) bundle wrapped in a micro/nanostructured PLGA membrane. We applied sequential fabrication processes, including photolithography, nano-electroforming, and polydimethylsiloxane casting to manufacture master molds for the repeated production of the PLGA subelements. After demolding it from the master molds, we rolled the microfibrous membrane into a bundle and then wrapped it in the micro/nanostructured membrane to form a nerve-guiding conduit. We used KT98/F1B-GFP cells to estimate the migration rate and guidance ability of the fabricated nerve conduit and found that both elements increased the migration rate 1.6-fold compared with a flat PLGA membrane. We also found that 90% of the cells in the hybrid nano/microstructured membrane grew in the direction of the designed patterns. After 3 days of culturing, the interior of the nerve conduit was filled with cells, and the microfiber bundle was also surrounded by cells. Our conduit cell culture results also demonstrate that the proposed micro/nanohybrid and microfibrous structures can retain their shapes. The proposed hybrid-structured conduit demonstrates a high capability for guiding nerve cells and promoting cell migration, and, as such, is feasible for use in clinical applications. PMID:28138239

  8. Ultrasound-stimulated peripheral nerve regeneration within asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.

    PubMed

    Park, Sang Chul; Oh, Se Heang; Seo, Tae Beom; Namgung, Uk; Kim, Jin Man; Lee, Jin Ho

    2010-08-01

    Recently, we developed a novel method to fabricate a nerve guide conduit (NGC) with asymmetrical pore structure and hydrophilicity using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a modified immersion precipitation method. From the animal study using a rat model (sciatic nerve defect of rat), we recognized that the unique PLGA/Pluronic F127 tube provided good environments for nerve regeneration. In this study, we applied low-intensity pulsed ultrasound as a simple and noninvasive stimulus at the PLGA/F127 NGC-implanted site transcutaneously in rats to investigate the feasibility of ultrasound for the enhanced nerve regeneration through the tube. The nerve regeneration behaviors within the ultrasound-stimulated PLGA/Pluronic F127 NGCs were compared with the NGCs without the ultrasound treatment as well as normal nerve by histological and immunohistochemical observations. It was observed that the PLGA/Pluronic F127 tube-implanted group applied with the ultrasound had more rapid nerve regeneration behavior (approximately 0.71 mm/day) than the tube-implanted group without the ultrasound treatment (approximately 0.48 mm/day). The ultrasound-treated tube group also showed greater neural tissue area as well as larger axon diameter and thicker myelin sheath than the tube group without the ultrasound treatment, indicating better nerve regeneration. The better nerve regeneration behavior in the our NGC/ultrasound system may be caused by the synergistic effect of the asymmetrically porous PLGA/Pluronic F127 tube with unique properties (selective permeability, hydrophilicity, and structural stability, which can provide good environment for nerve regeneration) and physical stimulus (stimulation of the Schwann cells and activation of the neurotrophic factors).

  9. Functional gait evaluation of collagen chitosan nerve guides for sciatic nerve repair.

    PubMed

    Patel, Minal; Vandevord, Pamela J; Matthew, Howard W; Desilva, Stephen; Wu, Bin; Wooley, Paul H

    2008-12-01

    The objective of this work was to use a functional gait analysis technique to evaluate sciatic nerve repair through tissue-engineered nerve guides in a rodent animal model. The nerve guides were fabricated by blending collagen with chitosan material and evaluated over a 12-week period for motor and sensory nerve recovery assessed by gait analysis and behavioral testing. Gastrocnemius muscle weight measurements were obtained at the end of each experimental time point and correlated to motor nerve recovery. Functional gait analysis studied both the stance and swing phase angle formations during a normal gait cycle. During the stance phase, functional results revealed that blended nerve guides promoted increased motor nerve recovery than unblended chitosan nerve guides. Similar results were obtained from behavioral tests, indicating that blended nerve guides created increased sensitivity to applied stimulus compared to unblended nerve guides. Muscle strength also correlated with functional recovery and was significantly higher when compared to the unblended nerve guides. From this study, we conclude that collagen-blended chitosan nerve guides enhanced motor and sensory nerve recovery assayed through gait and behavioral testing compared to unblended nerve guides.

  10. Diverse types of epineural conduits for bridging short nerve defects. An experimental study in the rabbit.

    PubMed

    Ignatiadis, Ioannis A; Yiannakopoulos, Christos K; Barbitsioti, Antonia D; Avram, Adrian M; Patralexis, Haralambos G; Tsolakis, Charilaos K; Papalois, Apostolos E; Xenakis, Theodoros H; Beris, Alexandros E; Soucacos, Panayiotis N

    2007-01-01

    In this study the process of peripheral nerve regeneration through an epineural flap conduit was examined using four groups of 126 New Zealand rabbits. There were three study groups (A, B, and C) and 1 control group (D). A 10-mm long sciatic nerve defect was bridged either with 3 variations of an epineural flap (Groups A, B, and C) or with a nerve autograft (Group D). Animals from all groups were examined 21, 42, and 91 days postoperatively to evaluate nerve regeneration employing light microscopy and immunocytochemistry. Nerve regeneration was studied in transverse sections at 3, 6, and 9 mm from the proximal stump. The gastrocnemius muscle contractility was also examined prior to euthanasia at 91 days postsurgery in all groups using electromyography. Immunohistochemical, histochemical and functional evaluation showed the presence of nerve regeneration resembling the control group D, especially in group A, where an advancement epineural flap was used. In this experimental model an epineural flap can be used to bridge a nerve defect successfully.

  11. A New Preparation Method for Anisotropic Silk Fibroin Nerve Guidance Conduits and Its Evaluation In Vitro and in a Rat Sciatic Nerve Defect Model.

    PubMed

    Teuschl, Andreas Herbert; Schuh, Christina; Halbweis, Robert; Pajer, Krisztián; Márton, Gábor; Hopf, Rudolf; Mosia, Shorena; Rünzler, Dominik; Redl, Heinz; Nógrádi, Antal; Hausner, Thomas

    2015-09-01

    Over the past decade, silk fibroin (SF) has been emergently used in peripheral nerve tissue engineering. Current approaches aiming at producing SF-based nerve guidance conduits (SF-NGCs) used dissolved silk based on either aqueous solutions or organic solvents. In this study, we describe a novel procedure to produce SF-NGCs: A braided tubular structure of raw Bombyx mori silk is subsequently processed with the ternary solvent CaCl2/H2O/ethanol, formic acid, and methanol to improve its mechanical and topographical characteristics. Topographically, the combination of the treatments results in a fusion of the outer single silk fibers to a closed layer with a thickness ranging from about 40 to 75 μm. In contrast to the outer wall, the inner lumen (not treated with processing solvents) still represents the braided structure of single fibers. Mechanical stability, elasticity, and kink characteristics were evaluated with a custom-made test system. The modification procedure described here drastically improved the elastic properties of our tubular raw scaffold, favoring its use as a NGC. A cell migration assay with NIH/3T3-fibroblasts revealed the impermeability of the SF-NGC wall for possible invading and scar-forming cells. Moreover, the potential of the SF-NGC to serve as a substratum for Schwann cells has been demonstrated by cytotoxicity tests and live-dead stainings of Schwann cells grown on the inner surface of the SF-NGC. In vivo, the SF-NGC was tested in a rat sciatic nerve injury model. In short-term in vivo studies, it was proved that SF-NGCs are not triggering host inflammatory reactions. After 12 weeks, we could demonstrate morphological and functional reinnervation of the distal targets. Filled with collagen, a higher number of axons could be found in the distal to the graft (1678±303), compared with the empty SF-NGC (1274±146). The novel SF-NGC presented here shows promising results for the treatment of peripheral nerve injuries. The modification of

  12. A New Preparation Method for Anisotropic Silk Fibroin Nerve Guidance Conduits and Its Evaluation In Vitro and in a Rat Sciatic Nerve Defect Model

    PubMed Central

    Schuh, Christina; Halbweis, Robert; Pajer, Krisztián; Márton, Gábor; Hopf, Rudolf; Mosia, Shorena; Rünzler, Dominik; Redl, Heinz; Nógrádi, Antal; Hausner, Thomas

    2015-01-01

    Over the past decade, silk fibroin (SF) has been emergently used in peripheral nerve tissue engineering. Current approaches aiming at producing SF-based nerve guidance conduits (SF-NGCs) used dissolved silk based on either aqueous solutions or organic solvents. In this study, we describe a novel procedure to produce SF-NGCs: A braided tubular structure of raw Bombyx mori silk is subsequently processed with the ternary solvent CaCl2/H2O/ethanol, formic acid, and methanol to improve its mechanical and topographical characteristics. Topographically, the combination of the treatments results in a fusion of the outer single silk fibers to a closed layer with a thickness ranging from about 40 to 75 μm. In contrast to the outer wall, the inner lumen (not treated with processing solvents) still represents the braided structure of single fibers. Mechanical stability, elasticity, and kink characteristics were evaluated with a custom-made test system. The modification procedure described here drastically improved the elastic properties of our tubular raw scaffold, favoring its use as a NGC. A cell migration assay with NIH/3T3-fibroblasts revealed the impermeability of the SF-NGC wall for possible invading and scar-forming cells. Moreover, the potential of the SF-NGC to serve as a substratum for Schwann cells has been demonstrated by cytotoxicity tests and live-dead stainings of Schwann cells grown on the inner surface of the SF-NGC. In vivo, the SF-NGC was tested in a rat sciatic nerve injury model. In short-term in vivo studies, it was proved that SF-NGCs are not triggering host inflammatory reactions. After 12 weeks, we could demonstrate morphological and functional reinnervation of the distal targets. Filled with collagen, a higher number of axons could be found in the distal to the graft (1678±303), compared with the empty SF-NGC (1274±146). The novel SF-NGC presented here shows promising results for the treatment of peripheral nerve injuries. The modification of

  13. Evaluation of biodegradable polymer conduits--poly(L-lactic acid)--for guiding sciatic nerve regeneration in mice.

    PubMed

    Goulart, Camila Oliveira; Lopes, Fátima Rosalina Pereira; Monte, Zulmira Oliveira; Dantas, Severino Valentim; Souto, Allana; Oliveira, Júlia Teixeira; Almeida, Fernanda Martins; Tonda-Turo, Chiara; Pereira, Cristina Cardoso; Borges, Cristiano Piacsek; Martinez, Ana Maria Blanco

    2016-04-15

    Polymeric biomaterials are often used for stimulating nerve regeneration. Among different conduits, poly(lactide acid) - PLA polymer is considered to be a good substrate due to its biocompatibility and resorbable characteristics. This polymer is an aliphatic polyester which has been mostly used in biomedical application. It is an organic compound with low allergenic potential, low toxicity, high biocompatibility and predictable kinetics of degradation. In this study we fabricated and evaluated a PLA microporous hollow fiber as a conduit for its ability to bridge a nerve gap in a mouse sciatic nerve injury model. The PLA conduit was prepared from a polymer solution, throughout extrusion technique. The left sciatic nerve of C57BL/6 mouse was transected and the nerve stumps were placed into a resorbable PLA (PLA group) or a PCL conduit (PCL group), n=5 each group. We have also used another group in which the nerves were repaired by autograft (autograft group, n=5). Motor function was analyzed according to sciatic functional index (SFI). After 56days, the regenerated nerves were processed for light and electron microscopy and morphometric analyses were performed. A quantitative analysis of regenerated nerves showed significant increase in the number of myelinated fibers and blood vessels in animals that received PLA conduit. The PLA group exhibited better overall tissue organization compared to other groups. Presenting well-organized bundles, many regenerating clusters composed of preserved nerve fibers surrounded by layers of compacted perineurium-like cells. Also the SFI revealed a significant improvement in functional recovery. This work suggests that PLA conduits are suitable substrate for cell survival and it provides an effective strategy to be used to support axonal growth becoming a potential alternative to autograft.

  14. Comparative study of the efficacy of decellularization treatment of allogenic and xenogeneic nerves as nerve conduits.

    PubMed

    Wang, Wei; Itoh, Soichiro; Takakuda, Kazuo

    2016-02-01

    The objective of this study was to compare the results of allogenic and xenogeneic nerve grafts that were treated using decellularization. The sciatic nerves of Sprague-Dawley rats and the median nerves of Japanese white rabbits were decellularized with sodium dodecyl sulfate and Triton X-100 and examined with a scanning electron microscope and immunofluorescence staining. A bridge-graft into the sciatic nerve in Wistar rats was performed with the decellularized nerves (10 mm in length for short-term evaluation; 15 mm in length for long-term evaluation). As a control, an isograft was performed. The specimens were harvested at 4 weeks postoperatively and prepared for immunohistochemistry. Function, electrophysiological and histomorphological analyses were performed to evaluate nerve recovery at 24 weeks postoperatively. The 3-dimensional structure of the basal lamina column, on which the cell adhesion molecules were integrated, was preserved through the decellularization protocols. Limited ED1-positive macrophage invasion was observed, and abundant NF 160-positive axons, which were accompanied by S-100-positive Schwann cells, penetrated through the implanted nerves. The sciatic nerve function and electrophysiological and histomorphological analyses suggest that the xenogeneic nerve graft was statistically indistinguishable from the allogenic nerve graft but slightly inferior to the isograft in supporting the axonal regeneration and functional recovery.

  15. An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material.

    PubMed

    Chen, Yueh-Sheng; Chang, Ju-Ying; Cheng, Chun-Yuan; Tsai, Fuu-Jen; Yao, Chun-Hsu; Liu, Bai-Shuan

    2005-06-01

    We evaluated peripheral nerve regeneration using a biodegradable nerve conduit, which was made of genipin-cross-linked gelatin. The genipin-cross-linked gelatin conduit (GGC) was dark blue in appearance, which was concentric and round with a rough outer surface whereas its inner lumen was smooth. After subcutaneous implantation on the dorsal side of the rat, the GGC only evoked a mild tissue response, forming a thin tissue capsule surrounding the conduit. Biodegradability of the GGC and its effectiveness as a guidance channel were examined as it was used to repair a 10 mm gap in the rat sciatic nerve. As a result, tube fragmentation was not obvious until 6 weeks post-implantation and successful regeneration through the gap occurred in all the conduits at the three experimental periods of 4, 6, and 8 weeks. Histological observation showed that numerous regenerated nerve fibers, mostly unmyelinated and surrounded by Schwann cells, crossed through and beyond the gap region 6 weeks after operation. Peak amplitude and area under the muscle action potential curve both showed an increase as a function of the recovery period, indicating that the nerve had undergone adequate regeneration. Thus, the GGC can not only be an effective aids for regenerating nerves but can also lead to favorable nerve functional recovery.

  16. Functional recovery guided by an electrospun silk fibroin conduit after sciatic nerve injury in rats.

    PubMed

    Park, Sook Young; Ki, Chang Seok; Park, Young Hwan; Lee, Kwang Gill; Kang, Seok Woo; Kweon, Hae Yong; Kim, Hyun Jeong

    2015-01-01

    The aim of this study was to evaluate the regenerative capacity of a newly developed nerve guidance conduit using electrospun silk fibroin (SFNC) implanted in a 10-mm defect of the sciatic nerve in rats. After evaluating the physical properties and cytocompatibility of SFNC in vitro, rats were randomly allocated into three groups: defect only, autograft and SFNC. To compare motor function and abnormal sensation among groups, ankle stance angle (ASA) and severity of autotomy were observed for 10 weeks after injury. Immunostaining with axonal neurofilament (NF) and myelin basic protein (MBP) antibodies were performed to investigate regenerated nerve fibres inside SFNC. ASA increased significantly in the SFNC group at 1, 7 and 10 weeks after injury compared to the defect only group (p<0.05). At one week, mean ASA of the SFNC group was significantly higher than that of the autograft group (p<0.05). Onset and severity of autotomy decreased significantly in the SFNC group compared to other groups (p<0.05). Autotomy in the SFNC group started at 4 weeks and maximally reached toe level. However, the defect only and autograft groups first showed autotomy at 2 and 1 weeks following injury, respectively, and then reached the sole level. Well myelinated nerve fibres stained with NF and MBP were found inside SFNC. In conclusion, SFNC could be helpful in restoring motor function and preventing abnormal sensations after nerve injury.

  17. Vein conduit associated with microsurgical suture for complete collateral digital nerve severance.

    PubMed

    Alligand-Perrin, P; Rabarin, F; Jeudy, J; Césari, B; Saint-Cast, Y; Fouque, P-A; Raimbeau, G

    2011-06-01

    The aim of this study is to present the long term results of a series of 53 vein conduit grafts as first line therapy to repair complete severance of one or more collateral digital nerves. The surgical technique included an epi-perineural suture of the nerve under minimal tension, associated with a vein graft harvested from the back of the hand to cover the nerve. None of the patients presented with a neuroma, spontaneous pain or had stopped using the injured finger. Sensibility results were good or very good in 67% of cases. The scar at the donor site was very light or invisible. A total of 96% of patients were satisfied or very satisfied. This simple technique, by protecting the injured nerve, results in a rate of sensory nerve recovery that is comparable or better than that of other series in the literature, without neuroma and with minimal scarring at the donor site. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  18. Electrospun Nerve Guide Scaffold of Poly (ε-caprolactone)/Collagen/Nano-Bioglass: An in-vitro Study in Peripheral Nerve Tissue Engineering.

    PubMed

    Mohamadi, Forouzan; Ebrahimi-Barough, Somayeh; Nourani, Mohammad Reza; Derakhshan, Mohammad Ali; Goodarzi, Vahabodin; Nazockdast, Mohammad Sadegh; Farokhi, Mehdi; Tajerian, Roksana; Faridi Majidi, Reza; Ai, Jafar

    2017-03-21

    In among of various methods, nerve tissue engineering (NTE) is one of the applicable methods to reconstruct damaged nerve tissues. Electrospinning technique and biomaterials are often considered to fabricate fibrous tissue engineered conduits which have great similarity to the extracellular matrix on fiber structure. Polymer blending is one of the most effective methods for production of new materials with outstanding features. In this research, conduit structures as main part of the peripheral nerve regeneration based on polymer blend nanocomposites PCL/Collagen/NBG (poly (ε-caprolactone)/Collagen/nano bioglass) were manufactured by electrospinning technique. The various properties of electrospun mats were investigated by using contact angle, tensile, degradation time, porosity, scanning electron microscopy (SEM), Fourier-transfer infrared (FTIR), and wide-angle X-ray scattering (WAXS). The SEM analysis was shown that size range and average pore size of polymer blend nanocomposite nanofibers were about 250-400 nm and 0.7µm respectively with an optimum porosity of 62.5%. The XRD result was shown that synthesized nanoparticles of NBG had amorphous structures. Also, FTIR analysis indicated that good interaction between polymer-polymer macromolecules and polymer-particles. The Contact-angle and tensile tests analysis were indicated that electrospun webs showed good hydrophilicity and toughness properties. According to SEM, MTT assay and DAPI staining technique, the ability to support cell attachment and viability of samples were characterized. In vitro study indicated electrospun collagen/PCL/NBG nanofibrous conduit promoted Human Endometrial Stem cells (hEnSCs) adhesion and proliferation. This article is protected by copyright. All rights reserved.

  19. The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model.

    PubMed

    Yurie, Hirofumi; Ikeguchi, Ryosuke; Aoyama, Tomoki; Kaizawa, Yukitoshi; Tajino, Junichi; Ito, Akira; Ohta, Souichi; Oda, Hiroki; Takeuchi, Hisataka; Akieda, Shizuka; Tsuji, Manami; Nakayama, Koichi; Matsuda, Shuichi

    2017-01-01

    Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

  20. The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model

    PubMed Central

    Yurie, Hirofumi; Ikeguchi, Ryosuke; Aoyama, Tomoki; Kaizawa, Yukitoshi; Tajino, Junichi; Ito, Akira; Ohta, Souichi; Oda, Hiroki; Takeuchi, Hisataka; Akieda, Shizuka; Tsuji, Manami; Nakayama, Koichi; Matsuda, Shuichi

    2017-01-01

    Background Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. Methods We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Results Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). Conclusions We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model. PMID:28192527

  1. Crosslinking of micropatterned collagen-based nerve guides to modulate the expected half-life.

    PubMed

    Salvatore, L; Madaghiele, M; Parisi, C; Gatti, F; Sannino, A

    2014-12-01

    The microstructural, mechanical, compositional, and degradative properties of a nerve conduit are known to strongly affect the regenerative process of the injured peripheral nerve. Starting from the fabrication of micropatterned collagen-based nerve guides, according to a spin-casting process reported in the literature, this study further investigates the possibility to modulate the degradation rate of the scaffolds over a wide time frame, in an attempt to match different rates of nerve regeneration that might be encountered in vivo. To this aim, three different crosslinking methods, that is, dehydrothermal (DHT), carbodiimide-based (EDAC), and glutaraldehyde-based (GTA) crosslinking, were selected. The elastically effective degree of crosslinking, attained by each method and evaluated according to the classical rubber elasticity theory, was found to significantly tune the in vitro half-life (t1/2 ) of the matrices, with an exponential dependence of the latter on the crosslink density. The high crosslinking efficacy of EDAC and GTA treatments, respectively threefold and fourfold when compared to the one attained by DHT, led to a sharp increase of the corresponding in vitro half-lives (ca., 10, 172, and 690 h, for DHT, EDAC, and GTA treated matrices, respectively). As shown by cell viability assays, the cytocompatibility of both DHT and EDAC treatments, as opposed to the toxicity of GTA, suggests that such methods are suitable to crosslink collagen-based scaffolds conceived for clinical use. In particular, nerve guides with expected high residence times in vivo might be produced by finely controlling the biocompatible reaction(s) adopted for crosslinking.

  2. Highly permeable genipin-cross-linked gelatin conduits enhance peripheral nerve regeneration.

    PubMed

    Chang, Ju-Ying; Ho, Tin-Yun; Lee, Han-Chung; Lai, Yen-Liang; Lu, Ming-Chin; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2009-12-01

    Here we have evaluated peripheral nerve regeneration with a porous biodegradable nerve conduit (PGGC), which was made from genipin-cross-linked gelatin. To examine the effect of pores, nonporous genipin-cross-linked gelatin conduit (GGC) was considered as the control. Both the PGGC and the GGC were dark blue in appearance with a concentric and round lumina. The PGGC featured an outer surface with pores of variable size homogeneously traversing, and a partially fenestrated inner surface connected by an open trabecular meshwork. The GGC had a rough outer surface whereas its inner lumen was smooth. Both PGGCs and GGCs had similar hydrophilicity on condition of the same material and cross-linking degree. The porosity of PGGCs and GGCs was 90.8 +/- 0.9% and 24.3 +/- 2.9%, respectively. The maximum tensile force of the GGCs (0.12 +/- 0.06 kN) exceeded that of the PGGCs (0.03 +/- 0.01 kN), but the PGGCs had a higher swelling ratio than GGCs at 0.5, 1, 3, 6, 12, 24, 48, 60, 72, and 84 h after soaking in deionized water. Cytotoxic testing revealed the soaking solutions of both of the tube composites would not produce cytotoxicity to cocultured Schwann cells. After subcutaneous implantation on the dorsal side of the rat, the PGGC was degraded completely after 12 weeks of implantation whereas a thin tissue capsule was formed encapsulating the partially degraded GGC. Biodegradability of both of the tube groups and their effectiveness as a guidance channel were examined as they were used to repair a 10 mm gap in the rat sciatic nerve. As a result, fragmentation of the GGC was still seen after 12 weeks of implantation, yet the PGGC had been completely degraded. Histological observation showed that numerous myelinated axons had crossed over the gap region in the PGGCs after 8 weeks of implantation despite only few myelinated axons and unmyelinated axons mostly surrounded by Schwann cells seen in the GGCs. In addition, the regenerated nerves in the PGGCs presented a significantly

  3. Combined use of decellularized allogeneic artery conduits with autologous transdifferentiated adipose-derived stem cells for facial nerve regeneration in rats.

    PubMed

    Sun, Fei; Zhou, Ke; Mi, Wen-juan; Qiu, Jian-hua

    2011-11-01

    Natural biological conduits containing seed cells have been widely used as an alternative strategy for nerve gap reconstruction to replace traditional nerve autograft techniques. The purpose of this study was to investigate the effects of a decellularized allogeneic artery conduit containing autologous transdifferentiated adipose-derived stem cells (dADSCs) on an 8-mm facial nerve branch lesion in a rat model. After 8 weeks, functional evaluation of vibrissae movements and electrophysiological assessment, retrograde labeling of facial motoneurons and morphological analysis of regenerated nerves were performed to assess nerve regeneration. The transected nerves reconstructed with dADSC-seeded artery conduits achieved satisfying regenerative outcomes associated with morphological and functional improvements which approached those achieved with Schwann cell (SC)-seeded artery conduits, and superior to those achieved with artery conduits alone or ADSC-seeded artery conduits, but inferior to those achieved with nerve autografts. Besides, numerous transplanted PKH26-labeled dADSCs maintained their acquired SC-phenotype and myelin sheath-forming capacity inside decellularized artery conduits and were involved in the process of axonal regeneration and remyelination. Collectively, our combined use of decellularized allogeneic artery conduits with autologous dADSCs certainly showed beneficial effects on nerve regeneration and functional restoration, and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Myelinated nerve bundles developed on the plano-concave fibers containing nerve conduit.

    PubMed

    Huang, Wei-Chin; Liao, Jiunn-Der; Lin, Chou-Ching K; Ju, Ming-Shaung

    2012-12-01

    Morphologically and chemically modified plano-concave fibers (PCFs) are designed as a unit of guided channels for supporting Schwann cells to facilitate mass transport and promote nerve regeneration. The surface-modified PCFs are imprinted with linearly patterned grooves (LPGs) to guide adherent Schwann cell elongation and axon extension. After being cocultured with PC12 neuron-like cells, Schwann cells differentiate into the myelinated type and interact with PC12 axons. The myelinated axons aggregate as a linear bundle and extend along the direction of LPGs on a PCF. The cross section of a myelin structure is examined using a transmission electron microscope. The PCFs can potentially bridge gaps in injured nerves, improving the therapeutic efficacy of nerve regeneration. Copyright © 2012 Wiley Periodicals, Inc.

  5. Effects of local administration of ibuprofen on sciatic nerve regeneration and reinnervation after egg shell membrane conduit repair in rat.

    PubMed

    Raisi, A; Mohammadi, R

    2015-03-24

    The objective was to assess the effect of locally administered ibuprofen (IBU) on transected peripheral nerve regeneration and functional recovery. Seventy--five male Wistar rats were divided into five experimental groups (n = 15), randomly: In authograft group (AUTO) a segment of sciatic nerve was transected and reimplanted reversely. In transected group (TC), left sciatic nerve was transected and stumps were fixed in the adjacent muscle. In treatment group defect was bridged using an egg shell membrane conduit (ESM/IBU) filled with 10 μL ibuprofen (100 ng/mL). In ESM conduit group (ESM), the conduit was filled with phosphate--buffered saline alone. In sham--operated group (SHAM), sciatic nerve was exposed and manipulated. Each group was subdivided into three subgroups of five animals each and regenerated nerve fibers were studied 4, 8 and 12 weeks after surgery. Behavioral testing, biomechanical studies, sciatic nerve functional study, electrophysiological, gastrocnemius muscle mass and morphometric indices confirmed faster recovery of regenerated axons in ESM/IBU than ESM group (p < 0.05). In immunohistochemistry, location of reactions to S--100 in ESM/IBU was clearly more positive than that in ESM group. Ibuprofen accelerated and improved functional recovery and morphometric indices of sciatic nerve. This study is expected to set a stage for testing the ibuprofen in the human patients.

  6. Sciatic nerve repair with tissue engineered nerve: Olfactory ensheathing cells seeded poly(lactic-co-glygolic acid) conduit in an animal model

    PubMed Central

    Tan, C W; Ng, M H; Ohnmar, H; Lokanathan, Y; Nur-Hidayah, H; Roohi, S A; Ruszymah, BHI; Nor-Hazla, M H; Shalimar, A; Naicker, A S

    2013-01-01

    Background and Aim: Synthetic nerve conduits have been sought for repair of nerve defects as the autologous nerve grafts causes donor site morbidity and possess other drawbacks. Many strategies have been investigated to improve nerve regeneration through synthetic nerve guided conduits. Olfactory ensheathing cells (OECs) that share both Schwann cell and astrocytic characteristics have been shown to promote axonal regeneration after transplantation. The present study was driven by the hypothesis that tissue-engineered poly(lactic-co-glycolic acid) (PLGA) seeded with OECs would improve peripheral nerve regeneration in a long sciatic nerve defect. Materials and Methods: Sciatic nerve gap of 15 mm was created in six adult female Sprague-Dawley rats and implanted with PLGA seeded with OECs. The nerve regeneration was assessed electrophysiologically at 2, 4 and 6 weeks following implantation. Histopathological examination, scanning electron microscopic (SEM) examination and immunohistochemical analysis were performed at the end of the study. Results: Nerve conduction studies revealed a significant improvement of nerve conduction velocities whereby the mean nerve conduction velocity increases from 4.2 ΁ 0.4 m/s at week 2 to 27.3 ΁ 5.7 m/s at week 6 post-implantation (P < 0.0001). Histological analysis revealed presence of spindle-shaped cells. Immunohistochemical analysis further demonstrated the expression of S100 protein in both cell nucleus and the cytoplasm in these cells, hence confirming their Schwann-cell-like property. Under SEM, these cells were found to be actively secreting extracellular matrix. Conclusion: Tissue-engineered PLGA conduit seeded with OECs provided a permissive environment to facilitate nerve regeneration in a small animal model. PMID:24379458

  7. Enhancing Peripheral Nerve Regeneration with a Novel Drug-Delivering Nerve Conduit

    DTIC Science & Technology

    2015-10-01

    Gale/Terry)(0-4months) b. Optimize nanoporous membrane dimensions ................... (Gale)(2-6months) c. Optimize reservoir...these goals? Major Activities Tasks/Subtasks: Task 1. Manufacture Devices for use in nerve gap a. Optimize PGLA ratios b. Optimize nanoporous ... material we initially chose was not the ideal material . We therefore wanted to choose a material that can maintain its structure for the duration of

  8. Adult Stem Cell Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

    DTIC Science & Technology

    2016-10-01

    regenerate and to reconnect across a limited gap , surgical intervention is often required to assist them in bridging a larger gap . Typically...provide better guidance for the microstructure of the nerve to bridge the injury gap . Our Specific Aims are as follows: (1) optimize the...accompolishments achieved to date with respect to each proposed task are: Task 1: Produce nanofibrous scaffolds of controlled thickness comprised of

  9. Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration.

    PubMed

    Kohn-Polster, Caroline; Bhatnagar, Divya; Woloszyn, Derek J; Richtmyer, Matthew; Starke, Annett; Springwald, Alexandra H; Franz, Sandra; Schulz-Siegmund, Michaela; Kaplan, Hilton M; Kohn, Joachim; Hacker, Michael C

    2017-05-21

    Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR.

  10. Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration

    PubMed Central

    Kohn-Polster, Caroline; Bhatnagar, Divya; Woloszyn, Derek J.; Richtmyer, Matthew; Starke, Annett; Springwald, Alexandra H.; Franz, Sandra; Schulz-Siegmund, Michaela; Kaplan, Hilton M.; Kohn, Joachim; Hacker, Michael C.

    2017-01-01

    Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR. PMID:28531139

  11. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury

    PubMed Central

    Wang, Ya-ling; Gu, Xiao-mei; Kong, Yan; Feng, Qi-lin; Yang, Yu-min

    2015-01-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  12. Enhancement of nerve regeneration and orientation across a gap with a nerve graft within a vein conduit graft: a functional, stereological, and electrophysiological study.

    PubMed

    Keskin, Mustafa; Akbaş, Hayati; Uysal, O Ata; Canan, Sinan; Ayyldz, Mustafa; Ağar, Erdal; Kaplan, Süleyman

    2004-04-15

    In this study, the right sciatic nerves of 40 rats were used to determine whether a nerve graft within a vein graft might accelerate and facilitate axonal regeneration, compared with a nerve graft alone. The animals were separated into four groups, as follows: group 1, sham control; group 2 (control), segmental nerve resection and no repair; group 3, segmental nerve resection and nerve grafting; group 4, segmental nerve resection and reconstruction with a nerve graft within a vein conduit graft. For all groups, sciatic functional indices were calculated before the operation and on postoperative days 7 and 90. On postoperative day 90, the sciatic nerves were reexposed and nerve conduction velocities were recorded. The sciatic nerves were harvested from all groups for counting of the myelinated axons with a stereological method. No statistically significant differences with respect to return of gait function, axon count, or nerve conduction were noted between groups 3 and 4 (p > 0.05). However, functional recovery in group 4 on postoperative day 90 was significant, compared with group 2 (p < 0.05); the recovery difference between groups 2 and 3 was not significant (p > 0.05). This study was not able to demonstrate any functional benefits with the use of a nerve graft within a vein graft, compared with standard nerve grafting.

  13. The effect of high outflow permeability in asymmetric poly(dl-lactic acid-co-glycolic acid) conduits for peripheral nerve regeneration.

    PubMed

    Chang, Chen-Jung; Hsu, Shan-Hui

    2006-03-01

    This study attempted to accelerate the peripheral nerve regeneration, using the high outflow rate of asymmetric poly(dl-lactic acid-co-glycolic acid) (PLGA) nerve conduits. Asymmetric PLGA nerve conduits of monomer ratio 85/15 were prepared by immersion-precipitation method to serve as possible materials. In this study, mandrels were immersed into a 20% (wt/wt) of PLGA/1,4-dioxane solution and precipitated in a non-solvent bath followed by freeze-drying. Different concentrations of isopropyl alcohol (95%, 40% and 20%) were used as precipitation baths where non-asymmetric (95%) and asymmetric (40% and 20%) conduits could easily form. The asymmetric nerve conduits that consisted of macrovoids on the outer layer, and interconnected micropores in the inner sublayer, possessed characters of larger outflow rate than inflow rate. The asymmetric conduits were implanted to 10mm right sciatic nerve defects in rats. Autografts, silicone and non-asymmetric PLGA conduits were performed as the control and the contrast groups. Implanted graft specimens of all groups were harvested for histological analysis at 4 and 6 weeks following surgery. The asymmetric PLGA conduits maintained a stable supporting structure and inhibited exogenous cells invasion during entire regeneration process. Asymmetric PLGA conduits were found to have statistically greater number of regenerated axons at the midconduit and distal nerve site of implanted grafts, as compared to the silicone and non-asymmetric groups at 4 and 6 weeks. Of interest was that the results of 4 weeks in asymmetric groups were better than the non-asymmetric groups at 6 weeks in number of axons. According to the results of permeability, the asymmetric structure in the conduit wall seemed to enhance the removal of the blockage of the waste drain from the inner inflamed wound in the early stage, which may have improved the efficacy of the peripheral nerve regeneration. The asymmetric structure could be adequately employed in the

  14. Electrospun micro/nanofibrous conduits composed of poly(epsilon-caprolactone) and small intestine submucosa powder for nerve tissue regeneration.

    PubMed

    Hong, Soongee; Kim, Geunhyung

    2010-08-01

    Three-dimensional biocompatible and biodegradable scaffolds play important roles in tissue engineering. In this study, fibrous mats composed of electrospun poly(epsilon-caprolactone) (PCL)/small intestine submucosa (SIS) tubes were fabricated with a high degree of longitudinal alignment as a conduit for peripheral nerves. Fourier transform infrared analyses of electrospun PCL/SIS mats with various amounts of SIS showed that the SIS was well embedded within the PCL matrix. The diameter of the PCL/SIS fibers with the 3 wt % of SIS in the PCL solution decreased 40% relative to that of pure PCL fibers due to increased electrical conductivity and decreased surface tension. PCL/SIS (3 wt %) electrospun mats exhibited various synergistic effects, including stronger mechanical properties (Young's modulus = more than 80%) and enhanced hydrophilicity (water contact angle at 30 min = 54 degrees ) relative to pure PCL (water contact angle at 30 min = 142 degrees ). Cell attachment and proliferation experiments demonstrated that the interactions between nerve cells (PC-12) and the PCL/SIS conduits were more favorable than those between PC-12 cells and a pure PCL conduit. This study contributes to the understanding of the effects of including SIS in electrospun composite mats. The ability to fabricate highly aligned tubes of PCL/SIS with appropriate mechanical properties and cellular interactions shows great potential for the design of nerve regeneration conduits.

  15. Collagen biomaterial doped with colominic acid for cell culture applications with regard to peripheral nerve repair.

    PubMed

    Bruns, Stephanie; Stark, Yvonne; Röker, Stefanie; Wieland, Martin; Dräger, Gerald; Kirschning, Andreas; Stahl, Frank; Kasper, Cornelia; Scheper, Thomas

    2007-09-15

    Colominic acid (CA) is a homopolymer of sialic acid residues and is solely composed of polymerised units of alpha-2,8-linked N-acetylneuraminic acid. CA is a specific derivative of polysialic acid (PSA), produced as the capsular polysaccharide of Escherichia coli K1 derived molecule of PSA. PSA in vivo plays a significant role in synaptic plasticity and neural development. The use of collagen materials doped with defined CA is presented for the cultivation of various cell lines relevant for possible applications in Tissue Engineering. First, the release behaviour under culture conditions of the collagen-based (C-CA) materials was investigated by thiobarbituric acid assay. Additionally, the established cell lines, PC-12 and immortalised Schwann cells (ISC), used for neurobiological and neurochemical studies and the model liver cell line Hep-G2 as indicator for biocompatibility testing, were cultured on the C-CA matrix. Cell proliferation (MTT-test) and cell adhesion (DAPI-staining) of the cell lines on the matrices were observed. Likewise, gene expression of the marker genes thyrosine hydroxylase for the PC-12 cells, and albumin, transferrin and CYP3A4 for the Hep-G2 cells was evaluated via RT-PCR. The results indicate that CA integration in established biomaterial constructs enhances cell proliferation and offers promising features as conduits additive in regarding peripheral nerve regeneration.

  16. Enhancement of median nerve regeneration by mesenchymal stem cells engraftment in an absorbable conduit: improvement of peripheral nerve morphology with enlargement of somatosensory cortical representation

    PubMed Central

    Oliveira, Julia T.; Bittencourt-Navarrete, Ruben Ernesto; de Almeida, Fernanda M.; Tonda-Turo, Chiara; Martinez, Ana Maria B.; Franca, João G.

    2014-01-01

    We studied the morphology and the cortical representation of the median nerve (MN), 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL) conduit with or without bone marrow-derived mesenchymal stem cell (MSC) transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1), electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in three groups: MN Intact (n = 4), PCL-Only (n = 3), and PCL+MSC (n = 3). Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group) or without (PCL-Only group) injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to five animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383 ± 390 fibers; 2.3 mm2, respectively) than the PCL-Only group (2,226 ± 575 fibers; 1.6 mm2). In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN. PMID:25360086

  17. Enhancement of median nerve regeneration by mesenchymal stem cells engraftment in an absorbable conduit: improvement of peripheral nerve morphology with enlargement of somatosensory cortical representation.

    PubMed

    Oliveira, Julia T; Bittencourt-Navarrete, Ruben Ernesto; de Almeida, Fernanda M; Tonda-Turo, Chiara; Martinez, Ana Maria B; Franca, João G

    2014-01-01

    We studied the morphology and the cortical representation of the median nerve (MN), 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL) conduit with or without bone marrow-derived mesenchymal stem cell (MSC) transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1), electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in three groups: MN Intact (n = 4), PCL-Only (n = 3), and PCL+MSC (n = 3). Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group) or without (PCL-Only group) injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to five animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383 ± 390 fibers; 2.3 mm(2), respectively) than the PCL-Only group (2,226 ± 575 fibers; 1.6 mm(2)). In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.

  18. Collagen microstructural factors influencing optic nerve head biomechanics.

    PubMed

    Zhang, Liang; Albon, Julie; Jones, Hannah; Gouget, Cecile L M; Ethier, C Ross; Goh, James C H; Girard, Michaël J A

    2015-03-03

    Previous studies have suggested that the lamina cribrosa (LC) and its surrounding sclera are biomechanically important in the pathogenesis of glaucoma, but many were limited by assumptions of tissue isotropy and homogeneity. Here, we used an improved biomechanical model driven by experimental measurements of scleral and LC collagen fiber organization to more accurately evaluate optic nerve head (ONH) biomechanics. Collagen fiber organization was quantitatively mapped across human ONH cryosections (three normal and three glaucomatous) using small-angle light scattering (SALS) and fed into two-dimensional finite element models loaded under biaxial stress to simulate raised intraocular pressure. Effects of artificial variations in collagen fiber microstructure and stiffness on LC and scleral strains were also investigated. Scleral collagen fibers were circumferential and exhibited the highest alignment in a region not immediately adjacent to, but at a distance (400-500 μm) away from, the LC. In models, such a fiber arrangement yielded rings of low strain (second principal and effective) in the scleral region immediately adjacent to the LC. Further sensitivity analyses showed that scleral fiber alignment was crucial in determining LC strain levels. Moderate scleral anisotropy (as observed physiologically) was more effective than isotropy or high anisotropy in limiting LC and scleral strain magnitude. The presence of a heterogeneous collagen fiber organization in the peripapillary sclera appears effective in limiting LC strain and is able to reduce strain levels at the scleral canal boundary: a transition zone prone to LC disinsertion, focal lamina cribrosa defects, and optic disc hemorrhages in glaucoma. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  19. Large-area irradiated low-level laser effect in a biodegradable nerve guide conduit on neural regeneration of peripheral nerve injury in rats.

    PubMed

    Shen, Chiung-Chyi; Yang, Yi-Chin; Liu, Bai-Shuan

    2011-08-01

    This study used a biodegradable composite containing genipin-cross-linked gelatin annexed with β-tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT), developed in a previous study, as a nerve guide conduit. The aim of this study was to analyse the influence of a large-area irradiated aluminium-gallium-indium phosphide (AlGaInP) diode laser (660 nm) on the neural regeneration of the transected sciatic nerve after bridging the GGT nerve guide conduit in rats. The animals were divided into two groups: group 1 comprised sham-irradiated controls and group 2 rats underwent low-level laser (LLL) therapy. A compact multi-cluster laser system with 20 AlGaInP laser diodes (output power, 50mW) was applied transcutaneously to the injured peripheral nerve immediately after closing the wound, which was repeated daily for 5 min for 21 consecutive days. Eight weeks after implantation, walking track analysis showed a significantly higher sciatic function index (SFI) score (P<0.05) and better toe spreading development in the laser-treated group than in the sham-irradiated control group. For electrophysiological measurement, both the mean peak amplitude and nerve conduction velocity of compound muscle action potentials (CMAPs) were higher in the laser-treated group than in the sham-irradiated group. The two groups were found to be significantly different during the experimental period (P<0.005). Histomorphometric assessments revealed that the qualitative observation and quantitative analysis of the regenerated nerve tissue in the laser-treated group were superior to those of the sham-irradiated group. Thus, the motor functional, electrophysiologic and histomorphometric assessments demonstrate that LLL therapy can accelerate neural repair of the corresponding transected peripheral nerve after bridging the GGT nerve guide conduit in rats.

  20. A Controlled Design of Aligned and Random Nanofibers for 3D Bi-functionalized Nerve Conduits Fabricated via a Novel Electrospinning Set-up

    PubMed Central

    Kim, Jeong In; Hwang, Tae In; Aguilar, Ludwig Erik; Park, Chan Hee; Kim, Cheol Sang

    2016-01-01

    Scaffolds made of aligned nanofibers are favorable for nerve regeneration due to their superior nerve cell attachment and proliferation. However, it is challenging not only to produce a neat mat or a conduit form with aligned nanofibers but also to use these for surgical applications as a nerve guide conduit due to their insufficient mechanical strength. Furthermore, no studies have been reported on the fabrication of aligned nanofibers and randomly-oriented nanofibers on the same mat. In this study, we have successfully produced a mat with both aligned and randomly-oriented nanofibers by using a novel electrospinning set up. A new conduit with a highly-aligned electrospun mat is produced with this modified electrospinning method, and this proposed conduit with favorable features, such as selective permeability, hydrophilicity and nerve growth directional steering, were fabricated as nerve guide conduits (NGCs). The inner surface of the nerve conduit is covered with highly aligned electrospun nanofibers and is able to enhance the proliferation of neural cells. The central part of the tube is double-coated with randomly-oriented nanofibers over the aligned nanofibers, strengthening the weak mechanical strength of the aligned nanofibers. PMID:27021221

  1. A Controlled Design of Aligned and Random Nanofibers for 3D Bi-functionalized Nerve Conduits Fabricated via a Novel Electrospinning Set-up.

    PubMed

    Kim, Jeong In; Hwang, Tae In; Aguilar, Ludwig Erik; Park, Chan Hee; Kim, Cheol Sang

    2016-03-29

    Scaffolds made of aligned nanofibers are favorable for nerve regeneration due to their superior nerve cell attachment and proliferation. However, it is challenging not only to produce a neat mat or a conduit form with aligned nanofibers but also to use these for surgical applications as a nerve guide conduit due to their insufficient mechanical strength. Furthermore, no studies have been reported on the fabrication of aligned nanofibers and randomly-oriented nanofibers on the same mat. In this study, we have successfully produced a mat with both aligned and randomly-oriented nanofibers by using a novel electrospinning set up. A new conduit with a highly-aligned electrospun mat is produced with this modified electrospinning method, and this proposed conduit with favorable features, such as selective permeability, hydrophilicity and nerve growth directional steering, were fabricated as nerve guide conduits (NGCs). The inner surface of the nerve conduit is covered with highly aligned electrospun nanofibers and is able to enhance the proliferation of neural cells. The central part of the tube is double-coated with randomly-oriented nanofibers over the aligned nanofibers, strengthening the weak mechanical strength of the aligned nanofibers.

