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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. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. [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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

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

    DTIC Science & Technology

    2015-10-01

    conduit. The shortcomings of current devices in terms of burst effect , non-uniform dosage, and uneven drug delivery, necessitates a new approach to...To evaluate the effectiveness of the conduit- drug delivery device at releasing bioactive concentrations of NGF and GDNF sufficient to enhance axon...evaluate the effectiveness of the conduit- drug delivery device to enhance nerve regeneration across a nerve gap in a mouse sciatic nerve model. 1. IACUC

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. Fibronectin provides a conduit for fibroblast transmigration from collagenous stroma into fibrin clot provisional matrix.

    PubMed

    Greiling, D; Clark, R A

    1997-04-01

    After injury, the wound space is filled with a fibrin/fibronectin clot containing growth factors released by platelets and monocytes. In response to these factors, fibroblasts migrate into the fibrin clot and contribute to the formation of granulation tissue. The functional mechanisms allowing fibroblasts to leave the collagenous matrix of normal connective tissue and invade the provisional matrix of the fibrin clot have not been fully defined. To investigate these mechanisms we established a new in vitro model which simulates specific aspects of early wound healing, that is, the migration of fibroblasts from a three-dimensional collagen matrix into a fibrin clot. This transmigration could be induced by physiological concentrations of platelet releasate or platelet-derived growth factor BB (PDGF-BB) in a concentration-dependent manner. At 24 hours irradiated fibroblasts invaded the fibrin gel almost as well as non-irradiated cells, indicating that transmigration was independent of proliferation. Plasminogen and its activators appear to be necessary for invasion of the fibrin clot since protease inhibitors decreased the amount of migration. These serine proteases, however, were not necessary for exit from the collagen gel as fibroblasts migrated out of the collagen gel onto a surface coated with fibrin fibrils even in the presence of inhibitors. Removal of fibronectin (FN) from either the collagen gel or the fibrin gel markedly decreased the number of migrating cells, suggesting that FN provides a conduit for transmigration. Cell movement in the in vitro model was inhibited by RGD peptide, and by monoclonal antibodies against the subunits of the alpha5 beta1 and alpha v beta3 integrin receptor. Thus, the functional requirements for fibroblast transmigration from collagen-rich to fibrin-rich matrices, such as occurs in early wound healing, have been partially defined using an in vitro paradigm of this important biologic process.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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).

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  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. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  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. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Drug Delivery for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2015-11-01

    hydrogels. The shortcomings of current devices in terms of burst effect , nonuniform dosage, and uneven drug delivery, necessitates a new approach to...Specific Aim 2 -- To evaluate the effectiveness of the conduit- drug delivery device to enhance nerve regeneration across a 15mm nerve gap in a rat sciatic...main tasks of Aim 1. Specific Aim 2 -- To evaluate the effectiveness of the conduit- drug delivery device to enhance nerve regeneration across a

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

    SciTech Connect

    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.

  3. 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.

  4. 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.

  5. Tissue-Engineered Nanofibrous Nerve Grafts for Enhancing the Rate of Nerve Regeneration

    DTIC Science & Technology

    2014-10-01

    bioactivity, transport features and mechanics ideal for enhancing the rate of nerve regeneration and healing critical sized nerve defects. We further...scaffolds in bioreactors prior to implantation in rat critical sized nerve defect model. 2. KEYWORDS: nerve regeneration, nerve guidance conduit...for an optimal nerve graft (Figure 1; Figure 2). Different wall thickness was achieved by using 6 different salt sizes . The 0.1mm wall thickness

  6. 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

  7. 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.

  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. 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

  11. 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.

  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. 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.

  14. 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

  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.; McIntire, L. V. (Principal Investigator)

    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. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.).

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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

  3. [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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2014-10-01

    AD_________________ Award Number: W81XWH-10-1-0894 TITLE: Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration...DATES COVERED 15 Sep 2013 - 14 Sep 2014 4. TITLE AND SUBTITLE Multicenter Clinical Trial of Keratin Biomaterial for 5a. CONTRACT NUMBER Peripheral...has developed a keratin biomaterial hydrogel that can be used as luminal filler in nerve guidance conduits to facilitate nerve regeneration

  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. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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....

  19. 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.

  20. 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...

  1. 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...

  2. Nerve biopsy

    MedlinePlus

    ... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Review Date 6/1/2015 ...

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Common peroneal nerve dysfunction

    MedlinePlus

    Neuropathy - common peroneal nerve; Peroneal nerve injury; Peroneal nerve palsy ... type of peripheral neuropathy (damage to nerves outside the brain ... nerve injuries. Damage to the nerve disrupts the myelin sheath ...

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. [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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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...

  8. 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

  9. 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.

  10. 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 ...

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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 ...

  16. 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 ...

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  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. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Temperature limited heater with a conduit substantially electrically isolated from the formation

    DOEpatents

    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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Carbon-nanotube-interfaced glass fiber scaffold for regeneration of transected sciatic nerve.