  2. Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

    NASA Astrophysics Data System (ADS)

    Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

    2014-08-01

    Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

  3. Glycomimetic functionalized collagen hydrogels for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

    Masand, Shirley Narain

    Despite the innate regenerative potential of the peripheral nervous system, functional recovery is often limited. The goal of this dissertation was to develop a clinically relevant biomaterial strategy to (1) encourage the regrowth of axons and (2) direct them down their appropriate motor tracts. To this end, we use peptide mimics of two glycans, polysialic acid (PSA) and an epitope first discovered on human natural killer cells (HNK-1), to functionalize type I collagen hydrogels. Previous studies have shown that these molecules, in their glycan and glycomimetic form, are associated with acceleration of neurite outgrowth, glial cell proliferation, and motoneuron targeting. In vitro, we demonstrated the retained functionality of the peptide glycomimetics after conjugation to a type I collagen backbone. While HNK-functionalized collagen increased motor neurite outgrowth, PSA-functionalized collagen encouraged motor and sensory neurite outgrowth and Schwann cell extension and proliferation. When we introduce these glycomimetic-functionalized collagen hydrogels into a critical gap femoral nerve model, we show that both PSA and HNK-functionalized hydrogels yielded a significant increase in functional recovery when compared to saline, native and scramble-coupled hydrogels. However, there was an interesting divergence in the morphological results: PSA-functionalized hydrogels increased axon count and HNK-functionalized hydrogels increased motoneuron targeting and myelination. We believed that these differences may be attributed to distinct mechanisms by which the glycomimetics impart their benefit. Interestingly, however, we found no synergistic gain in recovery with the use of our composite hydrogels which we speculated may be due to an inadequate dose of the individual glycomimetic. To address this possibility, we show that increasing the amount of functionalized peptide functionalized in our composite hydrogels led to increases in axon count and area of regeneration

  4. Pulsed electromagnetic fields accelerate functional recovery of transected sciatic nerve bridged by chitosan conduit: an animal model study.

    PubMed

    Mohammadi, Rahim; Faraji, Darab; Alemi, Hanieh; Mokarizadeh, Aram

    2014-12-01

    Effect of whole body exposure to pulsed electromagnetic fields (PEMF) on nerve regeneration in a rat sciatic nerve transection model was assessed. Sixty male white Wistar rats were divided into four experimental groups (n = 15), randomly: In transected group (TC) left sciatic nerve was transected and stumps were fixed in adjacent muscle. In chitosan group (CHIT) the defect was bridged using a chitosan conduit filled with phosphate-buffered saline. In treatment group (CHIT/PEMF) the whole body was exposed to PEMF (0.3 mT, 2 Hz) for 4 h/day within 1-5 days. In normal control group (NC) sciatic nerve was only dissected and manipulated. Each group was subdivided into three subgroups of five animals each and nerve fibers were studied 4, 8 and 12 weeks after surgery. Behavioral, functional, electrophysiological, biomechanical, gastrocnemius muscle mass findings and morphometric indices confirmed faster recovery of regenerated axons in CHIT/PEMF than in CHIT group (p < 0.05). Immunohistochemical reactions to S-100 in CHIT/PEMF were more positive than that in CHIT group. Whole body exposure to PEMF improved functional recovery and morphometric indices of sciatic nerve. Detailed mechanism of neuroprotective action remains to be investigated. PEMF combine with chitosan grafting could be considered as an effective, safe and tolerable treatment for peripheral nerve repair in clinical practice. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  5. Promotion of peripheral nerve regeneration and prevention of neuroma formation by PRGD/PDLLA/β-TCP conduit: report of two cases.

    PubMed

    Yin, Yixia; Li, Binbin; Yan, Qiongjiao; Dai, Honglian; Wang, Xinyu; Huang, Jifeng; Li, Shipu

    2015-06-01

    In the field of nerve repair, one major challenge is the formation of neuroma. However, reports on both the promotion of nerve regeneration and prevention of traumatic neuroma in the clinical settings are rare in the field of nerve repair. One of the reasons could be the insufficiency in the follow-up system. We have conducted 33 cases of nerve repair using PRGD/PDLLA/β-TCP conduit without any sign of adverse reaction, especially no neuroma formation. Among them, we have selected two cases as representatives to report in this article. The first case was a patient with an upper limb nerve wound was bridged by PRGD/PDLLA/β-TCP conduit and a plate fixation was given. After nearly 3-years' follow-up, the examination results demonstrated that nerve regeneration effect was very good. When the reoperation was performed to remove the steel plate we observed a uniform structure of the regenerated nerve without the formation of neuroma, and to our delight, the implanted conduit was completely degraded 23 months after the implantation. The second case had an obsolete nerve injury with neuroma formation. After removal of the neuroma, the nerve was bridged by PRGD/PDLLA/β-TCP conduit. Follow-up examinations showed that the structure and functional recovery were improved gradually in the 10-month follow-up; no end-enlargement and any other abnormal reaction associated with the characteristic of neuroma were found. Based on our 33-case studies, we have concluded that PRGD/PDLLA/β-TCP nerve conduit could both promote nerve regeneration and prevent neuroma formation; therefore, it is a good alternative for peripheral nerve repair.

  6. Effects of large-area irradiated laser phototherapy on peripheral nerve regeneration across a large gap in a biomaterial conduit.

    PubMed

    Shen, Chiung-Chyi; Yang, Yi-Chin; Liu, Bai-Shuan

    2013-01-01

    This paper proposes a novel biodegradable nerve conduit comprising 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) cross-linked gelatin, annexed with β-tricalcium phosphate (TCP) ceramic particles (EDC-Gelatin-TCP, EGT). In this study, the EGT-implant site in rats was irradiated using a large-area 660 nm AlGaInP diode laser (50 mW) to investigate the feasibility of laser stimulation in the regeneration of a 15-mm transected sciatic nerve. The animals were divided into three groups: a sham-irradiated group (EGT/sham); an experimental group undergoing low-level laser (LLL) therapy (EGT/laser); a control group undergoing autologous nerve grafts (autografts). Twelve weeks after implantation, walking track analysis showed a significantly higher sciatic functional index (p < 0.05) and improved toe spreading development in the EGT/laser and autograft groups than in the EGT/sham group. In electrophysiological measurement, both the mean peak amplitude and the area under the compound muscle action potential curves in the EGT/laser and autograft groups showed significantly improved functional recovery than the EGT/sham group (p < 0.05). Compared with the EGT/sham group, the EGT/laser and autograft groups displayed a reduction in muscular atrophy. Histomorphometric assessments revealed that the EGT/laser group had undergone more rapid nerve regeneration than the EGT/sham group. The laser-treated group also presented greater neural tissue area as well as larger axon diameter and thicker myelin sheath than the tube group without the laser treatment, indicating improved nerve regeneration. Thus, these assessments demonstrate that LLL therapy can accelerate the repair of a transected peripheral nerve in rats after being bridged with EGT conduit. Copyright © 2012 Wiley Periodicals, Inc.

  7. Material properties and electrical stimulation regimens through polycaprolactone fumarate-polypyrrole scaffolds as potential conductive nerve conduits

    PubMed Central

    Moroder, Philipp; Wang, Huan; Ruesink, Terry; Lu, Lichun; Windebank, Anthony J.; Yaszemski, Michael J.; Runge, M. Brett

    2010-01-01

    Mechanical and electrical properties of polycaprolactone fumarate-polypyrrole (PCLF-PPy) scaffolds were studied under physiological conditions to evaluate their ability to maintain material properties necessary for application as conductive nerve conduits. PC12 cells cultured on PCLF-PPy scaffolds were stimulated with regimens of 10 μA of constant or 20 Hz frequency current passed through the scaffolds for 1 h/day. PC12 cellular morphologies were analyzed by fluorescence microscopy after 48 h. PCLF-PPy scaffolds exhibited excellent mechanical properties at 37°C which would allow suturing and flexibility. The surface resistivity of the scaffolds was 2kΩ and the scaffolds were electrically stable during application of electrical stimulation (ES). In vitro studies showed significant increases in percentage of neurite bearing cells, number of neurites per cell and neurite length in the presence of ES compared to no ES. Additionally, extending neurites were observed to align in the direction of the applied current. This study shows that electrically conductive PCLF-PPy scaffolds possess material properties necessary for application as nerve conduits. Additionally, the capability to significantly enhance and direct neurite extension by passing electrical current through PCLF-PPy scaffolds renders them even more promising as future therapeutic treatments for severe nerve injuries. PMID:20965280

  8. Repair and regeneration of lumbosacral nerve defects in rats with chitosan conduits containing bone marrow mesenchymal stem cells.

    PubMed

    Zhu, Lei; Liu, Tao; Cai, Jiao; Ma, Jun; Chen, Ai-min

    2015-11-01

    Despite the great progress in surgical treatment of lumbosacral nerve injuries caused by high-energy trauma, functional recovery remains poor and insufficient. Bone marrow mesenchymal stem cells (BMSCs), which express neurotrophic factors and can also differentiate into nerve cells, have potential as an effective alternative therapy for lumbosacral nerve defects. The aim of the present study was to evaluate the functional recovery, nerve regeneration, motor neuron survival and apoptosis after lumbosacral nerve transection in rats receiving BMSC transplantation into the chitosan conduit. The right L4-L6 nerve roots of rats were transected and bridged with three 1-cm-long chitosan conduits, which were further injected with the BMSCs (MSC-treated group) or culture medium (DMEM group). The nerve regeneration and motor function recovery were assessed by the sciatic functional index (SFI) and analysed electrophysiologically and morphologically. At 6 and 12 weeks after surgery, the SFI values in MSC-treated group were significantly higher than those in DMEM group (P≤0.05). The peak amplitude of CMAP (compound muscle action potential) and nerve conduction velocity in MSC-treated group were significantly higher than that in DMEM group (P≤0.01), while the latency of CMAP onset in MSC-treated group was significantly shorter than that in DMEM group (P≤0.01). The diameter of the myelinated fibres and thickness of the myelin sheath in MSC-treated group were significantly higher than those in DMEM group (P≤0.05). There was no difference in the number of motor neurons in the anterior horn of the spinal cord at 6 weeks post-operation (P>0.05), while the number of motor neurons was significantly greater in MSC-treated group than that in DMEM group at 12 weeks post-operation (P≤0.001). The number of apoptotic cells was also significantly lower (P≤0.01). The results of the present study showed that BMSCs treatment improved lumbosacral nerve regeneration and motor function

  9. A novel artificial nerve graft for repairing long-distance sciatic nerve defects: a self-assembling peptide nanofiber scaffold-containing poly(lactic-co-glycolic acid) conduit

    PubMed Central

    Wang, Xianghai; Pan, Mengjie; Wen, Jinkun; Tang, Yinjuan; Hamilton, Audra D.; Li, Yuanyuan; Qian, Changhui; Liu, Zhongying; Wu, Wutian; Guo, Jiasong

    2014-01-01

    In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold (SAPNS)-containing poly(lactic-co-glycolic acid) (PLGA) conduit (SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury. PMID:25657734

  10. Neuroma-in-continuity of the median nerve managed by nerve expansion and direct suture with vein conduit.

    PubMed

    Jeudy, J; Raimbeau, G; Rabarin, F; Fouque, P A; Saint-Cast, Y; Césari, B; Bigorre, N

    2014-06-01

    Autologous nerve grafting is the current standard for bridging large gaps in major sensory and motor nerves. It allows both function and pain improvement with predictable results. Clinical observations of nerve elongation caused by tumours have prompted experimental animal studies of induced gradual elongation of the nerve stump proximal to the gap. This technique allows direct suturing of the two nerve ends to bridge the gap. Here, we describe a case of neuroma-in-continuity of the median nerve managed by resection and direct suture after nerve elongation with a tissue expander. We are not aware of similar reported cases. Secondary repair 3 years after the initial injury improved the pain and hypersensitivity and restored a modest degree of protective sensory function (grade S1). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Polymerizing Pyrrole Coated Poly (l-lactic acid-co-ε-caprolactone) (PLCL) Conductive Nanofibrous Conduit Combined with Electric Stimulation for Long-Range Peripheral Nerve Regeneration.

    PubMed

    Song, Jialin; Sun, Binbin; Liu, Shen; Chen, Wei; Zhang, Yuanzheng; Wang, Chunyang; Mo, Xiumei; Che, Junyi; Ouyang, Yuanming; Yuan, Weien; Fan, Cunyi

    2016-01-01

    Electrospinning and electric stimulation (ES) are both promising methods to support neuron adhesion and guide extension of neurons for nerve regeneration. Concurrently, all studies focus on either electrospinning for conduits material or ES in vitro study to accelerate nerve regeneration; few work on the combined use of these two strategies or ES in vivo study. Therefore, this study aimed to investigate the abilities of direct current ES through electrospinning conductive polymer composites composed of polypyrrole and Poly (l-lactic acid-co-ε-caprolactone) (PPY/PLCL) in peripheral nerve regeneration. PPY/PLCL composite conduits were synthesized by polymerizing pyrrole coated electrospun PLCL scaffolds. Morphologies and chemical compositions were characterized by scanning electron microscope and attenuated total reflection fourier transform infrared (ATR-FTIR) microscope. Rat pheochromocytoma 12 (PC12) cells and dorsal root ganglia (DRG) cells cultured on PPY/PLCL scaffolds were stimulated with 100 mV/cm for 4 h per day. The median neurite length and cell viability were measured in PC-12 cells. The levels of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) were analyzed in DRG cells. In rats, 15 mm gaps of sciatic nerves were bridged using an autograft, non-stimulated PPY/PLCL conduit and PPY/PLCL conduit stimulated with 100 mV potential, respectively. A 100 mV potential direct current ES was applied for 1 h per day at 1, 3, 5 and 7 days post-implantation. The PPY/PLCL conduits with ES showed a similar performance compared with the autograft group, and significantly better than the non-stimulated PPY/PLCL conduit group. These promising results show that the PPY/PLCL conductive conduits' combined use with ES has great potential for peripheral nerve regeneration.

  12. Collagen-GAG substrate enhances the quality of nerve regeneration through collagen tubes up to level of autograft.

    PubMed

    Chamberlain, L J; Yannas, I V; Hsu, H P; Strichartz, G; Spector, M

    1998-12-01

    Peripheral nerve regeneration was studied across a tubulated 10-mm gap in the rat sciatic nerve using histomorphometry and electrophysiological measurements of A-fiber, B-fiber, and C-fiber peaks of the evoked action potentials. Tubes fabricated from large-pore collagen (max. pore diameter, 22 nm), small-pore collagen (max. pore diameter, 4 nm), and silicone were implanted either saline-filled or filled with a highly porous, collagen-glycosaminoglycan (CG) matrix. The CG matrix was deliberately synthesized, based on a previous optimization study, to degrade with a half-life of about 6 weeks and to have a very high specific surface through a combination of high pore volume fraction (0.95) and relatively small average pore diameter (35 microm). Nerves regenerated through tubes fabricated from large-pore collagen and filled with the CG matrix had significantly more large-diameter axons, more total axons, and significantly higher A-fiber conduction velocities than any other tubulated group; and, although lower than normal, their histomorphometric and electrophysiological properties were statistically indistinguishable from those of the autograft control. Although the total number of myelinated axons in nerves regenerated by tubulation had reached a plateau by 30 weeks, the number of axons with diameter larger than 6 microm, which have been uniquely associated with the A-fiber peak of the action potential, continued to increase at substantial rates through the completion of the study (60 weeks). The kinetic data strongly suggest that a nerve trunk maturation process, not previously reported in studies of the tubulated 10-mm gap in the rat sciatic nerve, and consisting in increase of axonal tissue area with decrease in total tissue area, continues beyond 60 weeks after injury, resulting in a nerve trunk which increasingly approaches the structure of the normal control. Copyright 1998 Academic Press.

  13. Surgical repair of a 30 mm long human median nerve defect in the distal forearm by implantation of a chitosan-PGA nerve guidance conduit.

    PubMed

    Gu, Jianhui; Hu, Wen; Deng, Aidong; Zhao, Qing; Lu, Shibi; Gu, Xiaosong

    2012-02-01

    This paper describes a clinical case study in which a chitosan/polyglycolic acid nerve guidance conduit (chitosan-PGA NGC) was utilized to repair a 30 mm long median nerve defect in the right distal forearm of a 55 year-old male patient. Thirty-six months after the nerve repair, the palm abduction of the thumb and the thumb-index digital opposition recovered, facilitating the patient to accomplish fine activities, such as handling chopsticks. Static two-point discrimination measured 14, 9 and 9 mm in the thumb, index and middle fingers of the right hand. Reproducible compound muscle action potentials were recorded on the right abductor pollicis. The ninhydrin test, a classical method for assessing sympathetic nerve function, showed partial recovery of the perspiration function of the injured thumb, index and middle fingers. This repair case suggested a possible strategy for the clinical reconstruction of extended defects in human peripheral nerve trunks by the implantation of chitosan-PGA NGCs. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Posttraumatic neuroma of the radial nerve treated with an autogenous epineural conduit technique. A case report.

    PubMed

    Ignatiadis, I A; Yiannakopoulos, C K; Avram, A M; Gerostathopoulos, N E

    2009-01-01

    We present the outcome of the first clinical application of a new technique using an epineural flap to bridge a short nerve defect. A 28-year-old male had suffered a radial nerve laceration at the lower third of the arm, proximal to the brachioradialis branch, 3 weeks before surgery. During surgery, a neuroma-in-continuity was excised preserving the epineural sleeve. Two longitudinal epineural flaps were created, one from the proximal and one from the distal nerve stump and used to bridge a 1-cm-long nerve defect. Each epineurium flap was sutured to the intact epineurium of the other side and additionally to each other. An electromagnetic nerve stimulator was used to enhance the nerve regeneration process. Nerve regeneration was followed up for 17 months with excellent functional results.

  15. Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid)

    NASA Astrophysics Data System (ADS)

    Kakinoki, Sachiro; Nakayama, Midori; Moritan, Toshiyuki; Yamaoka, Tetsuji

    2014-07-01

    We developed a microfibrous poly(L-lactic acid) (PLLA) nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG)30) that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical stremgth to the conduit. A 10% poly(ethylene glycol) was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG)30 composisting of an elastin-like repetitive sequence (VPGIG)30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73) was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG)30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG)30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG)30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG)30 inner layer.

  16. Sciatic nerve regeneration by transplantation of Schwann cells via erythropoietin controlled-releasing polylactic acid/multiwalled carbon nanotubes/gelatin nanofibrils neural guidance conduit.

    PubMed

    Salehi, Majid; Naseri-Nosar, Mahdi; Ebrahimi-Barough, Somayeh; Nourani, Mohammdreza; Khojasteh, Arash; Hamidieh, Amir-Ali; Amani, Amir; Farzamfar, Saeed; Ai, Jafar

    2017-07-04

    The current study aimed to enhance the efficacy of peripheral nerve regeneration using an electrically conductive biodegradable porous neural guidance conduit for transplantation of allogeneic Schwann cells (SCs). The conduit was produced from polylactic acid (PLA), multiwalled carbon nanotubes (MWCNTs), and gelatin nanofibrils (GNFs) coated with the recombinant human erythropoietin-loaded chitosan nanoparticles (rhEpo-CNPs). The PLA/MWCNTs/GNFs/rhEpo-CNPs conduit had the porosity of 85.78 ± 0.70%, the contact angle of 77.65 ± 1.91° and the ultimate tensile strength and compressive modulus of 5.51 ± 0.13 MPa and 2.66 ± 0.34 MPa, respectively. The conduit showed the electrical conductivity of 0.32 S cm(-1) and lost about 11% of its weight after 60 days in normal saline. The produced conduit was able to release the rhEpo for at least 2 weeks and exhibited favorable cytocompatibility towards SCs. For functional analysis, the conduit was seeded with 1.5 × 10(4) SCs and implanted into a 10 mm sciatic nerve defect of Wistar rat. After 14 weeks, the results of sciatic functional index, hot plate latency, compound muscle action potential amplitude, weight-loss percentage of wet gastrocnemius muscle and Histopathological examination using hematoxylin-eosin and Luxol fast blue staining demonstrated that the produced conduit had comparable nerve regeneration to the autograft, as the gold standard to bridge the nerve gaps. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  17. Polymerizing Pyrrole Coated Poly (l-lactic acid-co-ε-caprolactone) (PLCL) Conductive Nanofibrous Conduit Combined with Electric Stimulation for Long-Range Peripheral Nerve Regeneration

    PubMed Central

    Song, Jialin; Sun, Binbin; Liu, Shen; Chen, Wei; Zhang, Yuanzheng; Wang, Chunyang; Mo, Xiumei; Che, Junyi; Ouyang, Yuanming; Yuan, Weien; Fan, Cunyi

    2016-01-01

    Electrospinning and electric stimulation (ES) are both promising methods to support neuron adhesion and guide extension of neurons for nerve regeneration. Concurrently, all studies focus on either electrospinning for conduits material or ES in vitro study to accelerate nerve regeneration; few work on the combined use of these two strategies or ES in vivo study. Therefore, this study aimed to investigate the abilities of direct current ES through electrospinning conductive polymer composites composed of polypyrrole and Poly (l-lactic acid-co-ε-caprolactone) (PPY/PLCL) in peripheral nerve regeneration. PPY/PLCL composite conduits were synthesized by polymerizing pyrrole coated electrospun PLCL scaffolds. Morphologies and chemical compositions were characterized by scanning electron microscope and attenuated total reflection fourier transform infrared (ATR-FTIR) microscope. Rat pheochromocytoma 12 (PC12) cells and dorsal root ganglia (DRG) cells cultured on PPY/PLCL scaffolds were stimulated with 100 mV/cm for 4 h per day. The median neurite length and cell viability were measured in PC-12 cells. The levels of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) were analyzed in DRG cells. In rats, 15 mm gaps of sciatic nerves were bridged using an autograft, non-stimulated PPY/PLCL conduit and PPY/PLCL conduit stimulated with 100 mV potential, respectively. A 100 mV potential direct current ES was applied for 1 h per day at 1, 3, 5 and 7 days post-implantation. The PPY/PLCL conduits with ES showed a similar performance compared with the autograft group, and significantly better than the non-stimulated PPY/PLCL conduit group. These promising results show that the PPY/PLCL conductive conduits’ combined use with ES has great potential for peripheral nerve regeneration. PMID:27877111

  18. Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury.

    PubMed

    Frattini, Flávia; Lopes, Fatima Rosalina Pereira; Almeida, Fernanda Martins; Rodrigues, Rafaela Fintelman; Boldrini, Leonardo Cunha; Tomaz, Marcelo A; Baptista, Abrahão Fontes; Melo, Paulo A; Martinez, Ana Maria Blanco

    2012-10-01

    Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwann-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell

  19. Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Carriel, Víctor; Garrido-Gómez, Juan; Hernández-Cortés, Pedro; Garzón, Ingrid; García-García, Salomé; Sáez-Moreno, José Antonio; Sánchez-Quevedo, María del Carmen; Campos, Antonio; Alaminos, Miguel

    2013-04-01

    Objective. The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. Approach. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. Main results. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. Significance. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

  20. Controlled release of vascular endothelial growth factor using poly-lactic-co-glycolic acid microspheres: In vitro characterization and application in polycaprolactone fumarate nerve conduits

    PubMed Central

    Rui, Jing; Dadsetan, Mahrokh; Runge, M. Brett; Spinner, Robert J.; Yaszemski, Michael J.; Windebank, Anthony J.; Wang, Huan

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of VEGF encapsulating poly-lactic-co-glycolic acid (PLGA) microspheres and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16% of the microspheres with a diameter < 53 µm. VEGF content measured by ELISA indicated 93.79 ±10.64% encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6±8.25% within the first 24 hours, followed by consistent release of approximately 0.34% per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation confirming that VEGF retained its bioactivity through the 4-week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold, robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system. PMID:22019759

  1. PDLLA/PRGD/β-TCP conduits build the neurotrophin-rich microenvironment suppressing the oxidative stress and promoting the sciatic nerve regeneration.

    PubMed

    Qiu, Tong; Yin, Yixia; Li, Binbin; Xie, Lijuan; Yan, Qiongjiao; Dai, Honglian; Wang, Xinyu; Li, Shipu

    2014-10-01

    A novel nerve guidance conduit comprising poly{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]} (PRGD), poly (d,l-lactic acid) (PDLLA) and β-tricalcium phosphate (β-TCP) was constructed to facilitate the peripheral nerve regeneration. From the comparative study, PDLLA/PRGD/β-TCP conduit achieved the best recovery in regard of the ultrastructure observation and the SFI evaluation. At the first stage of the injury (7 days), the maximum expression augments in ZnSOD (6.4 folds) and GPX4 (6.8 folds) were observed in PDLLA/PRGD/β-TCP group; while striking rise in actin (6.8 folds), tubulin (5.6 folds), and ERM components expressions were observed later (35 days). Meanwhile, compared with PDLLA and PDLLA/PRGD conduits, PDLLA/PRGD/β-TCP conduits achieved the highest local nerve growth factor (NGF) content and an accumulating BDNF content. We speculated that addition of RGD and β-TCP in the composites were the main positive factors to build the microenvironment rich in NGF and BDNF, which help to counteract with the oxidative stress and to boost the cytoskeletal protein expressions. Therefore, PDLLA/PRGD/β-TCP could be promising composites used in peripheral nerve regeneration.

  2. Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Nonhuman Primate

    DTIC Science & Technology

    2012-10-01

    nanofibers are deposited onto the gelatin films via electrospinning so that the fibers are aligned upon the short axis. The films are crosslinked with...covered with a random mesh of PCL nanofibers via electrospinning to generate suitably thick but porous conduit walls to protect the regenerating nerve

  3. Effect of chitosan/type I collagen/gelatin composites in biocompatibility and nerve repair.

    PubMed

    Wang, Qing; Yang, Xiaolei; Ren, Ming; Hu, Yulin; Chen, Qiang; Xing, Lei; Meng, Chunyang; Liu, Tiemei

    2012-05-25

    Chitosan, collagen I and gelatin were mixed in appropriate quantities to develop a new nerve repair material, with good arrangement and structure, as well as even aperture size. The composite material was sterilized by (60)Co irradiation for 24 hours prior to implantation in the right thigh of rats following sciatic nerve damage. Results showed that the material was nontoxic to the kidneys and the liver, and did not induce an inflammatory response in the muscles. The composite material enhanced the recovery of sciatic nerve damage in rats. These experimental findings indicate that the composite material offers good biocompatibility and has a positive effect on injured nerve rehabilitation.

  4. Recovery of erectile function comparing autologous nerve grafts, unseeded conduits, Schwann-cell-seeded guidance tubes and GDNF-overexpressing Schwann cell grafts

    PubMed Central

    Buchner, Alexander; Matiasek, Kaspar; Schlenker, Boris; Stief, Christian; Weidner, Norbert

    2016-01-01

    ABSTRACT Dissection of the cavernous nerves during radical prostatectomy for prostate cancer eliminates spontaneous erections. Using the rat as an experimental model, we compared the regenerative capacity of autologous nerve grafts and Schwann-cell-seeded nerve guides. After bilateral excision of cavernous nerve segments, cavernous nerves were reconstructed using unseeded silicon tubes, nerve autografts and silicon tubes seeded with either Glial-cell-line-derived (GDNF)-overexpressing or green fluorescent protein (GFP)-expressing Schwann cells (SCs) (16 study nerves per group). Control groups underwent either a sham operation or bilateral excision of cavernous nerve segments without repair. After 12 weeks erectile function was assessed by neurostimulation and intracavernous pressure (ICP) measurement. The reconstructed nerve segments were excised and histologically analyzed. We demonstrated an intact erectile response upon neurostimulation in 25% (4/16) of autologous nerve grafts, in 50% (8/16) of unseeded tubes, in 75% (12/16) of the Schwann-cell–GFP group and in 93.75% (15/16) of the GDNF group. ICP was significantly increased when comparing the Schwann-cell–GFP group with nerve autografts, unseeded conduits and negative controls (P<0.005). In conclusion, Schwann-cell-seeded scaffolds combined with neurotrophic factors are superior to unseeded tubes and autologous nerve grafts. They present a promising therapeutic approach for the repair of erectile nerve gaps. PMID:27874834

  5. Nerve Guidance Conduits Based on Double-Layered Scaffolds of Electrospun Nanofibers for Repairing the Peripheral Nervous System

    PubMed Central

    2015-01-01

    Compared to the nerve guidance conduits (NGCs) constructed from a single layer of aligned nanofibers, bilayer NGCs with random and aligned nanofibers in the outer and inner layers are more robust and tear-resistant during surgical procedures thanks to an isotropic mechanical property provided by the random nanofibers. However, it remains unclear whether the random nanofibers will interfere with the aligned nanofibers to alter the extension pattern of the neurites and impede regeneration. To answer this question, we seeded dorsal root ganglia (DRG) on a double-layered scaffold, with aligned and random nanofibers on the top and bottom layers, respectively, and evaluated the outgrowth of neurites. The random nanofibers in the bottom layer exerted a negative impact on the extension of neurites projecting from the DRG, giving neurites a less ordered structure compared to those cultured on a single layer of aligned nanofibers. The negative impact of the random nanofibers could be effectively mitigated by preseeding the double-layered scaffold with Schwann cells. DRG cultured on top of such a scaffold exhibited a neurite outgrowth pattern similar to that for DRG cultured on a single layer of aligned nanofibers. We further fabricated bilayer NGCs from the double-layered scaffolds and tested their ability to facilitate nerve regeneration in a rat sciatic nerve injury model. Both histomorphometric analysis and functional characterization demonstrated that bilayer NGCs with an inner surface that was preseeded with Schwann cells could reach 54%, 64.2%, and 74.9% of the performance of isografts in terms of nerve fiber number, maximum isometric tetanic force, and mass of the extensor digitorum longus muscle, respectively. It can be concluded that the bilayer NGCs hold great potential in facilitating motor axon regeneration and functional motor recovery. PMID:24806389

  6. Use of GDNF Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Nonhuman Primate

    DTIC Science & Technology

    2015-02-01

    intercostal nerve segment and avulsed ventral root. P.I.: Christe, Kari L 20 Figure 11. A.) Photomontage of lumbar spinal cord section from rhesus...AWARD NUMBER: W81XWH-10-1-0905 TITLE: Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina...3. DATES COVERED 30Sept2010 - 29Sept2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0905 Use of GDNF-Releasing Nanofiber Nerve Guide

  7. Functional Regeneration of Recurrent Laryngeal Nerve Injury During Thyroid Surgery Using an Asymmetrically Porous Nerve Guide Conduit in an Animal Model

    PubMed Central

    Choi, Jeong-Seok; Oh, Se Heang; An, Hye-Young; Kim, Young-Mo; Lee, Jin Ho

    2014-01-01

    Background: Vocal cord paralysis (VCP) caused by recurrent laryngeal nerve (RLN) damage during thyroidectomy commonly results in serious medico-legal problems. The purpose of this study was to evaluate the usefulness of an asymmetrically porous polycaprolactone (PCL)/Pluronic F127 nerve guide conduit (NGC) for functional regeneration in a RLN injury animal model. Methods: A biodegradable, asymmetrically porous PCL/F127 NGC with selective permeability was fabricated for use in this study. A 10-mm segment of left RLN was resected in 28 New Zealand white rabbits, and then an asymmetrically porous NGC or a nonporous silicone tube was interposed between both stumps and securely fixed. Vocal cord mobility was endoscopically evaluated at one, four, and eight weeks postoperatively. Nerve growth through NGCs was assessed by toluidine blue staining, and thyroarytenoid (TA) muscle atrophy was evaluated by hematoxylin and eosin staining. Immunohistochemical stainings for acetylcholinesterase (AchE), anti-neurofilament (NF), and anti-S100 protein were also conducted, and transmission electron microscopy (TEM) was used to evaluate functional nerve regeneration. Results: At eight weeks postoperatively, endoscopic evaluations showed significantly better recovery from VCP in the asymmetrically porous PCL/F127 NGC group (6 of 10 rabbits) than in the silicone tube group (1 of 10 rabbits). Continued nerve growth on the damaged nerve endings was observed with time in the asymmetrically porous PCL/F127 NGC-interposed RLNs. TA muscle dimensions and AchE expressions in TA muscle were significantly greater in the asymmetrically porous PCL/F127 NGC group than in the silicone tube group. Furthermore, immunohistochemical staining revealed the expression of NF and S100 protein in the regenerated nerves in the asymmetrically porous PCL/F127 NGC group at eight weeks postoperatively, and at this time, TEM imaging showed myelinated axons in the regenerated RLNs. Conclusion: The study shows that

  8. Manufacture of porous polymer nerve conduits through a lyophilizing and wire-heating process.

    PubMed

    Huang, Yi-Cheng; Huang, Yi-You; Huang, Chun-Chieh; Liu, Hwa-Chang

    2005-07-01

    We have developed a method for nerve tissue regeneration using longitudinally oriented channels within biodegradable polymers created by a combined lyophilizing and wire-heating process. This type of cell-adhesive scaffold provides increased area to support and guide extending axons subsequent to nerve injury. Utilizing Ni-Cr wires as mandrels to create channels in scaffold increased safety, effectiveness, and reproducibility. The scaffolds tested were made from different biodegradable polymers, chitosan and poly(D,L-lactide-co-glycolide) (PLGA), because of their availability, ease of processing, low inflammatory response, and approval by the FDA. According to our experimental results, the high permeability and the characteristic porous structure of chitosan proved to be a better material for nerve guidance than PLGA. The scanning electron micrographs revealed that the scaffolds were consistent along the longitudinal axis with channels being distributed evenly throughout the scaffolds. There was no evidence to suggest merging or splitting of individual channels. The diameter of the channels was about 100 mum, similar to the 115 micromameter of the Ni-Cr wire. Regulating the size and quantity of the Ni-Cr wires allow us to control the number and the diameter of the channels. Furthermore, the neutralizing processes significantly influenced the porous structure of chitosan scaffolds. Using weak base (NaHCO(3) 1M) to neutralize chitosan scaffolds made the porous structure more uniform. The innovative method of using Ni-Cr wires as mandrels could be easily tailored to other polymer and solvent systems. The high permeability and the characteristic porous structure of chitosan made it a superior material for nerve tissue engineering. These scaffolds could be useful for guiding regeneration of the peripheral nerve or spinal cord after a transection injury.

  9. Electrospun aligned PHBV/collagen nanofibers as substrates for nerve tissue engineering.

    PubMed

    Prabhakaran, Molamma P; Vatankhah, Elham; Ramakrishna, Seeram

    2013-10-01

    Nerve regeneration following the injury of nerve tissue remains a major issue in the therapeutic medical field. Various bio-mimetic strategies are employed to direct the nerve growth in vitro, among which the chemical and topographical cues elicited by the scaffolds are crucial parameters that is primarily responsible for the axon growth and neurite extension involved in nerve regeneration. We carried out electrospinning for the first time, to fabricate both random and aligned nanofibers of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate; PHBV) and composite PHBV/collagen nanofibers with fiber diameters in the range of 386-472 nm and 205-266 nm, respectively. To evaluate the potential of electrospun aligned nanofibers of PHBV and composite scaffolds as a substrate for nerve regeneration, we cultured nerve cells (PC12) and studied the biocompatibility effect along with neurite extension by immunostaining studies. Cell proliferation assays showed 40.01% and 5.48% higher proliferation of nerve cells on aligned PHBV/Coll50:50 nanofibers compared to cell proliferation on aligned PHBV and PHBV/Col75:25 nanofibers, respectively. Aligned nanofibers of PHBV/Coll provided contact guidance to direct the orientation of nerve cells along the direction of the fibers, thus endowing elongated cell morphology, with bi-polar neurite extensions required for nerve regeneration. Results showed that aligned PHBV/Col nanofibers are promising substrates than the random PHBV/Col nanofibers for application as bioengineered grafts for nerve tissue regeneration.

  10. A Modular, Plasmin-Sensitive, Clickable Poly(ethylene glycol)-Heparin-Laminin Microsphere System for Establishing Growth Factor Gradients in Nerve Guidance Conduits

    PubMed Central

    Roam, Jacob L.; Yan, Ying; Nguyen, Peter K.; Kinstlinger, Ian S.; Leuchter, Michael K; Hunter, Daniel A.; Wood, Matthew D.; Elbert, Donald L.

    2015-01-01

    Peripheral nerve regeneration is a complex problem that, despite many advancements and innovations, still has sub-optimal outcomes. Compared to biologically derived acelluar nerve grafts and autografts, completely synthetic nerve guidance conduits (NGC), which allow for precise engineering of their properties, are promising but still far from optimal. We have developed an almost entirely synthetic NGC that allows control of soluble growth factor delivery kinetics, cell-initiated degradability and cell attachment. We have focused on the spatial patterning of glial-cell derived human neurotrophic factor (GDNF), which promotes motor axon extension. The base scaffolds consisted of heparin-containing poly(ethylene glycol) (PEG) microspheres. The modular microsphere format greatly simplifies the formation of concentration gradients of reversibly bound GDNF. To facilitate axon extension, we engineered the microspheres with tunable plasmin degradability. ‘Click’ cross-linking chemistries were also added to allow scaffold formation without risk of covalently coupling the growth factor to the scaffold. Cell adhesion was promoted by covalently bound laminin. GDNF that was released from these microspheres was confirmed to retain its activity. Graded scaffolds were formed inside silicone conduits using 3D-printed holders. The fully formed NGC’s contained plasmin-degradable PEG/heparin scaffolds that developed linear gradients in reversibly bound GDNF. The NGC’s were implanted into rats with severed sciatic nerves to confirm in vivo degradability and lack of a major foreign body response. The NGC’s also promoted robust axonal regeneration into the conduit. PMID:26352518

  11. Immunohistochemical methods for semiquantitative analysis of collagen content in human peripheral nerve

    PubMed Central

    LOWRY, A.; WILCOX, D.; MASSON, E. A.; WILLIAMS, P. E.

    1997-01-01

    Methods are described for the semiquantitative analysis of the connective tissue components of human peripheral nerve using light microscopy. General histological preservation was assessed using haematoxylin and eosin staining and the distribution of collagen type IV was investigated using immunohistochemistry. Several techniques were investigated to establish the one giving optimum structural preservation, immunobinding and greatest contrast for image analysis. Frozen sections were unsuitable for this tissue and paraffin wax sections were therefore used. Alcohol fixation was rejected due to poor preservation of the endoneurium, although immunobinding was excellent. Ice-cold formalin fixation for 24 h was found to be adequate for structural preservation and antibody binding, provided that a protease step was introduced. Trypsin was found to be superior to pepsin for exposing collagen type IV epitopes. Of the detection systems investigated indirect immunofluorescence was not suitable due to considerable autofluorescence of the nerve. The avidin-biotin method provided the greatest contrast, and was therefore the detection method of choice for image analysis. The optimum techniques for image analysis were then used on control human sural nerve to ascertain the best comparative method for collagen type IV in the perineurium. A method of semiquantitative analysis is described which takes into account the fact that there is a close linear relationship between collagen content per unit of perineurium and perineurial perimeter as fascicle size increases in peripheral nerve. This means that data from 2 different sample groups can easily be compared, provided that a range of fascicle sizes is analysed in each case. PMID:9418993

  12. FK506-loaded chitosan conduit promotes the regeneration of injured sciatic nerves in the rat through the upregulation of brain-derived neurotrophic factor and TrkB.

    PubMed

    Zhao, Jia; Zheng, Xifu; Fu, Chongyang; Qu, Wei; Wei, Guoqiang; Zhang, Weiguo

    2014-09-15

    FK506 has been shown to exert neurotrophic and neuroprotective effects, but its long-term application for nerve regeneration is limited. This study evaluated the potential application of a novel FK506-loaded chitosan conduit for peripheral nerve repair, and explored the underlying mechanism. A sciatic nerve injury model was created in male Wistar rats, which were then randomly divided into three treatment groups (n=40, each): chitosan-only, chitosan+FK506 injection, and FK506-loaded chitosan. We found significant recovery of normal morphology of sciatic nerves and higher density of myelinated nerve fibers in rats treated with FK506-loaded chitosan. Similarly, the total number of myelinated nerve fibers, myelin sheath thickness, and axon diameters were significantly higher in this group compared with the others, and the compound muscle action potentials and motor nerve conduction velocity values of sciatic nerves were significantly higher. BDNF and TrkB levels in motor neurons were highest in rats treated with FK506-loaded chitosan. In conclusion, FK506-loaded chitosan promoted peripheral nerve repair and regeneration in a rat model of sciatic nerve injury. These effects are correlated with increased BDNF and TrkB expression in motor neurons.

  13. Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

    PubMed Central

    Su, Jianmin; Chen, Jiang; Lippold, Kumiko; Monavarfeshani, Aboozar; Carrillo, Gabriela Lizana; Jenkins, Rachel

    2016-01-01

    Inhibitory synapses comprise only ∼20% of the total synapses in the mammalian brain but play essential roles in controlling neuronal activity. In fact, perturbing inhibitory synapses is associated with complex brain disorders, such as schizophrenia and epilepsy. Although many types of inhibitory synapses exist, these disorders have been strongly linked to defects in inhibitory synapses formed by Parvalbumin-expressing interneurons. Here, we discovered a novel role for an unconventional collagen—collagen XIX—in the formation of Parvalbumin+ inhibitory synapses. Loss of this collagen results not only in decreased inhibitory synapse number, but also in the acquisition of schizophrenia-related behaviors. Mechanistically, these studies reveal that a proteolytically released fragment of this collagen, termed a matricryptin, promotes the assembly of inhibitory nerve terminals through integrin receptors. Collectively, these studies not only identify roles for collagen-derived matricryptins in cortical circuit formation, but they also reveal a novel paracrine mechanism that regulates the assembly of these synapses. PMID:26975851

  14. A dual laminin/collagen receptor acts in peripheral nerve regeneration.

    PubMed Central

    Toyota, B; Carbonetto, S; David, S

    1990-01-01

    A regeneration chamber was created in vivo by suturing a synthetic tube sealed at its distal end onto the proximal stump of a severed rat sciatic nerve. Nerves regenerated into tubes coated with laminin at a rate of 0.33 mm/day after a lag of about 2 days. At 25 days, regenerating nerves had extended 23% farther into laminin-coated tubes as compared with uncoated ones. Monoclonal antibody 3A3, which functionally interferes with a dual laminin/collagen receptor, inhibited nerve regeneration into laminin-coated tubes by 32%. In contrast, monoclonal antibody JG22, which inhibits chicken matrix receptors, had no significant effect on regeneration. Immunohistochemical studies of teased adult rat sciatic nerves indicate that 3A3 bound to Schwann cells and possibly to axons. In other studies, the heterodimeric, laminin/collagen receptor recognized by 3A3 has been shown to be a member of the integrin superfamily of adhesive receptors. These data provide evidence that an integrin receptor functions in nerve regeneration in vivo. Images PMID:2154740

  15. Influence of immobilization and sensory re-education on the sensory recovery after reconstruction of digital nerves with direct suture or muscle-in-vein conduits.

    PubMed

    Manoli, Theodora; Schiefer, Jennifer Lynn; Schulz, Lukas; Fuchsberger, Thomas; Schaller, Hans-Eberhard

    2016-02-01

    The influence of duration of immobilization and postoperative sensory re-education on the final outcome after reconstruction of digital nerves with direct suture or muscle-in-vein conduits was investigated. The final sensory outcome of 35 patients with 41 digital nerve injuries, who either underwent a direct suture (DS) or a nerve reconstruction with muscle-in-vein conduits (MVC), was assessed the earliest 12 months postoperatively using static and moving two-point discrimination as well as Semmes-Weinstein monofilaments. There was no significant difference in sensory recovery in cases with an immobilization of 3-7 days versus 10 days in the DS or MVC group. Moreover, no statistically significant difference in sensory recovery was found in cases receiving postoperative sensory re-education versus those not receiving in the DS or MVC group. An early mobilization does not seem to have a negative impact on the final outcome after digital nerve reconstruction. The effect of sensory re-education after digital nerve reconstruction should be reconsidered.

  16. Peripheral nerve morphogenesis induced by scaffold micropatterning

    PubMed Central

    Memon, Danish; Boneschi, Filippo Martinelli; Madaghiele, Marta; Brambilla, Paola; Del Carro, Ubaldo; Taveggia, Carla; Riva, Nilo; Trimarco, Amelia; Lopez, Ignazio D.; Comi, Giancarlo; Pluchino, Stefano; Martino, Gianvito; Sannino, Alessandro; Quattrini, Angelo

    2014-01-01

    Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous microstructure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold’s microstructure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration. PMID:24559639

  17. The role of microstructured and interconnected pore channels in a collagen-based nerve guide on axonal regeneration in peripheral nerves.

    PubMed

    Bozkurt, Ahmet; Lassner, Franz; O'Dey, Dan; Deumens, Ronald; Böcker, Arne; Schwendt, Tilman; Janzen, Christoph; Suschek, Christoph V; Tolba, Rene; Kobayashi, Eiji; Sellhaus, Bernd; Tholl, S; Eummelen, Lizette; Schügner, Frank; Damink, Leon Olde; Weis, Joachim; Brook, Gary A; Pallua, Norbert

    2012-02-01

    The use of bioengineered nerve guides as alternatives for autologous nerve transplantation (ANT) is a promising strategy for the repair of peripheral nerve defects. In the present investigation, we present a collagen-based micro-structured nerve guide (Perimaix) for the repair of 2 cm rat sciatic nerve defects. Perimaix is an open-porous biodegradable nerve guide containing continuous, longitudinally orientated channels for orientated nerve growth. The effects of these nerve guides on axon regeneration by six weeks after implantation have been compared with those of ANT. Investigation of the regenerated sciatic nerve indicated that Perimaix strongly supported directed axon regeneration. When seeded with cultivated rat Schwann cells (SC), the Perimaix nerve guide was found to be almost as supportive of axon regeneration as ANT. The use of SC from transgenic green-fluorescent-protein (GFP) rats allowed us to detect the viability of donor SC at 1 week and 6 weeks after transplantation. The GFP-positive SC were aligned in a columnar fashion within the longitudinally orientated micro-channels. This cellular arrangement was not only observed prior to implantation, but also at one week and 6 weeks after implantation. It may be concluded that Perimaix nerve guides hold great promise for the repair of peripheral nerve defects.

  18. Corneal Nerve Regeneration After Collagen Cross-Linking Treatment of Keratoconus: A 5-Year Longitudinal Study.

    PubMed

    Parissi, Marlen; Randjelovic, Stefan; Poletti, Enea; Guimarães, Pedro; Ruggeri, Alfredo; Fragkiskou, Sofia; Wihlmark, Thu Ba; Utheim, Tor Paaske; Lagali, Neil

    2016-01-01

    It is unknown whether a neurotrophic deficit or pathologic nerve morphology persists in keratoconus in the long term after corneal collagen cross-linking (CXL) treatment. Nerve pathology could impact long-term corneal status in patients with keratoconus. To determine whether CXL treatment of keratoconus results in normalization of subbasal nerve density and architecture up to 5 years after treatment. Observational study of 19 patients with early-stage keratoconus indicated for a first CXL treatment with longitudinal follow-up to 5 years postoperatively (examinations were performed from 2009 to 2015; analysis was performed from February to May 2015) and 19 age-matched healthy volunteers at a primary care center and a university hospital ophthalmology department. The patients with keratoconus underwent standard epithelial-off UV-A/riboflavin CXL treatment with 30-minute UV-A exposure at 3 mW/cm2 irradiance. Central corneal subbasal nerve density and subbasal nerve architecture by use of laser-scanning in vivo confocal microscopy; subbasal nerve analysis by 2 masked observers and by use of a fully automated method; wide-field mosaics of subbasal nerve architecture by use of an automated method; and ocular surface touch sensitivity by use of contact esthesiometry. Mean (SD) age of the 19 patients with keratoconus was 27.5 (7.1) years (range, 19-44 years), and minimal corneal thickness was 428 (36) μm (range, 372-497 μm). Compared with the mean (SD) preoperative subbasal nerve density of 21.0 (4.2) mm/mm2 in healthy corneas, the mean (SD) preoperative subbasal nerve density of 10.3 (5.6) mm/mm2 in the corneas of patients with stage 1 or 2 keratoconus was reduced 51% (mean difference, 10.7 mm/mm2 [95% CI, 6.8-14.6 mm/mm2]; P < .001). After CXL, nerves continued to regenerate for up to 5 years, but nerve density remained reduced relative to healthy corneas at final follow-up (mean reduction, 8.5 mm/mm2 [95% CI, 4.7-12.4 mm/mm2]; P < .001) despite recovery of touch

  19. Enhanced peripheral nerve regeneration by the combination of a polycaprolactone tubular prosthesis and a scaffold of collagen with supramolecular organization

    PubMed Central

    Maturana, Luiz G; Pierucci, Amauri; Simões, Gustavo F; Vidigal, Mateus; Duek, Eliana A R; Vidal, Benedicto C; Oliveira, Alexandre L R

    2013-01-01

    The purpose of this study was to investigate the influence of implanting collagen with a supramolecular organization on peripheral nerve regeneration, using the sciatic nerve tubulization technique. For this purpose, adult female Sprague Dawley rats were divided into five groups: (1) TP – sciatic nerve repaired with empty polyethylene tubular prothesis (n = 10), (2) TPCL – nerve repair with empty polycaprolactone (PCL) tubing (n = 8), (3) TPCLF – repair with PCL tubing filled with an implant of collagen with a supramolecular organization (n = 10), (4) AG – animals that received a peripheral nerve autograft (n = 8), and (5) Normal nerves (n = 8). The results were assessed by quantification of the regenerated fibers, nerve morphometry, and transmission electron microscopy, 60 days after surgery. Immunohistochemistry and polarization microscopy were also used to analyze the regenerated nerve structure and cellular elements. The results showed that the AG group presented a larger number of regenerated axons. However, the TPCL and TPCLF groups presented more compact regenerated fibers with a morphometric profile closer to normal, both at the tube midpoint and 2 mm distal to the prosthesis. These findings were reinforced by polarization microscopy, which indicated a better collagen/axons suprastructural organization in the TPCLF derived samples. In addition, the immunohistochemical results obtained using the antibody anti-p75NTR as a Schwann cell reactivity marker demonstrated that the Schwann cells were more reactive during the regenerative process in the TPCLF group as compared to the TPCL group and the normal sciatic nerve. Altogether, the results of this study indicated that the implant of collagen with a supramolecular organization positively influenced and stimulated the regeneration process through the nerve gap, resulting in the formation of a better morphologically arranged tissue. PMID:24381812

  20. Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve

    PubMed Central

    Huang, Lanfeng; Li, Rui; Liu, Wanguo; Dai, Jin; Du, Zhenwu; Wang, Xiaonan; Ma, Jianchao; Zhao, Jinsong

    2014-01-01

    Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material. PMID:25221594

  1. Incorporation of Chitosan Microspheres into Collagen-Chitosan Scaffolds for the Controlled Release of Nerve Growth Factor

    PubMed Central

    Xiao, Wei; Qi, Fengyu; Huang, Jinghui; Luo, Zhuojing

    2014-01-01

    Background Artifical nerve scaffold can be used as a promising alternative to autologous nerve grafts to enhance the repair of peripheral nerve defects. However, current nerve scaffolds lack efficient microstructure and neurotrophic support. Methods Microsphere–Scaffold composite was developed by incorporating chitosan microspheres loaded with nerve growth factor (NGF–CMSs) into collagen-chitosan scaffolds (CCH) with longitudinally oriented microchannels (NGF–CMSs/CCH). The morphological characterizations, in vitro release kinetics study, neurite outgrowth assay, and bioactivity assay were evaluated. After that, a 15-mm-long sciatic nerve gap in rats was bridged by the NGF–CMSs/CCH, CCH physically absorbed NGF (NGF/CCH), CCH or nerve autograft. 16 weeks after implantation, electrophysiology, fluoro-gold retrograde tracing, and nerve morphometry were performed. Results The NGF–CMSs were evenly distributed throughout the longitudinally oriented microchannels of the scaffold. The NGF–CMSs/CCH was capable of sustained release of bioactive NGF within 28 days as compared with others in vitro. In vivo animal study demonstrated that the outcomes of NGF–CMSs/CCH were better than those of NGF/CCH or CCH. Conclusion Our findings suggest that incorporation of NGF–CMSs into the CCH may be a promising tool in the repair of peripheral nerve defects. PMID:24983464

  2. Biocompatibility and Characterization of a Peptide Amphiphile Hydrogel for Applications in Peripheral Nerve Regeneration

    PubMed Central

    Black, Katie A.; Lin, Brian F.; Wonder, Emily A.; Desai, Seema S.; Chung, Eun Ji; Ulery, Bret D.; Katari, Ravi S.

    2015-01-01

    Peripheral nerve injury is a debilitating condition for which new bioengineering solutions are needed. Autografting, the gold standard in treatment, involves sacrifice of a healthy nerve and results in loss of sensation or function at the donor site. One alternative solution to autografting is to use a nerve guide conduit designed to physically guide the nerve as it regenerates across the injury gap. Such conduits are effective for short gap injuries, but fail to surpass autografting in long gap injuries. One strategy to enhance regeneration inside conduits in long gap injuries is to fill the guide conduits with a hydrogel to mimic the native extracellular matrix found in peripheral nerves. In this work, a peptide amphiphile (PA)-based hydrogel was optimized for peripheral nerve repair. Hydrogels consisting of the PA C16GSH were compared with a commercially available collagen gel. Schwann cells, a cell type important in the peripheral nerve regenerative cascade, were able to spread, proliferate, and migrate better on C16GSH gels in vitro when compared with cells seeded on collagen gels. Moreover, C16GSH gels were implanted subcutaneously in a murine model and were found to be biocompatible, degrade over time, and support angiogenesis without causing inflammation or a foreign body immune response. Taken together, these results help optimize and instruct the development of a new synthetic hydrogel as a luminal filler for conduit-mediated peripheral nerve repair. PMID:25626921

  3. Clinical and biometrical 12-month follow-up in patients after reconstruction of the sural nerve biopsy defect by the collagen-based nerve guide Neuromaix.

    PubMed

    Bozkurt, Ahmet; Claeys, Kristl G; Schrading, Simone; Rödler, Jana V; Altinova, Haktan; Schulz, Jörg B; Weis, Joachim; Pallua, Norbert; van Neerven, Sabien G A

    2017-09-22

    Many new strategies for the reconstruction of peripheral nerve injuries have been explored for their effectiveness in supporting nerve regeneration. However only a few of these materials were actually clinically evaluated and approved for human use. This open, mono-center, non-randomized clinical study summarizes the 12-month follow-up of patients receiving reconstruction of the sural nerve biopsy defect by the collagen-based nerve guide Neuromaix. Neuromaix was implanted as a micro-structured, two-component scaffold bridging 20-40 mm nerve defects after sural nerve biopsy in twenty patients (eighteen evaluated, two lost in follow-up). Safety of the material was evaluated by clinical examination of wound healing. Performance was assessed by sensory testing of modalities, pain assessment, and palpation for the Hoffmann-Tinel's sign as well as demarcating the asensitive area at each follow-up visit. Every patient demonstrated uneventful wound healing during the complete 12-month time course of the study. Two patients reported complete return of sensation, whereas eleven out of eighteen patients reported a positive Hoffmann-Tinel's sign at the lower leg with simultaneous reduction of the asensitive area by 12 months. Our data show that Neuromaix can be implanted safely in humans to bridge sural nerve gaps. No procedure-related, adverse events, or severe adverse events were reported. These first clinical data on Neuromaix provide promising perspectives for the bridging of larger nerve gaps in combined nerves, which should be investigated more through extensive, multi-center clinical trials in the near future.

  4. Long-term regeneration of the rat sciatic nerve through a biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guide: tissue reactions with focus on collagen III/IV reformation.

    PubMed

    Jansen, Koen; Meek, Marcel F; van der Werff, John F A; van Wachem, Pauline B; van Luyn, Marja J A

    2004-05-01

    Long-term studies on nerve-guide regeneration are scarce. Therefore, in rats, long-term (16 months) sciatic nerve regeneration through poly(DL-lactide-epsilon-caprolactone) [poly(DLLA-epsilon-CL)] nerve guides was studied and compared with the nonoperated control side. Poly(DLLA-epsilon-CL) degradation and possible long-term foreign body reaction against poly(DLLA-epsilon-CL) nerve guides, as well as the distribution of both collagen type III and IV were studied. In vivo poly(DLLA-epsilon-CL) studies have been performed before but not for such long time points; also, a detailed analysis of collagen III/IV has not been presented before. The results demonstrate that biodegradable poly(DLLA-epsilon-CL) nerve guides yield good nerve regeneration and collagen III/IV deposition relative to the anatomy of the control side. Regenerated nerve showed almost similar collagen type III/IV distribution patterns as compared with the nonoperated control side, although the delineation of matrix was clearer in the control side. The relative amount of collagen III and IV immunostaining in nerve cross-sections did not, however, differ between the control nerve tissue and the operated side after 16 months. After 16 months of implantation, however, some very small fragments of biomaterial could still be found on the edge of the epineurium of the regenerated nerve, indicating remnants of a secondary foreign body reaction. The biomaterial fragments and foreign body reaction did not influence the nerve regeneration process after 16 months. Biodegradable poly(DLLA-epsilon-CL) nerve guides are useful for long-term bridging of short peripheral nerve gaps.

  5. Sterilization of collagen scaffolds designed for peripheral nerve regeneration: Effect on microstructure, degradation and cellular colonization.

    PubMed

    Monaco, Graziana; Cholas, Rahmatullah; Salvatore, Luca; Madaghiele, Marta; Sannino, Alessandro

    2017-02-01

    In this study we investigated the impact of three different sterilization methods, dry heat (DHS), ethylene oxide (EtO) and electron beam radiation (β), on the properties of cylindrical collagen scaffolds with longitudinally oriented pore channels, specifically designed for peripheral nerve regeneration. Scanning electron microscopy, mechanical testing, quantification of primary amines, differential scanning calorimetry and enzymatic degradation were performed to analyze possible structural and chemical changes induced by the sterilization. Moreover, in vitro proliferation and infiltration of the rat Schwann cell line RSC96 within the scaffolds was evaluated, up to 10days of culture. No major differences in morphology and compressive stiffness were observed among scaffolds sterilized by the different methods, as all samples showed approximately the same structure and stiffness as the unsterilized control. Proliferation, infiltration, distribution and morphology of RSC96 cells within the scaffolds were also comparable throughout the duration of the cell culture study, regardless of the sterilization treatment. However, we found a slight increase of chemical crosslinking upon sterilization (EtO

  6. Nerve endoneurial microstructure facilitates uniform distribution of regenerative fibers: a post hoc comparison of midgraft nerve fiber densities.

    PubMed

    Johnson, Philip J; Newton, Piyaraj; Hunter, Daniel A; Mackinnon, Susan E

    2011-02-01

    Despite their inferiority to nerve autograft, clinical alternatives are commonly used for reconstruction of peripheral nerve injuries because of their convenient off-the-shelf availability. Previously, our group compared isografts with NeuraGen(®) (Integra, Plainsboro, NJ) nerve guides, which are a commercially available type I collagen conduit and processed rat allografts comparable to Avance(®) (AxoGen, Alachua, FL) human decellularized allograft product. From this study, qualitative observations were made of distinct differences in the pattern of regenerating fibers within conduits, acellular allografts, and isografts. In the current post hoc analysis, these observations were quantified. Using nerve density, we statistically compared the differential pattern of regenerating axon fibers within grafts and conduit. The conduits exhibited a consistent decrease in midgraft density when compared with the isograft and acellularized allografts at two gap lengths (14 mm and 28 mm) and time points (12 and 22 weeks). The decrease in density was accompanied by clustered distribution of nerve fibers in conduits, which contrasted the evenly distributed regeneration seen in processed allografts and isografts. We hypothesize that the lack of endoneurial microstructure of conduits results in the clustering regenerating fibers, and that the presence of microstructure in the acellularized allograft and isografts facilitates even distribution of regenerating fibers. © Thieme Medical Publishers.

  7. Sciatic nerve regeneration by transplantation of menstrual blood-derived stem cells.

    PubMed

    Farzamfar, Saeed; Naseri-Nosar, Mahdi; Ghanavatinejad, Alireza; Vaez, Ahmad; Zarnani, Amir Hassan; Salehi, Majid

    2017-10-04

    This is the first study demonstrating the efficacy of menstrual blood-derived stem cell (MenSC) transplantation via a neural guidance conduit, for peripheral nerve regeneration. The synthesized poly (ɛ-caprolactone)/Gelatin conduit, filled with collagen type I and seeded with 3 × 10(4) MenSCs, was implanted into a rat's 10 mm sciatic nerve defect. The results of hot plate latency, sciatic functional index and weight-loss percentage of wet gastrocnemius muscle demonstrated that the MenSC transplantation had comparable nerve regeneration outcome to autograft, as the gold standard of nerve bridging. The transplantation of MenSCs via a synthetic conduit could ameliorate the functional recovery of sciatic nerve-injured rats which make them a potential candidate for cell therapy of peripheral nervous system disorders.

  8. Hyperglycemic glucose concentrations up-regulate the expression of type VI collagen in vitro. Relevance to alterations of peripheral nerves in diabetes mellitus.

    PubMed Central

    Muona, P.; Jaakkola, S.; Zhang, R. Z.; Pan, T. C.; Pelliniemi, L.; Risteli, L.; Chu, M. L.; Uitto, J.; Peltonen, J.

    1993-01-01

    Electron microscopy of peripheral nerves obtained from two diabetic patients revealed large deposits of microfibrils and the presence of Luse bodies in the vicinity of perineurial cells. Microfibrils were found to accumulate also in the sciatic nerves of diabetic BB rats; these microfibrillar deposits were shown to contain type VI collagen by immunoelectron microscopy. Connective tissue cells cultured from rat sciatic nerves were exposed to high glucose concentrations. High glucose concentrations up-regulated the mRNA steady-state levels of alpha 1(VI), alpha 2(VI), and alpha 3(VI) chains of type VI collagen and caused accumulation of type VI collagen-containing fibrils in the cultures. Immunostaining and in situ hybridizations demonstrated that perineurial cells, Schwann cells, and fibroblasts expressed type VI collagen at the mRNA and protein levels. The results suggest that the turnover and supramolecular assembly of type VI collagen are perturbed in diabetic nerves and that glucose per se increases the expression of type VI collagen in vitro. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8494053

  9. High resolution three-dimensional reconstruction of the collagenous matrix of the human optic nerve head.

    PubMed

    Winkler, Moritz; Jester, Bryan; Nien-Shy, Chyong; Massei, Salina; Minckler, Don S; Jester, James V; Brown, Donald J

    2010-02-15

    Glaucoma is the second most common cause of blindness worldwide, leading to irreversible loss of vision. Prior studies indicate that ocular pressure-induced displacement of the lamina cribrosa (LC) may be responsible for retinal ganglion cell axon damage inside the neural canal. We present a novel approach to imaging the entire lamina cribrosa and the scleral canal at high lateral and axial resolution by using a combination of array tomography and nonlinear optical imaging of serial ultrathin orthogonal sections to detect second harmonic generated (SHG) signals from collagen. The resulting images can be analyzed individually or combined to form a three-dimensional reconstruction of the lamina. Due to the specificity of SHG generated from collagen the density and distribution of collagen inside the scleral canal can be objectively quantified with a high degree of accuracy. The reconstruction shows a non-uniform distribution of collagen along both the longitudinal and orthogonal axes. Mapping the collagen density by geographic region reveals significant differences in collagen content that result in "thin spots" with low collagen density as well as areas of very high collagen content. This suggests a non-uniform mechanical stiffness across the lamina that may account for increased axon damage observed in glaucoma patients. The inferior temporal region of the ONH in particular is marked by low collagen density, which corresponds with clinical observations identifying this region as being more susceptible to damage during the onset of glaucoma. Further application of this technique will help characterize the relationship of age, race and gender on the morphology of the LC.

  10. Methods of peripheral nerve tissue preparation for second harmonic generation imaging of collagen fibers.

    PubMed

    Vijayaraghavan, Surabhi; Huq, Rumana; Hausman, Michael R

    2014-03-15

    Second harmonic generation (SHG) imaging of the peripheral nerve using multi-photon microscopy is a novel technique with little documentation. It affords the significant possibility of non-destructive imaging of internal nerve anatomy. The nature of nerve tissue, especially its size and viscoelastic properties, present special challenges for microscopy. While nerves are under an innate in situ strain, they retract once dissected, thus distorting microscopic structure. The challenge is to preserve the nerve in its natural strain range to obtain images that most truly reveal its structure. This study examined backscattered SHG images of rat median nerve prepared by several different methods to compare image quality and content. Nerve segments were fixed under strained (constant load or length) and unstrained conditions and imaged as whole nerve as well as plastic (methyl methacrylate) and paraffin embedded sections. These were tested for optimal excitation wavelength, quantitative image contrast, and overall quality. Root mean squared (RMS) contrast proved to be a reliable measure of the level of image contrast perceived by eye. We concluded that images obtained from tissue sections (plastic and paraffin) provided the most accurate and revealing SHG images of peripheral nerve structure. Removing the embedding material prior to imaging significantly improved image quality. Optimal excitation wavelengths were consistent regardless of the preparation method. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Rapid repair and regeneration of damaged rabbit sciatic nerves by tissue-engineered scaffold made from nano-silver and collagen type I.

    PubMed

    Ding, Tan; Luo, Zhuo-Jing; Zheng, Yan; Hu, Xue-Yu; Ye, Zheng-Xu

    2010-05-01

    A tissue-engineered scaffold with nano-silver and collagen type I was constructed and investigated for its ability to adsorb laminin and the usefulness in the repair and regeneration of damaged peripheral nerves in animals. The nano-silver scaffold displayed ideal microtubule structure under electronic microscope; even distribution of the nano-silver particles was also seen with energy spectrometry. After immersion in a laminin solution, the laminin-attached scaffolds were implanted into rabbits to repair a 10-mm injury of the sciatic nerve. At 30 days post-implantation, regeneration of the damaged nerve was evaluated by transmission electron microscopy, electrophysiological examination and fluoro-gold (FG) retrograde labelling. Compared with the control collagen-scaffold without nano-silver, the nano-silver-containing scaffold showed a higher rate of laminin adsorption, regenerated a nerve with a thicker myelin sheath and improved the nerve conduction velocity and nerve potential amplitude. FG retrograde labelled the newly grown axons in the spinal cord cortex anterior horn and the dorsal root ganglion. These results demonstrate the superior functionality of the nano-silver-collagen scaffold in the adsorption to laminin and subsequent regeneration of damaged peripheral nerves.

  12. Effects of collagen membranes enriched with in vitro-differentiated N1E-115 cells on rat sciatic nerve regeneration after end-to-end repair

    PubMed Central

    2010-01-01

    Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat. PMID:20149260

  13. Patterns of production of collagen-rich deposits in peripheral nerves in response to injury: A pilot study in a rabbit model.

    PubMed

    Rivlin, Michael; Miller, Andrew; Tulipan, Jacob; Beredjiklian, Pedro K; Wang, Mark L; Fertala, Jolanta; Steplewski, Andrzej; Kostas, James; Fertala, Andrzej

    2017-07-01

    Although collagen-rich deposits are the main component of neural scars, the patterns of their formation are ill defined. Essential to the biosynthesis of collagen fibrils are enzymes catalyzing posttranslational modifications and chaperones that control the formation of the collagen triple helix. Prolyl-4-hydroxylase (P4H) and heat shock protein-47 (HSP47) play a key role, and their production is upregulated during scar formation in human tissues. Alpha smooth muscle actin (αSMA) is also produced during fibrotic processes in myofibroblasts that participate in fibrotic response. In injured peripheral nerves, however, the distribution of cells that produce these markers is poorly understood. The goal of this study was to determine the distribution of the αSMA-positive, HSP47-positive, and the P4H-positive cells to better understand the formation of collagen-rich fibrotic tissue (FT) in response to peripheral nerve injury. To reach this goal, we employed a rabbit model of crush-injury and partial-transection injury of the sciatic nerves. Our study demonstrated that αSMA is expressed in a relatively small number of cells seen in neural FT. In contrast, cells producing P4H and HSP47 are ubiquitously present in sites of injury of the sciatic nerves. We contemplate that these proteins may serve as valuable markers that define fibrotic activities in the injured peripheral nerves.

  14. Human Schwann Cells Seeded on a Novel Collagen-Based Microstructured Nerve Guide Survive, Proliferate, and Modify Neurite Outgrowth

    PubMed Central

    van Neerven, Sabien G. A.; Haastert-Talini, Kirsten; Tolba, René H.; Pallua, Norbert; Bozkurt, Ahmet

    2014-01-01

    A variety of new bioartificial nerve guides have been tested preclinically for their safety and nerve regeneration supporting properties. So far, only a limited number of biomaterials have been tested in humans since the step from preclinical work to a clinical application is challenging. We here present an in vitro model with human Schwann cells (hSCs) as an intermediate step towards clinical application of the nerve guide Perimaix, a collagen-based microstructured 3D scaffold containing numerous longitudinal guidance channels for directed axonal growth. hSCs were seeded onto different prototypes of Perimaix and cultivated for 14 days. hSC adhered to the scaffold, proliferated, and demonstrated healthy Schwann cell morphology (spindle shaped cell bodies, bipolar oriented processes) not only at the surface of the material, but also in the deeper layers of the scaffold. The general well-being of the cells was quantitatively confirmed by low levels of lactate dehydrogenase release into the culture medium. Moreover, conditioned medium of hSCs that were cultivated on Perimaix was able to modify neurite outgrowth from sensory dorsal root ganglion neurons. Overall these data indicate that Perimaix is able to provide a matrix that can promote the attachment and supports process extension, migration, and proliferation of hSC. PMID:24895582

  15. Neuromodulatory nerve regeneration: adipose tissue-derived stem cells and neurotrophic mediation in peripheral nerve regeneration.

    PubMed

    Widgerow, Alan D; Salibian, Ara A; Lalezari, Shadi; Evans, Gregory R D

    2013-12-01

    Peripheral nerve injury requiring nerve gap reconstruction remains a major problem. In the quest to find an alternative to autogenous nerve graft procedures, attempts have been made to differentiate mesenchymal stem cells into neuronal lineages in vitro and utilize these cellular constructs for nerve regeneration. Unfortunately, this has produced mixed results, with no definitive procedure matching or surpassing traditional nerve grafting procedures. This review presents a different approach to nerve regeneration. The literature was reviewed to evaluate current methods of using adipose-derived stem cells (ADSCs) for peripheral nerve regeneration in in vivo models of animal peripheral nerve injury. The authors present cited evidence for directing nerve regeneration through paracrine effects of ADSCs rather than through in vitro nerve regeneration. The paracrine effects rely mainly, but not solely, on the elaboration of nerve growth factors and neurotrophic mediators that influence surrounding host cells to orchestrate in vivo nerve regeneration. Although this paradigm has been indirectly referred to in a host of publications, few major efforts for this type of neuromodulatory nerve regeneration have been forthcoming. The ADSCs are initially "primed" in vitro using specialized controlled medium (not for neuronal differentiation but for sustainability) and then incorporated into a hydrogel base matrix designed for this purpose. This core matrix is then introduced into a natural collagen-based nerve conduit. The prototype design concepts, evidence for paracrine influences, and regulatory hurdles that are avoided using this approach are discussed. Copyright © 2013 Wiley Periodicals, Inc.

  16. Does the addition of a nerve wrap to a motor nerve repair affect motor outcomes?

    PubMed

    Lee, Joo-Yup; Parisi, Thomas J; Friedrich, Patricia F; Bishop, Allen T; Shin, Alexander Y

    2014-10-01

    The purpose of this study was to evaluate the effect of wrapping bioabsorbable nerve conduit around primary suture repair on motor nerve regeneration in a rat model. Forty rats were randomly divided into two experimental groups according to the type of repair of the rat sciatic nerve: group I had primary suture repair; group II had primary suture repair and bioabsorbable collagen nerve conduit (NeuraGen® 1.5 mm, Integra LifeSciences Corp., Plainsboro, NJ) wrapped around the repair. At 12 weeks, no significant differences in the percentage of recovery between the two groups were observed with respect to compound muscle action potentials, isometric muscle force, and muscle weight (P = 0.816, P = 0.698, P = 0.861, respectively). Histomorphometric analysis as compared to the non-operative sites was also not significantly different between the two groups in terms of number of myelinated axons, myelinated fiber area, and nerve fiber density (P = 0.368, P = 0.968, P = 0.071, respectively). Perineural scar tissue formation was greater in primary suture repair group (0.36 ± 0.15) than in primary repair plus conduit wrapping group (0.17 ± 0.08). This difference was statistically significant (P < 0.001). Wrapping bioabsorbable nerve conduit around primary nerve repair can decrease perineural scar tissue formation. Although the scar-decreasing effect of bioabsorbable nerve wrap does not translate into better motor nerve recovery in this study, it might have an effect on the functional outcome in humans where scar formation is much more evident than in rats.

  17. Surface biology of collagen scaffold explains blocking of wound contraction and regeneration of skin and peripheral nerves.

    PubMed

    Yannas, I V; Tzeranis, D; So, P T

    2015-12-23

    We review the details of preparation and of the recently elucidated mechanism of biological (regenerative) activity of a collagen scaffold (dermis regeneration template, DRT) that has induced regeneration of skin and peripheral nerves (PN) in a variety of animal models and in the clinic. DRT is a 3D protein network with optimized pore size in the range 20-125 µm, degradation half-life 14 ± 7 d and ligand densities that exceed 200 µM α1β1 or α2β1 ligands. The pore has been optimized to allow migration of contractile cells (myofibroblasts, MFB) into the scaffold and to provide sufficient specific surface for cell-scaffold interaction; the degradation half-life provides the required time window for satisfactory binding interaction of MFB with the scaffold surface; and the ligand density supplies the appropriate ligands for specific binding of MFB on the scaffold surface. A dramatic change in MFB phenotype takes place following MFB-scaffold binding which has been shown to result in blocking of wound contraction. In both skin wounds and PN wounds the evidence has shown clearly that contraction blocking by DRT is followed by induction of regeneration of nearly perfect organs. The biologically active structure of DRT is required for contraction blocking; well-matched collagen scaffold controls of DRT, with structures that varied from that of DRT, have failed to induce regeneration. Careful processing of collagen scaffolds is required for adequate biological activity of the scaffold surface. The newly understood mechanism provides a relatively complete paradigm of regenerative medicine that can be used to prepare scaffolds that may induce regeneration of other organs in future studies.

  18. Electrical stimulation does not enhance nerve regeneration if delayed after sciatic nerve injury: the role of fibrosis

    PubMed Central

    Han, Na; Xu, Chun-gui; Wang, Tian-bing; Kou, Yu-hui; Yin, Xiao-feng; Zhang, Pei-xun; Xue, Feng

    2015-01-01

    Electrical stimulation has been shown to accelerate and enhance nerve regeneration in sensory and motor neurons after injury, but there is little evidence that focuses on the varying degrees of fibrosis in the delayed repair of peripheral nerve tissue. In this study, a rat model of sciatic nerve transection injury was repaired with a biodegradable conduit at 1 day, 1 week, 1 month and 2 months after injury, when the rats were divided into two subgroups. In the experimental group, rats were treated with electrical stimuli of frequency of 20 Hz, pulse width 100 ms and direct current voltage of 3 V; while rats in the control group received no electrical stimulation after the conduit operation. Histological results showed that stained collagen fibers comprised less than 20% of the total operated area in the two groups after delayed repair at both 1 day and 1 week but after longer delays, the collagen fiber area increased with the time after injury. Immunohistochemical staining revealed that the expression level of transforming growth factor β (an indicator of tissue fibrosis) decreased at both 1 day and 1 week after delayed repair but increased at both 1 and 2 months after delayed repair. These findings indicate that if the biodegradable conduit repair combined with electrical stimulation is delayed, it results in a poor outcome following sciatic nerve injury. One month after injury, tissue degeneration and distal fibrosis are apparent and are probably the main reason why electrical stimulation fails to promote nerve regeneration after delayed repair. PMID:25788926

  19. A Human Hair Keratin Hydrogel Scaffold Enhances Median Nerve Regeneration in Nonhuman Primates: An Electrophysiological and Histological Study

    PubMed Central

    Pace, Lauren A.; Plate, Johannes F.; Mannava, Sandeep; Barnwell, Jonathan C.; Koman, L. Andrew; Li, Zhongyu; Smith, Thomas L.

    2014-01-01

    A human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve conduit luminal filler following median nerve transection injury in 10 Macaca fascicularis nonhuman primates (NHP). A 1 cm nerve gap was grafted with a NeuraGen® collagen conduit filled with either saline or keratin hydrogel and nerve regeneration was evaluated by electrophysiology for a period of 12 months. The keratin hydrogel-grafted nerves showed significant improvement in return of compound motor action potential (CMAP) latency and recovery of baseline nerve conduction velocity (NCV) compared with the saline-treated nerves. Histological evaluation was performed on retrieved median nerves and abductor pollicis brevis (APB) muscles at 12 months. Nerve histomorphometry showed a significantly larger nerve area in the keratin group compared with the saline group and the keratin APB muscles had a significantly higher myofiber density than the saline group. This is the first published study to show that an acellular biomaterial hydrogel conduit filler can be used to enhance peripheral nerve regeneration and motor recovery in an NHP model. PMID:24083825

  20. A human hair keratin hydrogel scaffold enhances median nerve regeneration in nonhuman primates: an electrophysiological and histological study.

    PubMed

    Pace, Lauren A; Plate, Johannes F; Mannava, Sandeep; Barnwell, Jonathan C; Koman, L Andrew; Li, Zhongyu; Smith, Thomas L; Van Dyke, Mark

    2014-02-01

    A human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve conduit luminal filler following median nerve transection injury in 10 Macaca fascicularis nonhuman primates (NHP). A 1 cm nerve gap was grafted with a NeuraGen® collagen conduit filled with either saline or keratin hydrogel and nerve regeneration was evaluated by electrophysiology for a period of 12 months. The keratin hydrogel-grafted nerves showed significant improvement in return of compound motor action potential (CMAP) latency and recovery of baseline nerve conduction velocity (NCV) compared with the saline-treated nerves. Histological evaluation was performed on retrieved median nerves and abductor pollicis brevis (APB) muscles at 12 months. Nerve histomorphometry showed a significantly larger nerve area in the keratin group compared with the saline group and the keratin APB muscles had a significantly higher myofiber density than the saline group. This is the first published study to show that an acellular biomaterial hydrogel conduit filler can be used to enhance peripheral nerve regeneration and motor recovery in an NHP model.

  1. Functional regeneration of the transected recurrent laryngeal nerve using a collagen scaffold loaded with laminin and laminin-binding BDNF and GDNF

    PubMed Central

    Wang, Baoxin; Yuan, Junjie; Chen, Xinwei; Xu, Jiafeng; Li, Yu; Dong, Pin

    2016-01-01

    Recurrent laryngeal nerve (RLN) injury remains a challenge due to the lack of effective treatments. In this study, we established a new drug delivery system consisting of a tube of Heal-All Oral Cavity Repair Membrane loaded with laminin and neurotrophic factors and tested its ability to promote functional recovery following RLN injury. We created recombinant fusion proteins consisting of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) fused to laminin-binding domains (LBDs) in order to prevent neurotrophin diffusion. LBD-BDNF, LBD-GDNF, and laminin were injected into a collagen tube that was fitted to the ends of the transected RLN in rats. Functional recovery was assessed 4, 8, and 12 weeks after injury. Although vocal fold movement was not restored until 12 weeks after injury, animals treated with the collagen tube loaded with laminin, LBD-BDNF and LBD-GDNF showed improved recovery in vocalisation, arytenoid cartilage angles, compound muscle action potentials and regenerated fibre area compared to animals treated by autologous nerve grafting (p < 0.05). These results demonstrate the drug delivery system induced nerve regeneration following RLN transection that was superior to that induced by autologus nerve grafting. It may have potential applications in nerve regeneration of RLN transection injury. PMID:27558932

  2. Median nerve biodegradable wrapping : Clinical outcome of 10 patients.

    PubMed

    Kokkalis, S T; Mavrogenis, A F; Vottis, C; Papatheodorou, L; Papagelopoulos, P J; Soucacos, P N; Sotereanos, D G

    2016-08-01

    Nerve wrap protectors are bioabsorbable synthetic materials made of collagen or extracellular matrix that provide a non-constricting encasement for injured peripheral nerves. They are designed to be used as an interface between the nerve and the surrounding tissue. After hydrated, they transform into a soft, pliable, nonfriable, easy to handle porous conduit. The wall of the nerve wrap has a longitudinal slit that allows to be placed around the injured nerve. Τhis article presents the surgical technique for median nerve neurolysis and nerve coverage using a collagen or an extracellular matrix nerve wrap protector in 10 patients with recurrent or persistent carpal -tunnel syndrome. All patients had a mean of three previous open carpal tunnel operations, which were not successful. The mean follow-up was 3 years. -Under axillary nerve block anaesthesia with the use of -pneumatic tourniquet, a standard open carpal tunnel approach was done incorporating the previous incision. Scar tissue was excised in a healthy bed and the median nerve was thoroughly released with external neurolysis. An appropriate length of nerve wrap protector was cut longitudinally according to the length of nerve release. The nerve wrap was loosely sutured with separate polypropylene sutures No. 7-0. A volar splint was applied for a mean of 2 weeks followed by progressive passive and active range of motion rehabilitation exercises of the wrist and fingers. At the last follow-up, all patients showed improvement of clinical symptoms, static two-point discrimination test and median nerve conduction studies, and absence of Tinel sign. Differences in outcome and complications with respect to the nerve wrap materials used were not observed.

  3. Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Non-Human Primate

    DTIC Science & Technology

    2013-10-01

    study is evaluating a surgical approach for repair of conus medullaris/cauda equina injury in rhesus macaques using a biodegradable bridging graft that...translational research study investigates the effects of neural repair in the rhesus macaques using a GDNF-releasing nerve guidance channel as a bridging...to the start of surgical procedures, each enrolled rhesus macaque underwent extensive screening and training. Behavioral records and profiles were

  4. The effect of intraluminal contact mediated guidance signals on axonal mismatch during peripheral nerve repair.

    PubMed

    Daly, William T; Yao, Li; Abu-rub, Mohammad T; O'Connell, Claire; Zeugolis, Dimitrios I; Windebank, Anthony J; Pandit, Abhay S

    2012-10-01

    The current microsurgical gold standard for repairing long gap nerve injuries is the autograft. Autograft provides a protective environment for repair and a natural internal architecture, which is essential for regeneration. Current clinically approved hollow nerve guidance conduits allow provision of this protective environment; however they fail to provide an essential internal architecture to the regenerating nerve. In the present study both structured and unstructured intraluminal collagen fibres are investigated to assess their ability to enhance conduit mediated nerve repair. This study presents a direct comparison of both structured and unstructured fibres in vivo. The addition of intraluminal guidance structures was shown to significantly decrease axonal dispersion within the conduit and reduced axonal mismatch of distal nerve targets (p < 0.05). The intraluminal fibres were shown to be successfully incorporated into the host regenerative process, acting as a platform for Schwann cell migration and axonal regeneration. Ultimately the fibres were able to provide a platform for nerve regeneration in a long term regeneration study (16 weeks) and facilitated increased guidance of regenerating axons towards their distal nerve targets. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Axonal regeneration and remyelination evaluation of chitosan/gelatin-based nerve guide combined with transforming growth factor-β1 and Schwann cells.

    PubMed

    Nie, Xin; Deng, Manjing; Yang, Maojin; Liu, Luchuan; Zhang, Yongjie; Wen, Xiujie

    2014-01-01

    Despite efforts in peripheral nerve injury and regeneration, it is difficult to achieve a functional recovery following extended peripheral nerve lesions. Even if artificial nerve conduit, cell components and growth factors can enhance nerve regeneration, integration in peripheral nerve repair and regeneration remains yet to be explored. For this study, we used chitosan/gelatin nerve graft constructed with collagenous matrices as a vehicle for Schwann cells and transforming growth factor-β1 to bridge a 10-mm gap of the sciatic nerve and explored the feasibility of improving regeneration and reinnervation in rats. The nerve regeneration was assessed with functional recovery, electrophysiological test, retrograde labeling, and immunohistochemistry analysis during the post-operative period of 16 weeks. The results showed that the internal sides of the conduits were compact enough to prevent the connective tissues from ingrowth. Nerve conduction velocity, average regenerated myelin area, and myelinated axon count were similar to those treated with autograft (p > 0.05) but significantly higher than those bridged with chitosan/gelatin nerve graft alone (p < 0.05). Evidences from retrograde labeling and immunohistochemistry analysis are further provided in support of improving axonal regeneration and remyelination. A designed graft incorporating all of the tissue-engineering strategies for peripheral nerve regeneration may provide great progress in tissue engineering for nerve repair.

  6. Seal arrangement for intersecting conduits

    DOEpatents

    Goedicke, Friedrich E.

    1980-01-01

    A seal arrangement in which two intersecting conduits are sealed from each other. A sleeve insert is locked in a sealed relationship within one conduit enclosing the openings of the intersecting conduit.

  7. A composite SWNT-collagen matrix: characterization and preliminary assessment as a conductive peripheral nerve regeneration matrix.

    PubMed

    Tosun, Z; McFetridge, P S

    2010-12-01

    Unique in their structure and function, single-walled carbon nanotubes (SWNTs) have received significant attention due to their potential to create unique conductive materials. For neural applications, these conductive materials hold promise as they may enhance regenerative processes. However, like other nano-scaled biomaterials it is important to have a comprehensive understanding how these materials interact with cell systems and how the biological system responds to their presence. These investigations aim to further our understanding of SWNT-cell interactions by assessing the effect SWNT/collagen hydrogels have on PC12 neuronal-like cells seeded within and (independently) on top of the composite material. Two types of collagen hydrogels were prepared: (1) SWNTs dispersed directly within the collagen (SWNT/COL) and (2) albumin-coated SWNTs prepared using the surfactant 'sodium cholate' to improve dispersion (AL-SWNT/COL) and collagen alone serving as a control (COL). SWNT dispersion was significantly improved when using surfactant-assisted dispersion. The enhanced dispersion resulted in a stiffer, more conductive material with an increased collagen fiber diameter. Short-term cell interactions with PC12 cells and SWNT composites have shown a stimulatory effect on cell proliferation relative to plain collagen controls. In parallel to these results, p53 gene displayed normal expression levels, which indicates the absence of nanoparticle-induced DNA damage. In summary, these mechanically tunable SWNT-collagen scaffolds show the potential for enhanced electrical activity and have shown positive in vitro biocompatibility results offering further evidence that SWNT-based materials have an important role in promoting neuronal regeneration.

  8. Electrospun Collagen Fibers with Spatial Patterning of SDF1α for the Guidance of Neural Stem Cells.

    PubMed

    Li, Xiaoran; Liang, Hui; Sun, Jie; Zhuang, Yan; Xu, Bai; Dai, Jianwu

    2015-08-26

    Producing gradients of biological cues into nerve conduits is crucial for nerve guidance and regeneration. Herein, the fabrication of gradients of stromal cell-derived factor-1α (SDF1α) on electrospun collagen mats is reported using an electrohydrodynamic jet printing technique. The fabrication of various SDF1α gradated patterns on collagen fibrous mats is successfully demonstrated including shallow continuous gradient, steep continuous gradient, and step gradient by controlling the processing parameters. The SDF1α graded collagen scaffolds show a long-term stable gradient, as SDF1α is fused with a unique peptide of collagen binding domain (CBD), and CBD-SDF1α can specifically bind to the collagen mat. Such graded scaffolds exhibit sustained release of SDF1α. Further examination of neural stem cell (NSC) response to the CBD-SDF1α gradients with various patterns show that the NSCs can sense the CBD-SDF1α gradients, display a polarized morphology, and tend to migrate toward the region with a higher CBD-SDF1α content. The collagen mats with CBD-SDF1α gradients guide gradual distribution of NSCs, and NSC-differentiated neurons and astrocytes after seeding for 1 and 7 d. This new class of CBD-SDF1α gradient scaffolds can potentially be employed for guided nerve regeneration.

  9. Engineered neural tissue with aligned, differentiated adipose-derived stem cells promotes peripheral nerve regeneration across a critical sized defect in rat sciatic nerve.

    PubMed

    Georgiou, Melanie; Golding, Jon P; Loughlin, Alison J; Kingham, Paul J; Phillips, James B

    2015-01-01

    Adipose-derived stem cells were isolated from rats and differentiated to a Schwann cell-like phenotype in vitro. The differentiated cells (dADSCs) underwent self-alignment in a tethered type-1 collagen gel, followed by stabilisation to generate engineered neural tissue (EngNT-dADSC). The pro-regenerative phenotype of dADSCs was enhanced by this process, and the columns of aligned dADSCs in the aligned collagen matrix supported and guided neurite extension in vitro. EngNT-dADSC sheets were rolled to form peripheral nerve repair constructs that were implanted within NeuraWrap conduits to bridge a 15 mm gap in rat sciatic nerve. After 8 weeks regeneration was assessed using immunofluorescence imaging and transmission electron microscopy and compared to empty conduit and nerve graft controls. The proportion of axons detected in the distal stump was 3.5 fold greater in constructs containing EngNT-dADSC than empty tube controls. Our novel combination of technologies that can organise autologous therapeutic cells within an artificial tissue construct provides a promising new cellular biomaterial for peripheral nerve repair.

  10. Conduit purging device and method

    NASA Technical Reports Server (NTRS)

    Wilks, Michael T. (Inventor)

    2011-01-01

    A device for purging gas comprises a conduit assembly defining an interior volume. The conduit assembly comprises a first conduit portion having an open first end and an open second end and a second conduit portion having an open first end and a closed second end. The open second end of the first conduit portion is disposed proximate to the open first end of the second conduit portion to define a weld region. The device further comprises a supply element supplying a gas to the interior volume at a substantially constant rate and a vent element venting the gas from the interior volume at a rate that maintains the gas in the interior volume within a pressure range suitable to hold a weld bead in the weld region in equilibrium during formation of a weld to join the first conduit portion and the second conduit portion.

  11. A nanofibrous PHBV tube with Schwann cell as artificial nerve graft contributing to rat sciatic nerve regeneration across a 30-mm defect bridge.

    PubMed

    Biazar, Esmaeil; Heidari Keshel, Saeed

    2013-02-01

    A nanofibrous PHBV nerve conduit has been used to evaluate its efficiency based on the promotion of nerve regeneration in rats. The designed conduits were investigated by physical, mechanical and microscopic analyses. The conduits were implanted into a 30-mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently high mechanical properties to serve as a nerve guide. The results demonstrated that in the nanofibrous graft with cells, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. For the grafts especially the nanofibrous conduits with cells, muscle cells of gastrocnemius on the operated side were uniform in their size and structures. This study proves the feasibility of artificial conduit with Schwann cells for nerve regeneration by bridging a longer defect in a rat model.

  12. Seal between metal and ceramic conduits

    DOEpatents

    Underwood, Richard Paul; Tentarelli, Stephen Clyde

    2015-02-03

    A seal between a ceramic conduit and a metal conduit of an ion transport membrane device consisting of a sealing surface of ceramic conduit, a sealing surface of ceramic conduit, a single gasket body, and a single compliant interlayer.

  13. Flexible cryogenic conduit

    SciTech Connect

    Brindza, P.D.; Wines, R.R.; Takacs, J.J.

    1999-12-21

    A flexible and relatively low cost cryogenic conduit is described. The flexible cryogenic conduit of the present invention comprises a first inner corrugated tube with single braided serving, a second outer corrugated tube with single braided serving concentric with the inner corrugated tube, and arranged outwardly about the periphery of the inner corrugated tube and between the inner and outer corrugated tubes: a superinsulation layer; a one half lap layer of polyester ribbon; a one half lap layer of copper ribbon; a spirally wound refrigeration tube; a second one half lap layer of copper ribbon; a second one half lap layer of polyester ribbon; a second superinsulation layer; a third one half lap layer of polyester ribbon; and a spirally wound stretchable and compressible filament.