    PubMed

    Ahn, Hong-Sun; Hwang, Ji-Young; Kim, Min Soo; Lee, Ja-Yeon; Kim, Jong-Wan; Kim, Hyun-Soo; Shin, Ueon Sang; Knowles, Jonathan C; Kim, Hae-Won; Hyun, Jung Keun

    2015-02-01

    Carbon nanotubes (CNTs), with their unique and unprecedented properties, have become very popular for the repair of tissues, particularly for those requiring electrical stimuli. Whilst most reports have demonstrated in vitro neural cell responses of the CNTs, few studies have been performed on the in vivo efficacy of CNT-interfaced biomaterials in the repair and regeneration of neural tissues. Thus, we report here for the first time the in vivo functions of CNT-interfaced nerve conduits in the regeneration of transected rat sciatic nerve. Aminated CNTs were chemically tethered onto the surface of aligned phosphate glass microfibers (PGFs) and CNT-interfaced PGFs (CNT-PGFs) were successfully placed into three-dimensional poly(L/D-lactic acid) (PLDLA) tubes. An in vitro study confirmed that neurites of dorsal root ganglion outgrew actively along the aligned CNT-PGFs and that the CNT interfacing significantly increased the maximal neurite length. Sixteen weeks after implantation of a CNT-PGF nerve conduit into the 10 mm gap of a transected rat sciatic nerve, the number of regenerating axons crossing the scaffold, the cross-sectional area of the re-innervated muscles and the electrophysiological findings were all significantly improved by the interfacing with CNTs. This first in vivo effect of using a CNT-interfaced scaffold in the regeneration process of a transected rat sciatic nerve strongly supports the potential use of CNT-interfaced PGFs at the interface between the nerve conduit and peripheral neural tissues.

  2. 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

  3. Collagen vascular disease

    MedlinePlus

    ... developed these disorders were previously said to have "connective tissue" or "collagen vascular" disease. We now have names ... be used. These include as undifferentiated systemic rheumatic (connective tissue) diseases or overlap syndromes. Images Dermatomyositis, heliotrope eyelids ...

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  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. 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 ...

  12. 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.

  13. 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

  14. 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.

  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. 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.

  17. 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)

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Structure of a bacterial cell surface decaheme electron conduit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. 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...

  4. 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...

  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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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

  13. 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%).

  14. 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

  15. 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

  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. Laminin targeting of a peripheral nerve-highlighting peptide enables degenerated nerve visualization

    PubMed Central

    Glasgow, Heather L.; Whitney, Michael A.; Gross, Larry A.; Friedman, Beth; Adams, Stephen R.; Crisp, Jessica L.; Hussain, Timon; Frei, Andreas P.; Novy, Karel; Wollscheid, Bernd; Nguyen, Quyen T.; Tsien, Roger Y.

    2016-01-01

    Target-blind activity-based screening of molecular libraries is often used to develop first-generation compounds, but subsequent target identification is rate-limiting to developing improved agents with higher specific affinity and lower off-target binding. A fluorescently labeled nerve-binding peptide, NP41, selected by phage display, highlights peripheral nerves in vivo. Nerve highlighting has the potential to improve surgical outcomes by facilitating intraoperative nerve identification, reducing accidental nerve transection, and facilitating repair of damaged nerves. To enable screening of molecular target-specific molecules for higher nerve contrast and to identify potential toxicities, NP41’s binding target was sought. Laminin-421 and -211 were identified by proximity-based labeling using singlet oxygen and by an adapted version of TRICEPS-based ligand-receptor capture to identify glycoprotein receptors via ligand cross-linking. In proximity labeling, photooxidation of a ligand-conjugated singlet oxygen generator is coupled to chemical labeling of locally oxidized residues. Photooxidation of methylene blue–NP41-bound nerves, followed by biotin hydrazide labeling and purification, resulted in light-induced enrichment of laminin subunits α4 and α2, nidogen 1, and decorin (FDR-adjusted P value < 10−7) and minor enrichment of laminin-γ1 and collagens I and VI. Glycoprotein receptor capture also identified laminin-α4 and -γ1. Laminins colocalized with NP41 within nerve sheath, particularly perineurium, where laminin-421 is predominant. Binding assays with phage expressing NP41 confirmed binding to purified laminin-421, laminin-211, and laminin-α4. Affinity for these extracellular matrix proteins explains the striking ability of NP41 to highlight degenerated nerve “ghosts” months posttransection that are invisible to the unaided eye but retain hollow laminin-rich tubular structures. PMID:27791138

  18. 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.

  19. Structure and function of collagen types

    SciTech Connect

    Mayne, R.; Burgeson, R.E.

    1987-01-01

    This book contains 10 chapters. Some of the chapter titles are: The Classical Collagens: Types I, II, and III; Type IV Collagen; Type IX Collagen; and Analysis of Collagen Structure by Molecular Biology Techniques.