  14. Flexible cryogenic conduit

    DOEpatents

    Brindza, Paul Daniel; Wines, Robin Renee; Takacs, James Joseph

    1999-01-01

    A flexible and relatively low cost cryogenic conduit is described. The flexible cryogenic conduit of the present invention comprises a first inner corrugated tube with single braided serving, a second outer corrugated tube with single braided serving concentric with the inner corrugated tube, and arranged outwardly about the periphery of the inner corrugated tube and between the inner and outer corrugated tubes: a superinsulation layer; a one half lap layer of polyester ribbon; a one half lap layer of copper ribbon; a spirally wound refrigeration tube; a second one half lap layer of copper ribbon; a second one half lap layer of polyester ribbon; a second superinsulation layer; a third one half lap layer of polyester ribbon; and a spirally wound stretchable and compressible filament.

  15. Subglacial conduits in sediments

    NASA Astrophysics Data System (ADS)

    Hewitt, Ian

    2016-04-01

    Much of the current understanding of subglacial hydrology is based on the R-channel type model, in which turbulent dissipation and melting causes a roughly semi-circular incision upwards into the ice. The prevalence of such R-channels beneath the Greenland and Antarctic ice sheets is poorly known. Beneath sediment-based ice, distributed water flow may prevail, or some form of conduits may still form due to a combination of upwards melting as well as downwards erosion into the subglacial sediments (often referred to as a canal). This study examines the dynamics of such conduits, and implications for large-scale subglacial drainage. Although a relatively standard set of equations has developed to model the evolution and efficiency of R-channels, models of sediment-floored conduits are much less well established; previous models assume steady state, or make ad hoc assumptions about the balance of processes controlling the channel walls. In this study I suggest a (relatively) simple model analogous to that for an R-channel. The model requires consideration of the energy balance that results in melting of the ice roof, and also the erosion, deposition, and creep of the sediments. Implications for the evolution of large-scale drainage systems over subglacial sediment will be discussed, for subglacial floods in Antarctica, and for subglacial erosion and landform development.

  16. Multicenter Clinical Trial of Keratin Biomaterials for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2013-10-01

    purity (size exclusion chromatography for molecular weight, amino acids analysis, ELISA for protein identification, and gel rheology ) and 2) a cell...distribution study. Labeled keratin gel will be placed inside nerve conduits. The ends of the conduits will be closed, and the conduits will be implanted in...Marra KG. Keratin gel filler for peripheral nerve repair in a rodent sciatic nerve injury model. Plast Reconstr Surg 2012;129:67-78. Pace LA

  17. Pore structure and dielectric behaviour of the 3D collagen-DAC scaffolds designed for nerve tissue repair.

    PubMed

    Pietrucha, Krystyna; Marzec, Ewa; Kudzin, Marcin

    2016-11-01

    The design and selection of a suitable scaffold with well-defined pores size distribution and dielectric properties are critical features for neural tissue engineering. In this study we use mercury porosimetry and the dielectric spectroscopy in the alpha-dispersion region of the electric field to determine the microarchitecture and activation energy of collagen (Col) modified by 2,3 dialdehyde cellulose (DAC). The scaffold was synthesized in three steps: (i) preparation of DAC by oxidation of cellulose, (ii) construction of a 3D Col sponge-shape or film, (iii) cross-linkage of the Col samples using DAC. The activation energy needed to break the bonds formed by water in the Col-DAC composite is approximately 2 times lower than that in the unmodified Col. In addition, the magnitude of conductivity for modified Col at 70°C is approximately 40% lower than that recorded for the unmodified Col. The largest fraction, of which at least 70% of the total pore volume comprises the sponge, is occupied by pores ranging from 20 to 100μm in size. The knowledge on the dielectric behaviour and microstructure of the Col-DAC scaffold may prove relevant to neural tissue engineering focused on the regeneration of the nervous system.

  18. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    PubMed Central

    Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

    2011-01-01

    Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

  19. Pathophysiology of nerve regeneration and nerve reconstruction in burned patients.

    PubMed

    Coert, J Henk

    2010-08-01

    In extensive burns peripheral nerves can be involved. The injury to the nerve can be direct by thermal or electrical burns, but nerves can also be indirectly affected by the systemic reaction that follows the burn. Mediators will be released causing a neuropathy to nerves remote from the involved area. Involved mediators and possible therapeutic options will be discussed. In burned patients nerves can be reconstructed using autologous nerve grafts or nerve conduits. A key factor is an adequate wound debridement and a well-vascularized bed to optimize the outgrowth of the axons. Early free tissue transfers have shown promising results.

  20. Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head

    PubMed Central

    Jones, H. J.; Girard, M. J.; White, N.; Fautsch, M. P.; Morgan, J. E.; Ethier, C. R.; Albon, J.

    2015-01-01

    The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse. PMID:25808336

  1. Portable conduit retention apparatus for releasably retaining a conduit therein

    DOEpatents

    Metzger, Richard H.

    1998-01-01

    Portable conduit retention apparatus for releasably retaining a conduit therein. The apparatus releasably retains the conduit out of the way of nearby personnel and equipment. The apparatus includes a portable support frame defining a slot therein having an open mouth portion in communication with the slot for receiving the conduit through the open mouth portion and into the slot. A retention bar is pivotally connected to the support frame adjacent the mouth portion for releasably retaining the conduit in the slot. The retention bar freely pivots to a first position, so that the mouth portion is unblocked in order that the conduit is received through the mouth portion and into the slot. In addition, the retention bar freely pivots to a second position, so that the mouth portion is blocked in order that the conduit is retained in the slot. The conduit is released from the slot by pivoting the retention bar to the first position to unblock the mouth portion and thereafter manipulating the conduit from the slot and through the mouth portion. The apparatus may further include a mounting member attached to the support frame for mounting the apparatus on a vertical support surface. Another embodiment of the apparatus includes a shoe assembly of predetermined weight removably connected to the support frame for resting the apparatus on a floor in such a manner that the apparatus is substantially stationary on the floor.

  2. Portable conduit retention apparatus for releasably retaining a conduit therein

    DOEpatents

    Metzger, R.H.

    1998-07-07

    Portable conduit retention apparatus is described for releasably retaining a conduit therein. The apparatus releasably retains the conduit out of the way of nearby personnel and equipment. The apparatus includes a portable support frame defining a slot therein having an open mouth portion in communication with the slot for receiving the conduit through the open mouth portion and into the slot. A retention bar is pivotally connected to the support frame adjacent the mouth portion for releasably retaining the conduit in the slot. The retention bar freely pivots to a first position, so that the mouth portion is unblocked in order that the conduit is received through the mouth portion and into the slot. In addition, the retention bar freely pivots to a second position, so that the mouth portion is blocked in order that the conduit is retained in the slot. The conduit is released from the slot by pivoting the retention bar to the first position to unblock the mouth portion and thereafter manipulating the conduit from the slot and through the mouth portion. The apparatus may further include a mounting member attached to the support frame for mounting the apparatus on a vertical support surface. Another embodiment of the apparatus includes a shoe assembly of predetermined weight removably connected to the support frame for resting the apparatus on a floor in such a manner that the apparatus is substantially stationary on the floor. 6 figs.

  3. Conduit Coating Abrasion Testing

    NASA Technical Reports Server (NTRS)

    Sullivan, Mary K.

    2013-01-01

    During my summer internship at NASA I have been working alongside the team members of the RESTORE project. Engineers working on the RESTORE project are creating ·a device that can go into space and service satellites that no longer work due to gas shortage or other technical difficulties. In order to complete the task of refueling the satellite a hose needs to be used and covered with a material that can withstand effects of space. The conduit coating abrasion test will help the researchers figure out what type of thermal coating to use on the hose that will be refueling the satellites. The objective of the project is to determine whether or not the conduit coating will withstand the effects of space. For the RESTORE project I will help with various aspects of the testing that needed to be done in order to determine which type of conduit should be used for refueling the satellite. During my time on the project I will be assisting with wiring a relay board that connected to the test set up by soldering, configuring wires and testing for continuity. Prior to the testing I will work on creating the testing site and help write the procedure for the test. The testing will take place over a span of two weeks and lead to an informative conclusion. Working alongside various RESTORE team members I will assist with the project's documentation and records. All in all, throughout my internship at NASA I hope to learn a number of valuable skills and be a part of a hard working team of engineers.

  4. Cell-free artificial implants of electrospun fibres in a three-dimensional gelatin matrix support sciatic nerve regeneration in vivo.

    PubMed

    Kriebel, Andreas; Hodde, Dorothee; Kuenzel, Thomas; Engels, Jessica; Brook, Gary; Mey, Jörg

    2017-01-27

    Surgical repair of larger peripheral nerve lesions requires the use of autologous nerve grafts. At present, clinical alternatives to avoid nerve transplantation consist of empty tubes, which are only suitable for the repair over short distances and have limited success. We developed a cell-free, three-dimensional scaffold for axonal guidance in long-distance nerve repair. Sub-micron scale fibres of biodegradable poly-ε-caprolactone (PCL) and collagen/PCL (c/PCL) blends were incorporated in a gelatin matrix and inserted in collagen tubes. The conduits were tested by replacing 15-mm-long segments of rat sciatic nerves in vivo. Biocompatibility of the implants and nerve regeneration were assessed histologically, with electromyography and with behavioural tests for motor functions. Functional repair was achieved in all animals with autologous transplants, in 12 of 13 rats that received artificial implants with an internal structure and in half of the animals with empty nerve conduits. In rats with implants containing c/PCL fibres, the extent of recovery (compound muscle action potentials, motor functions of the hind limbs) was superior to animals that had received empty implants, but not as good as with autologous nerve transplantation. Schwann cell migration and axonal regeneration were observed in all artificial implants, and muscular atrophy was reduced in comparison with animals that had received no implants. The present design represents a significant step towards cell-free, artificial nerve bridges that can replace autologous nerve transplants in the clinic. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Decellularisation and histological characterisation of porcine peripheral nerves

    PubMed Central

    Zilic, Leyla

    2016-01-01

    ABSTRACT Peripheral nerve injuries affect a large proportion of the global population, often causing significant morbidity and loss of function. Current treatment strategies include the use of implantable nerve guide conduits (NGC's) to direct regenerating axons between the proximal and distal ends of the nerve gap. However, NGC's are limited in their effectiveness at promoting regeneration Current NGCs are not suitable as substrates for supporting either neuronal or Schwann cell growth, as they lack an architecture similar to that of the native extracellular matrix (ECM) of the nerve. The aim of this study was to create an acellular porcine peripheral nerve using a novel decellularisation protocol, in order to eliminate the immunogenic cellular components of the tissue, while preserving the three‐dimensional histoarchitecture and ECM components. Porcine peripheral nerve (sciatic branches were decellularised using a low concentration (0.1%; w/v) sodium dodecyl sulphate in conjunction with hypotonic buffers and protease inhibitors, and then sterilised using 0.1% (v/v) peracetic acid. Quantitative and qualitative analysis revealed a ≥95% (w/w) reduction in DNA content as well as preservation of the nerve fascicles and connective tissue. Acellular nerves were shown to have retained key ECM components such as collagen, laminin and fibronectin. Slow strain rate to failure testing demonstrated the biomechanical properties of acellular nerves to be comparable to fresh controls. In conclusion, we report the production of a biocompatible, biomechanically functional acellular scaffold, which may have use in peripheral nerve repair. Biotechnol. Bioeng. 2016;113: 2041–2053. © 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc. PMID:26926914

  6. Nanofiber-reinforced biological conduit in cardiac surgery: preliminary report.

    PubMed

    Guhathakurta, Soma; Galla, Satish; Ramesh, Balasundari; Venugopal, Jayarama Reddy; Ramakrishna, Seeram; Cherian, Kotturathu Mammen

    2011-06-01

    Several options are available for right ventricular outflow tract reconstruction, including commercially available bovine jugular vein and cryo-preserved homografts. Homograft non-availability and the problems of commercially available conduits led us to develop indigenously processed bovine jugular vein conduits with competent valves. They were made completely acellular and strengthened by non-conventional cross-linking without disturbing the extracellular matrix, which improved the luminal surface characteristics for hemocompatibility. Biocompatibility in vitro and in vivo, along with thermal stability, matrix stability, and mechanical strength have been evaluated. Sixty-nine patients received these conduits for right ventricular outflow tract reconstruction. Seven conduits dilated and 4 required replacement. To counteract dilatation, biodegradable polymeric nanofibers in various combinations and in isolation (collagen, polycaprolactone, polylactic acid) were characterized and used to reinforce the conduit circumferentially. Physical validation by mechanical testing, scanning electron microscopy, and in-vitro cytotoxicity was conducted. Thermal stability, spectroscopy studies of the polymer, and preclinical studies of the coated bovine jugular vein in animals are in progress. The feasibility studies have been completed, and the final polymer selection depends on evaluation of the functional superiority of the coated bovine jugular vein.

  7. In Vitro Study of Directly Bioprinted Perfusable Vasculature Conduits

    PubMed Central

    Zhang, Yahui; Yu, Yin; Akkouch, Adil; Dababneh, Amer; Dolati, Farzaneh

    2014-01-01

    The ability to create three dimensional (3D) thick tissues is still a major tissue engineering challenge. It requires the development of a suitable vascular supply for an efficient media exchange. An integrated vasculature network is particularly needed when building thick functional tissues and/or organs with high metabolic activities, such as the heart, liver and pancreas. In this work, human umbilical vein smooth muscle cells (HUVSMCs) were encapsulated in sodium alginate and printed in the form of vasculature conduits using a coaxial deposition system. Detailed investigations were performed to understand the dehydration, swelling and degradation characteristics of printed conduits. In addition, because perfusional, permeable and mechanical properties are unique characteristics of natural blood vessels, for printed conduits these properties were also explored in this work. The results show that cells encapsulated in conduits had good proliferation activities and that their viability increased during prolonged in vitro culture. Deposition of smooth muscle matrix and collagen was observed around the peripheral and luminal surface in long-term cultured cellular vascular conduit through histology studies. PMID:25574378

  8. Repairing Peripheral Nerves: Is there a Role for Carbon Nanotubes?

    PubMed

    Oprych, Karen M; Whitby, Raymond L D; Mikhalovsky, Sergey V; Tomlins, Paul; Adu, Jimi

    2016-06-01

    Peripheral nerve injury continues to be a major global health problem that can result in debilitating neurological deficits and neuropathic pain. Current state-of-the-art treatment involves reforming the damaged nerve pathway using a nerve autograft. Engineered nerve repair conduits can provide an alternative to the nerve autograft avoiding the inevitable tissue damage caused at the graft donor site. Commercially available nerve repair conduits are currently only considered suitable for repairing small nerve lesions; the design and performance of engineered conduits requires significant improvements to enable their use for repairing larger nerve defects. Carbon nanotubes (CNTs) are an emerging novel material for biomedical applications currently being developed for a range of therapeutic technologies including scaffolds for engineering and interfacing with neurological tissues. CNTs possess a unique set of physicochemical properties that could be useful within nerve repair conduits. This progress report aims to evaluate and consolidate the current literature pertinent to CNTs as a biomaterial for supporting peripheral nerve regeneration. The report is presented in the context of the state-of-the-art in nerve repair conduit design; outlining how CNTs may enhance the performance of next generation peripheral nerve repair conduits.

  9. Circadian Rhythm Influences the Promoting Role of Pulsed Electromagnetic Fields on Sciatic Nerve Regeneration in Rats

    PubMed Central

    Zhu, Shu; Ge, Jun; Liu, Zhongyang; Liu, Liang; Jing, Da; Ran, Mingzi; Wang, Meng; Huang, Liangliang; Yang, Yafeng; Huang, Jinghui; Luo, Zhuojing

    2017-01-01

    Circadian rhythm (CR) plays a critical role in the treatment of several diseases. However, the role of CR in the treatment of peripheral nerve defects has not been studied. It is also known that the pulsed electromagnetic fields (PEMF) can provide a beneficial microenvironment to quicken the process of nerve regeneration and to enhance the quality of reconstruction. In this study, we evaluate the impact of CR on the promoting effect of PEMF on peripheral nerve regeneration in rats. We used the self-made “collagen-chitosan” nerve conduits to bridge the 15-mm nerve gaps in Sprague-Dawley rats. Our results show that PEMF stimulation at daytime (DPEMF) has most effective outcome on nerve regeneration and rats with DPEMF treatment achieve quickly functional recovery after 12 weeks. These findings indicate that CR is an important factor that determines the promoting effect of PEMF on peripheral nerve regeneration. PEMF exposure in the daytime enhances the functional recovery of rats. Our study provides a helpful guideline for the effective use of PEMF mediations experimentally and clinically. PMID:28360885

  10. CONDUIT: Control Designer's Unified Interface

    NASA Technical Reports Server (NTRS)

    Levine, William S.; Tischler, Mark B.

    1999-01-01

    CONDUIT, which stands for control designer's unified interface, is a computer software package. Its purpose is to assist a human control system designer in designing control systems for aircraft. At the present time CONDUIT is being used by most of the major U. S. rotorcraft and fixed-wing aircraft manufacturers to assist in the design of stability and control augmentation systems. Work is also continuing on the development of additional features for CONDUIT, including tools for analyzing the sensitivity of solutions, and on further enhancements to the basic package. The purpose of this paper is to describe CONDUIT, its operation, and the sensitivity tools that are being developed for inclusion in the next release of the package.

  11. Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

    DTIC Science & Technology

    2015-01-01

    guide conduits (NGCs) made of biodegradable materials offer a potential solution to this problem. Based on our previous accomplishments in developing...completed Task 2 and finalized the design of the nerve conduits. Optimizing Nanofiber Guidance (tasks 2a-2d) Final Composition of the Optimized NGC...WL, Cui FZ, Korgel BA, Gerecht S, Mao HQ. Creating polymer hydrogel microfibres with internal alignment via electrical and mechanical stretching

  12. A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

    PubMed Central

    Yalom, Anisa; Berns, Eric J.; Stephanopoulos, Nicholas; McClendon, Mark T.; Segovia, Luis A.; Spigelman, Igor; Stupp, Samuel I.; Jarrahy, Reza

    2014-01-01

    Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may

  13. A comparison of the performance of mono- and bi-component electrospun conduits in a rat sciatic model.

    PubMed

    Cirillo, Valentina; Clements, Basak A; Guarino, Vincenzo; Bushman, Jared; Kohn, Joachim; Ambrosio, Luigi

    2014-10-01

    Synthetic nerve conduits represent a promising strategy to enhance functional recovery in peripheral nerve injury repair. However, the efficiency of synthetic nerve conduits is often compromised by the lack of molecular factors to create an enriched microenvironment for nerve regeneration. Here, we investigate the in vivo response of mono (MC) and bi-component (BC) fibrous conduits obtained by processing via electrospinning poly(ε-caprolactone) (PCL) and gelatin solutions. In vitro studies demonstrate that the inclusion of gelatin leads to uniform electrospun fiber size and positively influences the response of Dorsal Root Ganglia (DRGs) neurons as confirmed by the preferential extensions of neurites from DRG bodies. This behavior can be attributed to gelatin as a bioactive cue for the cultured DRG and to the reduced fibers size. However, in vivo studies in rat sciatic nerve defect model show an opposite response: MC conduits stimulate superior nerve regeneration than gelatin containing PCL conduits as confirmed by electrophysiology, muscle weight and histology. The G-ratio, 0.71 ± 0.07 for MC and 0.66 ± 0.05 for autograft, is close to 0.6, the value measured in healthy nerves. In contrast, BC implants elicited a strong host response and infiltrating tissue occluded the conduits preventing the formation of myelinated axons. Therefore, although gelatin promotes in vitro nerve regeneration, we conclude that bi-component electrospun conduits are not satisfactory in vivo due to intrinsic limits to their mechanical performance and degradation kinetics, which are essential to peripheral nerve regeneration in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Electrospun collagen-chitosan-TPU nanofibrous scaffolds for tissue engineered tubular grafts.

    PubMed

    Huang, Chen; Chen, Rui; Ke, Qinfei; Morsi, Yosry; Zhang, Kuihua; Mo, Xiumei

    2011-02-01

    The objective of this study is to design a novel kind of scaffolds for blood vessel and nerve repairs. Random and aligned nanofibrous scaffolds based on collagen-chitosan-thermoplastic polyurethane (TPU) blends were electrospun to mimic the componential and structural aspects of the native extracellular matrix, while an optimal proportion was found to keep the balance between biocompatibility and mechanical strength. The scaffolds were crosslinked by glutaraldehyde (GTA) vapor to prevent them from being dissolved in the culture medium. Fiber morphology was characterized using scanning electron microscopy (SEM) and atomic-force microscopy (AFM). Fourier transform infrared spectroscopy (FTIR) showed that the three-material system exhibits no significant differences before and after crosslinking, whereas pore size of crosslinked scaffolds decreased drastically. The mechanical properties of the scaffolds were found to be flexible with a high tensile strength. Cell viability studies with endothelial cells and Schwann cells demonstrated that the blended nanofibrous scaffolds formed by electrospinning process had good biocompatibility and aligned fibers could regulate cell morphology by inducing cell orientation. Vascular grafts and nerve conduits were electrospun or sutured based on the nanofibrous scaffolds and the results indicated that collagen-chitosan-TPU blended nanofibrous scaffolds might be a potential candidate for vascular repair and nerve regeneration. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration

    NASA Technical Reports Server (NTRS)

    Widmer, M. S.; Gupta, P. K.; Lu, L.; Meszlenyi, R. K.; Evans, G. R.; Brandt, K.; Savel, T.; Gurlek, A.; Patrick, C. W. Jr; Mikos, A. G.; hide

    1998-01-01

    We have fabricated porous, biodegradable tubular conduits for guided tissue regeneration using a combined solvent casting and extrusion technique. The biodegradable polymers used in this study were poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). A polymer/salt composite was first prepared by a solvent casting process. After drying, the composite was extruded to form a tubular construct. The salt particles in the construct were then leached out leaving a conduit with an open-pore structure. PLGA was studied as a model polymer to analyze the effects of salt weight fraction, salt particle size, and processing temperature on porosity and pore size of the extruded conduits. The porosity and pore size were found to increase with increasing salt weight fraction. Increasing the salt particle size increased the pore diameter but did not affect the porosity. High extrusion temperatures decreased the pore diameter without altering the porosity. Greater decrease in molecular weight was observed for conduits manufactured at higher temperatures. The mechanical properties of both PLGA and PLLA conduits were tested after degradation in vitro for up to 8 weeks. The modulus and failure strength of PLLA conduits were approximately 10 times higher than those of PLGA conduits. Failure strain was similar for both conduits. After degradation for 8 weeks, the molecular weights of the PLGA and PLLA conduits decreased to 38% and 43% of the initial values, respectively. However, both conduits maintained their shape and did not collapse. The PLGA also remained amorphous throughout the time course, while the crystallinity of PLLA increased from 5.2% to 11.5%. The potential of seeding the conduits with cells for transplantation or with biodegradable polymer microparticles for drug delivery was also tested with dyed microspheres. These porous tubular structures hold great promise for the regeneration of tissues which require tubular scaffolds such as peripheral nerve

  16. Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration.

    PubMed

    Widmer, M S; Gupta, P K; Lu, L; Meszlenyi, R K; Evans, G R; Brandt, K; Savel, T; Gurlek, A; Patrick, C W; Mikos, A G

    1998-11-01

    We have fabricated porous, biodegradable tubular conduits for guided tissue regeneration using a combined solvent casting and extrusion technique. The biodegradable polymers used in this study were poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). A polymer/salt composite was first prepared by a solvent casting process. After drying, the composite was extruded to form a tubular construct. The salt particles in the construct were then leached out leaving a conduit with an open-pore structure. PLGA was studied as a model polymer to analyze the effects of salt weight fraction, salt particle size, and processing temperature on porosity and pore size of the extruded conduits. The porosity and pore size were found to increase with increasing salt weight fraction. Increasing the salt particle size increased the pore diameter but did not affect the porosity. High extrusion temperatures decreased the pore diameter without altering the porosity. Greater decrease in molecular weight was observed for conduits manufactured at higher temperatures. The mechanical properties of both PLGA and PLLA conduits were tested after degradation in vitro for up to 8 weeks. The modulus and failure strength of PLLA conduits were approximately 10 times higher than those of PLGA conduits. Failure strain was similar for both conduits. After degradation for 8 weeks, the molecular weights of the PLGA and PLLA conduits decreased to 38% and 43% of the initial values, respectively. However, both conduits maintained their shape and did not collapse. The PLGA also remained amorphous throughout the time course, while the crystallinity of PLLA increased from 5.2% to 11.5%. The potential of seeding the conduits with cells for transplantation or with biodegradable polymer microparticles for drug delivery was also tested with dyed microspheres. These porous tubular structures hold great promise for the regeneration of tissues which require tubular scaffolds such as peripheral nerve

  17. Patterned substrates and methods for nerve regeneration

    DOEpatents

    Mallapragada, Surya K.; Heath, Carole; Shanks, Howard; Miller, Cheryl A.; Jeftinija, Srdija

    2004-01-13

    Micropatterned substrates and methods for fabrication of artificial nerve regeneration conduits and methods for regenerating nerves are provided. Guidance compounds or cells are seeded in grooves formed on the patterned substrate. The substrates may also be provided with electrodes to provide electrical guidance cues to the regenerating nerve. The micropatterned substrates give physical, chemical, cellular and/or electrical guidance cues to promote nerve regeneration at the cellular level.

  18. Electrical stimulation promotes regeneration of defective peripheral nerves after delayed repair intervals lasting under one month.

    PubMed

    Xu, Chungui; Kou, Yuhui; Zhang, Peixun; Han, Na; Yin, Xiaofeng; Deng, Jiuxu; Chen, Bo; Jiang, Baoguo

    2014-01-01

    Electrical stimulation (ES) has been proven to be an effective means of enhancing the speed and accuracy of nerve regeneration. However, these results were recorded when the procedure was performed almost immediately after nerve injury. In clinical settings, most patients cannot be treated immediately. Some patients with serious trauma or contaminated wounds need to wait for nerve repair surgery. Delays in nerve repair have been shown to be associated with poorer results than immediate surgery. It is not clear whether electrical stimulation still has any effect on nerve regeneration after enough time has elapsed. A delayed nerve repair model in which the rats received delayed nerve repair after 1 day, 1 week, 1 month, and 2 months was designed. At each point in time, the nerve stumps of half the rats were bridged with an absorbable conduit and the rats were given 1 h of weak electrical stimulation. The other half was not treated. In order to analyze the morphological and molecular differences among these groups, 6 ES rats and 6 sham ES rats per point in time were killed 5 days after surgery. The other rats in each group were allowed to recover for 6 weeks before the final functional test and tissue observation. The amounts of myelinated fibers in the distal nerve stumps decreased as the delay in repair increased for both ES rats and sham ES rats. In the 1-day-delay and 1-week-delay groups, there were more fibers in ES rats than in sham ES rats. And the compound muscle action potential (CMAP) and motor nerve conduction velocity (MNCV) results were better for ES rats in these two groups. In order to analyze the mechanisms underlying these differences, Masson staining was performed on the distal nerves and quantitative PCR on the spinal cords. Results showed that, after delays in repair of 1 month and 2 months, there was more collagen tissue hyperplasia in the distal nerve in all rats. The brain-derived neurotrophic factor (BDNF) and trkB expression levels in the

  19. Electrical Stimulation Promotes Regeneration of Defective Peripheral Nerves after Delayed Repair Intervals Lasting under One Month

    PubMed Central

    Zhang, Peixun; Han, Na; Yin, Xiaofeng; Deng, Jiuxu; Chen, Bo; Jiang, Baoguo

    2014-01-01

    Background Electrical stimulation (ES) has been proven to be an effective means of enhancing the speed and accuracy of nerve regeneration. However, these results were recorded when the procedure was performed almost immediately after nerve injury. In clinical settings, most patients cannot be treated immediately. Some patients with serious trauma or contaminated wounds need to wait for nerve repair surgery. Delays in nerve repair have been shown to be associated with poorer results than immediate surgery. It is not clear whether electrical stimulation still has any effect on nerve regeneration after enough time has elapsed. Methods A delayed nerve repair model in which the rats received delayed nerve repair after 1 day, 1 week, 1 month, and 2 months was designed. At each point in time, the nerve stumps of half the rats were bridged with an absorbable conduit and the rats were given 1 h of weak electrical stimulation. The other half was not treated. In order to analyze the morphological and molecular differences among these groups, 6 ES rats and 6 sham ES rats per point in time were killed 5 days after surgery. The other rats in each group were allowed to recover for 6 weeks before the final functional test and tissue observation. Results The amounts of myelinated fibers in the distal nerve stumps decreased as the delay in repair increased for both ES rats and sham ES rats. In the 1-day-delay and 1-week-delay groups, there were more fibers in ES rats than in sham ES rats. And the compound muscle action potential (CMAP) and motor nerve conduction velocity (MNCV) results were better for ES rats in these two groups. In order to analyze the mechanisms underlying these differences, Masson staining was performed on the distal nerves and quantitative PCR on the spinal cords. Results showed that, after delays in repair of 1 month and 2 months, there was more collagen tissue hyperplasia in the distal nerve in all rats. The brain-derived neurotrophic factor (BDNF) and trk

  20. Rat sciatic nerve reconstruction across a 30 mm defect bridged by an oriented porous PHBV tube with Schwann cell as artificial nerve graft.

    PubMed

    Karimi, Mina; Biazar, Esmaeil; Keshel, Saeed Heidari; Ronaghi, Abdolaziz; Doostmohamadpour, Jafar; Janfada, Alireza; Montazeri, Arash

    2014-01-01

    An oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit has been used to evaluate its efficiency based on the promotion of peripheral nerve regeneration in rats. The oriented porous micropatterned artificial nerve conduit was designed onto the micropatterned silicon wafers, and then their surfaces were modified with oxygen plasma to increase cell adhesion. The designed conduits were investigated by cell culture analyses with Schwann cells (SCs). The conduits were implanted into a 30 mm gap in sciatic nerves of rats. Four months after surgery, the regenerated nerves were monitored and evaluated by macroscopic assessments and histology and behavioral analyses. Results of cellular analyses showed suitable properties of designed conduit for nerve regeneration. The results demonstrated that in the polymeric graft with SCs, the rat sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. Histological results demonstrated the presence of Schwann and glial cells in regenerated nerves. Functional recovery such as walking, swimming, and recovery of nociceptive function was illustrated for all the grafts especially conduits with SCs. This study proves the feasibility of the artificial nerve graft filled with SCs for peripheral nerve regeneration by bridging a longer defect in an animal model.

  1. Rat Sciatic Nerve Reconstruction Across a 30 mm Defect Bridged by an Oriented Porous PHBV Tube With Schwann Cell as Artificial Nerve Graft

    PubMed Central

    2014-01-01

    An oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit has been used to evaluate its efficiency based on the promotion of peripheral nerve regeneration in rats. The oriented porous micropatterned artificial nerve conduit was designed onto the micropatterned silicon wafers, and then their surfaces were modified with oxygen plasma to increase cell adhesion. The designed conduits were investigated by cell culture analyses with Schwann cells (SCs). The conduits were implanted into a 30 mm gap in sciatic nerves of rats. Four months after surgery, the regenerated nerves were monitored and evaluated by macroscopic assessments and histology and behavioral analyses. Results of cellular analyses showed suitable properties of designed conduit for nerve regeneration. The results demonstrated that in the polymeric graft with SCs, the rat sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. Histological results demonstrated the presence of Schwann and glial cells in regenerated nerves. Functional recovery such as walking, swimming, and recovery of nociceptive function was illustrated for all the grafts especially conduits with SCs. This study proves the feasibility of the artificial nerve graft filled with SCs for peripheral nerve regeneration by bridging a longer defect in an animal model. PMID:24399063

  2. Polymeric biomaterials for nerve regeneration: fabrication and implantation of a biodegradable nerve guide.

    PubMed

    Sivak, Wesley N; Bliley, Jacqueline M; Marra, Kacey G

    2014-01-01

    Optimizing the quantity, quality, and speed of axon regeneration is important in maximizing functional outcomes following peripheral nerve injury. When severed, injured nerves must be able to regenerate and reconnect to the structures they previously controlled within 12-18 months before sensation and motion are permanently lost. Nerve sprouts from the proximal stump will spontaneously migrate toward the distal stump in the event of a nerve transection. However, surgical intervention remains necessary to repair transection injuries. Regeneration becomes particularly troublesome with large gaps, where autologous nerve grafts or nerve guides are used to repair transected nerves. Nerve conduits function as therapeutic adjuncts, guiding axonal regeneration across gap defects. Despite the availability of several FDA-approved nerve conduits, functional outcomes following their use remain less than optimal. Much work has been focused on developing nerve conduits to improve peripheral nerve repair outcomes. This chapter describes fabrication of a poly(caprolactone) nerve guide and demonstrates its use in a rat sciatic nerve model.

  3. Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

    PubMed Central

    Panseri, Silvia; Cunha, Carla; Lowery, Joseph; Del Carro, Ubaldo; Taraballi, Francesca; Amadio, Stefano; Vescovi, Angelo; Gelain, Fabrizio

    2008-01-01

    Background Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number of natural and synthetic components, showing high porosity and remarkable surface/volume ratio. Results In this study we used electrospun tubes made of biodegradable polymers (a blend of PLGA/PCL) to regenerate a 10-mm nerve gap in a rat sciatic nerve in vivo. Experimental groups comprise lesioned animals (control group) and lesioned animals subjected to guide conduits implantated at the severed nerve stumps, where the tubular scaffolds are filled with saline solution. Four months after surgery, sciatic nerves failed to reconnect the two stumps of transected nerves in the control animal group. In most of the treated animals the electrospun tubes induced nervous regeneration and functional reconnection of the two severed sciatic nerve tracts. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers. No significant inflammatory response has been found. Neural tracers revealed the re-establishment of functional neuronal connections and evoked potential results showed the reinnervation of the target muscles in the majority of the treated animals. Conclusion Corroborating previous works, this study indicates that electrospun tubes, with no additional biological coating or drug loading treatment, are promising scaffolds for functional nervous regeneration. They can be knitted in meshes

  4. A Romanian therapeutic approach to peripheral nerve injury.

    PubMed

    Zegrea, I; Chivu, Laura Ioana; Albu, Mădălina Georgiana; Zamfirescu, D; Chivu, R D; Ion, Daniela Adriana; Lascăr, I

    2012-01-01

    The study of nerve regeneration and functional recovery of the injured peripheral nerves represents a worldwide subject of clinical and scientific research. Our team aimed to obtain the first guide for nerve regeneration, bioartificial and biodegradable, using exclusively Romanian resources and having the advantages of price and quality, over the imported nerve conduits already used in clinical practice. First steps of this project consisted in obtaining the prototype of nerve guide conduit and its' testing in vitro and in vivo. Tests of physicochemical characterization, FTIR (Fourier Transform Infrared) spectrometry, thermal analysis (differential calorimetry, thermo-gravimetry), electron microscopy, water absorption and enzymatic degradation of the obtained prototype were followed by in vivo testing. The first results, obtained on a group of Brown Norway rats who suffered experimental lesions of 1 cm at the level of left sciatic nerve, which have then been repaired using the Romanian conduit prototype, are favorable in terms of biocompatibility, biodegradable capacity and support of nerve regeneration.

  5. Biomaterials and strategies for nerve regeneration.

    PubMed

    Huang, Yi-Cheng; Huang, Yi-You

    2006-07-01

    Nerve regeneration is a complex biological phenomenon. Once the nervous system is impaired, its recovery is difficult and malfunctions in other parts of the body may occur because mature neurons do not undergo cell division. To increase the prospects of axonal regeneration and functional recovery, researches have focused on designing "nerve guidance channels" or "nerve conduits." When developing ideal tissue-engineered nerve conduits, several components come to mind. They include a biodegradable and porous channel wall, the ability to deliver bioactive growth factors, incorporation of support cells, an internal oriented matrix to support cell migration, intraluminal channels to mimic the structure of nerve fascicles, and electrical activities. This article reviews the factors that are critical for nerve repair, and the advanced technologies that are explored to fabricate nerve conduits. To more accurately mimic natural repair in the body, recent studies have focused on the use of various advanced approaches to create ideal nerve conduits that combine multiple stimuli in an effort to better mimic the complex signals normally found in the body.

  6. Phosphate glass fibres promote neurite outgrowth and early regeneration in a peripheral nerve injury model.

    PubMed

    Kim, Young-Phil; Lee, Gil-Su; Kim, Jong-Wan; Kim, Min Soo; Ahn, Hong-Sun; Lim, Jae-Young; Kim, Hae-Won; Son, Young-Jin; Knowles, Jonathan C; Hyun, Jung Keun

    2015-03-01

    Three-dimensional (3D) scaffolds, which are bioactive and aid in neuronal guidance, are essential in the repair and regeneration of injured peripheral nerves. In this study, we used novel inorganic microfibres guided by phosphate glass (PG). PG fibres (PGfs) were aligned on compressed collagen that was rolled into a nerve conduit. In vitro tests confirmed that adult dorsal root ganglion (DRG) neurons showed active neurite outgrowth along the fibres, with a maximum number and length of neurites being significantly higher than those cultured on tissue culture plastic. In vivo experiments with nerve conduits that either contained PGfs (PGf/Col) or lacked them (Col) were conducted on transected sciatic nerves of rats for up to 12 weeks. One week after implantation, the PGf/Col group showed many axons extending along the scaffold, whereas the Col group showed none. Eight weeks after implantation, the PGf/Col group exhibited greater recovery of plantar muscle atrophy than the Col group. Electrophysiological studies revealed that some animals in the PGf/Col group at 6 and 7 weeks post-implantation (5.3% and 15.8%, respectively) showed compound muscle action potential. The Col group over the same period showed no response. Motor function also showed faster recovery in the PGf/Col group compared to the Col group up to 7 weeks. However, there was no significant difference in the number of axons, muscle atrophy or motor and sensory functions between the two groups at 12 weeks post-implantation. In summary, phosphate glass fibres can promote directional growth of axons in cases of peripheral nerve injury by acting as physical guides. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Polymer scaffolds with preferential parallel grooves enhance nerve regeneration.

    PubMed

    Mobasseri, Atefeh; Faroni, Alessandro; Minogue, Ben M; Downes, Sandra; Terenghi, Giorgio; Reid, Adam J

    2015-03-01

    We have modified the surface topography of poly ɛ-caprolactone (PCL) and polylactic acid (PLA) blended films to improve cell proliferation and to guide the regeneration of peripheral nerves. Films with differing shaped grooves were made using patterned silicon templates, sloped walls (SL), V-shaped (V), and square-shaped (SQ), and compared with nongrooved surfaces with micropits. The solvent cast films were tested in vitro using adult adipose-derived stem cells differentiated to Schwann cell-like cells. Cell attachment, proliferation, and cell orientation were all improved on the grooved surfaces, with SL grooves giving the best results. We present in vivo data on Sprague-Dawley rat sciatic nerve injury with a 10-mm gap, evaluating nerve regeneration at 3 weeks across a polymer nerve conduit modified with intraluminal grooves (SL, V, and SQ) and differing wall thicknesses (70, 100, 120, and 210 μm). The SL-grooved nerve conduit showed a significant improvement over the other topographical-shaped grooves, while increasing the conduit wall thickness saw no positive effect on the biological response of the regenerating nerve. Furthermore, the preferred SL-grooved conduit (C) with 70 μm wall thickness was compared with the current clinical gold standard of autologous nerve graft (Ag) in the rat 10-mm sciatic nerve gap model. At 3 weeks postsurgery, all nerve gaps across both groups were bridged with regenerated nerve fibers. At 16 weeks, features of regenerated axons were comparable between the autograft (Ag) and conduit (C) groups. End organ assessments of muscle weight, electromyography, and skin reinnervation were also similar between the groups. The comparable experimental outcome between conduit and autograft, suggests that the PCL/PLA conduit with inner lumen microstructured grooves could be used as a potential alternative treatment for peripheral nerve repair.

  8. Elastic chitosan conduits with multiple channels and well defined microstructure.

    PubMed

    Zhu, Jixiang; Xiong, Yi; Zeng, Chenguang; Qiang, Na; Quan, Daping; Wan, Jun

    2012-01-01

    Four kinds of chitosan conduits with longitudinal multi-channels and controlled internal microstructures were prepared using a special mold and a freeze-drying method. One of the conduits was fabricated from a chitosan solution (ab NC), while the other three groups were made from a pre-gelled chitosan solution using genipin as a chemical cross-linker (ab gNC), dibasic sodium phosphate as a physical cross-linker (ab pNC) or a combined ionic and covalent co-cross-linker (ab gpNC), respectively. The porosity of the chitosan conduits ranged from 88 to 90%. The gpNC showed highly interconnected and uniformly distributed pores compared to NC, the gNC and pNC. In contrast, the gNC and gpNC showed about 10% of the volume swelling ratio in 37°C PBS solution, although the gpNC scaffold's water uptake was the highest, at more than 17 times its original mass. Compressive tests showed that gpNC had significant elasticity and maintained its physical integrity even after compressing them down to 20% of their original height. The elastic modulus of gpNC reached 80 kPa, which was more than twice that of the other groups. Adhesion and proliferation of PC12 cells on chitosan gpNC scaffolds showed excellent properties by MTT and SEM observation, which indicated the potential of gpNC scaffolds for nerve tissue engineering applications.

  9. Method and apparatus for inspecting conduits

    DOEpatents

    Spisak, Michael J.; Nance, Roy A.

    1997-01-01

    An apparatus and method for ultrasonic inspection of a conduit are provided. The method involves directing a first ultrasonic pulse at a particular area of the conduit at a first angle, receiving the reflected sound from the first ultrasonic pulse, substantially simultaneously or subsequently in very close time proximity directing a second ultrasonic pulse at said area of the conduit from a substantially different angle than said first angle, receiving the reflected sound from the second ultrasonic pulse, and comparing the received sounds to determine if there is a defect in that area of the conduit. The apparatus of the invention is suitable for carrying out the above-described method. The method and apparatus of the present invention provide the ability to distinguish between sounds reflected by defects in a conduit and sounds reflected by harmless deposits associated with the conduit.

  10. Nonlinear wavetrains in viscous conduits

    NASA Astrophysics Data System (ADS)

    Maiden, Michelle; Hoefer, Mark

    2016-11-01

    Viscous fluid conduits provide an ideal system for the study of dissipationless, dispersive hydrodynamics. A dense, viscous fluid serves as the background medium through which a lighter, less viscous fluid buoyantly rises. If the interior fluid is continuously injected, a deformable pipe forms. The long wave interfacial dynamics are well-described by a dispersive nonlinear partial differential equation. In this talk, experiments, numerics, and asymptotics of the viscous fluid conduit system will be presented. Structures at multiple length scales are discussed, including solitons, dispersive shock waves, and periodic waves. Modulations of periodic waves will be explored in the weakly nonlinear regime with the Nonlinear Schrödinger (NLS) equation. Modulational instability (stability) is identified for sufficiently short (long) periodic waves due to a change in dispersion curvature. These asymptotic results are confirmed by numerical simulations of perturbed nonlinear periodic wave solutions. Also, numerically observed are envelope bright and dark solitons well approximated by NLS. This work was partially supported by NSF CAREER DMS-1255422 (M.A.H.) and NSF GRFP (M.D.M.).

  11. Bioengineered collagens

    PubMed Central

    Ramshaw, John AM; Werkmeister, Jerome A; Dumsday, Geoff J

    2014-01-01

    Mammalian collagen has been widely used as a biomedical material. Nevertheless, there are still concerns about the variability between preparations, particularly with the possibility that the products may transmit animal-based diseases. Many groups have examined the possible application of bioengineered mammalian collagens. However, translating laboratory studies into large-scale manufacturing has often proved difficult, although certain yeast and plant systems seem effective. Production of full-length mammalian collagens, with the required secondary modification to give proline hydroxylation, has proved difficult in E. coli. However, recently, a new group of collagens, which have the characteristic triple helical structure of collagen, has been identified in bacteria. These proteins are stable without the need for hydroxyproline and are able to be produced and purified from E. coli in high yield. Initial studies indicate that they would be suitable for biomedical applications. PMID:24717980

  12. Polyurethane/Gelatin Nanofibrils Neural Guidance Conduit Containing Platelet-Rich Plasma and Melatonin for Transplantation of Schwann Cells.

    PubMed

    Salehi, Majid; Naseri-Nosar, Mahdi; Ebrahimi-Barough, Somayeh; Nourani, Mohammdreza; Khojasteh, Arash; Farzamfar, Saeed; Mansouri, Korosh; Ai, Jafar

    2017-08-19

    The current study aimed to enhance the efficacy of peripheral nerve regeneration using a biodegradable porous neural guidance conduit as a carrier to transplant allogeneic Schwann cells (SCs). The conduit was prepared from polyurethane (PU) and gelatin nanofibrils (GNFs) using thermally induced phase separation technique and filled with melatonin (MLT) and platelet-rich plasma (PRP). The prepared conduit had the porosity of 87.17 ± 1.89%, the contact angle of 78.17 ± 5.30° and the ultimate tensile strength and Young's modulus of 5.40 ± 0.98 MPa and 3.13 ± 0.65 GPa, respectively. The conduit lost about 14% of its weight after 60 days in distilled water. The produced conduit enhanced the proliferation of SCs demonstrated by a tetrazolium salt-based assay. For functional analysis, the conduit was seeded with 1.50 × 10(4) SCs (PU/GNFs/PRP/MLT/SCs) and implanted into a 10-mm sciatic nerve defect of Wistar rat. Three control groups were used: (1) PU/GNFs/SCs, (2) PU/GNFs/PRP/SCs, and (3) Autograft. The results of sciatic functional index, hot plate latency, compound muscle action potential amplitude and latency, weight-loss percentage of wet gastrocnemius muscle and histopathological examination using hematoxylin-eosin and Luxol fast blue staining, demonstrated that using the PU/GNFs/PRP/MLT conduit to transplant SCs to the sciatic nerve defect resulted in a higher regenerative outcome than the PU/GNFs and PU/GNFs/PRP conduits.

  13. Collagen scaffolds loaded with collagen-binding NGF-beta accelerate ulcer healing.

    PubMed

    Sun, Wenjie; Lin, Hang; Chen, Bing; Zhao, Wenxue; Zhao, Yannan; Xiao, Zhifeng; Dai, Jianwu

    2010-03-01

    Studies have shown that exogenous nerve growth factor (NGF) accelerates ulcer healing, but the inefficient growth factor delivery system limits its clinical application. In this report, we found that the native human NGF-beta fused with a collagen-binding domain (CBD) could form a collagen-based NGF targeting delivery system, and the CBD-fused NGF-beta could bind to collagen membranes efficiently. Using the rabbit dermal ischemic ulcer model, we have found that this targeting delivery system maintains a higher concentration and stronger bioactivity of NGF-beta on the collagen membranes by promoting peripheral nerve growth. Furthermore, it enhances the rate of ulcer healing through accelerating the re-epithelialization of dermal ulcer wounds and the formation of capillary lumens within the newly formed tissue area. Thus, collagen membranes loaded with collagen-targeting human NGF-beta accelerate ulcer healing efficiently.

  14. Chapter 8: Current techniques and concepts in peripheral nerve repair.

    PubMed

    Siemionow, Maria; Brzezicki, Grzegorz

    2009-01-01

    Despite the progress in understanding the pathophysiology of peripheral nervous system injury and regeneration, as well as advancements in microsurgical techniques, peripheral nerve injuries are still a major challenge for reconstructive surgeons. Thorough knowledge of anatomy, pathophysiology, and surgical reconstruction is a prerequisite of proper peripheral nerve injury management. This chapter reviews the currently available surgical treatment options for different types of nerve injuries in clinical conditions. In overview of direct nerve repair, various end-to-end coaptation techniques and the role of end-to-side repair for proximal nerve injuries is described. When primary repair cannot be performed without undue tension, nerve grafting or tubulization techniques are required. Current gold standard for bridging nerve gaps is nerve autografting. However, disadvantages of this approach, such as donor site morbidity and limited length of available graft material encouraged the search for alternative means of nerve gap reconstruction. Nerve allografting was introduced for repair of extensive nerve injuries. Tubulization techniques with natural or artificial conduits are applicable as an alternative for bridging short nerve defects without the morbidities associated with harvesting of autologous nerve grafts. Achieving better outcomes depends both on the advancements in microsurgical techniques and introduction of molecular biology discoveries into clinical practice. The field of peripheral nerve research is dynamically developing and concentrates on more sophisticated approaches tested at the basic science level. Future directions in peripheral nerve reconstruction including, tolerance induction and minimal immunosuppression for nerve allografting, cell based supportive therapies and bioengineering of nerve conduits are also reviewed in this chapter.

  15. The early history of tubulation in nerve repair.

    PubMed

    IJpma, F F A; Van De Graaf, R C; Meek, M F

    2008-10-01

    The first experiments for bridging peripheral nerve gaps using nerve tubulation emerged in the 19th century. Because Gluck (1853-1942) is said to have performed the first animal experiment of nerve tubulation in 1880, it is interesting to explore the background and veracity of this claim. The original documents on nerve tubulation in the 19th century were studied. We conclude that the conduit that was initially used for nerve tubulation was derived from a resorbable decalcified bone tube developed for wound drainage by Neuber (1850-1932) in 1879. Gluck proposed the use of the bone tube as a guided conduit for regenerating nerves in 1881 but stated briefly that his experiments failed because of scar formation. Vanlair (1839-1914) documented the first successful application of nerve tubulation using a bone tube to bridge a 3 cm sciatic nerve defect in a dog in 1882.

  16. Facilitation of facial nerve regeneration using chitosan-β-glycerophosphate-nerve growth factor hydrogel.

    PubMed

    Chao, Xiuhua; Xu, Lei; Li, Jianfeng; Han, Yuechen; Li, Xiaofei; Mao, YanYan; Shang, Haiqiong; Fan, Zhaomin; Wang, Haibo

    2016-06-01

    Conclusion C/GP hydrogel was demonstrated to be an ideal drug delivery vehicle and scaffold in the vein conduit. Combined use autologous vein and NGF continuously delivered by C/GP-NGF hydrogel can improve the recovery of facial nerve defects. Objective This study investigated the effects of chitosan-β-glycerophosphate-nerve growth factor (C/GP-NGF) hydrogel combined with autologous vein conduit on the recovery of damaged facial nerve in a rat model. Methods A 5 mm gap in the buccal branch of a rat facial nerve was reconstructed with an autologous vein. Next, C/GP-NGF hydrogel was injected into the vein conduit. In negative control groups, NGF solution or phosphate-buffered saline (PBS) was injected into the vein conduits, respectively. Autologous implantation was used as a positive control group. Vibrissae movement, electrophysiological assessment, and morphological analysis of regenerated nerves were performed to assess nerve regeneration. Results NGF continuously released from C/GP-NGF hydrogel in vitro. The recovery rate of vibrissae movement and the compound muscle action potentials of regenerated facial nerve in the C/GP-NGF group were similar to those in the Auto group, and significantly better than those in the NGF group. Furthermore, larger regenerated axons and thicker myelin sheaths were obtained in the C/GP-NGF group than those in the NGF group.

  17. Sciatic nerve regeneration using a nerve growth factor-containing fibrin glue membrane.

    PubMed

    Ma, Shengzhong; Peng, Changliang; Wu, Shiqing; Wu, Dongjin; Gao, Chunzheng

    2013-12-25

    Our previous findings confirmed that the nerve growth factor-containing fibrin glue membrane provides a good microenvironment for peripheral nerve regeneration; however, the precise mechanism remains unclear. p75 neurotrophin receptor (p75(NTR)) plays an important role in the regulation of peripheral nerve regeneration. We hypothesized that a nerve growth factor-containing fibrin glue membrane can promote neural regeneration by up-regulating p75(NTR) expression. In this study, we used a silicon nerve conduit to bridge a 15 mm-long sciatic nerve defect and injected a mixture of nerve growth factor and fibrin glue at the anastomotic site of the nerve conduit and the sciatic nerve. Through RT-PCR and western blot analysis, nerve growth factor-containing fibrin glue membrane significantly increased p75(NTR) mRNA and protein expression in the Schwann cells at the anastomotic site, in particular at 8 weeks after injection of the nerve growth factor/fibrin glue mixture. These results indicate that nerve growth factor-containing fibrin glue membrane can promote peripheral nerve regeneration by up-regulating p75(NTR) expression in Schwann cells.

  18. Electrical Conduit Distributes Weld Gas Evenly

    NASA Technical Reports Server (NTRS)

    Ambrisco, D. P.

    1983-01-01

    Purge-gas distributor, made from flexible electrical conduit by drilling small holes along its length, provides even gas flow for welding. Flexible conduit adjusts to accomodate almost any shape and is used for gas coverage in other applications that previously needed formed and drilled solid tubing.

  19. Conduit options in coronary artery bypass surgery.

    PubMed

    Canver, C C

    1995-10-01

    The choice of graft conduit is crucial to the success of coronary artery bypass grafting (CABG) because the patency of a coronary conduit is closely associated with an uneventful postoperative course and a better long-term patient survival. The standard conduits used for CABG are the greater saphenous vein (GSV) and the internal thoracic artery (ITA). An excellent substitute conduit for coronary bypass operations that can be taken "off the shelf" is certainly the dream of every practicing cardiac surgeon. However, virtually every synthetic and biologic alternative to arterial conduits or autologous fresh saphenous vein has proved disappointing. Fortunately, patients with absolutely no autologous conduit alternatives are uncommon. Circumstances exist, however, that often necessitate the use of alternative conduits such as young hyperlipemic patients, absent or unsuitable autologous ITAs and GSV as a result of previous myocardial revascularization, peripheral arterial reconstruction, and varicose vein ligation procedures. This review provides an update on the clinical work done with all coronary conduits available for myocardial surgical revascularization.

  20. Morphology of nerve fiber regeneration along a biodegradable poly (DLLA-epsilon-CL) nerve guide filled with fresh skeletal muscle.

    PubMed

    Varejão, Artur S P; Cabrita, António M; Meek, Marcel F; Fornaro, Michele; Geuna, Stefano; Giacobini-Robecchi, Maria G

    2003-01-01

    Previous morphological and morphometrical studies showed that fresh-skeletal-muscle-enriched vein segments are good conduits for leading peripheral nerve regeneration. In the present study, we investigated the morphological features of peripheral nerve fibers regenerated along a 10-mm-long biodegradable poly (DLLA-epsilon-CL) nerve guide enriched with fresh skeletal muscle, comparing them to nerve fiber regeneration along 10-mm-long phosphate-buffered saline (PBS)-enriched poly (DLLA-epsilon-CL) tubes. Repaired nerves were analyzed at weeks 6 and 24 postoperatively. Structural and ultrastructural observation showed that good nerve fiber regeneration occurred in both PBS-enriched and fresh-skeletal-muscle-enriched nerve guides, and histomorphometrical analysis of regenerated myelinated fibers revealed no statistically significant differences between the two experimental groups at week 24 after surgery. The employment of fresh-muscle-enriched conduits for the repair of nerve defects is critically discussed in the light of these results.

  1. Stability of volcanic conduits during explosive eruptions

    NASA Astrophysics Data System (ADS)

    Aravena, Álvaro; de'Michieli Vitturi, Mattia; Cioni, Raffaello; Neri, Augusto

    2017-06-01

    Geological evidences of volcanic conduit widening are common in most pyroclastic deposits (e.g. presence of lithic fragments from different depths), suggesting a continuous modification of the conduit geometry during volcanic eruptions. However, the controlling factors of the mechanisms driving conduit enlargement (e.g. erosion, local collapse) are still partially unclear, as well as the influence of conduit geometry on the eruptive dynamics. Although numerical models have been systematically employed to study volcanic conduits, their mechanical stability and the eruptive dynamics related to non-cylindrical conduits have been poorly addressed. We present here a 1D steady-state model which includes the main processes experimented by ascending magmas (i.e. crystallization, rheological changes, fragmentation, drag forces, outgassing and degassing), and the application of two mechanical stability criteria (Mohr-Coulomb and Mogi-Coulomb), in order to study the collapse conditions of volcanic conduits during a representative explosive rhyolitic eruption. It emerges that mechanical stability of volcanic conduits is mainly controlled by its radial dimension, and a minimum radius for reaching stable conditions can be computed, as a function of water content and inlet overpressure. Additionally, for a set of input parameters thought typical of explosive rhyolitic volcanism, we estimated a minimum magma flux for developing a mechanically stable conduit ( 7 • 107 - 3 • 108 kg/s). Results are consistent with the unsteady character usually observed in sub-Plinian eruptions, opposite to mainly stationary Plinian eruptions, commonly characterized by higher magma discharge rates. We suggest that cylindrical conduits represent a mechanically stable configuration only for large radii. Because the instability conditions are not uniform along the conduit, the widening processes probably lead to conduit geometries with depth-varying width. Consequently, as our model is able to

  2. Electrospun poly(L-lactide-co-glycolide) biodegradable polymer nanofibre tubes for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Bini, T. B.; Gao, Shujun; Chyan Tan, Ter; Wang, Shu; Lim, Aymeric; Ben Hai, Lim; Ramakrishna, S.

    2004-11-01

    Nanotechnology is an area receiving increasing attention as progress is made towards tailoring the morphology of polymeric biomaterial for a variety of applications. In the present study an attempt was made to electrospin poly(L-lactide-co-glycolide) biodegradable polymer nanofibres. In this process, polymer fibres with diameters down to the nanometre range are formed by subjecting a fluid jet to a high electric field. The nanofibres were collected on to a rotating Teflon mandrel and fabricated to tubes or conduits, to function as nerve guidance channels. The feasibility of in vivo nerve regeneration was investigated through several of these conduits. The biological performance of the conduits were examined in the rat sciatic nerve model with a 10 mm gap length. After implantation of the nanofibre nerve guidance conduit to the right sciatic nerve of the rat, there was no inflammatory response. One month after implantation five out of eleven rats showed successful nerve regeneration. None of the implanted tubes showed tube breakage. The nanofibre nerve guidance conduits were flexible, permeable and showed no swelling. Thus, these new poly(L-lactide-co-glycolide) nanofibre conduits can be effective aids for nerve regeneration and repair. Improvements could be done by impregnating nerve growth factors or Schwann cells and may lead to clinical applications.

  3. Chitosan-cross-linked nanofibrous PHBV nerve guide for rat sciatic nerve regeneration across a defect bridge.

    PubMed

    Biazar, Esmaeil; Keshel, Saeed Heidari

    2013-01-01

    The aim of this study was to produce a chitosan-cross-linked nanofibrous biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit. The artificial nerve scaffold designed by electrospinning method and cross-linked with chitosan by chemical method. Afterwards, the scaffolds were evaluated by microscopic, physical, and mechanical analyses and cell culture assays with Schwann cells. The conduits were implanted into a 10 mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently good mechanical properties to serve as a nerve guide. Cellular experiments showed a better cell adhesion, growth, and proliferation inside the cross-linked nanofibrous scaffolds compared with un-cross-linked ones, also Schwann cells well attached on chitosan-cross-linked nanofibrous surface. The in vivo results demonstrated that in the nanofibrous graft, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. This neural conduit appears to have the right organization for testing in vivo nerve tissue engineering studies.

  4. Stochastic simulation of karst conduit networks

    NASA Astrophysics Data System (ADS)

    Pardo-Igúzquiza, Eulogio; Dowd, Peter A.; Xu, Chaoshui; Durán-Valsero, Juan José

    2012-01-01

    Karst aquifers have very high spatial heterogeneity. Essentially, they comprise a system of pipes (i.e., the network of conduits) superimposed on rock porosity and on a network of stratigraphic surfaces and fractures. This heterogeneity strongly influences the hydraulic behavior of the karst and it must be reproduced in any realistic numerical model of the karst system that is used as input to flow and transport modeling. However, the directly observed karst conduits are only a small part of the complete karst conduit system and knowledge of the complete conduit geometry and topology remains spatially limited and uncertain. Thus, there is a special interest in the stochastic simulation of networks of conduits that can be combined with fracture and rock porosity models to provide a realistic numerical model of the karst system. Furthermore, the simulated model may be of interest per se and other uses could be envisaged. The purpose of this paper is to present an efficient method for conditional and non-conditional stochastic simulation of karst conduit networks. The method comprises two stages: generation of conduit geometry and generation of topology. The approach adopted is a combination of a resampling method for generating conduit geometries from templates and a modified diffusion-limited aggregation method for generating the network topology. The authors show that the 3D karst conduit networks generated by the proposed method are statistically similar to observed karst conduit networks or to a hypothesized network model. The statistical similarity is in the sense of reproducing the tortuosity index of conduits, the fractal dimension of the network, the direction rose of directions, the Z-histogram and Ripley's K-function of the bifurcation points (which differs from a random allocation of those bifurcation points). The proposed method (1) is very flexible, (2) incorporates any experimental data (conditioning information) and (3) can easily be modified when

  5. Repair of peripheral nerve defects in rabbits using keratin hydrogel scaffolds.

    PubMed

    Hill, Paulina S; Apel, Peter J; Barnwell, Jonathan; Smith, Tom; Koman, L Andrew; Atala, Anthony; Van Dyke, Mark

    2011-06-01

    Entubulation of transected nerves using bioabsorbable conduits is a promising alternative to sural nerve autografting, but full functional recovery is rarely achieved. Numerous studies have suggested that scaffold-based conduit fillers may promote axon regeneration, but no neuroinductive biomaterial filler has been identified. We previously showed that a nerve guide filled with keratin hydrogel actively stimulates regeneration in a mouse model, and results in functional outcomes superior to empty conduits at early time points. The goal of the present study was to develop a peripheral nerve defect model in a rabbit and assess the effectiveness of a keratin hydrogel filler. Although repairs with keratin-filled conduits were not as consistently successful as autograft overall, the use of keratin resulted in a significant improvement in conduction delay compared to both empty conduits and autograft, as well as a significant improvement in amplitude recovery compared to empty conduits when measurable regeneration did occur. Taking into account all study animals (i.e., regenerated and nonregenerated), histological assessment showed that keratin-treated nerves had significantly greater myelin thickness than empty conduits. These data support the findings of our earlier study and suggest that keratin hydrogel fillers have the potential to be used clinically to improve conduit repair.

  6. 47 CFR 32.2441 - Conduit systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... necessary in the construction of conduit plant. (b) The cost of pumping water out of manholes and of cleaning manholes and ducts in connection with construction work and the cost of permits and privileges...

  7. 47 CFR 32.2441 - Conduit systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... necessary in the construction of conduit plant. (b) The cost of pumping water out of manholes and of cleaning manholes and ducts in connection with construction work and the cost of permits and privileges...

  8. 47 CFR 32.2441 - Conduit systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... necessary in the construction of conduit plant. (b) The cost of pumping water out of manholes and of cleaning manholes and ducts in connection with construction work and the cost of permits and privileges...

  9. 47 CFR 32.2441 - Conduit systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... necessary in the construction of conduit plant. (b) The cost of pumping water out of manholes and of cleaning manholes and ducts in connection with construction work and the cost of permits and privileges...

  10. 47 CFR 32.2441 - Conduit systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... necessary in the construction of conduit plant. (b) The cost of pumping water out of manholes and of..., as appropriate. (d) The cost of pipes or other protective covering for underground drop and...

  11. Phase distribution in complex geometry conduits

    SciTech Connect

    Lahey, R.T. Jr.; Lopez de Bertodano, M.; Jones, O.C. Jr.

    1992-12-31

    Some of the most important and challenging problems in two-phase flow today have to do with the understanding and prediction of multidimensional phenomena, in particular, lateral phase distribution in both simple and complex geometry conduits. A prior review paper summarized the state-of-the-art in the understanding of phase distribution phenomena, and the ability to perform mechanistic multidimensional predictions. The purpose of this paper is to update that review, with particular emphasis on complex geometry conduit predictive capabilities.

  12. Pumped Storage and Potential Hydropower from Conduits

    SciTech Connect

    none,

    2015-02-25

    Th is Congressional Report, Pumped Storage Hydropower and Potential Hydropower from Conduits, addresses the technical flexibility that existing pumped storage facilities can provide to support intermittent renewable energy generation. This study considered potential upgrades or retrofit of these facilities, the technical potential of existing and new pumped storage facilities to provide grid reliability benefits, and the range of conduit hydropower opportunities available in the United States.

  13. [The continent colon-conduit stoma].

    PubMed

    Jonas, U; Wetzel, W; Hohenfellner, R

    1978-07-01

    A conduit occlusor is presented consisting of a tube surrounded by foam rubber and covered by a latex membrane, with a polyurethane cap attached to the other end. A valve imbedded in the cap allows voluntary urine drainage. This atraumatic, pneumatic, non-invasive occlusor device was used quite succesfully in 3 volunteers who had had a colon conduit urinary diversion. The device was well-tolerated, leakage was effectively prevented. Further experience, however, will be necessary for final evaluation.

  14. Efficacy of Acellular Nerve Allografts in Trigeminal Nerve Reconstruction.

    PubMed

    Yampolsky, Andrew; Ziccardi, Vincent; Chuang, Sung-Kiang

    2017-10-01

    During trigeminal nerve repair, a gap is sometimes encountered that prevents the tension-free apposition of nerve endings. The use of a processed acellular nerve allograft is a novel technique that shows promise in overcoming this problem. The goal of the present study was to support the slowly evolving body of evidence that acellular processed nerve allografts (Avance; Axogen, Alachua, FL) are a viable alternative to autogenous nerve grafting and the use of conduits for reconstructing defects of the trigeminal nerve. The study design consisted of a retrospective review of the medical records of patients referred to Rutgers School of Dental Medicine for management of trigeminal nerve injuries from July 2008 to August 2014. Sixteen patients met the inclusion criteria for the present study. All patients underwent nerve grafting using a processed nerve allograft. All operations were performed by the same surgeon (V.Z.). Serial neurosensory testing was performed by 1 clinician (V.Z.) in a standardized fashion. The primary outcome variable was the interval to functional sensory recovery as defined by the Medical Research Council Scale. The participants ranged in age from 16 to 62 years (mean 32). Of the 16 patients, 12 were female (75%) and 4 were male (25%), and 3 were smokers (18.75%) and 13 were nonsmokers (81.25%). One half of the patients (n = 8; 50%) underwent surgery on the inferior alveolar nerve, and 8 (50%) underwent surgery on the lingual nerve. The most common mechanism of injury was impacted third molar removal (n = 9; 56.25%) Of the 16 patients, 15 (93.75%) achieved functional sensory recovery during the study period. The results of the present study support the hypothesis that processed nerve allografts are effective in reconstructing small (<2-cm) trigeminal nerve defects. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Injured Nerve Regeneration using Cell-Based Therapies: Current Challenges

    PubMed Central

    Petrova, E. S.

    2015-01-01

    This paper reviews the recent research progress in the past several years on promoting peripheral nerve recovery using stem and progenitory cells. The emphasis is placed on studies aimed at assessing various stem cells capable of expressing neurotrophic and growth factors and surviving after implantation in the nerve or a conduit. Approaches to improving nerve conduit design are summarized. The contribution of stem cells to axonal regeneration and neural repair is discussed. The side effects associated with cell-based treatment are highlighted. From the studies reviewed, it is concluded that the fate of transplanted stem cells needs further elucidation in a microenvironment-dependent manner. PMID:26483958

  16. Microsurgical anatomy of the trigeminal nerve.

    PubMed

    Joo, Wonil; Yoshioka, Fumitaka; Funaki, Takeshi; Mizokami, Koji; Rhoton, Albert L

    2014-01-01

    The objective of this study is to review surgical anatomy of the trigeminal nerve. We also demonstrate some pictures involving the trigeminal nerve and its surrounding connective and neurovascular structures. Ten adult cadaveric heads were studied, using a magnification ranging from 3× to 40×, after perfusion of the arteries and veins with colored latex. The trigeminal nerve is the largest and most complex of the cranial nerves. It serves as a major conduit of sensory input from the face and provides motor innervation to the muscles of mastication. Because of its size and complexity, it is essential to have thorough knowledge of the nerve before diagnoses and treatment of the pathologic processes in the orofacial, temporomandibular, infratemporal, and pterygopalatine areas. The trigeminal nerve is encountered with imaging or surgery of the skull base surgery. Thus, a comprehensive knowledge of the anatomy of the trigeminal nerve is crucial for performing the surgical procedures without significant complication.

  17. Nerve root replantation.

    PubMed

    Carlstedt, Thomas

    2009-01-01

    Traumatic avulsion of nerve roots from the spinal cord is a devastating event that usually occurs in the brachial plexus of young adults following motor vehicle or sports accidents or in newborn children during difficult childbirth. A strategy to restore motor function in the affected arm by reimplanting into the spinal cord the avulsed ventral roots or autologous nerve grafts connected distally to the avulsed roots has been developed. Surgical outcome is good and useful recovery in shoulder and proximal arm muscles occurs. Pain is alleviated with motor recovery but sensory improvement is poor when only motor conduits have been reconstructed. In experimental studies, restoration of sensory connections with general improvement in the outcome from this surgery is pursued.

  18. Collagenous gastritis.

    PubMed

    Jin, Xiaoyi; Koike, Tomoyuki; Chiba, Takashi; Kondo, Yutaka; Ara, Nobuyuki; Uno, Kaname; Asano, Naoki; Iijima, Katsunori; Imatani, Akira; Watanabe, Mika; Shirane, Akio; Shimosegawa, Tooru

    2013-09-01

    In the present paper, we report a case of rare collagenous gastritis. The patient was a 25-year-old man who had experienced nausea, abdominal distention and epigastralgia since 2005. Esophagogastroduodenoscopy (EGD) carried out at initial examination by the patient's local doctor revealed an extensively discolored depression from the upper gastric body to the lower gastric body, mainly including the greater curvature, accompanied by residual mucosa with multiple islands and nodularity with a cobblestone appearance. Initial biopsies sampled from the nodules and accompanying atrophic mucosa were diagnosed as chronic gastritis. In August, 2011, the patient was referred to Tohoku University Hospital for observation and treatment. EGD at our hospital showed the same findings as those by the patient's local doctor. Pathological findings included a membranous collagen band in the superficial layer area of the gastric mucosa, which led to a diagnosis of collagenous gastritis. Collagenous gastritis is an extremely rare disease, but it is important to recognize its characteristic endoscopic findings to make a diagnosis.

  19. Collagenous colitis.

    PubMed Central

    Kingham, J G; Levison, D A; Morson, B C; Dawson, A M

    1986-01-01

    Clinical and pathological aspects of six patients with collagenous colitis are presented. These patients have been observed for between four and 15 years and the evolution of the condition is documented in three (cases 1, 3 and 5). Management and possible pathogenetic mechanisms of this enigmatic condition are discussed. Images Fig. 1 Fig. 2 PMID:3699567

  20. Multifunctional Silk Nerve Guides for Axon Outgrowth

    NASA Astrophysics Data System (ADS)

    Tupaj, Marie C.

    Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long

  1. Principles of Nerve Repair in Complex Wounds of the Upper Extremity

    PubMed Central

    Moore, Amy M.; Wagner, I. Janelle; Fox, Ida K.

    2015-01-01

    Peripheral nerve injuries are common in the setting of complex upper extremity trauma. Early identification of nerve injuries and intervention is critical for maximizing return of function. In this review, the principles of nerve injury, patient evaluation, and surgical management are discussed. An evidence-based approach to nerve reconstruction is reviewed, including the benefits and limitations of direct repair and nerve gap reconstruction with the use of autografts, processed nerve allografts, and conduits. Further, the principles and indications of commonly used nerve transfers in proximal nerve injuries are also addressed. PMID:25685102

  2. Detergent-free Decellularized Nerve Grafts for Long-gap Peripheral Nerve Reconstruction.

    PubMed

    Vasudevan, Srikanth; Huang, Jiying; Botterman, Barry; Matloub, Hani S; Keefer, Edward; Cheng, Jonathan

    2014-08-01

    Long-gap peripheral nerve defects arising from tumor, trauma, or birth-related injuries requiring nerve reconstruction are currently treated using nerve autografts and nerve allografts. Autografts are associated with limited supply and donor-site morbidity. Allografts require administration of transient immunosuppressants, which has substantial associated risks. To overcome these limitations, we investigated the use of detergent-free decellularized nerve grafts to reconstruct long-gap nerve defects in a rodent model and compared it with existing detergent processing techniques. Nerve grafts were harvested from the sciatic nerves of 9 donor rats. Twenty-four recipient rats were divided into 4 groups (6 animals per group): (1) nerve grafts (NG, positive control), (2) detergent-free decellularized (DFD) grafts, (3) detergent decellularized grafts, and (4) silicone tube conduits (negative control). Each recipient rat had a 3.5-cm graft or conduit sutured across a sciatic nerve transection injury. All animals were harvested at 12 weeks postimplantation for functional muscle analysis and nerve histomorphometry. Histomorphometry results indicated maximum growth in NG when compared with other groups. DFD and detergent decellularized groups showed comparable regeneration at 12 weeks. Silicone tube group showed no regeneration as expected. Muscle force data indicated functional recovery in NG and DFD groups only. This study describes a detergent-free nerve decellularization technique for reconstruction of long-gap nerve injuries. We compared DFD grafts with an established detergent processing technique and found that DFD nerve grafts are successful in promoting regeneration across long-gap peripheral nerve defects as an alternative to existing strategies.

  3. Detergent-free Decellularized Nerve Grafts for Long-gap Peripheral Nerve Reconstruction

    PubMed Central

    Vasudevan, Srikanth; Huang, Jiying; Botterman, Barry; Matloub, Hani S.; Keefer, Edward

    2014-01-01

    Background: Long-gap peripheral nerve defects arising from tumor, trauma, or birth-related injuries requiring nerve reconstruction are currently treated using nerve autografts and nerve allografts. Autografts are associated with limited supply and donor-site morbidity. Allografts require administration of transient immunosuppressants, which has substantial associated risks. To overcome these limitations, we investigated the use of detergent-free decellularized nerve grafts to reconstruct long-gap nerve defects in a rodent model and compared it with existing detergent processing techniques. Methods: Nerve grafts were harvested from the sciatic nerves of 9 donor rats. Twenty-four recipient rats were divided into 4 groups (6 animals per group): (1) nerve grafts (NG, positive control), (2) detergent-free decellularized (DFD) grafts, (3) detergent decellularized grafts, and (4) silicone tube conduits (negative control). Each recipient rat had a 3.5-cm graft or conduit sutured across a sciatic nerve transection injury. All animals were harvested at 12 weeks postimplantation for functional muscle analysis and nerve histomorphometry. Results: Histomorphometry results indicated maximum growth in NG when compared with other groups. DFD and detergent decellularized groups showed comparable regeneration at 12 weeks. Silicone tube group showed no regeneration as expected. Muscle force data indicated functional recovery in NG and DFD groups only. Conclusions: This study describes a detergent-free nerve decellularization technique for reconstruction of long-gap nerve injuries. We compared DFD grafts with an established detergent processing technique and found that DFD nerve grafts are successful in promoting regeneration across long-gap peripheral nerve defects as an alternative to existing strategies. PMID:25426384

  4. Blood Pressure Regulation VIII: Resistance Vessel Tone and Implications for a Pro-Atherogenic Conduit Artery Endothelial Cell Phenotype

    PubMed Central

    Padilla, Jaume; Jenkins, Nathan T.; Laughlin, M. Harold; Fadel, Paul J.

    2013-01-01

    Dysfunction of the endothelium is proposed as the primary initiator of atherosclerotic peripheral artery disease, which occurs mainly in medium to large-sized conduit arteries of the lower extremities (e.g., iliac, femoral, popliteal arteries). In this review article, we propose the novel concept that conduit artery endothelial cell phenotype is determined, in part, by microvascular tone in skeletal muscle resistance arteries through both changes in arterial blood pressure as well as upstream conduit artery shear stress patterns. First, we summarize the literature supporting the involvement of sympathetic nerve activity (SNA) and nitric oxide (NO) in the modulation of microvascular tone and arterial blood pressure. We then focus on the role of elevated blood pressure and shear stress profiles in modulating conduit artery endothelial cell phenotype. Last, we discuss findings from classic and emerging studies indicating that increased vascular resistance, as it occurs in the context of increased SNA and/or reduced NO bioavailability, is associated with greater oscillatory shear stress (e.g., increased retrograde shear) in upstream conduit arteries. The ideas put forth in this review set the stage for a new paradigm concerning the mechanistic link between increased microvascular tone and development of conduit artery endothelial dysfunction and thus increased risk for peripheral artery disease. Indeed, a vast amount of evidence supports the notion that excessive blood pressure and oscillatory shear stress are potent pro-atherogenic signals to the endothelium. PMID:23860841

  5. Nerve regeneration with aid of nanotechnology and cellular engineering.

    PubMed

    Sedaghati, Tina; Yang, Shi Yu; Mosahebi, Afshin; Alavijeh, Mohammad S; Seifalian, Alexander M

    2011-01-01

    Repairing nerve defects with large gaps remains one of the most operative challenges for surgeons. Incomplete recovery from peripheral nerve injuries can produce a diversity of negative outcomes, including numbness, impairment of sensory or motor function, possibility of developing chronic pain, and devastating permanent disability. In the last few years, numerous microsurgical techniques, such as coaptation, nerve autograft, and different biological or polymeric nerve conduits, have been developed to reconstruct a long segment of damaged peripheral nerve. A few of these techniques are promising and have become popular among surgeons. Advancements in the field of tissue engineering have led to development of synthetic nerve conduits as an alternative for the nerve autograft technique, which is the current practice to bridge nerve defects with gaps larger than 30 mm. However, to date, despite significant progress in this field, no material has been found to be an ideal alternative to the nerve autograft. This article briefly reviews major up-to-date published studies using different materials as an alternative to the nerve autograft to bridge peripheral nerve gaps in an attempt to assess their ability to support and enhance nerve regeneration and their prospective drawbacks, and also highlights the promising hope for nerve regeneration with the next generation of nerve conduits, which has been significantly enhanced with the tissue engineering approach, especially with the aid of nanotechnology in development of the three-dimensional scaffold. The goal is to determine potential alternatives for nerve regeneration and repair that are simply and directly applicable in clinical conditions. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

  6. Management of Iatrogenic Ulnar Nerve Transection.

    PubMed

    Henry, Mark

    2015-06-01

    A case of iatrogenic ulnar nerve laceration at the elbow is presented. Five subsequent surgeries over the course of the ensuing 20 months were performed to address this complication. The article examines the scientific basis for the various decisions needed to formulate a strategy that effectively addresses the problem. Emphasis is placed on the microsurgery of nerve topics: direct nerve repair, autogenous cable nerve grafting, biodegradable conduits, decellularized nerve allograft, and transfer of the anterior interosseous nerve to the ulnar motor branch. The discussion covers the relationship between choices made at the level of the original injury at the cubital tunnel to the timing and selection of distal reconstructive efforts, with specific attention to the distinction between end-to-end anterior interosseous to ulnar motor branch transfer as opposed to the supercharged end-to-side variation of this procedure.

  7. Gelatin-based 3D conduits for transdifferentiation of mesenchymal stem cells into Schwann cell-like phenotypes.

    PubMed

    Uz, Metin; Büyüköz, Melda; Sharma, Anup D; Sakaguchi, Donald S; Altinkaya, Sacide Alsoy; Mallapragada, Surya K

    2017-02-16

    In this study, gelatin-based 3D conduits with three different microstructures (nanofibrous, macroporous and ladder-like) were fabricated for the first time via combined molding and thermally induced phase separation (TIPS) technique for peripheral nerve regeneration. The effects of conduit microstructure and mechanical properties on the transdifferentiation of bone marrow-derived mesenchymal stem cells (MSCs) into Schwann cell (SC) like phenotypes were examined to help facilitate neuroregeneration and understand material-cell interfaces. Results indicated that 3D macroporous and ladder-like structures enhanced MSC attachment, proliferation and spreading, creating interconnected cellular networks with large numbers of viable cells compared to nanofibrous and 2D-tissue culture plate counterparts. 3D-ladder-like conduit structure with complex modulus of ∼0.4×10(6)Pa and pore size of ∼150μm provided the most favorable microenvironment for MSC transdifferentiation leading to ∼85% immunolabeling of all SC markers. On the other hand, the macroporous conduits with complex modulus of ∼4×10(6)Pa and pore size of ∼100μm showed slightly lower (∼65% for p75, ∼75% for S100 and ∼85% for S100β markers) immunolabeling. Transdifferentiated MSCs within 3D-ladder-like conduits secreted significant amounts (∼2.5pg/mL NGF and ∼0.7pg/mL GDNF per cell) of neurotrophic factors, while MSCs in macroporous conduits released slightly lower (∼1.5pg/mL NGF and 0.7pg/mL GDNF per cell) levels. PC12 cells displayed enhanced neurite outgrowth in media conditioned by conduits with transdifferentiated MSCs. Overall, conduits with macroporous and ladder-like 3D structures are promising platforms in transdifferentiation of MSCs for neuroregeneration and should be further tested in vivo.

  8. Enhanced noradrenergic axon regeneration into schwann cell-filled PVDF-TrFE conduits after complete spinal cord transection.

    PubMed

    Lee, Yee-Shuan; Wu, Siliang; Arinzeh, Treena Livingston; Bunge, Mary Bartlett

    2017-02-01

    Schwann cell (SC) transplantation has been utilized for spinal cord repair and demonstrated to be a promising therapeutic strategy. In this study, we investigated the feasibility of combining SC transplantation with novel conduits to bridge the completely transected adult rat spinal cord. This is the first and initial study to evaluate the potential of using a fibrous piezoelectric polyvinylidene fluoride trifluoroethylene (PVDF-TrFE) conduit with SCs for spinal cord repair. PVDF-TrFE has been shown to enhance neurite growth in vitro and peripheral nerve repair in vivo. In this study, SCs adhered and proliferated when seeded onto PVDF-TrFE scaffolds in vitro. SCs and PVDF-TrFE conduits, consisting of random or aligned fibrous inner walls, were transplanted into transected rat spinal cords for 3 weeks to examine early repair. Glial fibrillary acidic protein (GFAP)(+) astrocyte processes and GFP (green fluorescent protein)-SCs were interdigitated at both rostral and caudal spinal cord/SC transplant interfaces in both types of conduits, indicative of permissivity to axon growth. More noradrenergic/DβH(+) (dopamine-beta-hydroxylase) brainstem axons regenerated across the transplant when greater numbers of GFAP(+) astrocyte processes were present. Aligned conduits promoted extension of DβH(+) axons and GFAP(+) processes farther into the transplant than random conduits. Sensory CGRP(+) (calcitonin gene-related peptide) axons were present at the caudal interface. Blood vessels formed throughout the transplant in both conduits. This study demonstrates that PVDF-TrFE conduits harboring SCs are promising for spinal cord repair and deserve further investigation. Biotechnol. Bioeng. 2017;114: 444-456. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Alignment and composition of laminin-polycaprolactone nanofiber blends enhance peripheral nerve regeneration.

    PubMed

    Neal, Rebekah A; Tholpady, Sunil S; Foley, Patricia L; Swami, Nathan; Ogle, Roy C; Botchwey, Edward A

    2012-02-01

    Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and laminin-polycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber-filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber-filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of natural-synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. Copyright © 2011 Wiley Periodicals, Inc.

  10. Alignment and composition of laminin–polycaprolactone nanofiber blends enhance peripheral nerve regeneration

    PubMed Central

    Neal, Rebekah A.; Tholpady, Sunil S.; Foley, Patricia L.; Swami, Nathan; Ogle, Roy C.; Botchwey, Edward A.

    2012-01-01

    Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and laminin–polycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber-filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber-filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of natural–synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. PMID:22106069

  11. A model of bubble growth leading to xylem conduit embolism.

    PubMed

    Hölttä, T; Vesala, T; Nikinmaa, E

    2007-11-07

    The dynamics of a gas bubble inside a water conduit after a cavitation event was modeled. A distinction was made between a typical angiosperm conduit with a homogeneous pit membrane and a typical gymnosperm conduit with a torus-margo pit membrane structure. For conduits with torus-margo type pits pit membrane deflection was also modeled and pit aspiration, the displacement of the pit membrane to the low pressure side of the pit chamber, was found to be possible while the emboli was still small. Concurrent with pit aspiration, the high resistance to water flow out of the conduit through the cell walls or aspirated pits will make the embolism process slow. In case of no pit aspiration and always for conduits with homogeneous pit membranes, embolism growth is more rapid but still much slower than bubble growth in bulk water under similar water tension. The time needed for the embolism to fill a whole conduit was found to be dependent on pit and cell wall conductance, conduit radius, xylem water tension, pressure rise in adjacent conduits due to water freed from the embolising conduit, and the rigidity and structure of the pits in the case of margo-torus type pit membrane. The water pressure in the conduit hosting the bubble was found to occur almost immediately after bubble induction inside a conduit, creating a sudden tension release in the conduit, which can be detected by acoustic and ultra-acoustic monitoring of xylem cavitation.

  12. Muscle-in-vein nerve guide for secondary reconstruction in digital nerve lesions.

    PubMed

    Marcoccio, Ignazio; Ignazio, Marcoccio; Vigasio, Adolfo; Adolfo, Vigasio

    2010-09-01

    Although vein conduits filled with fresh skeletal muscle have been used to bridge nerve defects both experimentally and clinically with good results, this approach has never been considered a valuable tool for reconstruction of nerve defects, and the technique has been abandoned. The purpose of this study was to evaluate the application of muscle-in-vein conduits for secondary digital nerves reconstruction, with particular emphasis on the surgical technique and results. We present a retrospectively selected consecutive series of 21 digital nerve defects in 17 patients who were treated with vein conduits filled with fresh skeletal muscle for secondary nerve reconstruction. After a minimum follow-up of 18 months, all patients were studied with static and moving 2-point discrimination, Semmes-Weinstein monofilament testing, Visual Analog Scale, and Disabilities of the Arm, Shoulder, and Hand questionnaire. Outcome data were stratified according to the American Society for Surgery of the Hand guidelines, the modified Highet and Sander's criteria, and the Logic Tree. The average nerve gap bridged with the muscle-in-vein conduit was 2.2 cm (range, 1-3.5 cm). We classified 14 of 22 reconstructed nerves as excellent or good according to American Society for Surgery of the Hand guidelines, whereas 17 were between S4 and S3 using modified Highet and Sander's criteria. The Logic Tree yielded results between S4 and S3 in 14 of 21 reconstructed nerves. The average Disabilities of the Arm, Shoulder, and Hand survey scores were 22.5 for the disability/symptoms module and 21.4 and 17 for the sports/music and work subcomponents, respectively. Use of muscle-in-vein conduits should be considered and promoted for sensory nerve reconstruction for a number of reasons: the encouraging results with the technique; the abundant availability of both donor tissues; the flexibility of the conduit resulting from the combination of muscle and vein; the simplicity with which tubes can be

  13. 77 FR 22480 - Conduit Financing Arrangements; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... Internal Revenue Service 26 CFR Part 1 RIN 1545-BH77 Conduit Financing Arrangements; Correction AGENCY... correction to final regulations (TD 9562) that were published in the Federal Register on Friday, December 9... arrangement. DATES: This correction is effective on April 16, 2012 and is applicable on December 9, 2011....

  14. 30 CFR 18.39 - Hose conduit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hose conduit. 18.39 Section 18.39 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements...

  15. 30 CFR 18.39 - Hose conduit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hose conduit. 18.39 Section 18.39 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements...

  16. Controlling Wavebreaking in a Viscous Fluid Conduit

    NASA Astrophysics Data System (ADS)

    Anderson, Dalton; Maiden, Michelle; Hoefer, Mark

    2015-11-01

    This poster will present a new technique in the experimental investigation of dispersive hydrodynamics. In shallow water flows, internal ocean waves, superfluids, and optical media, wave breaking can be resolved by a dispersive shock wave (DSW). In this work, an experimental method to control the location of DSW formation (gradient catastrophe) is explained. The central idea is to convert an initial value problem (Riemann problem) into an equivalent boundary value problem. The system to which this technique is applied is a fluid conduit resulting from high viscosity contrast between a buoyant interior and heavier exterior fluid. The conduit cross-sectional area is modeled by a nonlinear, conservative, dispersive, third order partial differential equation. Using this model, the aim is to predict the breaking location of a DSW by controlling one boundary condition. An analytical expression for this boundary condition is derived by solving the dispersionless equation backward in time from the desired step via the method of characteristics. This is used in experiment to generate an injection rate profile for a high precision piston pump. This translates to the desired conduit shape. Varying the jump height and desired breaking location indicates good control of DSW formation. This result can be improved by deriving a conduit profile by numerical simulation of the full model equation. Controlling the breaking location of a DSW allows for the investigation of dynamics independent of the boundary. Support provided by NSF CAREER DMS-1255422 , NSF EXTREEMS.

  17. 30 CFR 18.39 - Hose conduit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hose conduit. 18.39 Section 18.39 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design...

  18. 30 CFR 18.39 - Hose conduit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hose conduit. 18.39 Section 18.39 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design...

  19. 30 CFR 18.39 - Hose conduit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hose conduit. 18.39 Section 18.39 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design...

  20. BD™ PuraMatrix™ peptide hydrogel seeded with Schwann cells for peripheral nerve regeneration.

    PubMed

    McGrath, Aleksandra M; Novikova, Liudmila N; Novikov, Lev N; Wiberg, Mikael

    2010-10-30

    This study investigated the effects of a membrane conduit filled with a synthetic matrix BD™ PuraMatrix™ peptide (BD) hydrogel and cultured Schwann cells on regeneration after peripheral nerve injury in adult rats. After sciatic axotomy, a 10mm gap between the nerve stumps was bridged using ultrafiltration membrane conduits filled with BD hydrogel or BD hydrogel containing Schwann cells. In control experiments, the nerve defect was bridged using either membrane conduits with alginate/fibronectin hydrogel or autologous nerve graft. Axonal regeneration within the conduit was assessed at 3 weeks and regeneration of spinal motoneurons and recovery of muscle weight evaluated at 16 weeks postoperatively. Schwann cells survived in the BD hydrogel both in culture and after transplantation into the nerve defect. Regenerating axons grew significantly longer distances within the conduits filled with BD hydrogel when compared with the alginate/fibronectin hydrogel and alginate/fibronectin with Schwann cells. Addition of Schwann cells to the BD hydrogel considerably increased regeneration distance with axons crossing the injury gap and entering into the distal nerve stump. The conduits with BD hydrogel showed a linear alignment of nerve fibers and Schwann cells. The number of regenerating motoneurons and recovery of the weight of the gastrocnemius muscle was inferior in BD hydrogel and alginate/fibronectin groups compared with nerve grafting. Addition of Schwann cells did not improve regeneration of motoneurons or muscle recovery. The present results suggest that BD hydrogel with Schwann cells could be used within biosynthetic conduits to increase the rate of axonal regeneration across a nerve defect. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Initial observations on using magnesium metal in peripheral nerve repair.

    PubMed

    Vennemeyer, J J; Hopkins, T; Hershcovitch, M; Little, K D; Hagen, M C; Minteer, D; Hom, D B; Marra, K; Pixley, S K

    2015-03-01

    Biodegradable magnesium metal filaments placed inside biodegradable nerve conduits might provide the physical guidance support needed to improve the rate and extent of regeneration of peripheral nerves across injury gaps. In this study, we examined basic issues of magnesium metal resorption and biocompatibility by repairing sub-critical size gap injuries (6 mm) in one sciatic nerve of 24 adult male Lewis rats. Separated nerve stumps were connected with poly(caprolactone) nerve conduits, with and without magnesium filaments (0.25 mm diameter, 10 mm length), with two different conduit filler substances (saline and keratin hydrogel). At 6 weeks after implantation, magnesium degradation was examined by micro-computed tomography and histological analyses. Magnesium degradation was significantly greater when the conduits were filled with an acidic keratin hydrogel than with saline (p < 0.05). But magnesium filaments in some animals remained intact for 6 weeks. Using histological and immunocytochemical analyses, good biocompatibility of the magnesium implants was observed at 6 weeks, as shown by good development of regenerating nerve mini-fascicles and only mild inflammation in tissues even after complete degradation of the magnesium. Nerve regeneration was not interrupted by complete magnesium degradation. An initial functional evaluation, determination of size recovery of the gastrocnemius muscle, showed a slight improvement due to magnesium with the saline but not the keratin filler, compared with respective control conduits without magnesium. These results suggest that magnesium filament implants have the potential to improve repair of injured peripheral nerve defects in this rodent model.

  2. Drill pipes and casings utilizing multi-conduit tubulars

    SciTech Connect

    Curlett, H.B.

    1989-01-24

    A seal adapted for use with a multi-conduit well tubular, or the like, is described which consists of: a plate with fluid passages, each passage corresponding to an opening of a conduit of the multiconduit tubular, and a groove on the plate around each passage; and elastomer means partially embeddable into each groove for sealing each conduit of a tubular to a corresponding conduit of another similar tubular.

  3. Laminin-based Nanomaterials for Peripheral Nerve Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Neal, Rebekah Anne

    Peripheral nerve transection occurs commonly in traumatic injury, causing motor and sensory deficits distal to the site of injury. One option for surgical repair is the nerve conduit. Conduits currently on the market are hollow tubes into which the nerve ends are sutured. Although these conduits fill the gap, they often fail due to the slow rate of regeneration over long gaps. To facilitate increased speed of regeneration and greater potential for functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in peripheral nerve regeneration. In this dissertation, I fabricated laminin-1 and laminin-polycaprolactone (PCL) blend nanofibers that mimic the geometry and functionality of the peripheral nerve basement membrane. These fibers resist hydration in aqueous media and require no harsh chemical crosslinkers. Adhesion and differentiation of both neuron-like and neuroprogenitor cells is improved on laminin nanofibrous meshes over two-dimensional laminin substrates. Blend meshes with varying laminin content were characterized for composition, tensile properties, degradation rates, and bioactivity in terms of cell attachment and axonal elongation. I have established that 10% (wt) laminin content is sufficient to retain the significant neurite-promoting effects of laminin critical in peripheral nerve repair. In addition, I utilized modified collector plate design to manipulate electric field gradients during electrospinning for the fabrication of aligned nanofibers. These aligned substrates provide enhanced directional guidance cues to the regenerating axons. Finally, I replicated the clinical problem of peripheral nerve transection using a rat tibial nerve defect model for conduit implantation. When the lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment, I observed significant recovery of sensory and motor function over six weeks. This recovery was

  4. An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering.

    PubMed

    Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

    2015-09-01

    Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons.

  5. An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

    PubMed Central

    Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

    2015-01-01

    Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons. PMID:26200940

  6. Acoustic signal propagation characterization of conduit networks

    NASA Astrophysics Data System (ADS)

    Khan, Muhammad Safeer

    Analysis of acoustic signal propagation in conduit networks has been an important area of research in acoustics. One major aspect of analyzing conduit networks as acoustic channels is that a propagating signal suffers frequency dependent attenuation due to thermo-viscous boundary layer effects and the presence of impedance mismatches such as side branches. The signal attenuation due to side branches is strongly influenced by their numbers and dimensions such as diameter and length. Newly developed applications for condition based monitoring of underground conduit networks involve measurement of acoustic signal attenuation through tests in the field. In many cases the exact installation layout of the field measurement location may not be accessible or actual installation may differ from the documented layout. The lack of exact knowledge of numbers and lengths of side branches, therefore, introduces uncertainty in the measurements of attenuation and contributes to the random variable error between measured results and those predicted from theoretical models. There are other random processes in and around conduit networks in the field that also affect the propagation of an acoustic signal. These random processes include but are not limited to the presence of strong temperature and humidity gradients within the conduits, blockages of variable sizes and types, effects of aging such as cracks, bends, sags and holes, ambient noise variations and presence of variable layer of water. It is reasonable to consider that the random processes contributing to the error in the measured attenuation are independent and arbitrarily distributed. The error, contributed by a large number of independent sources of arbitrary probability distributions, is best described by an approximately normal probability distribution in accordance with the central limit theorem. Using an analytical approach to model the attenuating effect of each of the random variable sources can be very complex and

  7. Comparisons of outcomes from repair of median nerve and ulnar nerve defect with nerve graft and tubulization: a meta-analysis.

    PubMed

    Yang, Mei; Rawson, Jeremy L; Zhang, Elizabeth W; Arnold, Peter B; Lineaweaver, William; Zhang, Feng

    2011-10-01

    In this study, an updated meta-analysis of all published human studies was presented to evaluate the recovery of the median and the ulnar nerves in the forearm after defect repair by nerve conduit and autologous nerve graft. Up to June of 2010, search for English language articles was conducted to collect publications on the outcome of median or ulnar nerve defect repair. A total of 33 studies and 1531 cases were included in this study. Patient information was extracted from these publications and the postoperative outcome was analyzed using meta-analysis. There was no significant difference in the postoperative recovery between the median and the ulnar nerves (odds ratio = 0.98). Sensory nerves were found to achieve a more satisfactory recovery after nerve defect repair than motor nerves (P < 0.05). Median nerve can also achieve more satisfactory recovery in both sensory and motor function than ulnar nerve (P < 0.05). There was no statistical difference between tubulization and autologous nerve graft in repairing defects less than 5 cm. Based on the results of this study, a median nerve with sensory impairment was associated with improved postoperative prognosis, while an ulnar nerve with motor nerve damage was prone to a worse prognosis. Tubulization can be a good alternative in the reconstruction of small defects. © Thieme Medical Publishers.

  8. Breast Reinnervation: DIEP Neurotization Using the Third Anterior Intercostal Nerve

    PubMed Central

    Menn, Zachary K.; Eldor, Liron; Kaufman, Yoav; Dellon, A. Lee

    2013-01-01

    Background: The purpose of this article is to evaluate a new method of DIEP flap neurotization using a reliably located recipient nerve. We hypothesize that neurotization by this method (with either nerve conduit or direct nerve coaptation) will have a positive effect on sensory recovery. Methods: Fifty-seven deep inferior epigastric perforator (DIEP) flaps were performed on 35 patients. Neurotizations were performed to the third anterior intercostal nerve by directly coapting the flap donor nerve or coapting with a nerve conduit. Nine nonneurotized DIEP flaps served as controls and received no attempted neurotization. All patients were tested for breast sensibility in 9 areas of the flap skin-island and adjacent postmastectomy skin. Testing occurred at an average of 111 weeks (23–309) postoperatively. Results: At a mean of 111 weeks after breast reconstruction, neurotization of the DIEP flap resulted in recovery of sensibility that was statistically significantly better (lower threshold) in the flap skin (P < 0.01) and statistically significantly better than in the native mastectomy skin into which the DIEP flap was inserted (P < 0.01). Sensibility recovered in DIEP flaps neurotized using the nerve conduit was significantly better (lower threshold) than that in the corresponding areas of the DIEP flaps neurotized by direct coaptation (P < 0.01). Conclusion: DIEP flap neurotization using the third anterior intercostal nerve is an effective technique to provide a significant increase in sensory recovery for breast reconstruction patients, while adding minimal surgical time. Additionally, the use of a nerve conduit produces increased sensory recovery when compared direct coaptation. PMID:25289267

  9. Comparison of conduits for leg revascularization.

    PubMed

    Weisel, R D; Johnston, K W; Baird, R J; Drezner, A D; Oates, T K; Lipton, I H

    1981-01-01

    The saphenous vein (SV) remains the conduit of choice for lower limb revascularization. When SV is unavailable, or unsuitable, two alternative conduits have been employed: gluteraldehydestablized human umbilical vein (HUV) and polytetrafluoroethylene (PTFE). In this study of the 218 patients who underwent lower limb revascularization, 3-year patency of 85 SV graft was 75% compared to 34% for the 66 HUV grafts and 33% for the 67 PFTE grafts. Three factors were found to independently influence patency: the indication for surgery, the site of the distal anastomosis, and the angiographic runoff. The SV group had significantly better patency than either HUV or PFTE in each of these subgroups. No consistent difference between HUV and PTFE was found. A risk score was obtained by assigning a value of 1 to 3 for each of the factors influencing patency--indication: 1 = claudication, 2 = rest pain, 3 = ischemic lesions; site: 1 = above knee (AK), 2 = below knee (BK), 3 = tibial; runoff 1 = good (two or three vessels), 2 = fair (one vessel), 3 = poor (no vessel). Patients with the lowest risk scores (3 to 4) had the best 3-year patency: SV, 78%; HUV, 44%; and PTFE, 48%. Patients with the highest risk scores (7 to 9) had the worst 3-year patency: SV, 68%; HUV, 32%; and PTFE, 28%. SVs had better patency under high- and low-risk conditions and remain the conduit of choice for lower limb revascularization. Both HUV and PTFE have equivalent and acceptable patency when SV is unavailable or unstable.

  10. High temperature lined conduits, elbows and tees

    DOEpatents

    De Feo, Angelo; Drewniany, Edward

    1982-01-01

    A high temperature lined conduit comprising, a liner, a flexible insulating refractory blanket around and in contact with the liner, a pipe member around the blanket and spaced therefrom, and castable rigid refractory material between the pipe member and the blanket. Anchors are connected to the inside diameter of the pipe and extend into the castable material. The liner includes male and female slip joint ends for permitting thermal expansion of the liner with respect to the castable material and the pipe member. Elbows and tees of the lined conduit comprise an elbow liner wrapped with insulating refractory blanket material around which is disposed a spaced elbow pipe member with castable refractory material between the blanket material and the elbow pipe member. A reinforcing band is connected to the elbow liner at an intermediate location thereon from which extend a plurality of hollow tubes or pins which extend into the castable material to anchor the lined elbow and permit thermal expansion. A method of fabricating the high temperature lined conduit, elbows and tees is also disclosed which utilizes a polyethylene layer over the refractory blanket after it has been compressed to maintain the refractory blanket in a compressed condition until the castable material is in place. Hot gases are then directed through the interior of the liner for evaporating the polyethylene and setting the castable material which permits the compressed blanket to come into close contact with the castable material.

  11. Assessment of conduit artery vasomotion using photoplethysmography

    NASA Astrophysics Data System (ADS)

    Kanders, Karlis; Grabovskis, Andris; Marcinkevics, Zbignevs; Aivars, Juris Imants

    2013-11-01

    Vasomotion is a spontaneous oscillation of vascular tone. The phenomenon has been observed in small arterioles and capillaries as well as in the large conduit arteries. The layer of smooth muscle cells that surrounds a blood vessel can spontaneously and periodically change its tension and thereby the arterial wall stiffness also changes. As the understanding of the phenomenon is still rather obscure, researchers would benefit from a low-cost and reliable investigation technique such as photoplethysmography (PPG). PPG is an optical blood pulsation measurement technique that can offer substantial information about the arterial stiffness. The aims of this pilot study were to evaluate the usefulness of the PPG technique in the research of vasomotion and to investigate vasomotion in the relatively large conduit arteries. Continuous 15 minute long measurements of posterior tibial artery wall stiffness were taken. Artery diameter, electrocardiogram, blood pressure and respiration were also simultaneously registered. Fast Fourier Transform power spectra were calculated to identify unique stiffness oscillations that did not correspond to fluctuations in the systemic parameters and thus would indicate vasomotion. We concluded that photoplethysmography is a convenient method for the research of the vasomotion in large arteries. Local stiffness parameter b/a is more accurate to use and easier to measure than the pulse wave velocity which describes stiffness of a segment of an artery. Conduit arteries might exhibit a low amplitude high frequency vasomotion ( 9 to 27 cycles per minute). Low frequency vasomotion is problematic to distinguish from the passive oscillations imposed by the arterial pressure.

  12. DEFORMATION OF SCORIA CONE BY CONDUIT PRESSURIZATION

    SciTech Connect

    E.S. Gaffney; B. Damjanac; D. Krier; G. Valentine

    2005-08-26

    A simplified mechanical model is used to simulate the deformation of a scoria cone due to pressurization of magma in a feeder conduit. The scoria cone is modeled as consisting of a cone of stabilized scoria with an axial region of loose scoria (height h{sub 1}), all overlying a vertically oriented cylindrical conduit intruded into rhyolite tuff country rock. For our analyses, the conduit is filled with basalt magma, usually with the upper length (h{sub 2}) solidified. The style of deformation of the cone depends on both h{sub 1} and h{sub 2}. If magma is prevented from hydrofracturing out of the conduit (as, for example, might be the case if the magma is surrounded by a solidified, but plastically deformable layer acting as a gasket backed up by the brittle country rock) pressures in the magma can build to 10s of MPa. When h{sub 1} is 100 m, not unusual for a small isolated basaltic cinder cone, the magma pressure needed to destabilize the cone when molten magma extends all the way to the original ground surface (h{sub 2} = 0) is only about one-third of the pressure when the upper part of the conduit is solidified (h{sub 2} = 25m). In the former case, almost the entire upper third of the cone is at failure in tension when the configuration becomes unstable. In the latter case, small portions of the surface of the cone are failing in tension when instability occurs, but a large volume in the central core of the cone is failing in shear or compressions. These results may provide insight into the status of volcanic plumbing, either past or present, beneath scoria cones. Field observations at the Lathrop Wells volcano in southern Nevada identify structures at the outer edge just below the crater rim that appear to be inward-dipping listric normal faults. This may indicate that, near the end of its active stage, the cone was close to failing in this fashion. A companion paper suggests that such a failure could have been quite energetic had it occurred.

  13. The use of autogenous veins for microsurgical repair of the sural nerve after nerve biopsy.

    PubMed

    Flores, Leandro Pretto

    2010-06-01

    This study evaluates the results of an alternative technique developed to minimize the risk of complications associated with sural nerve biopsy for histopathological analysis. Twelve subjects underwent sural nerve biopsy and the defect created in the nerve was bridged by a 50-mm-length segment of the saphenous vein; the control group enrolled 23 patients in whom the entire length of the nerve was harvested to be used as autograft for reconstruction of nerves in the upper limb. Sensory reinnervation was quantified by use of the monofilament test and the static 2-point discrimination test, after a follow-up period of 18 months. The mean time for recovery of protective sensation was 8.7 months in patients submitted to nerve repair, and 10.3 months in the control group (P > .05). The monofilament test and static 2-point discrimination testing demonstrated a mean value of 3.22 and 8 mm (S3), respectively, in the group who underwent sural nerve repair; and 4.17 and 13 mm (S2), respectively, for the control group (P <.05). The use of vein as conduits for the repair of the sural nerve did not shorten the time for sensory recovery at the autonomous zone of the nerve; however, the quality of the reinnervation was considered better than the control group. This study suggests that empty veins could be used as conduits to bridge gaps with a length up to 50 mm in cases of injuries of the sural nerve and, possibly, for injuries of other pure sensory nerves as well.

  14. The role of peripheral nerve ECM components in the tissue engineering nerve construction.

    PubMed

    Gao, Xupeng; Wang, Yu; Chen, Jifeng; Peng, Jiang

    2013-01-01

    The extracellular matrix (ECM) is the naturally occurring substrate that provides a support structure and an attachment site for cells. It also produces a biological signal, which plays an important role in and has significant impact on cell adhesion, migration, proliferation, differentiation, and gene expression. Peripheral nerve repair is a complicated process involving Schwann cell proliferation and migration, 'bands of Büngner' formation, and newborn nerve extension. In the ECM of peripheral nerves, macromolecules are deposited among cells; these constitute the microenvironment of Schwann cell growth. Such macromolecules include collagen (I, III, IV, V), laminin, fibronectin, chondroitin sulfate proteoglycans (CSPGs), and other nerve factors. Collagen, the main component of ECM, provides structural support and guides newborn neurofilament extension. Laminin, fibronectin, CSPGs, and neurotrophic factors, are promoters or inhibitors, playing different roles in nerve repair after injury. By a chemical decellularization process, acellular nerve allografting eliminates the antigens responsible for allograft rejection and maintains most of the ECM components, which can effectively guide and enhance nerve regeneration. Thus, the composition and features of peripheral nerve ECM suggest its superiority as nerve repair material. This review focuses on the structure, function, and application in the tissue engineering nerve construction of the peripheral nerve ECM components.

  15. Composite and plain tubular synthetic graft conduits in right ventricle-pulmonary artery position: fate in growing lambs.

    PubMed

    Molina, J E; Edwards, J E; Bianco, R W; Clack, R W; Lang, G; Molina, J R

    1995-08-01

    Our goal was to identify the most appropriate material for right ventricle-pulmonary artery conduits in growing animals. We used 100 lambs that were 3 to 4 weeks old (mean weight 11.7 kg). Follow-up was up to 24 months. Group I received plain tubular conduits: (1) Dacron knitted fabric, (2) collagen-coated knitted fabric, (3) Milliknit and Microknit material, (4) woven Dacron fabric, (5) three-dimensional Dacron fabric (crossweave 500 and 800), or (6) polytetrafluoroethylene. Group II received either a (1) woven Dacron fabric conduit with a built-in tissue valve or (2) polytetrafluoroethylene graft with a built-in St. Jude Medical valve. We did angiograms and catheterizations every 3 to 6 months and killed the lambs at 6, 12, 18, or 24 months. Tubular Dacron fabric woven or knitted grafts, regardless of matrix, pore size, thickness, or coating, caused formation of a thick acellular pseudointima buildup, which led to progressive obstruction starting as early as 3 months. Polytetrafluoroethylene grafts in groups I and II showed the formation of thin inner and outer capsules (0.5 mm) and none developed obstruction despite wall calcification. Conduits of woven Dacron fabric with a built-in tissue valve degenerated rapidly, leading to calcification thrombosis and obstruction within 3 months; no lamb survived 12 months. Polytetrafluoroethylene conduits with a St. Jude Medical valve in lambs receiving anticoagulants remained free of obstruction and continued to function well. It appears that synthetic conduits of polytetrafluoroethylene perform well in either of the situations here tested and may be the best choice at present.

  16. System and method measuring fluid flow in a conduit

    DOEpatents

    Ortiz, M.G.; Kidd, T.G.

    1999-05-18

    A system is described for measuring fluid mass flow in a conduit in which there exists a pressure differential in the fluid between at least two spaced-apart locations in the conduit. The system includes a first pressure transducer disposed in the side of the conduit at a first location for measuring pressure of fluid at that location, a second or more pressure transducers disposed in the side of the conduit at a second location, for making multiple measurements of pressure of fluid in the conduit at that location, and a computer for computing the average pressure of the multiple measurements at the second location and for computing flow rate of fluid in the conduit from the pressure measurement by the first pressure transducer and from the average pressure calculation of the multiple measurements. 3 figs.

  17. System and method measuring fluid flow in a conduit

    DOEpatents

    Ortiz, Marcos German; Kidd, Terrel G.

    1999-01-01

    A system for measuring fluid mass flow in a conduit in which there exists a pressure differential in the fluid between at least two spaced-apart locations in the conduit. The system includes a first pressure transducer disposed in the side of the conduit at a first location for measuring pressure of fluid at that location, a second or more pressure transducers disposed in the side of the conduit at a second location, for making multiple measurements of pressure of fluid in the conduit at that location, and a computer for computing the average pressure of the multiple measurements at the second location and for computing flow rate of fluid in the conduit from the pressure measurement by the first pressure transducer and from the average pressure calculation of the multiple measurements.

  18. Gas slug ascent through rheologically stratified conduits

    NASA Astrophysics Data System (ADS)

    Capponi, Antonio; James, Mike R.; Lane, Steve J.

    2016-04-01

    Textural and petrological evidence has indicated the presence of viscous, degassed magma layers at the top of the conduit at Stromboli. This layer acts as a plug through which gas slugs burst and it is thought to have a role in controlling the eruptive dynamics. Here, we present the results of laboratory experiments which detail the range of slug flow configurations that can develop in a rheologically stratified conduit. A gas slug can burst (1) after being fully accommodated within the plug volume, (2) whilst its base is still in the underlying low-viscosity liquid or (3) within a low-viscosity layer dynamically emplaced above the plug during the slug ascent. We illustrate the relevance of the same flow configurations at volcanic-scale through a new experimentally-validated 1D model and 3D computational fluid dynamic simulations. Applied to Stromboli, our results show that gas volume, plug thickness, plug viscosity and conduit radius control the transition between each configuration; in contrast, the configuration distribution seems insensitive to the viscosity of magma beneath the plug, which acts mainly to deliver the slug into the plug. Each identified flow configuration encompasses a variety of processes including dynamic narrowing and widening of the conduit, generation of instabilities along the falling liquid film, transient blockages of the slug path and slug break-up. All these complexities, in turn, lead to variations in the slug overpressure, mirrored by changes in infrasonic signatures which are also associated to different eruptive styles. Acoustic amplitudes are strongly dependent on the flow configuration in which the slugs burst, with both acoustic peak amplitudes and waveform shapes reflecting different burst dynamics. When compared to infrasonic signals from Stromboli, the similarity between real signals and laboratory waveforms suggests that the burst of a slug through a plug may represent a viable first-order mechanism for the generation of

  19. Conduits for Coronary Bypass: Vein Grafts

    PubMed Central

    Farkas, Emily A

    2012-01-01

    The saphenous vein has been the principal conduit for coronary bypass grafting from the beginning, circa 1970. This report briefly traces this history and concomitantly presents one surgeons experience and personal views on use of the vein graft. As such it is not exhaustive but meant to be practical with a modest number of references. The focus is that of providing guidance and perspective which may be at variance with that of others and recognizing that there may be many ways to accomplish the task at hand. Hopefully the surgeon in training/early career may find this instructive on the journey to surgical maturity. PMID:23130300

  20. Impact of electrospun conduit fiber diameter and enclosing pouch pore size on vascular constructs grown within rat peritoneal cavities.

    PubMed

    Bashur, Chris A; Eagleton, Matthew J; Ramamurthi, Anand

    2013-04-01

    The generation of vascular grafts by recruiting autologous cells within the peritoneal cavity has shown promise. However, the microenvironment affects cell differentiation and elastic matrix production. Therefore, this study determined the impact of systematic changes in the average fiber diameter of electrospun poly(ɛ-caprolactone) conduits, and the pore size of pouches used to enclose the conduits, on recruited cells. After 2 weeks in the peritoneal cavity, fibrous capsules formed containing macrophages, α-smooth muscle actin (α-SMA)(+) and SM22α(+) myofibroblastic or smooth muscle like-cells, and what appeared to be mesothelial cells on the outer surfaces. These cells infiltrated and deposited matrix (e.g., collagen, hyaluoronan, and limited elastin) within conduit walls. Constructs enclosed within the largest pore pouches exhibited significantly better tissue generation responses (e.g., better cell infiltration, elongation, and matrix deposition). Additionally, the healing response was impacted by the conduit average fiber diameter, and consequently, the effective pore diameter, with the largest diameter fibers promoting the most positive healing response (e.g., greater total cellularity, extracellular matrix deposition, and α-SMA(+) cells). Six weeks post-intra-aortal grafting, constructs were occluded, but significant remodeling also occurred in the arterial microenvironment. Overall, these results demonstrate the importance of microenvironmental cues on recruited peritoneal cells and the necessity of developing strategies to further improve elastic matrix synthesis.

  1. The Collagen Family

    PubMed Central

    Ricard-Blum, Sylvie

    2011-01-01

    Collagens are the most abundant proteins in mammals. The collagen family comprises 28 members that contain at least one triple-helical domain. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies. Four collagens are type II membrane proteins that also exist in a soluble form released from the cell surface by shedding. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Some collagens have a restricted tissue distribution and hence specific biological functions. PMID:21421911

  2. Delayed complication of pelvic lymphocele: Ileal conduit obstruction.

    PubMed

    Bankar, Sanket S; Bakshi, Ganesh K; Prakash, Gagan; Sable, Nilesh P

    2015-01-01

    Radical cystectomy is the standard treatment for muscle invasive bladder cancer. Lymphocele is a common sequalae of pelvic lymphadenectomy. We report an unusual presentation of pelvic lymphocele developing after radical cystectomy reconstructed with an ileal conduit where the patient developed obstruction of the ileal conduit loop due to external pressure of the lymphocele. Catheter drainage of the conduit relieved the symptoms and a computerized tomography scan showed a large lymphocele causing acute angulation and resultant obstruction of the ileal conduit. The patient was treated with percutaneous drainage of the lymphocele and remains symptom-free on follow-up at 1 year.

  3. Delayed complication of pelvic lymphocele: Ileal conduit obstruction

    PubMed Central

    Bankar, Sanket S.; Bakshi, Ganesh K.; Prakash, Gagan; Sable, Nilesh P.

    2015-01-01

    Radical cystectomy is the standard treatment for muscle invasive bladder cancer. Lymphocele is a common sequalae of pelvic lymphadenectomy. We report an unusual presentation of pelvic lymphocele developing after radical cystectomy reconstructed with an ileal conduit where the patient developed obstruction of the ileal conduit loop due to external pressure of the lymphocele. Catheter drainage of the conduit relieved the symptoms and a computerized tomography scan showed a large lymphocele causing acute angulation and resultant obstruction of the ileal conduit. The patient was treated with percutaneous drainage of the lymphocele and remains symptom-free on follow-up at 1 year. PMID:26166973

  4. Pumice, a window into the volcanic conduit

    NASA Astrophysics Data System (ADS)

    Degruyter, W.; Dufek, J.; Bachmann, O.

    2009-12-01

    To better understand pumice microtextures and stress distribution within the volcanic conduit, a numerical study is performed using passive tracers to map the type and amount of shear in different parts of the conduit. During an explosive eruption pumices are formed by fragmenting the rising magmatic foam (i.e. highly vesicular magma). Provided they are quenched fast enough, pumices reflect the state of the magma just prior to fragmentation and their microtextures carry information on the stresses applied during magma ascent. Numerous deposits contain both tube pumice, with highly elongated vesicles and frothy pumice, with nearly spherical vesicles showing evidence that they were exposed to different stresses during magma ascent (e.g. Kos Plateau Tuff and Campanian Ignimbrite). The main aim of this investigation is to determine the strain histories of magmatic parcels that eventually become pumice We have modified the Multiphase Flow with Interphase Exchanges (MFIX) code to simulate a two-phase (bubbles and magma), two-dimensional, isothermal flow with disequilibrium bubble growth. We include a rheology model depending on water content with outlet expansion into the atmosphere. Furthermore, different fragmentation criteria (i.e. critical gas volume fraction, strain rate and gas overpressure) are examined. Strain histories are investigated by releasing passive tracers within simulated magma rise, which record the pure and simple shear strain rates during ascent. The range of accumulated stresses at fragmentation shown by the passive tracers can then be linked to the range of different microtextures found within pumices.

  5. Further Development, Support and Enhancement of CONDUIT

    NASA Technical Reports Server (NTRS)

    Veronica, Moldoveanu; Levine, William S.

    1999-01-01

    From the first airplanes steered by handles, wheels, and pedals to today's advanced aircraft, there has been a century of revolutionary inventions, all of them contributing to flight quality. The stability and controllability of aircraft as they appear to a pilot are called flying or handling qualities. Many years after the first airplanes flew, flying qualities were identified and ranked from desirable to unsatisfactory. Later on engineers developed design methods to satisfy these practical criteria. CONDUIT, which stands for Control Designer's Unified Interface, is a modern software package that provides a methodology for optimization of flight control systems in order to improve the flying qualities. CONDUIT is dependent on an the optimization engine called CONSOL-OPTCAD (C-O). C-O performs multicriterion parametric optimization. C-O was successfully tested on a variety of control problems. The optimization-based computational system, C-O, requires a particular control system description as a MATLAB file and possesses the ability to modify the vector of design parameters in an attempt to satisfy performance objectives and constraints specified by the designer, in a C-type file. After the first optimization attempts on the UH-60A control system, an early interface system, named GIFCORCODE (Graphical Interface for CONSOL-OPTCAD for Rotorcraft Controller Design) was created.

  6. Large Extremity Peripheral Nerve Repair

    DTIC Science & Technology

    2014-10-01

    nerves in Aim 3 will use AxoGuard we feel that the single layer SIS material is totally appropriate for these small animal studies Biomechanical ...rates of dehiscence, the technique has not been clinically adopted16,17,18,19,20,21. The introduction of biological solder such as fascia or bovine...hydroxysuccinimide (NHS), EDC has been successfully used to improve biomechanical strength and resistance to degradation of several collagen-based biomaterials

  7. Large Extremity Peripheral Nerve Repair

    DTIC Science & Technology

    2014-10-01

    caliber nerves in Aim 3 will use AxoGuard we feel that the single layer SIS material is totally appropriate for these small animal studies Biomechanical ...dehiscence, the technique has not been clinically adopted16,17,18,19,20,21. The introduction of biological solder such as fascia or bovine albumin promised...EDC has been successfully used to improve biomechanical strength and resistance to degradation of several collagen-based biomaterials, including

  8. Concepts in Neural Coaptation: Using the Facial Nerve as a Paradigm in Understanding Principles Surrounding Nerve Injury and Repair.

    PubMed

    Kadakia, Sameep; Helman, Samuel; Saman, Masoud; Cooch, Nisha; Wood-Smith, Donald

    2015-06-01

    Individuals with nerve transection face unpredictable outcomes, and microsurgical interventions have variable success. The facial nerve in particular is prone to traumatic transection and leads to debilitating sequelae. Surgeons have used multiple modalities of enhancing nerve regeneration and restoring premorbid functionality. The success of nerve regeneration is predicated on multiple physiologic factors. This article sought to collate the literature on factors influencing nerve damage and repair, using the facial nerve as a paradigm. As such, facial reanimation will also be briefly discussed as it relates to the central theme. A PubMed search was conducted to find articles published on nerve physiology and anatomy, as well as repair. Articles from 1947 to 2013 were studied; however, the preponderance of articles in the study was from the past 15 years to include recent advances. The type and severity of nerve injury, as well as timing of intervention, influence the anatomical and functional outcomes of nerve repair. As there is no uniform solution for all reconstructive challenges, multiple factors must be considered when planning an intervention. Future advances suggest a potential role for engineered nerve conduits in providing a tool for nerve regrowth. Our review has detailed mechanisms of nerve injury, physiology, interventions in nerve repair, and future direction of this expanding field. This review provides a guide for the microsurgeon in factors involved in restorative success.

  9. Collagen-mediated hemostasis.

    PubMed

    Manon-Jensen, T; Kjeld, N G; Karsdal, M A

    2016-03-01

    Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or degradation may result in pathologic conditions such as fibrosis. Thickening of the vessel wall because of accumulation of collagens may lead to arterial occlusion or thrombosis. Thinning of the wall because of collagen degradation or deficiency may lead to rupture of the vessel wall or aneurysm. Preventing excessive hemorrhage or thrombosis relies on collagen-mediated actions. Von Willebrand factor, integrins and glycoprotein VI, as well as clotting factors, can bind collagen to restore normal hemostasis after trauma. This review outlines the essential roles of collagens in mediating hemostasis, with a focus on collagens types I, III, IV, VI, XV, and XVIII.

  10. Biomedical applications of collagens.

    PubMed

    Ramshaw, John A M

    2016-05-01

    Collagen-based biomedical materials have developed into important, clinically effective materials used in a range of devices that have gained wide acceptance. These devices come with collagen in various formats, including those based on stabilized natural tissues, those that are based on extracted and purified collagens, and designed composite, biosynthetic materials. Further knowledge on the structure and function of collagens has led to on-going developments and improvements. Among these developments has been the production of recombinant collagen materials that are well defined and are disease free. Most recently, a group of bacterial, non-animal collagens has emerged that may provide an excellent, novel source of collagen for use in biomaterials and other applications. These newer collagens are discussed in detail. They can be modified to direct their function, and they can be fabricated into various formats, including films and sponges, while solutions can also be adapted for use in surface coating technologies.

  11. Sourcing different neuro-progenitor cell for the use of nerve construct.

    PubMed

    Yazid, A G M; Anuar, A; Onhmar, H T W E; Ng, A M H; Ruszymah, B H I; Amaramalar, S N

    2008-07-01

    Spinal cord, sciatic nerve, olfactory ensheathing cell and bone marrow derived mesenchymal stem cells were evaluated as an alternative source for tissue engineering of nerve conduit. All cell sources were cultured in alpha-MEM medium. Olfactory Ensheathing Cell (OEC) showed the best result with higher growth kinetic compared to the others. Spinal cord and sciatic nerve were positive for GFAP, OEC were positive for GFAP, S100b and anti-cytokeratin 18 but negative for anti-Human Fibroblast.

  12. 26 CFR 1.881-3 - Conduit financing arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Conduit financing arrangements. 1.881-3 Section 1.881-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Foreign Corporations § 1.881-3 Conduit financing arrangements. (a) General rules and definitions—(1) Purpose and scope....

  13. Biopsy of ureteral tumor in patient with ileal conduit.

    PubMed

    Shental, J; Nussinson, E; Schmitz, A; Sudarsky, M

    1985-11-01

    A patient with ileal conduit and recent dilation of the left upper collecting system had flexible fiberoptic endoscopy of the ileal loop. The entire lumen of the intestinal conduit and the ureteroileal anastomosis were visualized. In addition retrograde pyelography and direct vision biopsy of a tumor in the ureter were performed.

  14. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Conduit financing arrangements. 1.7701(l)-1 Section 1.7701(l)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.7701(l)-1 Conduit...

  15. 26 CFR 1.881-3 - Conduit financing arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 9 2014-04-01 2014-04-01 false Conduit financing arrangements. 1.881-3 Section 1.881-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Foreign Corporations § 1.881-3 Conduit financing arrangements. (a) General rules and definitions—(1) Purpose...

  16. 26 CFR 1.881-3 - Conduit financing arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Conduit financing arrangements. 1.881-3 Section 1.881-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Foreign Corporations § 1.881-3 Conduit financing arrangements. (a) General rules and definitions—(1) Purpose...

  17. 26 CFR 1.881-3 - Conduit financing arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 9 2012-04-01 2012-04-01 false Conduit financing arrangements. 1.881-3 Section 1.881-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Foreign Corporations § 1.881-3 Conduit financing arrangements. (a) General rules and definitions—(1) Purpose...

  18. Water Flow in Karst Aquifer Considering Dynamically Variable Saturation Conduit

    NASA Astrophysics Data System (ADS)

    Tan, Chaoqun; Hu, Bill X.

    2017-04-01

    The karst system is generally conceptualized as dual-porosity system, which is characterized by low conductivity and high storage continuum matrix and high conductivity and quick flow conduit networks. And so far, a common numerical model for simulating flow in karst aquifer is MODFLOW2005-CFP, which is released by USGS in 2008. However, the steady-state approach for conduit flow in CFP is physically impractical when simulating very dynamic hydraulics with variable saturation conduit. So, we adopt the method proposed by Reimann et al. (2011) to improve current model, in which Saint-Venant equations are used to model the flow in conduit. Considering the actual background that the conduit is very big and varies along flow path and the Dirichlet boundary varies with rainfall in our study area in Southwest China, we further investigate the influence of conduit diameter and outflow boundary on numerical model. And we also analyze the hydraulic process in multi-precipitation events. We find that the numerical model here corresponds well with CFP for saturated conduit, and it could depict the interaction between matrix and conduit during very dynamic hydraulics pretty well compare with CFP.

  19. 18 CFR 358.6 - No conduit rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false No conduit rule. 358.6 Section 358.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY STANDARDS OF CONDUCT FOR TRANSMISSION PROVIDERS STANDARDS OF CONDUCT § 358.6 No conduit...

  20. 18 CFR 358.6 - No conduit rule.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false No conduit rule. 358.6 Section 358.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY STANDARDS OF CONDUCT FOR TRANSMISSION PROVIDERS STANDARDS OF CONDUCT § 358.6 No conduit...

  1. 18 CFR 358.6 - No conduit rule.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false No conduit rule. 358.6 Section 358.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY STANDARDS OF CONDUCT FOR TRANSMISSION PROVIDERS STANDARDS OF CONDUCT § 358.6 No conduit...

  2. 18 CFR 358.6 - No conduit rule.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false No conduit rule. 358.6 Section 358.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY STANDARDS OF CONDUCT FOR TRANSMISSION PROVIDERS STANDARDS OF CONDUCT § 358.6 No conduit...

  3. 18 CFR 358.6 - No conduit rule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false No conduit rule. 358.6 Section 358.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY STANDARDS OF CONDUCT FOR TRANSMISSION PROVIDERS STANDARDS OF CONDUCT § 358.6 No conduit...

  4. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Conduit financing arrangements. 1.7701(l)-1 Section 1.7701(l)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7701(l)-1 Conduit...

  5. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Conduit financing arrangements. 1.7701(l)-1 Section 1.7701(l)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7701(l)-1 Conduit...

  6. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Conduit financing arrangements. 1.7701(l)-1 Section 1.7701(l)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7701(l)-1 Conduit...

  7. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Conduit financing arrangements. 1.7701(l)-1 Section 1.7701(l)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7701(l)-1 Conduit...

  8. The role of exosomes in peripheral nerve regeneration

    PubMed Central

    Ching, Rosanna C.; Kingham, Paul J.

    2015-01-01

    Peripheral nerve injuries remain problematic to treat, with poor functional recovery commonly observed. Injuries resulting in a nerve gap create specific difficulties for axonal regeneration. Approaches to address these difficulties include autologous nerve grafts (which are currently the gold standard treatment) and synthetic conduits, with the latter option being able to be impregnated with Schwann cells or stem cells which provide an appropriate micro-environment for neuronal regeneration to occur. Transplanting stem cells, however, infers additional risk of malignant transformation as well as manufacturing difficulties and ethical concerns, and the use of autologous nerve grafts and Schwann cells requires the sacrifice of a functioning nerve. A new approach utilizing exosomes, secreted extracellular vesicles, could avoid these complications. In this review, we summarize the current literature on exosomes, and suggest how they could help to improve axonal regeneration following peripheral nerve injury. PMID:26109947

  9. How to quantify conduits in wood?

    PubMed Central

    Scholz, Alexander; Klepsch, Matthias; Karimi, Zohreh; Jansen, Steven

    2013-01-01

    Vessels and tracheids represent the most important xylem cells with respect to long distance water transport in plants. Wood anatomical studies frequently provide several quantitative details of these cells, such as vessel diameter, vessel density, vessel element length, and tracheid length, while important information on the three dimensional structure of the hydraulic network is not considered. This paper aims to provide an overview of various techniques, although there is no standard protocol to quantify conduits due to high anatomical variation and a wide range of techniques available. Despite recent progress in image analysis programs and automated methods for measuring cell dimensions, density, and spatial distribution, various characters remain time-consuming and tedious. Quantification of vessels and tracheids is not only important to better understand functional adaptations of tracheary elements to environment parameters, but will also be essential for linking wood anatomy with other fields such as wood development, xylem physiology, palaeobotany, and dendrochronology. PMID:23507674

  10. How to quantify conduits in wood?

    PubMed

    Scholz, Alexander; Klepsch, Matthias; Karimi, Zohreh; Jansen, Steven

    2013-01-01

    Vessels and tracheids represent the most important xylem cells with respect to long distance water transport in plants. Wood anatomical studies frequently provide several quantitative details of these cells, such as vessel diameter, vessel density, vessel element length, and tracheid length, while important information on the three dimensional structure of the hydraulic network is not considered. This paper aims to provide an overview of various techniques, although there is no standard protocol to quantify conduits due to high anatomical variation and a wide range of techniques available. Despite recent progress in image analysis programs and automated methods for measuring cell dimensions, density, and spatial distribution, various characters remain time-consuming and tedious. Quantification of vessels and tracheids is not only important to better understand functional adaptations of tracheary elements to environment parameters, but will also be essential for linking wood anatomy with other fields such as wood development, xylem physiology, palaeobotany, and dendrochronology.

  11. Cardiac compression secondary to a massively dilated substernal colon conduit.

    PubMed

    Khan, Babar A; Ionescu, Ruxandra C; Halal, Ahmed M; Kesler, Kenneth A

    2012-11-01

    With the growing success of surgical repairs of congenital defects previously incompatible with life, it is expected of these patients to live longer and experience the complications of these corrective procedures. Esophageal atresia is a congenital defect that occurs in 1 out of 4000 births and is oftentimes a surgical emergency in which colonic conduits are routinely used for esophageal reconstruction. Colonic conduit redundancy and dilatation are well-recognized late complications of colon conduit surgeries for esophageal reconstructions. We report a rare case of symptomatic cardiac compression secondary to a massively dilated substernal colon conduit occurring 44 years after the initial childhood surgery in 1964 with rapid reversal of hemodynamic compromise after conduit removal. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. [Tissue adhesives in facial-nerve surgery].

    PubMed

    Murata, K; Fisch, U

    1976-01-01

    Large amounts of the tissue glue Histoacryl applied over the circumference of the epi- and perineurium of the facial nerve produced a rapid decrease of the summation potentials of the face in acute and chronic experiments performed in cats and guinea pigs. No toxic action on the motor neurons of the facial nerve was seen after application of 1 or 2 drops of the tissue glue over the epi- or perineurium of the facial nerve in association with or without a collagen tube splint.

  13. Collagen reconstitution is inversely correlated with induction of limb regeneration in Ambystoma mexicanum.

    PubMed

    Satoh, Akira; Hirata, Ayako; Makanae, Aki

    2012-03-01

    Amphibians can regenerate missing body parts, including limbs. The regulation of collagen has been considered to be important in limb regeneration. Collagen deposition is suppressed during limb regeneration, so we investigated collagen deposition and apical epithelial cap (AEC) formation during axolotl limb regeneration. The accessory limb model (ALM) has been developed as an alternative model for studying limb regeneration. Using this model, we investigated the relationship between nerves, epidermis, and collagen deposition. We found that Sp-9, an AEC marker gene, was upregulated by direct interaction between nerves and epidermis. However, collagen deposition hindered this interaction, and resulted in the failure of limb regeneration. During wound healing, an increase in deposition of collagen caused a decrease in the blastema induction rate in ALM. Wound healing and limb regeneration are alternate processes.

  14. Alternative Fuels Compatibility with Army Equipment Testing - Aged Niedner Rifts Conduit Testing

    DTIC Science & Technology

    2012-02-01

    ends of the conduit using IPDS couplings to attach them to the conduit end fittings. 2 Setup the plumbing for the pump to pressurize the conduit. 3...Cyclic Testing Procedure Step No. Description 1 End Plugs should be installed on both ends of the conduit using IPDS couplings to attach them to the...testing site. Pressurization Cycles 12 End Plugs should be installed on both ends of the conduit using IPDS couplings to attach them to the conduit

  15. Effects of melatonin on peripheral nerve regeneration.

    PubMed

    Turgut, Mehmet; Kaplan, Süleyman

    2011-05-01

    In the available literature, there are thousands of studies on peripheral nerve regeneration using many nerves of several animals at different ages with various types of lesions and different methods of evaluation at certain time of follow-up. Despite many experimental data and clinical observations, there is still no ideal treatment method enhancing peripheral nerve regeneration. In clinical practice, various types of surgical nerve repair techniques do not frequently result in complete recovery due to neuroma formation, lipid peroxidative damage, ischemia and other factors. Recently, a number of neuroscientists demonstrated that pineal neurohormone melatonin (MLT) has an effect on the morphologic features of the nerve tissue, suggesting its neuroprotective, free radical scavenging, antioxidative, and analgesic effects in degenerative diseases of peripheral nerves. At present, it is widely accepted that MLT has a useful effect on axon length and sprouting after traumatic events to peripheral nerves. Our studies using various experimental injury models clearly suggest positive effects of MLT on the number of axons, thickness of myelin sheath by inhibition of collagen accumulation and neuroma formation following traumatic events to peripheral nerves, myelination of developing peripheral nerve after intrauterine ethanol exposure. Nevertheless, further experimental and randomized controlled clinical studies are vital to identify the clinical use of MLT hormone. This is an overview of recent patents and current literature in terms of the effects of MLT on peripheral nerve regeneration based on a critical analysis of electrophysiological, biochemical and light and electron microscopic findings, in addition to functional observations.

  16. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation.

    PubMed

    Xue, Feng; Wu, Er-Jun; Zhang, Pei-Xun; Li-Ya, A; Kou, Yu-Hui; Yin, Xiao-Feng; Han, Na

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  17. Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode

    PubMed Central

    MacEwan, Matthew R.; Zellmer, Erik R.; Wheeler, Jesse J.; Burton, Harold; Moran, Daniel W.

    2016-01-01

    Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation. PMID:28008303

  18. Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode.

    PubMed

    MacEwan, Matthew R; Zellmer, Erik R; Wheeler, Jesse J; Burton, Harold; Moran, Daniel W

    2016-01-01

    Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm(2) surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation.

  19. Implantable electrode for recording nerve signals in awake animals

    NASA Technical Reports Server (NTRS)

    Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

    1976-01-01

    An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

  20. Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells.

    PubMed

    Duan, B; Kapetanovic, E; Hockaday, L A; Butcher, J T

    2014-05-01

    Tissue engineering has great potential to provide a functional de novo living valve replacement, capable of integration with host tissue and growth. Among various valve conduit fabrication techniques, three-dimensional (3-D) bioprinting enables deposition of cells and hydrogels into 3-D constructs with anatomical geometry and heterogeneous mechanical properties. Successful translation of this approach, however, is constrained by the dearth of printable and biocompatible hydrogel materials. Furthermore, it is not known how human valve cells respond to these printed environments. In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC). Increasing Me-Gel concentration resulted in lower stiffness and higher viscosity, facilitated cell spreading, and better maintained HAVIC fibroblastic phenotype. Bioprinting accuracy was dependent upon the relative concentrations of Me-Gel and Me-HA, but when optimized enabled the fabrication of a trileaflet valve shape accurate to the original design. HAVIC encapsulated within bioprinted heart valves maintained high viability, and remodeled the initial matrix by depositing collagen and glyosaminoglycans. These findings represent the first rational design of bioprinted trileaflet valve hydrogels that regulate encapsulated human VIC behavior. The use of anatomically accurate living valve scaffolds through bioprinting may accelerate understanding of physiological valve cell interactions and progress towards de novo living valve replacements.

  1. 3D Printed Trileaflet Valve Conduits Using Biological Hydrogels and Human Valve Interstitial Cells

    PubMed Central

    Duan, Bin; Kapetanovic, Edi; Hockaday, Laura A.; Butcher, Jonathan T.

    2014-01-01

    Tissue engineering has great potential to provide a functional de novo living valve replacement capable of integration with host tissue and growth. Among various valve conduit fabrication techniques, 3D bioprinting enables deposition of cells and hydrogels into 3D constructs with anatomical geometry and heterogeneous mechanical properties. Successful translation of this approach is however constrained by the dearth of printable and biocompatible hydrogel materials. Furthermore, it is not known how human valve cells respond to these printed environments. In this study, we develop 3D printable formulations of hybrid hydrogels based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and utilize them to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC). Increasing Me-Gel concentration resulted in lower stiffness and higher viscosity, facilitated cell spreading, and better maintained HAVIC fibroblastic phenotype. Bioprinting accuracy was dependent upon the relative concentrations of Me-Gel and Me-HA, but when optimized enabled the fabrication of a trileaflet valve shape accurate to the original design. HAVIC encapsulated within bioprinted heart valves maintained high viability, and remodeled the initial matrix by depositing collagen and glyosaminoglycans. These findings represent the first rational design of bioprinted trileaflet valve hydrogels that regulate encapsulated human VIC behavior. The use of anatomically accurate living valve scaffolds through bioprinting may accelerate our understanding of physiological valve cell interactions and our progress towards de novo living valve replacements. PMID:24334142

  2. Clinical Evaluation After Peripheral Nerve Repair With Caprolactone Neurotube.

    PubMed

    Costa Serrão de Araújo, Gabriel; Couto Neto, Bernardo; Harley Santos Botelho, Renato; Carpi Malta, Marcio

    2017-03-01

    Background: Peripheral nerve injuries with substance loss are challenges to surgeons because direct suture repair may result in malfunction due to nerve suture tension. Autologous nerve grafts are alternatives for treating those lesions; however, harvesting grafts adds morbidity at donor sites. Synthetic substitutes are options to bridge the gaps in these situations. The caprolactone neurotubes are used to assist nerve regeneration, but the literature lacks studies that evaluate their results. Methods: This research was designed to clinically evaluate patients undergoing repair of peripheral nerves with that conduit. We described results of 12 case series consisting of operations with Neurolac®. All nerves severed were sensory and had small gaps (ie, less than 25 mm). Subjective and objective clinical evaluations were performed and registered. Results: Physical examination by monofilament testing and 2-point discrimination showed results rated as good or excellent. However, the patients had complaints regarding sensory changes. Conclusions: Synthetic bioabsorbable guides for nerve repair are promising. The caprolactone conduits were demonstrated to be a safe option treatment and with a simple technique. Although in our study there were some operative complications, they were in line with previous descriptions in the literature. This case series added information about the treatment prognosis, but a higher evidence level study is necessary for decision making.

  3. Arterial conduits for hepatic artery revascularisation in adult liver transplantation.

    PubMed

    Muralidharan, Vijayaragavan; Imber, Charles; Leelaudomlipi, Surasak; Gunson, Bridget K; Buckels, John A C; Mirza, Darius F; Mayer, A David; Bramhall, Simon R

    2004-05-01

    Arterial complications after orthotopic liver transplantation (OLT), including hepatic artery thrombosis (HAT), are important causes of early graft failure. The use of an arterial conduit is an accepted alternative to the utilisation of native recipient hepatic artery for specific indications. This study aims to determine the efficacy of arterial conduits and the outcome in OLT. We retrospectively reviewed 1,575 cadaveric adult OLTs and identified those in which an arterial conduit was used for hepatic revascularisation. Data on the primary disease, indication for using arterial conduit, type of vascular graft, operative technique and outcome were obtained. Thirty-six (2.3%) patients underwent OLT in which arterial conduits were used for hepatic artery (HA) revascularisation. Six of these were performed on the primary transplant, while the rest (n=30) were performed in patients undergoing re-transplantation, including six who had developed hepatic artery aneurysms. The incidence of arterial conduits was 0.4% (6/1,426 cases) in all primary OLTs and 20.1% (30/149 cases) in all re-transplants. Twenty-nine procedures utilised iliac artery grafts from the same donor as the liver, six used iliac artery grafts from a different donor, and a single patient underwent a polytetrafluoroethylene (PTFE) graft. Two techniques were used: infra-renal aorto-hepatic artery conduit and interposition between the donor and recipient native HAs, or branches of the HAs. The 30-day mortality rate for operations using an arterial conduit was 30.6%. Three conduits thrombosed at 9, 25 and 155 months, respectively, but one liver graft survived without re-transplantation. The arterial conduits had 1- and 5-year patency rates of 88.5% and 80.8%. The 1- and 5-year patient survival rates were 66.7% and 44%. We can thus conclude that an arterial conduit is a viable alternative option for hepatic revascularisation in both primary and re-transplantation. Despite a lower patency rate than that of

  4. Nerve Blocks

    MedlinePlus

    ... Sometimes the needle has to be inserted fairly deep to reach the nerve causing your problem. This ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed ...

  5. Enigmatic insight into collagen

    PubMed Central

    Deshmukh, Shrutal Narendra; Dive, Alka M; Moharil, Rohit; Munde, Prashant

    2016-01-01

    Collagen is a unique, triple helical molecule which forms the major part of extracellular matrix. It is the most abundant protein in the human body, representing 30% of its dry weight. It is the fibrous structural protein that makes up the white fibers (collagen fibers) of skin, tendons, bones, cartilage and all other connective tissues. Collagens are not only essential for the mechanical resistance and resilience of multicellular organisms, but are also signaling molecules defining cellular shape and behavior. The human body has at least 16 types of collagen, but the most prominent types are I, II and III. Collagens are produced by several cell types and are distinguishable by their molecular compositions, morphologic characteristics, distribution, functions and pathogenesis. This is the major fibrous glycoprotein present in the extracellular matrix and in connective tissue and helps in maintaining the structural integrity of these tissues. It has a triple helical structure. Various studies have proved that mutations that modify folding of the triple helix result in identifiable genetic disorders. Collagen diseases share certain similarities with autoimmune diseases, because autoantibodies specific to each collagen disease are produced. Therefore, this review highlights the role of collagen in normal health and also the disorders associated with structural and functional defects in collagen. PMID:27601823

  6. Collagen and gelatin.

    PubMed

    Liu, Dasong; Nikoo, Mehdi; Boran, Gökhan; Zhou, Peng; Regenstein, Joe M

    2015-01-01

    Collagen and gelatin have been widely used in the food, pharmaceutical, and cosmetic industries due to their excellent biocompatibility, easy biodegradability, and weak antigenicity. Fish collagen and gelatin are of renewed interest, owing to the safety and religious concerns of their mammalian counterparts. The structure of collagen has been studied using various modern technologies, and interpretation of the raw data should be done with caution. The structure of collagen may vary with sources and seasons, which may affect its applications and optimal extraction conditions. Numerous studies have investigated the bioactivities and biological effects of collagen, gelatin, and their hydrolysis peptides, using both in vitro and in vivo assay models. In addition to their established nutritional value as a protein source, collagen and collagen-derived products may exert various potential biological activities on cells in the extracellular matrix through the corresponding food-derived peptides after ingestion, and this might justify their applications in dietary supplements and pharmaceutical preparations. Moreover, an increasing number of novel applications have been found for collagen and gelatin. Therefore, this review covers the current understanding of the structure, bioactivities, and biological effects of collagen, gelatin, and gelatin hydrolysates as well as their most recent applications.

  7. Development of chitosan-crosslinked nanofibrous PHBV guide for repair of nerve defects.

    PubMed

    Biazar, Esmaeil; Heidari Keshel, Saeed

    2014-12-01

    The aim of this study was to produce a chitosan-crosslinked nanofibrous biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nerve conduit. The artificial scaffold was designed by electrospinning method, and cross-linked with chitosan by chemical method. The scaffolds were evaluated by microscopic, physical, and mechanical analyses, and cell culture assays with Schwann cells. Results of analyses showed a good resilience and compliance with movement as a neural graft. Cellular experiments showed a better cell adhesion and growth inside the crosslinked nanofibrous scaffolds compared with un-crosslinked ones. This neural conduit appears to have the right organization for testing in vivo nerve tissue engineering studies.

  8. 35. CONDUIT LAYOUT FOR BASCULE General overview with motors, brakes, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. CONDUIT LAYOUT FOR BASCULE General overview with motors, brakes, etc. Courtesy of Norwood Noonan Company, Chicago, 1930. - Congress Street Bascule Bridge, Spanning Fort Point Channel at Congress Street, Boston, Suffolk County, MA

  9. 79. COVERED CONDUIT ACROSS ANTELOPE VALLEY WITH WIND FARM IN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    79. COVERED CONDUIT ACROSS ANTELOPE VALLEY WITH WIND FARM IN DISTANCE - Los Angeles Aqueduct, From Lee Vining Intake (Mammoth Lakes) to Van Norman Reservoir Complex (San Fernando Valley), Los Angeles, Los Angeles County, CA

  10. 87. AQUEDUCT IN COVERED CONDUIT LOOKING NORTHWEST Los Angeles ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    87. AQUEDUCT IN COVERED CONDUIT LOOKING NORTHWEST - Los Angeles Aqueduct, From Lee Vining Intake (Mammoth Lakes) to Van Norman Reservoir Complex (San Fernando Valley), Los Angeles, Los Angeles County, CA

  11. 98. (Credit BLV) Detail of gravity, flow conduit intake at ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    98. (Credit BLV) Detail of gravity, flow conduit intake at cross Lake dam Cribbing supports extra suction intake installed in 1930. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

  12. 2. DETAIL, CONDUITS ALONG BASE OF NORTH FRONT. Looking east. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. DETAIL, CONDUITS ALONG BASE OF NORTH FRONT. Looking east. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-4, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

  13. 11. INTERIOR DETAIL, BASEMENT, SHOWING CONDUITS LEADING UNDERGROUND TO SWITCHES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. INTERIOR DETAIL, BASEMENT, SHOWING CONDUITS LEADING UNDERGROUND TO SWITCHES AND SIGNALS - Baltimore & Potomac Interlocking Tower, Adjacent to AMTRAK railroad tracks in block bounded by Howard Street, Jones Falls Expressway, Maryland Avenue & Falls Road, Baltimore, Independent City, MD

  14. Superconducting cable-in-conduit low resistance splice

    DOEpatents

    Artman, Thomas A.

    2003-06-24

    A low resistance splice connects two cable-in-conduit superconductors to each other. Dividing collars for arranging sub-cable units from each conduit are provided, along with clamping collars for mating each sub-cable wire assembly to form mated assemblies. The mated assemblies ideally can be accomplished by way of splicing collar. The mated assemblies are cooled by way of a flow of coolant, preferably helium. A method for implementing such a splicing is also described.

  15. Conduit properties and karstification in the unconfined Floridan aquifer.

    PubMed

    Screaton, Elizabeth; Martin, Jonathan B; Ginn, Brian; Smith, Lauren

    2004-01-01

    Exchange of water between conduits and matrix is an important control on regional chemical compositions, karstification, and quality of ground water resources in karst aquifers. A sinking stream (Santa Fe River Sink) and its resurgence (River Rise) in the unconfined portion of the Floridan Aquifer provide the opportunity to monitor conduit inflow and outflow. The use of temperature as a tracer allows determination of residence times and velocities through the conduit system. Based on temperature records from two high water events, flow is reasonably represented as pipe flow with a cross-sectional area of 380 m2, although this model may be complicated by losses of water from the conduit system at higher discharge rates. Over the course of the study year, the River Rise discharged a total of 1.9 x 10(7) m3 more water than entered the River Sink, reflecting net contribution of ground water from the matrix into the conduit system. However, as River Sink discharge rates peaked following three rainfall events during the study period, the conduit system lost water, presumably into the matrix. Surface water in high flow events is typically undersaturated with respect to calcite and thus may lead to dissolution, depending on its residence time in the matrix. A calculation of local denudation is larger than other regional estimates, perhaps reflecting return of water to conduits before calcite equilibrium is reached. The exchange of matrix and conduit water is an important variable in karst hydrology that should be considered in management of these water resources.

  16. Valved Polytetrafluoroethylene Conduits for Right Ventricular Outflow Tract Reconstruction.

    PubMed

    Shinkawa, Takeshi; Tang, Xinyu; Gossett, Jeffrey M; Mustafa, Thikra; Hategekimana, Festus; Watanabe, Fumiya; Miyazaki, Takako; Yamagishi, Masaaki; Imamura, Michiaki

    2015-07-01

    The purposes of this study were to review our early outcomes using valved expanded polytetrafluoroethylene (ePTFE) conduits, with or without bulging sinus structure, for right ventricular outflow tract reconstruction and to examine the mechanical properties of the ePTFE material after bulging sinuses were created. A retrospective review was performed of all patients who received the valved ePTFE conduit between 2008 and 2014 at a single institution. The surface morphologies and the mechanical strengths of the ePTFE conduit with bulging sinuses examined by scanning electron microscopy and unidirectional pull test were compared with those of the original ePTFE material. There were 120 operations with the valved ePTFE conduit (60 with bulging sinuses). The patients median age and weight were 6.9 years and 23.7 kg. The conduits were a median size of 22 mm. At 5 years, freedom from conduit reoperation was 92.7% (95% confidence interval, 82.7% to 97.0%), and freedom from severe conduit insufficiency or more than a 50 mm Hg gradient was 74.8% (95% confidence interval, 60.8% to 84.4%). No significant differences in the surface morphologies were observed by the scanning electron microscopy or in the maximum tolerated loads obtained by the pull test between the original ePTFE material and the ePTFE with bulging sinuses (121 and 122 N in longitudinal direction and 115 and 121 N in circumferential direction; p = 0.88 and p = 0.68). The valved ePTFE conduits demonstrated excellent early clinical outcomes. The mechanical property examinations showed no obvious difference after bulging sinuses were created on the ePTFE material. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats.

    PubMed

    Huang, Jinghui; Zhang, Yongguang; Lu, Lei; Hu, Xueyu; Luo, Zhuojing

    2013-12-01

    The present study aims to investigate the potential of brief electrical stimulation (ES; 3 V, 20 Hz, 20 min) in improving functional recovery in delayed nerve injury repair (DNIR). The sciatic nerve of Sprague Dawley rats was transected, and the repair of nerve injury was delayed for different time durations (2, 4, 12 and 24 weeks). Brief depolarizing ES was applied to the proximal nerve stump when the transected nerve stumps were bridged with a hollow nerve conduit (5 mm in length) after delayed periods. We found that the diameter and number of regenerated axons, the thickness of myelin sheath, as well as the number of Fluoro-Gold retrograde-labeled motoneurons and sensory neurons were significantly increased by ES, suggesting that brief ES to proximal nerve stumps is capable of promoting nerve regeneration in DNIR with different delayed durations, with the longest duration of 24 weeks. In addition, the amplitude of compound muscle action potential (gastrocnemius muscle) and nerve conduction velocity were also enhanced, and gastrocnemius muscle atrophy was partially reversed by brief ES, indicating that brief ES to proximal nerve stump was able to improve functional recovery in DNIR. Furthermore, brief ES was capable of increasing brain-derived neurotrophic factor (BDNF) expression in the spinal cord in DNIR, suggesting that BDNF-mediated neurotrophin signaling might be one of the contributing factors to the beneficial effect of brief ES on DNIR. In conclusion, the present findings indicate the potential of using brief ES as a useful method to improve functional recovery for delayed repair of peripheral nerve lesions. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Non-Newtonian flow of bubbly magma in volcanic conduits

    NASA Astrophysics Data System (ADS)

    Colucci, Simone; Papale, Paolo; Montagna, Chiara Paola

    2017-04-01

    The dynamics of magma ascent along volcanic conduits towards the Earth's surface affects eruptive styles and contributes to volcanic hazard. The rheology of ascending magmatic mixtures is known to play a major role on mass flow rate as well as on pressure and exit velocity at the vent, even determining effusive vs explosive eruptive behaviour. In this work we explore the effects of bubble-induced non-Newtonian rheology on the dynamics of magma flow in volcanic conduits. We develop a quasi-2D model of magma ascent that incorporates a rheological constitutive equation describing the strain-dependent effect of gas bubbles on the viscosity of the multiphase magma. Non-Newtonian magma flow is investigated through a parametric study where the viscosity of the melt and the water content are varied over natural ranges. Our results show that non-Newtonian rheology leads to greater exit velocity, mass flow, and density. The pressure distribution along the conduit remains very similar to the Newtonian case, deviating only at the conduit exit. Plug-like velocity profiles develop approaching the conduit exit, when mixture velocity is high, and are favored by smaller liquid viscosity. Since the mass flow rate, the density and the velocity of the mixture exiting from the conduit are fundamental for quantifying and assessing the transport and emplacement dynamics, neglecting the non-Newtonian effect of bubble-bearing magmas may result in misinterpretation of the deposit and, consequently, eruptive behavior.

  19. Non-Newtonian flow of bubbly magma in volcanic conduits

    NASA Astrophysics Data System (ADS)

    Colucci, S.; Papale, P.; Montagna, C. P.

    2017-03-01

    The dynamics of magma ascent along volcanic conduits toward the Earth's surface affects eruptive styles and contributes to volcanic hazard. The rheology of ascending magmatic mixtures is known to play a major role on mass flow rate as well as on pressure and exit velocity at the vent, even determining effusive versus explosive eruptive behavior. In this work we explore the effects of bubble-induced non-Newtonian rheology on the dynamics of magma flow in volcanic conduits. We develop a quasi 2-D model of magma ascent that incorporates a rheological constitutive equation describing the strain-dependent effect of gas bubbles on the viscosity of the multiphase magma. Non-Newtonian magma flow is investigated through a parametric study where the viscosity of the melt and the water content are varied over natural ranges. Our results show that non-Newtonian rheology leads to greater exit velocity, mass flow, and density. The pressure distribution along the conduit remains very similar to the Newtonian case, deviating only at the conduit exit. Plug-like velocity profiles develop approaching the conduit exit, when mixture velocity is high, and are favored by smaller liquid viscosity. Since the mass flow rate, the density and the velocity of the mixture exiting from the conduit are fundamental for quantifying and assessing the transport and emplacement dynamics, neglecting that the non-Newtonian effect of bubble-bearing magmas may result in misinterpretation of the deposit and, consequently, eruptive behavior.

  20. CONDUIT: A New Multidisciplinary Integration Environment for Flight Control Development

    NASA Technical Reports Server (NTRS)

    Tischler, Mark B.; Colbourne, Jason D.; Morel, Mark R.; Biezad, Daniel J.; Levine, William S.; Moldoveanu, Veronica

    1997-01-01

    A state-of-the-art computational facility for aircraft flight control design, evaluation, and integration called CONDUIT (Control Designer's Unified Interface) has been developed. This paper describes the CONDUIT tool and case study applications to complex rotary- and fixed-wing fly-by-wire flight control problems. Control system analysis and design optimization methods are presented, including definition of design specifications and system models within CONDUIT, and the multi-objective function optimization (CONSOL-OPTCAD) used to tune the selected design parameters. Design examples are based on flight test programs for which extensive data are available for validation. CONDUIT is used to analyze baseline control laws against pertinent military handling qualities and control system specifications. In both case studies, CONDUIT successfully exploits trade-offs between forward loop and feedback dynamics to significantly improve the expected handling, qualities and minimize the required actuator authority. The CONDUIT system provides a new environment for integrated control system analysis and design, and has potential for significantly reducing the time and cost of control system flight test optimization.

  1. Development of a bioartificial nerve graft. I. Design based on a reaction-diffusion model.

    PubMed

    Rutkowski, Gregory E; Heath, Carole A

    2002-01-01

    A simple reaction-diffusion model has been developed to describe the mass transport of nutrients and nerve growth factor within a bioartificial nerve graft (BNG). The BNG consists of a porous polymer conduit that is preseeded with Schwann cells in its lumen. The Schwann cells produce growth factors to stimulate nerve regeneration within the lumen of the conduit. The model can predict the wall thickness, porosity, and Schwann cell seeding density needed to maximize the axon extension rate while ensuring that sufficient nutrients, especially oxygen, are made available to the neurons until the formation of the neovasculature. The model predicts a sixteen-fold increase in the levels of nerve growth factor by dropping the porosity from 95 to 55% but only at the expense of reducing the oxygen concentration. At higher porosities, increasing the wall thickness and increasing the Schwann cell seeding density both have the same effect of increasing the concentration of nerve growth factor within the lumen of the conduit. This model provides a simple tool for evaluating various conduit designs before continuing with experimental studies in vivo.

  2. Comminution and frictional melting in volcanic conduits

    NASA Astrophysics Data System (ADS)

    Lavallee, Y.; Mitchell, T. M.; Heap, M. J.; Kendrick, J. E.; kennedy, B.; Ashwell, P. A.; Hirose, T.; Dingwell, D. B.

    2011-12-01

    Shearing and faulting at active volcanoes may differ to tectonic faulting due to their distinct temperature conditions above those of the Earth's geotherm. In particular, the ascent of high-viscosity magma/rocks in upper conduits leads to shear/fault zones, with/without gouge formation and sometimes frictional melting; yet, details of the deformation and fracture mechanisms in these magma/rocks with different crystallinities reveal a different synopsis. For instance, the extrusion of lava domes proceeds endogenously or exogenically - a distinction generally understood as a shift in magma rheology to brittle failure, without consideration of the subsequent slip process. Exogenic growth and formation of a spine follow the dynamic rupture of the lava and the dome carapace, and suffer slip along the fault surface. Here, we present experimental investigations of the ability of volcanic rocks (with different glass/crystal and vesicle ratios) to sustain friction, and in cases melt, using a high-velocity rotary apparatus. During high-velocity rotary shear test, we find that slip of along andesite and basalt rocks generate heat which leads to frictional melting at temperature of ca. 1000 C, conciding to a total slip of 10-40 m (for slip initiating at room temperature). In contrast, slip along dense obsidian rocks or porous rocks cannot sustain slip along a discrete plane. Alternatively, obsidian can be slipped against a crystalline material. The width of the slip zone decreases in the presence of crystals. The findings suggest that the comminution of crystals is a requirement to the development of a localised slip zone. In absence of crystals, obsidian (and crystal-free magma) shatter catastrophically. We discuss the implication of our findings to the cases of tectonic faults, stability of volcanic edifices and evolution of lava dome eruptions.

  3. Haemorrhoids - a collagen disease?

    PubMed

    Willis, S; Junge, K; Ebrahimi, R; Prescher, A; Schumpelick, V

    2010-12-01

    The cause of haemorrhoidal disease is unknown, epidemiological data and histopathological findings support the hypothesis that reduced connective tissue stability is associated with the incidence of haemorrhoids. Therefore the aim of this study was to analyse the quantity and quality of collagen formation in the corpus cavernosum recti in patients with III°/IV° haemorrhoids in comparison with persons without haemorrhoids. Haemorrhoidectomy specimens of 31 patients with III°/IV° haemorrhoids were examined. The specimens of 20 persons who died a natural death and who had no haemorrhoidal disease served as the controls. The amount of collagen was estimated photometrically by calculating the collagen/protein ratio. The collagen I/III ratio served as parameter for the quality of collagen formation and was calculated using cross polarization spectroscopy. Patients with haemorrhoids had a significantly reduced collagen/protein ratio (42.2 ± 16.2μg/mg vs 72.5±31.0μg/mg; P= 0.02) and a significantly reduced collagen I/III ratio (2.0±0.1 vs 4.6±0.3; P<0.001) compared with persons without haemorrhoidal disease. There was no correlation with patients' age or gender.  There is a fundamental disorder of collagen metabolism in patients with haemorrhoidal disease. It remains unclear whether this is due to exogenous or endogenous influences. © 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.

  4. Optic Nerve Decompression

    MedlinePlus

    ... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Optic Nerve Decompression John Lee, MD Introduction Optic nerve decompression is a surgical procedure aimed at ...

  5. Ulnar nerve dysfunction

    MedlinePlus

    Neuropathy - ulnar nerve; Ulnar nerve palsy; Mononeuropathy; Cubital tunnel syndrome ... compressed in the elbow, a problem called cubital tunnel syndrome may result. When damage destroys the nerve ...

  6. Temperature limited heater with a conduit substantially electrically isolated from the formation

    SciTech Connect

    Vinegar, Harold J.; Sandberg, Chester Ledlie

    2009-07-14

    A system for heating a hydrocarbon containing formation is described. A conduit may be located in an opening in the formation. The conduit includes ferromagnetic material. An electrical conductor is positioned inside the conduit, and is electrically coupled to the conduit at or near an end portion of the conduit so that the electrical conductor and the conduit are electrically coupled in series. Electrical current flows in the electrical conductor in a substantially opposite direction to electrical current flow in the conduit during application of electrical current to the system. The flow of electrons is substantially confined to the inside of the conduit by the electromagnetic field generated from electrical current flow in the electrical conductor so that the outside surface of the conduit is at or near substantially zero potential at 25.degree. C. The conduit may generate heat and heat the formation during application of electrical current.

  7. Nerve Tissue Prefabrication Inside the Rat Femoral Bone: Does It Work?

    PubMed

    Ozbek, Zuhtu; Kocman, Atacan Emre; Ozatik, Orhan; Soztutar, Erdem; Ozkara, Emre; Kose, Aydan; Arslantas, Ali; Cetin, Cengiz

    2017-01-01

    To investigate whether nerve regeneration can be induced in the tubular bone between distal and proximal cut nerve ends. Twenty adult Wistar rats were used for the study. Rats were divided into three groups; femoral bone conduit group, nerve transection group, sham group. The sciatic nerve was surgically cut and from both ends inserted into the adjacent femoral bone tunnel in the femoral bone conduit group. The sciatic nerve was cut transversely in the nerve transection group. In the Sham group, only sciatic nerve exploration was performed, without a nerve cut. The groups were evaluated functionally and morphologically. All results showed that axonal growth existed through the osseous canal. To the best of our knowledge, this is the first study to evaluate neural regeneration inside the bone. We can speculate that the bone marrow provides a convenient microenvironment for peripheral nerve regeneration. In addition to prefabricating peripheral nerves, this novel model may help to establish further strategies for engineering of other tissues in the bone marrow.

  8. Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat.

    PubMed

    Farahpour, Mohammad Reza; Ghayour, Sina Jangkhahe

    2014-12-01

    The repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery, plastic and orthopedic surgery. Effect of acetyl-L-carnitine (ALC) loaded chitosan conduit as an in situ delivery system of ALC in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit (CHIT/ALC) filled with 10 μL ALC (100 ng/mL). In control group (CHIT), the conduit was filled with the same volume of the phosphate buffered solution. The regenerated fibers were studied 4, 8, 12 and 16 weeks after surgery. The functional and electrophysiological studies confirmed faster recovery of the regenerated axons in ALC treated than control group (P < 0.05). The mean ratios of gastrocnemius muscles weight were measured. There was statistically significant difference between the muscle weight ratios of CHIT/ALC and CHIT groups (P<0.05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers in CHIT/ALC were significantly higher than in control group. In immuohistochemistry, the location of reactions to S-100 in CHIT/ALC was clearly more positive than CHIT group. ALC when loaded in a chitosan conduit resulted in improvement of functional recovery and quantitative morphometric indices of sciatic nerve.

  9. Topography, Cell Response, and Nerve Regeneration

    PubMed Central

    Hoffman-Kim, Diane; Mitchel, Jennifer A.; Bellamkonda, Ravi V.

    2010-01-01

    In the body, cells encounter a complex milieu of signals, including topographical cues. Imposed topography can affect cells on surfaces by promoting adhesion, spreading, alignment, morphological changes, and changes in gene expression. Neural response to topography is complex, and depends on the dimensions and shapes of physical features. Looking toward repair of nerve injuries, strategies are being explored to engineer guidance conduits with precise surface topographies. How neurons and other cell types sense and interpret topography remains to be fully elucidated. Studies reviewed here include those of topography on cellular organization and function as well as potential cellular mechanisms of response. PMID:20438370

  10. Extraforaminal ligament attachments of human lumbar nerves.

    PubMed

    Kraan, G A; Delwel, E J; Hoogland, P V J M; van der Veen, M R; Wuisman, P I J M; Stoeckart, R; Kleinrensink, G J; Snijders, C J

    2005-03-15

    An anatomic study of the extraforaminal attachments of the lumbar spinal nerves was performed using human lumbar spinal columns. To identify and describe the existence of ligamentous structures at each lumbar level that attach lumbar spinal nerves to structures at the level of the extraforaminal region. During the last 120 years, several mechanisms to protect the spinal nerve against traction have been described. All these structures involved are located in the spinal canal, proximal to the intervertebral foramen. Five embalmed human lumbar spines (T12-S1) were used. Bilaterally, the extraforaminal region was dissected to describe and measure anatomic structures and their relationships. Histology was performed with staining on the sites of attachment and along the ligament. The levels T12-L2 show bilaterally 2 ligaments, a superior extraforaminal ligament and an inferior extraforaminal ligament. The superior extraforaminal ligament emerges from the joint capsule of the facet joints and inserts in both, the intervertebral disc and the ventral crista of the intervertebral foramen, passing the spinal nerve laterally. In one specimen on level L2-L3, the superior extraforaminal ligament is not attached to the spinal nerve. The inferior extraforaminal ligament emerges from the intervertebral disc, passing the nerve medially and attaching the spinal nerve. At the levels L2-L5, the inferior extraforaminal ligaments are only attached to the intervertebral disc, not to the joint capsule. Histologically, the ligaments consisted of mainly collagenous structures. Ligamentous connections exist between lumbar extraforaminal spinal nerves and nearby structures.

  11. Peripheral Nerve Disorders

    MedlinePlus

    ... Like static on a telephone line, peripheral nerve disorders distort or interrupt the messages between the brain ... are more than 100 kinds of peripheral nerve disorders. They can affect one nerve or many nerves. ...

  12. Vagus Nerve Stimulation

    MedlinePlus

    Vagus nerve stimulation Overview By Mayo Clinic Staff Vagus nerve stimulation is a procedure that involves implantation of a device that stimulates the vagus nerve with electrical impulses. There's one vagus nerve on ...

  13. Nerve biopsy (image)

    MedlinePlus

    Nerve biopsy is the removal of a small piece of nerve for examination. Through a small incision, a sample ... is removed and examined under a microscope. Nerve biopsy may be performed to identify nerve degeneration, identify ...

  14. Acellular Vascular Grafts Generated from Collagen and Elastin Analogues

    PubMed Central

    Kumar, Vivek A.; Caves, Jeffrey M.; Haller, Carolyn A.; Dai, Erbin; Li, Liying; Grainger, Stephanie; Chaikof, Elliot L.

    2013-01-01

    Tissue engineered vascular grafts require long fabrication times, in part, due to the requirement of cells from a variety of cell sources to produce a robust load bearing, extracellular matrix. Herein, we propose a design strategy for the fabrication of tubular conduits comprised of collagen fiber networks and elastin-like protein polymers to mimic native tissue structure and function. Dense fibrillar collagen networks exhibited an ultimate tensile strength (UTS) of 0.71 ± 0.06 MPa, strain to failure of 37.1 ± 2.2%, and Young’s modulus of 2.09 ± 0.42 MPa, comparing favorably to an UTS and a Young’s modulus for native blood vessels of 1.4 – 11.1 MPa and 1.5 ± 0.3 MPa, respectively. Resilience, a measure of recovered energy during unloading of matrices, demonstrated that 58.9 ± 4.4% of the energy was recovered during loading-unloading cycles. Rapid fabrication of multilayer tubular conduits with maintenance of native collagen ultrastructure was achieved with internal diameters ranging between 1 to 4 mm. Compliance and burst pressures exceeded 2.7 ± 0.3%/100 mmHg and 830 ± 131 mmHg, respectively, with a significant reduction in observed platelet adherence as compared to ePTFE (6.8 ± 0.05 × 105 vs. 62 ± 0.05 × 105 platelets/mm2, p < 0.01). Using a rat aortic interposition model, early in vivo responses were evaluated at 2 weeks via Doppler ultrasound and CT angiography with immunohistochemistry confirming a limited early inflammatory response (n=8). Engineered collagen-elastin composites represent a promising strategy for fabricating synthetic tissues with defined extracellular matrix content, composition, and architecture. PMID:23743129

  15. Thermomechanical milling of accessory lithics in volcanic conduits

    NASA Astrophysics Data System (ADS)

    Campbell, Michelle E.; Russell, James K.; Porritt, Lucy A.

    2013-09-01

    Accessory lithic clasts recovered from pyroclastic deposits commonly result from the failure of conduit wall rocks, and represent an underutilized resource for constraining conduit processes during explosive volcanic eruptions. The morphological features of lithic clasts provide distinctive 'textural fingerprints' of processes that have reshaped them during transport in the conduit. Here, we present the first study focused on accessory lithic clast morphology and show how the shapes and surfaces of these accessory pyroclasts can inform on conduit processes. We use two main types of accessory lithic clasts from pyroclastic fallout deposits of the 2360 B.P. subplinian eruption of Mount Meager, British Columbia, as a case study: (i) rough and subangular dacite clasts, and (ii) variably rounded and smoothed monzogranite clasts. The quantitative morphological data collected on these lithics include: mass, volume, density, 2-D image analysis of convexity (C), and 3-D laser scans for sphericity (Ψ) and smoothness (S). Shaping and comminution (i.e. milling) of clasts within the conduit are ascribed to three processes: (1) disruptive fragmentation due to high-energy impacts between clasts or between clasts and conduit walls, (2) ash-blasting of clasts suspended within the volcanic flux, and (3) thermal effects. We use a simplified conduit eruption model to predict ash-blasting velocities and lithic residence times as a function of clast size and source depth, thereby constraining the lithic milling processes. The extent of shape and surface modification (i.e. rounding and honing) is directly proportional to clast residence times within the conduit prior to evacuation. We postulate that the shallow-seated dacite clasts remain subangular and rough due to short (<2 min) residence times, whereas monzogranite clasts are much more rounded and smoothed due to deeper source depths and consequently longer residence times (up to ˜1 h). Larger monzogranite clasts are smoother than

  16. Access to the native atria following conduit total cavopulmonary anastomosis.

    PubMed

    Petersen, Robert L; Danon, Saar; Jureidini, Saadeh

    2017-08-01

    We describe the use of trans-thoracic and trans-conduit puncture to access the atria and perform interventional procedures in patients who have undergone conduit total cavopulmonary anastomosis. Catheter access to the atria following intra or extra-cardiac Fontan is desirable when there is a need for trans-atrial interventions. Between 2009 and 2014, 5 patients ages 7 to 28 years underwent this approach; three trans-thoracic and 2 trans-conduit punctures. Various therapeutic aims were achieved. Included are: placement of pacing wire in the left atrial appendage, access to re-canalized left superior vena cava via the coronary sinus for device occlusion eliminating cyanosis, access with subsequent device closure of a dormant pulmonary valve thought to be the nidus of an embolic event, and access to the atria for ablation of an atrial tachycardia. Entry to the atria was successful in all five patients with either trans-thoracic access or trans-conduit puncture with subsequent intended intervention performed successfully. Trans-conduit puncture and trans-thoracic access may allow therapeutic procedures which mitigate the need for further open heart surgery. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. The utility of ultrasound in the assessment of traumatic peripheral nerve lesions: report of 4 cases.

    PubMed

    Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D

    2015-09-01

    Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.

  18. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    PubMed

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration.

  19. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves.

    PubMed

    Gil, Ziv; Cavel, Oren; Kelly, Kaitlyn; Brader, Peter; Rein, Avigail; Gao, Sizhi P; Carlson, Diane L; Shah, Jatin P; Fong, Yuman; Wong, Richard J

    2010-01-20

    The ability of cancer to infiltrate along nerves is a common clinical observation in pancreas, head and neck, prostate, breast, and gastrointestinal carcinomas. For these tumors, nerves may provide a conduit for local cancer progression into the central nervous system. Although neural invasion is associated with poor outcome, the mechanism that triggers it is unknown. We used an in vitro Matrigel dorsal root ganglion and pancreatic cancer cell coculture model to assess the dynamic interactions between nerves and cancer cell migration and the role of glial cell-derived neurotrophic factor (GDNF). An in vivo murine sciatic nerve model was used to study how nerve invasion affects sciatic nerve function. Nerves induced a polarized neurotrophic migration of cancer cells (PNMCs) along their axons, which was more efficient than in the absence of nerves (migration distance: mean = 187.1 microm, 95% confidence interval [CI] = 148 to 226 microm vs 14.4 microm, 95% CI = 9.58 to 19.22 microm, difference = 143 microm; P < .001; n = 20). PNMC was induced by secretion of GDNF, via phosphorylation of the RET-Ras-mitogen-activated protein kinase pathway. Nerves from mice deficient in GDNF had reduced ability to attract cancer cells (nerve invasion index: wild type vs gdnf+/-, mean = 0.76, 95% CI = 0.75 to 0.77 vs 0.43, 95% CI = 0.42 to 0.44; P < .001; n = 60-66). Tumor specimens excised from patients with neuroinvasive pancreatic carcinoma had higher expression of the GDNF receptors RET and GRFalpha1 as compared with normal tissue. Finally, systemic therapy with pyrazolopyrimidine-1, a tyrosine kinase inhibitor targeting the RET pathway, suppressed nerve invasion toward the spinal cord and prevented paralysis in mice. These data provide evidence for paracrine regulation of pancreatic cancer invasion by nerves, which may have important implications for potential therapy directed against nerve invasion by cancer.

  20. Conducting polymers with immobilised fibrillar collagen for enhanced neural interfacing.

    PubMed

    Liu, Xiao; Yue, Zhilian; Higgins, Michael J; Wallace, Gordon G

    2011-10-01

    Conducting polymers with pendant functionality are advantageous in various bionic and organic bioelectronic applications, as they allow facile incorporation of bio-regulative cues to provide bio-mimicry and conductive environments for cell growth, differentiation and function. In this work, polypyrrole substrates doped with chondroitin sulfate (CS), an extracellular matrix molecule bearing carboxylic acid moieties, were electrochemically synthesized and conjugated with type I collagen. During the coupling process, the conjugated collagen formed a 3-dimensional fibrillar matrix in situ at the conducting polymer interface, as evidenced by atomic force microscopy (AFM) and fluorescence microscopy under aqueous physiological conditions. Cyclic voltammetry (CV) and impedance measurement confirmed no significant reduction in the electroactivity of the fibrillar collagen-modified conducting polymer substrates. Rat pheochromocytoma (nerve) cells showed increased differentiation and neurite outgrowth on the fibrillar collagen, which was further enhanced through electrical stimulation of the underlying conducting polymer substrate. Our study demonstrates that the direct coupling of ECM components such as collagen, followed by their further self-assembly into 3-dimensional matrices, has the potential to improve the neural-electrode interface of implant electrodes by encouraging nerve cell attachment and differentiation.

  1. Aeration efficiency of free-surface conduit flow systems.

    PubMed

    Unsal, M; Baylar, A; Tugal, M; Ozkan, F

    2009-12-14

    Dissolved oxygen is a measure of the quantity of oxygen present in water and is one of the best indicators of the health of a water ecosystem. Dissolved oxygen levels in water can be increased by creating turbulent conditions where fine air bubbles are carried into the bulk of the flow. This is achieved by hydraulic structures. A free-surface conduit is a particular instance of this. In the present work, a series of experiments were conducted to investigate the aeration efficiency of free-surface conduit flow systems. The results indicate that free-surface conduit flow systems are very effective for oxygen transfer. At Froude numbers greater than 15, almost full oxygen transfer up to the saturation value was reached. Moreover, from experimental data, a regression equation was obtained with a very high correlation coefficient, showing the effect of various parameters on the aeration efficiency.

  2. Endoscopic Treatment of Stump Leakage Related to the Ileal Conduit

    PubMed Central

    Odemis, Bulent; Oztas, Erkin; Akpinar, Muhammet Yener; Olcucuoglu, Erkan; Kayacetin, Ertugrul

    2016-01-01

    Abstract Background: Ileal conduit with leakage from either the anastomotic site or the stump is associated with high morbidity and mortality rates. The standard treatment of stump leakage is surgery. Case Presentation: A 60-year-old male patient was admitted to our hospital with complaint of hematuria and bladder carcinoma was diagnosed. After performing radical cystectomy and ileal conduit, he developed fever with abdominal pain within the first week of surgery. Stump leakage was diagnosed by endoscopic examination performed through a gastroscope. After two over-the-scope clips (OTSCs) were applied to the stump, vinyl mesh was inserted into the space between the OTSCs. Later, cyanoacrylat and lipiodol were repelled on the OTSCs and vinyl mesh. Subsequently, stump leakage was resolved. Conclusion: This is the first case of stump leakage related to ileal conduit that has been treated endoscopically, according to the current literature. PMID:27579432

  3. Understanding Volcanic Conduit Dynamics: from Experimental Fragmentation to Volcanic Eruptions

    NASA Astrophysics Data System (ADS)

    Arciniega-Ceballos, A.; Alatorre-Ibarguengoitia, M. A.; Scheu, B.; Dingwell, D. B.

    2011-12-01

    The investigation of conduit dynamics at high pressure, under controlled laboratory conditions is a powerful tool to understand the physics behind volcanic processes before an eruption. In this work, we analyze the characteristics of the seismic response of an "experimental volcano" focusing on the dynamics of the conduit behavior during the fragmentation process of volcanic rocks. The "experimental volcano" is represented by a shock tube apparatus, which consists of a low-pressure voluminous tank (3 x 0.40 m), for sample recovery; and a high-pressure pipe-like conduit (16.5 x 2,5 cm), which represents the volcanic source mechanism, where rock samples are pressurized and fragmented. These two serial steel pipes are connected and sealed by a set of diaphragms that bear pressures in a range of 4 to 20 MPa. The history of the overall process of an explosion consists of four steps: 1) the slow pressurization of the pipe-like conduit filled with solid pumice and gas, 2) the sudden removal of the diaphragms, 3) the rapid decompression of the system and 4) the ejection of the gas-particle mixture. Each step imprints distinctive features on the microseismic records, reflecting the conduit dynamics during the explosion. In this work we show how features such as waveform characteristics, the three components of the force system acting on the conduit, the independent components of the moment tensor, the volumetric change of the source mechanism, the arrival time of the shock wave and its velocity, are quantified from the experimental microseismic data. Knowing these features, each step of the eruptive process, the conduit conditions and the source mechanism characteristics can be determined. The procedure applied in this experimental approach allows the use of seismic field data to estimate volcanic conduit conditions before an eruption takes place. We state on the hypothesis that the physics behind the pressurization and depressurization process of any conduit is the same

  4. Nanomechanics of collagen microfibrils

    PubMed Central

    Vesentini, Simone; Redaelli, Alberto; Gautieri, Alfonso

    2013-01-01

    Summary Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to organisms and is thus the prime construction material in biology. Collagen is also the dominating material in the extracellular matrix where its stiffness controls cell differentiation, growth and pathology. We use atomistic-based hierarchical multiscale modeling to describe this complex biological material from the bottom up. This includes the use and development of large-scale computational modeling tools to investigate several aspects related to collagen-based tissues, including source of visco-elasticity and deformation mechanisms at the nanoscale level. The key innovation of this research is that until now, collagen materials have primarily been described at macroscopic scales, without explicitly understanding the mechanical contributions at the molecular and fibrillar levels. The major impact of this research will be the development of fundamental models of collagenous tissues, important to the design of new scaffolding biomaterials for regenerative medicine as well as for the understanding of collagen-related diseases. PMID:23885342

  5. In vivo application of poly-3-hydroxyoctanoate as peripheral nerve graft

    PubMed Central

    Hazer, D. Burcu; Bal, Ercan; Nurlu, Gülay; Benli, Kemal; Balci, Serdar; Öztürk, Feral; Hazer, Baki

    2013-01-01

    Objective: This study aims to investigate the degree of biocompatibility and neuroregeneration of a polymer tube, poly-3-hydroxyoctanoate (PHO) in nerve gap repair. Methods: Forty Wistar Albino male rats were randomized into two groups: autologous nerve gap repair group and PHO tube repair group. In each group, a 10-mm right sciatic nerve defect was created and reconstructed accordingly. Neuroregeneration was studied by sciatic function index (SFI), electromyography, and immunohistochemical studies on Days 7, 21, 45 and 60 of implantation. Biocompatibility was analyzed by the capsule formation around the conduit. Biodegradation was analyzed by the molecular weight loss in vivo. Results: Electrophysiological and histomorphometric assessments demonstrated neuroregeneration in both groups over time. In the experimental group, a straight alignment of the Schwann cells parallel to the axons was detected. However, autologous nerve graft seems to have a superior neuroregeneration compared to PHO grafts. Minor biodegradation was observed in PHO conduit at the end of 60 d. Conclusions: Although neuroregeneration is detected in PHO grafts with minor degradation in 60 d, autologous nerve graft is found to be superior in axonal regeneration compared to PHO nerve tube grafts. PHO conduits were found to create minor inflammatory reaction in vivo, resulting in good soft tissue response. PMID:24190445

  6. Advances and Future Applications of Augmented Peripheral Nerve Regeneration

    PubMed Central

    Jones, Salazar; Eisenberg, Howard M.; Jia, Xiaofeng

    2016-01-01

    Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested. PMID:27618010

  7. Linking Volcano Infrasound Observations to Conduit Processes for Vulcanian Eruptions

    NASA Astrophysics Data System (ADS)

    Watson, L. M.; Dunham, E. M.; Almquist, M.; Mattsson, K.; Ampong, K.

    2016-12-01

    Volcano infrasound observations have been used to infer a range of eruption parameters, such as volume flux and exit velocity, with the majority of work focused on subaerial processes. Here, we propose using infrasound observations to investigate the subsurface processes of the volcanic system. We develop a one-dimensional model of the volcanic system, coupling an unsteady conduit model to a description of a volcanic jet with sound waves generated by the expansion of the jet. The conduit model describes isothermal two-phase flow with no relative motion between the phases. We are currently working on including crystals and adding conservation of energy to the governing equations. The model captures the descent of the fragmentation front into the conduit and approaches a steady state solution with choked flow at the vent. The descending fragmentation front influences the time history of mass discharge from the vent, which is linked to the infrasound signal through the volcanic jet model. The jet model is coupled to the conduit by conservation of mass, momentum, and energy. We compare simulation results for a range of models of the volcanic jet, ranging in complexity from assuming conservation of volume, as has been done in some previous infrasound studies, to solving the Euler equations for the surrounding compressible atmosphere and accounting for entrainment. Our model is designed for short-lived, impulsive Vulcanian eruptions, such as those seen at Sakurajima Volcano, with activity triggered by a sudden drop in pressure at the top of the conduit. The intention is to compare the simulated signals to observations and to devise an inverse procedure to enable inversion for conduit properties.

  8. Peripheral nerve palsy by torsional nerve injury.

    PubMed

    Guerra, Waltraud Kleist-Welch; Schroeder, Henry W S

    2011-04-01

    Peripheral nerve palsy caused by torsional nerve injury is rare. Only a few patients have been reported in the literature. The etiology of this type of nerve lesion is poorly understood. To report on 5 patients presenting with peripheral nerve palsy caused by a torsional nerve injury. Five patients presented with 6 upper peripheral nerve palsy involving the axillary nerve (n = 2), musculocutaneous nerve (n = 2), radial nerve (n = 1), and suprascapular nerve (n = 1). There was no history of trauma in 3 patients, but in the other 2 patients, nerve palsy occurred after a traumatic event. Because of a lack of spontaneous recovery, surgical exploration was performed. Torsion of the whole nerve (n = 5) or only 1 fascicle (n = 1) was found. Epifascicular epineurectomy and detorsion, as well as resection of the torsion site with subsequent primary nerve suture, were performed in 3 lesions. Good to excellent recovery of motor function was achieved in all 5 patients. In the last patient who presented with 2 nerve torsions, the follow-up period after the last surgery is too short to allow evaluation. Although not a frequent event, torsional nerve injury should be taken into consideration when dealing with peripheral nerve injuries. Surgical exploration with detorsion or suture results in good recovery.

  9. Optic Nerve.

    PubMed

    Gordon, Lynn K

    2016-10-28

    Optic nerve diseases arise from many different etiologies including inflammatory, neoplastic, genetic, infectious, ischemic, and idiopathic. Understanding some of the characteristics of the most common optic neuropathies along with therapeutic approaches to these diseases is helpful in designing recommendations for individual patients. Although many optic neuropathies have no specific treatment, some do, and it is those potentially treatable or preventable conditions which need to be recognized in order to help patients regain their sight or develop a better understanding of their own prognosis. In this chapter several diseases are discussed including idiopathic intracranial hypertension, optic neuritis, ischemic optic neuropathies, hereditary optic neuropathies, trauma, and primary tumors of the optic nerve. For each condition there is a presentation of the signs and symptoms of the disease, in some conditions the evaluation and diagnostic criteria are highlighted, and where possible, current therapy or past trials are discussed.

  10. Apparatus for controlling fluid flow in a conduit wall

    DOEpatents

    Glass, S. Jill; Nicolaysen, Scott D.; Beauchamp, Edwin K.

    2003-05-13

    A frangible rupture disk and mounting apparatus for use in blocking fluid flow, generally in a fluid conducting conduit such as a well casing, a well tubing string or other conduits within subterranean boreholes. The disk can also be utilized in above-surface pipes or tanks where temporary and controllable fluid blockage is required. The frangible rupture disk is made from a pre-stressed glass with controllable rupture properties wherein the strength distribution has a standard deviation less than approximately 5% from the mean strength. The frangible rupture disk has controllable operating pressures and rupture pressures.

  11. Estrogen-induced collagen reorientation correlates with sympathetic denervation of the rat myometrium.

    PubMed

    Martínez, G F; Bianchimano, P; Brauer, M M

    2016-12-01

    Estrogen inhibits the growth and causes the degeneration (pruning) of sympathetic nerves supplying the rat myometrium. Previous cryoculture studies evidenced that substrate-bound signals contribute to diminish the ability of the estrogenized myometrium to support sympathetic nerve growth. Using electron microscopy, here we examined neurite-substrate interactions in myometrial cryocultures, observing that neurites grew associated to collagen fibrils present in the surface of the underlying cryosection. In addition, we assessed quantitatively the effects of estrogen on myometrial collagen organization in situ, using ovariectomized rats treated with estrogen and immature females undergoing puberty. Under low estrogen levels, most collagen fibrils were oriented in parallel to the muscle long axis (83% and 85%, respectively). Following estrogen treatment, 89% of fibrils was oriented perpendicularly to the muscle main axis; while after puberty, 57% of fibrils acquired this orientation. Immunohistochemistry combined with histology revealed that the vast majority of fine sympathetic nerve fibers supplying the myometrium courses within the areas where collagen realignment was observed. Finally, to assess whether depending on their orientation collagen fibrils can promote or inhibit neurite outgrowth, we employed cryocultures, now using as substrate tissue sections of rat-tail tendon. We observed that neurites grew extensively in the direction of the parallel-aligned collagen fibrils in the tendon main axis but were inhibited to grow perpendicularly to this axis. Collectively, these findings support the hypothesis that collagen reorientation may be one of the factors contributing to diminish the neuritogenic capacity of the estrogen-primed myometrial substrate.

  12. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

    SciTech Connect

    Chen, Chih-Hao; Kuo, Shyh Ming; Liu, Guei-Sheung; Chen, Wan-Nan U.; Chuang, Chin-Wen; Liu, Li-Feng

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. Black-Right-Pointing-Pointer Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. Black-Right-Pointing-Pointer 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 {mu}m porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  13. Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions.

    PubMed

    Brooks, Darrell N; Weber, Renata V; Chao, Jerome D; Rinker, Brian D; Zoldos, Jozef; Robichaux, Michael R; Ruggeri, Sebastian B; Anderson, Kurt A; Bonatz, Ekkehard E; Wisotsky, Scott M; Cho, Mickey S; Wilson, Christopher; Cooper, Ellis O; Ingari, John V; Safa, Bauback; Parrett, Brian M; Buncke, Gregory M

    2012-01-01

    As alternatives to autograft become more conventional, clinical outcomes data on their effectiveness in restoring meaningful function is essential. In this study we report on the outcomes from a multicenter study on processed nerve allografts (Avance® Nerve Graft, AxoGen, Inc). Twelve sites with 25 surgeons contributed data from 132 individual nerve injuries. Data was analyzed to determine the safety and efficacy of the nerve allograft. Sufficient data for efficacy analysis were reported in 76 injuries (49 sensory, 18 mixed, and 9 motor nerves). The mean age was 41 ± 17 (18-86) years. The mean graft length was 22 ± 11 (5-50) mm. Subgroup analysis was performed to determine the relationship to factors known to influence outcomes of nerve repair such as nerve type, gap length, patient age, time to repair, age of injury, and mechanism of injury. Meaningful recovery was reported in 87% of the repairs reporting quantitative data. Subgroup analysis demonstrated consistency, showing no significant differences with regard to recovery outcomes between the groups (P > 0.05 Fisher's Exact Test). No graft related adverse experiences were reported and a 5% revision rate was observed. Processed nerve allografts performed well and were found to be safe and effective in sensory, mixed and motor nerve defects between 5 and 50 mm. The outcomes for safety and meaningful recovery observed in this study compare favorably to those reported in the literature for nerve autograft and are higher than those reported for nerve conduits. Copyright © 2011 Wiley-Liss, Inc.

  14. Glomerular Collagen V Codeposition and Hepatic Perisinusoidal Collagen III Accumulation in Canine Collagen Type III Glomerulopathy.

    PubMed

    Rørtveit, R; Reiten, M R; Lingaas, F; Sveri, S B; Brech, A; Espenes, A; Jansen, J H

    2015-11-01

    Collagen type III glomerulopathy, also known as collagenofibrotic glomerulopathy, is a rare renal disease of unknown pathogenesis. The disease occurs in humans and animals and is characterized by massive glomerular accumulations of collagen type III. In the present study, we describe a Drever dog litter affected by an early onset variant of this glomerular disease, where 4 of 9 puppies developed renal failure within 50 days of age. Necropsy specimens of kidney from the 4 affected cases were studied by light microscopy, electron microscopy, and immunohistochemistry, and characteristic lesions compatible with a diagnosis of collagen type III glomerulopathy were found. In addition, 2 cases showed atypical epithelium in the collecting ducts of the medulla, so-called adenomatoid change. Immunohistochemistry of renal specimens from collagen type III glomerulopathy-affected dogs (n = 10) originating from two different dog strains, the Drever dogs and a mixed-breed strain, demonstrated that the deposited glomerular collagen is composed of a mixture of collagen III and collagen V. The distribution of the collagen V corresponded to the localization of collagen III; however, differences in staining intensity showed that collagen type III is the dominating component. Immunohistochemistry for collagen III (n = 9) and a transmission electron microscopic study (n = 1) showed hepatic perisinusoidal collagen type III deposition in affected cases from both dog strains. This is the first report documenting glomerular accumulations of collagen type V and perisinusoidal liver collagen III deposition in canine collagen type III glomerulopathy. © The Author(s) 2014.

  15. Use of electrospinning to construct biomaterials for peripheral nerve regeneration.

    PubMed

    Quan, Qi; Chang, Biao; Meng, Hao Ye; Liu, Ruo Xi; Wang, Yu; Lu, Shi Bi; Peng, Jiang; Zhao, Qing

    2016-10-01

    A number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.

  16. Development of multifunctional collagen scaffolds directed by collagen mimetic peptides

    NASA Astrophysics Data System (ADS)

    Wang, Yi-Lan (Allen)

    Collagen is widely used for soft tissue replacement and tissue engineering scaffold. Functionalized collagen may offer new and improved applications for collagen-based biomaterials. But passively adsorbed molecules readily diffuse out from collagen matrix, and conventional chemical reactions on collagen are difficult to control and may compromise the biochemical feature of natural collagen. Hence, the aim of this dissertation is to develop a new physical collagen modification method through the non-covalent immobilization of collagen mimetic peptides (CMPs) and CMP derivatives on collagen scaffolds, thereby evading the drawbacks of passive and chemical modifications. Most of the research on CMPs over the past three decades has focused on synthesizing CMPs and understanding the effects of amino acid sequence on the peptide structural stability. Although few attempts have been made to develop biomaterials based on pure CMP, CMP has never used in complex with natural collagen. We demonstrate that CMPs with varying chain lengths have strong propensity to associate with natural 2-D and 3-D collagen substrates. We also show that CMPs can recognize and bind to reconstituted type I collagen fibers as well as collagens of ex vivo human liver tissue. The practical use of CMPs conjugated with linear and multi-arm poly(ethylene glycol)s allows to control cell organization in 2-D collagen substrates. Our cell adhesion studies suggest that under certain conditions (e.g. high incubation temperature, small CMP size), the bound CMP derivatives can be released from the collagen matrix, which may provide new opportunities for manipulating cell behavior especially by dynamically controlling the amount of signaling molecules in the collagen matrix. Polyanionic charged CMP was synthesized to modulate tubulogenesis of endothelial cells by attracting VEGF with 3-D collagen gel and a new PEG hydrogel using bifunctional CMP conjugates was synthesized as physico-chemical crosslinkers for

  17. 24. Lake Hodges Flume conduit enlargement. April 1930. Courtesy of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Lake Hodges Flume conduit enlargement. April 1930. Courtesy of the Mandeville Department of Special Collections, Central Library, University of California, San Diego. - Lake Hodges Flume, Along San Dieguito River between Lake Hodges & San Dieguito Reservoir, Rancho Santa Fe, San Diego County, CA

  18. Evaluation of the MODFLOW-2005 Conduit Flow Process.

    PubMed

    Hill, Melissa E; Stewart, Mark T; Martin, Angel

    2010-01-01

    The recent development of the Conduit Flow Process (CFP) by the U.S. Geological Survey (USGS) provides hydrogeologic modelers with a new tool that incorporates the non-Darcian, multiporosity components of flow characteristic of karst aquifers. CFP introduces new parameters extending beyond those of traditional Darcian groundwater flow codes. We characterize a karst aquifer to collect data useful for evaluating this new tool at a test site in west-central Florida, where the spatial distribution and cross-sectional area of the conduit network are available. Specifically, we characterize: (1) the potential for Darcian/non-Darcian flow using estimates of specific discharge vs. observed hydraulic gradients, and (2) the temporal variation for the direction and magnitude of fluid exchange between the matrix and conduit network during extreme hydrologic events. We evaluate the performance of CFP Mode 1 using a site-scale dual-porosity model and compare its performance with a comparable laminar equivalent continuum model (ECM) using MODFLOW-2005. Based on our preliminary analyses, hydraulic conductivity coupled with conduit wall conductance improved the match between observed and simulated discharges by 12% to 40% over turbulent flow alone (less than 1%).

  19. Structure of a bacterial cell surface decaheme electron conduit

    USDA-ARS?s Scientific Manuscript database

    Some bacterial species are able to utilize extracellular mineral forms of iron and manganese as respiratory electron acceptors. In Shewanella oneidensis this involves decaheme cytochromes that are located on the bacterial cell surface at the termini of trans-outer-membrane electron transfer conduits...

  20. Robotic implantation of biodegradable regenerative urinary conduit: experimental study.

    PubMed

    de Castro Abreu, Andre Luis; Azhar, Raed A; Berger, Andre K; Chopra, Sameer; Marien, Arnaud; Santomauro, Michael; Satkunasivam, Raj; Sun, Yi; Aron, Monish; Ukimura, Osamu; Desai, Mihir M; Gill, Inderbir S

    2015-01-01

    To determine the feasibility and develop a robotic technique for intracorporeal implantation of a biodegradable tubular scaffold seeded with adipose-sourced smooth muscle cells (Neo-Urinary-Conduit) that, when implanted as a conduit for urinary diversion, facilitates regeneration of native-like neourinary tissue. Robotic NUC implantation was performed in two fresh male cadavers. The greater omentum was widely detached from the greater curvature of the stomach, in preparation for final wrapping of the conduit. Bilateral ureters were mobilized for implantation. The NUC, with two precreated ureteral openings, was inserted into the abdomen. Bilateral, stented uretero-NUC anastomoses were created. The NUC was circumferentially wrapped with the predissected omentum, exteriorized through the abdominal wall, and maturated. Both procedures were successfully completed intracorporeally. Operative time for NUC implantation was 90 and 100 minutes, respectively. Examination of gross anatomy showed no injury to other organs. There was no omental kinking, rotation, eversion, or stripping from the NUC. Bilateral stents were confirmed to be in situ with the proximal coil in the kidney. Uretero-NUC anastomoses and omentum were tension free. The entire NUC, including its distal edge and posterior aspect, was circumferentially wrapped 360 degrees. We demonstrated the feasibility and developed a robotic technique for intracorporeal implantation of a biodegradable regenerative urinary conduit. This study serves as the foundation for the robotic surgical technique before the clinical application.

  1. 32. ISOMETRIC VIEW OF PIPING PLAN, SHOWING PATH OF CONDUIT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. ISOMETRIC VIEW OF PIPING PLAN, SHOWING PATH OF CONDUIT FROM CONTROL BUNKER TO SHIELDING TANK. F.C. TORKELSON DRAWING NUMBER 842-ARVFS-701-P-1. INEL INDEX CODE NUMBER: 075 0701 60 851 151977. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

  2. Growth of normal zones in cable-in-conduit superconductors

    SciTech Connect

    Dresner, L.

    1983-01-01

    A picture is proposed in which the growth of normal zones in cable-in-conduit superconductors is caused by the expansion of hot helium along the length of the conductor. Quantitative results suitable for experimental testing have been obtained by dimensional and similarity arguments. The results indicate non-uniform propagation at velocities of tens of meters per second.

  3. Intraoperative in situ radial artery conduit flow assessment.

    PubMed

    Canver, Charles C; Yousafzai, Sajjad M

    2008-01-01

    A technique is described for simple flow assessment of the in situ radial artery conduit during coronary bypass via a small incision. This technique allows morphologic and physiologic direct intraoperative assessment of radial artery quality and expands the use of radial artery during coronary artery surgery.

  4. 21. COMPLETION OF INTAKE CONDUITS REVISED, PIPE SECTIONS AND PLANS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. COMPLETION OF INTAKE CONDUITS REVISED, PIPE SECTIONS AND PLANS, SHEET 117 OF 117, 1922. - Sacramento River Water Treatment Plant Intake Pier & Access Bridge, Spanning Sacramento River approximately 175 feet west of eastern levee on river; roughly .5 mile downstream from confluence of Sacramento & American Rivers, Sacramento, Sacramento County, CA

  5. 14. PROJECT PLAN, INTAKE PIER, RAW WATER CONDUITS, PUMPING STATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. PROJECT PLAN, INTAKE PIER, RAW WATER CONDUITS, PUMPING STATION FORCE MAINS, TREATED WATER PIPELINES, AND FILTRATION PLANT, SHEET 1 OF 117, 1920. - Sacramento River Water Treatment Plant Intake Pier & Access Bridge, Spanning Sacramento River approximately 175 feet west of eastern levee on river; roughly .5 mile downstream from confluence of Sacramento & American Rivers, Sacramento, Sacramento County, CA

  6. In vivo study of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration

    NASA Astrophysics Data System (ADS)

    Koh, H. S.; Yong, T.; Teo, W. E.; Chan, C. K.; Puhaindran, M. E.; Tan, T. C.; Lim, A.; Lim, B. H.; Ramakrishna, S.

    2010-08-01

    A novel nanofibrous construct for promoting peripheral nerve repair was fabricated and tested in a rat sciatic nerve defect model. The conduit is made out of bilayered nanofibrous membranes with the nanofibers longitudinally aligned in the lumen and randomly oriented on the outer surface. The intra-luminal guidance channel is made out of aligned nanofibrous yarns. In addition, biomolecules such as laminin and nerve growth factor were incorporated in the nanofibrous nerve construct to determine their efficacy in in vivo nerve regeneration. Muscle reinnervation, withdrawal reflex latency, histological, axon density and electrophysiology tests were carried out to compare the efficacy of nanofibrous constructs with an autograft. Our study showed mixed results when comparing the artificial constructs with an autograft. In some cases, the nanofibrous conduit with aligned nanofibrous yarn as an intra-luminal guidance channel performs better than the autograft in muscle reinnervation and withdrawal reflex latency tests. However, the axon density count is highest in the autograft at mid-graft. Functional recovery was improved with the use of the nerve construct which suggested that this nerve implant has the potential for clinical usage in reconstructing peripheral nerve defects.

  7. Design and fabrication of a nanofibrous polycaprolactone tubular nerve guide for peripheral nerve tissue engineering using a two-pole electrospinning system.

    PubMed

    Panahi-Joo, Y; Karkhaneh, A; Nourinia, A; Abd-Emami, B; Negahdari, B; Renaud, P; Bonakdar, S

    2016-04-12

    Nerve guidance conduits are considered to be the new generation of scaffolds designed for nerve disorders. A tubular construct with a highly aligned fibrous structure, mimicking the endoneurium layer surrounding inner axons of a nerve fascicle, is a suitable candidate for a nerve guide. In this paper a new approach for the fabrication of 3D tubular nerve guides is introduced using simulation of a two-pole electrospinning system and describing its mechanism. The structure of this scaffold is then optimized using the Taguchi statistical method and after morphological studies by scanning electron microscopy, the crystallinity, tensile strength and protein adsorption of these highly aligned fibres are investigated, comparing them with semi-aligned and random fibres produced via conventional mandrel electrospinning. Cell attachment, proliferation and migration of PC12 neuronal like cells are studied on highly aligned, semi aligned and random structures, and morphological change and elongation are observed in PC12 cells. The results of these studies suggest that conduits fabricated using two-pole electrospinning are a suitable and promising scaffold for peripheral and even spinal nerve regeneration. This nerve guide has a great potential for further advanced modifications and regeneration in higher levels.

  8. Collagen fibrils: nanoscale ropes.

    PubMed

    Bozec, Laurent; van der Heijden, Gert; Horton, Michael

    2007-01-01

    The formation of collagen fibrils from staggered repeats of individual molecules has become "accepted" wisdom. However, for over thirty years now, such a model has failed to resolve several structural and functional questions. In a novel approach, it was found, using atomic force microscopy, that tendon collagen fibrils are composed of subcomponents in a spiral disposition-that is, their structure is similar to that of macroscale ropes. Consequently, this arrangement was modeled and confirmed using elastic rod theory. This work provides new insight into collagen fibril structure and will have wide application-from the design of scaffolds for tissue engineering and a better understanding of pathogenesis of diseases of bone and tendon, to the conservation of irreplaceable parchment-based museum exhibits.

  9. Fabrication and Evaluation of PLLA Multichannel Conduits with Nanofibrous Microstructure for the Differentiation of NSCs In Vitro

    PubMed Central

    Zeng, Chen-guang; Xiong, Yi; Xie, Gaoyi; Dong, Peng

    2014-01-01

    Nerve conduits (NCs) with multiple longitudinally aligned channels, being mimicking the natural nerves anatomical structure, have been attracted more and more attentions. However, some specific structural parameters of a conduit that would be beneficial for further improvement of neural tissue regeneration were not comprehensively considered. Using a systematized device and combining low-pressure injection molding and thermal-induced phase separation, we fabricated 33-channel NCs (outer diameter 3.5 mm, channel diameter 200 μm) with different well-defined microscopic features, including NCs with a nano-fibrous microstructure (NNC), NCs with microspherical pores and nano-fibrous pore walls (MNC), and NCs with a ladder-like microstructure (LNC). The porosities of these NCs were ∼90% and were independent of the fine microstructures, whereas the pore size distributions were clearly distinct. The adsorption of bovine serum albumin for the NNC was a result of having the highest specific surface area, which was 3.5 times that of the LNC. But the mechanical strength of NNC was lower than that of two groups because of a relative high crystallinity and brittle characteristics. In vitro nerve stem cells (NSCs) incubation revealed that 14 days after seeding the NSCs, 31.32% cells were Map2 positive in the NNC group, as opposed to 15.76% in the LNC group and 23.29% in the MNC group. Addition of NGF into the culture medium, being distinctive specific surface area and a high adsorption of proteon for NNC, 81.11% of neurons derived from the differentiation of the seeded NSCs was obtained. As a result of imitating the physical structure of the basement membrane of the neural matrix, the nanofibrous structure of the NCs has facilitated the differentiation of NSCs into neurons. PMID:24138342

  10. Draining mafic magma from conduits during Strombolian eruption

    NASA Astrophysics Data System (ADS)

    Wadsworth, F. B.; Kennedy, B.; Branney, M. J.; Vasseur, J.; von Aulock, F. W.; Lavallée, Y.; Kueppers, U.

    2014-12-01

    During and following eruption, mafic magmas can readily drain downward in conduits, dykes and lakes producing complex and coincident up-flow and down-flow textures. This process can occur at the top of the plumbing system if the magma outgases as slugs or through porous foam, causing the uppermost magma surface to descend and the magma to densify. In this scenario the draining volume is limited by the gas volume outgassed. Additionally, magma can undergo wholesale backflow when the pressure at the base of the conduit or feeder dyke exceeds the driving pressure in the chamber beneath. This second scenario will continue until pressure equilibrium is established. These two scenarios may occur coincidently as local draining of uppermost conduit magma by outgassing can lead to wholesale backflow because the densification of magma is an effective way to modify the vertical pressure profile in a conduit. In the rare case where conduits are preserved in cross section, the textural record of draining is often complex and great care should be taken in interpreting bimodal kinematic trends in detail. Lateral cooling into country rock leads to lateral profiles of physical and flow properties and, ultimately, outgassing potential, and exploration of such profiles elucidates the complexity involved. We present evidence from Red Crater volcano, New Zealand, and La Palma, Canary Islands, where we show that at least one draining phase followed initial ascent and eruption. We provide a rheological model approach to understand gravitational draining velocities and therefore, the timescales of up- and down-flow cycles predicted. These timescales can be compared with observed geophysical signals at monitored mafic volcanoes worldwide. Finally, we discuss the implications of shallow magma draining for edifice stability, eruption longevity and magma-groundwater interaction.

  11. Sleep and quality of life in people with ileal conduit.

    PubMed

    Cavdar, Ikbal; Temiz, Zeynep; Ozbas, Ayfer; Can, Gulbeyaz; Tarhan, Fatih; Findik, Ummu Yildiz; Kutlu, Fatma Yasemin; Akyuz, Nuray

    2016-12-01

    The aim of this study was to determine the sleep quality and the association between sleep quality and quality of life in people with ileal conduit. A descriptive and cross-sectional design was adopted. The study sample comprised 111 people with ileal conduit operated on in urology clinics in a state hospital between January 2011 and May 2014. Six months after the operation, they were called by telephone to participate in the study. Data for the study were collected using a questionnaire form, the Pittsburgh Sleep Quality Index (PSQI) and the Stoma Quality of Life Scale (SQLS). The mean ± SD total PSQI score of the people with ileal conduit was 10.20 ± 2.95, mean total score of SQLS was 43.63 ± 7.21, mean Work/Social Function domain score was 37.27 ± 5.80 and mean Stoma Function domain score was 50.0 ± 12.56. The total sleep quality had a low degree of negative correlation with total SQLS score, a medium degree of negative correlation with Work/Social Function (r = -0.327, p < .001) and no correlation with Stoma Function (r = -0.096, p > .001). People using a night drainage system had higher sleep quality. This study determined that quality of life and sleep deteriorate in people with ileal conduit. The quality of life decreases when the sleep quality is poor, and decreased quality of life affects quality of sleep in people with ileal conduit.

  12. Spectral Analysis of Surface Waves to Detect Buried Concrete Conduits

    NASA Astrophysics Data System (ADS)

    Hajiani, P.; Anderson, N.; Rogers, J. D.; Elkrry, A.

    2016-12-01

    The detection of underground cavities is of significant concern to geotechnical engineers working in karst terrain. In spite of the marked progress in nondestructive geophysical methods for detecting shallow underground voids, no unique methodology has emerged that can be applied globally. Various studies have been performed on the use of Rayleigh waves to detect shallow tunnels. In this study, we examined the potential of both Rayleigh and Love waves for detecting subsurface voids. Vertical geophones with Eigen-frequencies of 4.5 Hz, 14 Hz, and 100 Hz were utilized to evaluate Rayleigh waves to resolve near-surface tunnels. Seismic surveys were carried out using horizontal 14 Hz geophones to verify the feasibility of using Love waves to detect shallow tunnels. Two buried conduits of known size and embedment were chosen for the study. One conduit serves as a spillway outfall for an embankment dam, and the other as a low flow outlet for aa flood retention basin. Attenuation analyses of surface waves were performed on all of the data sets to identify locations of the buried concrete conduits. In order to minimize the far-field effects, such as body-wave domination, or low signal-to-noise ratio, it was suggested that we try muting the direct waves, refraction, reflection, air wave, and ambient noise. An amplification of energy on, or in front of the near boundary of the conduits was thereby observed. The muting process greatly reduced the number of false positives. The results of this study not only confirmed previous work, but also displayed the ability of Love waves in detecting the shallow subsurface tunnels or conduits.

  13. Combined physical and chemical nonequilibrium transport model for solution conduits.

    PubMed

    Field, Malcolm S; Leij, Feike J

    2014-02-01

    Solute transport in karst aquifers is primarily constrained to relatively complex and inaccessible solution conduits where transport is often rapid, turbulent, and at times constrictive. Breakthrough curves generated from tracer tests in solution conduits are typically positively-skewed with long tails evident. Physical nonequilibrium models to fit breakthrough curves for tracer tests in solution conduits are now routinely employed. Chemical nonequilibrium processes are likely important interactions, however. In addition to partitioning between different flow domains, there may also be equilibrium and nonequilibrium partitioning between the aqueous and solid phases. A combined physical and chemical nonequilibrium (PCNE) model was developed for an instantaneous release similar to that developed by Leij and Bradford (2009) for a pulse release. The PCNE model allows for partitioning open space in solution conduits into mobile and immobile flow regions with first-order mass transfer between the two regions to represent physical nonequilibrium in the conduit. Partitioning between the aqueous and solid phases proceeds either as an equilibrium process or as a first-order process and represents chemical nonequilibrium for both the mobile and immobile regions. Application of the model to three example breakthrough curves demonstrates the applicability of the combined physical and chemical nonequilibrium model to tracer tests conducted in karst aquifers, with exceptionally good model fits to the data. The three models, each from a different state in the United States, exhibit very different velocities, dispersions, and other transport properties with most of the transport occurring via the fraction of mobile water. Fitting the model suggests the potentially important interaction of physical and chemical nonequilibrium processes.

  14. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia.

    PubMed

    Li, Qinwen; Chen, Jianghai; Chen, Yanhua; Cong, Xiaobin; Chen, Zhenbing

    2016-03-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription‑quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post‑compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR‑labeled DRG neurons were significantly higher, relative to the sham‑operated group, however, the numbers of FG‑labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor‑β1 (TGF‑β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)‑extracellular signal‑regulated kinase 1/2, and significantly lower levels of p‑c‑Jun N‑terminal kinase and p‑p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF‑β1, CTGF and collagen type I, with involvement of the mitogen‑activated protein kinase signaling pathway.

  15. Custom prefabrication of silicone tubes from urinary catheters for experimental peripheral nerve surgery

    PubMed Central

    Saray, Aydin

    2004-01-01

    The entubulation principle represents a neurobiological approach to nerve surgery in which the role of the surgeon is limited and intrinsic healing capabilities of the nerve play the primary role. Herein, a technique for fabricating custom-made silicone tubes from a silicone urinary catheter is described. Silicone tubes with varying size and dimensions can be tailored depending on the diameter of the silicone urinary catheter (14 F to 18 F). Tubes crafted from silicone urinary catheters were used either as a nerve conduit to facilitate regeneration or as compressive nerve banding to simulate compressive neuropathy in the rat sciatic nerve. Custom-made silicone tubes have similar pros and cons to the commercially available silicone tubes regarding the capsule and foreign body reaction. It can be concluded that these cost effective tubes can be easily cut and used in experimental peripheral nerve surgery in developing countries where the cost of such materials becomes an important issue for the researchers. PMID:24115867

  16. Collagen in organ development

    NASA Technical Reports Server (NTRS)

    Hardman, P.; Spooner, B. S.

    1992-01-01

    It is important to know whether microgravity will adversely affect developmental processes. Collagens are macromolecular structural components of the extracellular matrix (ECM) which may be altered by perturbations in gravity. Interstitial collagens have been shown to be necessary for normal growth and morphogenesis in some embryonic organs, and in the mouse salivary gland, the biosynthetic pattern of these molecules changes during development. Determination of the effects of microgravity on epithelial organ development must be preceded by crucial ground-based studies. These will define control of normal synthesis, secretion, and deposition of ECM macromolecules and the relationship of these processes to morphogenesis.

  17. Collagen in organ development

    NASA Technical Reports Server (NTRS)

    Hardman, P.; Spooner, B. S.

    1992-01-01

    It is important to know whether microgravity will adversely affect developmental processes. Collagens are macromolecular structural components of the extracellular matrix (ECM) which may be altered by perturbations in gravity. Interstitial collagens have been shown to be necessary for normal growth and morphogenesis in some embryonic organs, and in the mouse salivary gland, the biosynthetic pattern of these molecules changes during development. Determination of the effects of microgravity on epithelial organ development must be preceded by crucial ground-based studies. These will define control of normal synthesis, secretion, and deposition of ECM macromolecules and the relationship of these processes to morphogenesis.

  18. Hemiresective reconstruction of a redundant ileal conduit with severe bilateral ileal conduit-ureteral re fl ux.

    PubMed

    Fujimura, Tetsuya; Minowada, Shigeru; Kishi, Hiroichi; Hamasaki, Kimihisa; Saito, Kiyoshi; Kitamura, Tadaichi

    2005-10-01

    A 58-year-old man was referred to our hospital with high fever and anuria. Since undergoing a total pelvic exenteration due to bladder-invasive sigmoid colon cancer, urinary tract infections had frequently occurred. We treated with the construction of a bilateral percutaneous nephrostomy (PCN), and chemotherapy. Although we replaced the PCN with a single J ureteral catheter after an improvement of infection, urinary infection recurred because of an obstruction of the catheter. Urological examinations showed that an ileal conduit-ureteral reflux caused by kinking of the ileal loop was the reason why frequent pyelonephritis occurred. We decided to resect the proximal segment to improve conduit-ureteral reflux for the resistant pyelonephritis. After the surgery, the excretory urogram showed improvement and the urinary retention at the ileal conduit disappeared. Three years after the operation, renal function has been stable without episodes of pyelonephritis. Here we report a case of open repair surgery of an ileal conduit in a patient with severe urinary infection.

  19. Results and analysis of the hot-spot temperature experiment for a cable-in-conduit conductor with thick conduit

    NASA Astrophysics Data System (ADS)

    Sedlak, Kamil; Bruzzone, Pierluigi

    2015-12-01

    In the design of future DEMO fusion reactor a long time constant (∼23 s) is required for an emergency current dump in the toroidal field (TF) coils, e.g. in case of a quench detection. This requirement is driven mainly by imposing a limit on forces on mechanical structures, namely on the vacuum vessel. As a consequence, the superconducting cable-in-conduit conductors (CICC) of the TF coil have to withstand heat dissipation lasting tens of seconds at the section where the quench started. During that time, the heat will be partially absorbed by the (massive) steel conduit and electrical insulation, thus reducing the hot-spot temperature estimated strictly from the enthalpy of the strand bundle. A dedicated experiment has been set up at CRPP to investigate the radial heat propagation and the hot-spot temperature in a CICC with a 10 mm thick steel conduit and a 2 mm thick glass epoxy outer electrical insulation. The medium size, ∅ = 18 mm, NbTi CICC was powered by the operating current of up to 10 kA. The temperature profile was monitored by 10 temperature sensors. The current dump conditions, namely the decay time constant and the quench detection delay, were varied. The experimental results show that the thick conduit significantly contributes to the overall enthalpy balance, and consequently reduces the amount of copper required for the quench protection in superconducting cables for fusion reactors.

  20. The effect of arterial wall shear stress on the incremental elasticity of a conduit artery.

    PubMed

    Kelly, R F; Snow, H M

    2011-05-01

    The purpose of this investigation was to determine the effects of flow mediated dilatation on arterial incremental elasticity (E(inc) ).   In four female anaesthetized pigs, the iliac artery and vein were connected by a shunt with a variable resistance which allowed blood flow and therefore shear stress to be regulated. E(inc) was calculated from simultaneous records of diameter and pressure throughout a minimum of four cardiac cycles. Passive increases in diameter (∼1-2%) throughout a cardiac cycle, brought about by pressure, resulted in a two- to threefold increase in E(inc) . In contrast, increases in shear stress caused active smooth muscle relaxation and a significant increase in diameter from 3.663 ± 0.215 mm to 4.488 ± 0.163 mm (mean ± SEM, P < 0.05) equivalent to a fractional increase in diameter (fD) of 1.5 with no significant change in mean arterial pressure, 108 ± 2 mmHg to 106 ± 1 mmHg (mean ± SEM). The average value of E(inc) per cardiac cycle at baseline was 2.17 ± 0.10 × 10(3) kPa and remained relatively constant until fD exceeded 1.3 thereafter increasing to a maximum of 9.23 ± 1.0 × 10(3) kPa. These results show that in a conduit artery during the dilatory response to shear stress, the interaction between smooth muscle and collagen operates so as to maintain E(inc) relatively constant over much of the working range of dilatation. This is consistent with a model of the arterial wall in which collagen is recruited both by passive stretch, in response to an increase in pressure and therefore wall stress, and also by active contraction of smooth muscle. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  1. 30 CFR 75.700 - Grounding metallic sheaths, armors, and conduits enclosing power conductors.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... conduits enclosing power conductors. 75.700 Section 75.700 Mineral Resources MINE SAFETY AND HEALTH... Grounding § 75.700 Grounding metallic sheaths, armors, and conduits enclosing power conductors. All metallic sheaths, armors, and conduits enclosing power conductors shall be electrically continuous throughout...

  2. Nerve conduction velocity

    MedlinePlus

    ... polyneuropathy Tibial nerve dysfunction Ulnar nerve dysfunction Any peripheral neuropathy can cause abnormal results. Damage to the spinal ... Herniated disk Lambert-Eaton syndrome Mononeuropathy Multiple ... azotemia Primary amyloidosis Radial nerve dysfunction Sciatica ...

  3. [The genetics of collagen diseases].

    PubMed

    Kaplan, J; Maroteaux, P; Frezal, J

    1986-01-01

    Heritable disorders of collagen include Ehler-Danlos syndromes (11 types are actually known), Larsen syndrome and osteogenesis imperfecta. Their clinical, genetic and biochemical features are reviewed. Marfan syndrome is closely related to heritable disorders of collagen.

  4. Bubble Rise and Break-Up in Volcanic Conduits

    NASA Astrophysics Data System (ADS)

    Soldati, A.; Cashman, K. V.; Rust, A.; Rosi, M.

    2013-12-01

    The continual passive degassing occurring at open-vent mafic volcanoes is often punctuated by bursts of active degassing. The latter are generally thought to be the result of slug flow: large, conduit-filling bubbles periodically rising up the feeder conduit and bursting at the magma-air interface. Existing models of volcanic degassing systems make the simplifying assumption that the conduit is cylindrical; however, while this may be true at shallow levels, a flaring probably connects it to a dyke-like geometry at depth. The overall goal of this research is to assess the influence of conduit geometry on the speed and stability of bubbles rising in open-vent systems, and ultimately to devise a model to infer conduit shape from emerging bubbles size. In order to do that an analogue experimental approach was used. All of the experiments were two-phase (melt+volatiles); the analogue materials of choice were golden syrup-water mixtures ranging in viscosity from 10-1 to 104 Pa*s and air. Two experimental apparatuses were used: a bi-dimensional and a tri-dimensional one. The bi-dimensional set-up is a cell made of two flat transparent PVC plates (44x23cm) 10mm or 5mm apart (the front one having a hole at the bottom permitting bubble injection) containing a variety of parallelepipeds apt to outline different plumbing system geometries. The tri-dimensional one consists of a cylindrical tube (r=1,5cm; l=7cm) allowing bubble injection through the bottom rubber tap and terminating into a square tank (l=22cm). Results indicate that conduit geometry directly controls the slug rise velocity and the surrounding liquid descending speed, which in turn control the slug stability. Small enough bubbles simply deform as they go through the flaring, while bigger ones split into two daughter bubbles. A regime diagram has been constructed, illustrating the bubble break-up threshold dependence on the flare geometry and initial slug size, the two main controlling factors. The phenomenon of

  5. Engineered neural tissue for peripheral nerve repair.

    PubMed

    Georgiou, Melanie; Bunting, Stephen C J; Davies, Heather A; Loughlin, Alison J; Golding, Jonathan P; Phillips, James B

    2013-10-01

    A new combination of tissue engineering techniques provides a simple and effective method for building aligned cellular biomaterials. Self-alignment of Schwann cells within a tethered type-1 collagen matrix, followed by removal of interstitial fluid produces a stable tissue-like biomaterial that recreates the aligned cellular and extracellular matrix architecture associated with nerve grafts. Sheets of this engineered neural tissue supported and directed neuronal growth in a co-culture model, and initial in vivo tests showed that a device containing rods of rolled-up sheets could support neuronal growth during rat sciatic nerve repair (5 mm gap). Further testing of this device for repair of a critical-sized 15 mm gap showed that, at 8 weeks, engineered neural tissue had supported robust neuronal regeneration across the gap. This is, therefore, a useful new approach for generating anisotropic engineered tissues, and it can be used with Schwann cells to fabricate artificial neural tissue for peripheral nerve repair.

  6. Extracellular matrix components in peripheral nerve regeneration.

    PubMed

    Gonzalez-Perez, Francisco; Udina, Esther; Navarro, Xavier

    2013-01-01

    Injured axons of the peripheral nerve are able to regenerate and, eventually, reinnervate target organs. However, functional recovery is usually poor after severe nerve injuries. The switch of Schwann cells to a proliferative state, secretion of trophic factors, and the presence of extracellular matrix (ECM) molecules (such as collagen, laminin, or fibronectin) in the distal stump are key elements to create a permissive environment for axons to grow. In this review, we focus attention on the ECM components and their tropic role in axonal regeneration. These components can also be used as molecular cues to guide the axons through artificial nerve guides in attempts to better mimic the natural environment found in a degenerating nerve. Most used scaffolds tested are based on natural molecules that form the ECM, but use of synthetic polymers and functionalization of hydrogels are bringing new options. Progress in tissue engineering will eventually lead to the design of composite artificial nerve grafts that may replace the use of autologous nerve grafts to sustain regeneration over long gaps.

  7. Nerve Impulses in Plants

    ERIC Educational Resources Information Center

    Blatt, F. J.

    1974-01-01

    Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

  8. Nerve Impulses in Plants

    ERIC Educational Resources Information Center

    Blatt, F. J.

    1974-01-01

    Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

  9. Extraforaminal ligament attachments of the thoracic spinal nerves in humans.

    PubMed

    Kraan, G A; Hoogland, P V J M; Wuisman, P I J M

    2009-04-01

    An anatomical study of the extraforaminal attachments of the thoracic spinal nerves was performed using human spinal columns. The objectives of the study are to identify and describe the existence of ligamentous structures at each thoracic level that attach spinal nerves to structures at the extraforaminal region. During the last 120 years, several mechanisms have been described to protect the spinal nerve against traction. All the described structures were located inside the spinal canal proximal to the intervertebral foramen. Ligaments with a comparable function just outside the intervertebral foramen are mentioned ephemerally. No studies are available about ligamentous attachments of thoracic spinal nerves to the spine. Five embalmed human thoracic spines (Th2-Th11) were dissected. Bilaterally, the extraforaminal region was dissected to describe and measure anatomical structures and their relationships with the thoracic spinal nerves. Histology was done at the sites of attachment of the ligaments to the nerves and along the ligaments. The thoracic spinal nerves are attached to the transverse process of the vertebrae cranial and caudal to the intervertebral foramen. The ligaments consist mainly of collagenous fibers. In conclusion, at the thoracic level, direct ligamentous connections exist between extraforaminal thoracic spinal nerves and nearby structures. They may serve as a protective mechanism against traction and compression of the nerves by positioning the nerve in the intervertebral foramen.

  10. Cryovolcanic Conduit Evolution and Eruption on Icy Satellites

    NASA Astrophysics Data System (ADS)

    Mitchell, K. L.

    2014-12-01

    In silicate volcanism, such as on Earth or Io, eruptions typically result from fracture formation caused by interaction of tectonic stresses with inflating, pressurized magma sources, leading to transport of melt through an evolving conduit. On icy satellites the paradigm may be similar, resulting from some combination of tidal stresses and expansion of freezing water within, or near the base of, an ice shell. Such a fracture will result in eruption if mass continuity can be established, with buoyancy aided by exsolution and expansion of dissolved volatiles. After onset, conduit shape evolves due to: (1) shear-stresses or frictional erosional; (2) wallrock "bursting" due to massive wall stresses; (3) wall melting or condensation of particles due to heat transfer; or (4) changes in applied stresses. Preliminary thermodynamic and fluid mechanical analysis suggests some initial cooling during ascent resulting from exsolution and expansion of volatiles, thermally buffered by freezing, Conduit contraction may occur, and so evolution towards a deep, gas-filled plume chamber is difficult to accommodate without evoking a co-incidental process. Conduit flaring occurs near the surface where velocities are greatest, enhancing erosion. Here, viscous dissipative heating exceeds adiabatic cooling, and so some boiling (a few wt%) may occur. In contrast with silicate volcanism, decompression to below the triple point will occur within conduit, vent or jet, resulting in rapid freezing and boiling of the remaining water at a 6.8:1 ratio. Subsequent isentropic or adiabatic expansion within erupting jets may result in a few percent net of condensation or sublimation. These effects combined lead to ~4:1-7:1 solid:vapor ratios in the jet for most eruption conditions. These figures are consistent with the ~6:1 inferred in Enceladus' jets, supporting the hypothesis that the Enceladus plume draws from a subsurface body of liquids through a conduit. Similar results are anticipated if

  11. Collagen hydrolysate based collagen/hydroxyapatite composite materials

    NASA Astrophysics Data System (ADS)

    Ficai, Anton; Albu, Madalina Georgiana; Birsan, Mihaela; Sonmez, Maria; Ficai, Denisa; Trandafir, Viorica; Andronescu, Ecaterina

    2013-04-01

    The aim of this study was to study the influence of collagen hydrolysate (HAS) on the formation of ternary collagen-hydrolysate/hydroxyapatite composite materials (COLL-HAS/HA). During the precipitation process of HA, a large amount of brushite is resulted at pH = 7 but, practically pure HA is obtained at pH ⩾ 8. The FTIR data reveal the duplication of the most important collagen absorption bands due to the presence of the collagen hydrolysate. The presence of collagen hydrolysate is beneficial for the management of bone and joint disorders such as osteoarthritis and osteoporosis.