  20. [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.

  1. 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.

  2. 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.

  3. 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...

  4. Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: A sciatic nerve transection model

    PubMed Central

    Golzadeh, Atefeh; Mohammadi, Rahim

    2016-01-01

    Background: Effects of platelet-derived growth factor B (PDGF-B) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Materials and Methods: Forty-five male, white Wistar rats were divided into three experimental groups (n = 15), randomly: Normal control group (NC), silicon group (SIL), and PDGF-B treated group (SIL/PDGF). In NC group, left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the SIL group, the left sciatic nerve was exposed in the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone conduit and filled with 10 μL phosphate buffered solution. In SIL/PDGF group, the silicon conduit was filled with 10 μL PDGF-B (0.5 ng/mL). Each group was subdivided into three subgroups of five and were studied in 4, 8, 12 weeks after surgery. Results: Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass, and histomorphometric studies showed earlier regeneration of axons in SIL/PDGF than in SIL group (P < 0.05). Conclusion: Local administration of PDGF-B combined with silicon grafting could accelerate functional recovery and may have clinical implications for the surgical management of patients after facial nerve transection. PMID:27274342

  5. 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

  6. PERIPHERAL NERVE REGENERATION: CELL THERAPY AND NEUROTROPHIC FACTORS

    PubMed Central

    Sebben, Alessandra Deise; Lichtenfels, Martina; da Silva, Jefferson Luis Braga

    2015-01-01

    Peripheral nerve trauma results in functional loss in the innervated organ, and recovery without surgical intervention is rare. Many surgical techniques can be used for nerve repair. Among these, the tubulization technique can be highlighted: this allows regenerative factors to be introduced into the chamber. Cell therapy and tissue engineering have arisen as an alternative for stimulating and aiding peripheral nerve regeneration. Therefore, the aim of this review was to provide a survey and analysis on the results from experimental and clinical studies that used cell therapy and tissue engineering as tools for optimizing the regeneration process. The articles used came from the LILACS, Medline and SciELO scientific databases. Articles on the use of stem cells, Schwann cells, growth factors, collagen, laminin and platelet-rich plasma for peripheral nerve repair were summarized over the course of the review. Based on these studies, it could be concluded that the use of stem cells derived from different sources presents promising results relating to nerve regeneration, because these cells have a capacity for neuronal differentiation, thus demonstrating effective functional results. The use of tubes containing bioactive elements with controlled release also optimizes the nerve repair, thus promoting greater myelination and axonal growth of peripheral nerves. Another promising treatment is the use of platelet-rich plasma, which not only releases growth factors that are important in nerve repair, but also serves as a carrier for exogenous factors, thereby stimulating the proliferation of specific cells for peripheral nerve repair. PMID:27027067

  7. The connective tissue and glial framework in the optic nerve head of the normal human eye: light and scanning electron microscopic studies.

    PubMed

    Oyama, Tokuhide; Abe, Haruki; Ushiki, Tatsuo

    2006-12-01

    The arrangement of connective tissue components (i.e., collagen, reticular, and elastic fibers) and glial elements in the optic nerve head of the human eye was investigated by the combined use of light microscopy and scanning electron microscopy (SEM). Light-microscopically, the optic nerve head could be subdivided into four parts from the different arrangements of the connective tissue framework: a surface nerve fiber layer, and prelaminar, laminar, and postlaminar regions. The surface nerve fiber layer only possessed connective tissue elements around blood vessels. In the prelaminar region, collagen fibrils, together with delicate elastic fibers, formed thin interrupted sheaths for accommodating small nerve bundles. Immunohistochemistry for the glial fibrillary acidic protein (GFAP) showed that GFAP-positive cells formed columnar structures (i.e., glial columns), with round cell bodies piled up into layers. These glial columns were located in the fibrous sheaths of collagen fibrils and elastic fibers. In the laminar region, collagen fibrils and elastic fibers ran transversely to the optic nerve axis to form a thick membranous layer - the lamina cribrosa - which had numerous round openings for accommodating optic nerve fiber bundles. GFAP-positive cellular processes also ran transversely in association with collagen and elastin components. The postlaminar region had connective tissues which linked the lamina cribrosa with fibrous sheaths for accommodating nerve bundles in the extraocular optic nerve, where GFAP-positive cells acquired characteristics typical of fibrous astrocytes. These findings indicate that collagen fibrils, as a whole, form a continuous network which serves as a skeletal framework of the optic nerve head for protecting optic nerve fibers from mechanical stress as well as for sustaining blood vessels in the optic nerve. The lamina cribrosa containing elastic fibers are considered to be plastic against the mechanical force affected by elevation

  8. Single-friction-surface triboelectric generator with human body conduit

    SciTech Connect

    Meng, Bo; Cheng, Xiaoliang; Zhang, Xiaosheng; Han, Mengdi; Liu, Wen; Zhang, Haixia

    2014-03-10

    We present a transparent single-friction-surface triboelectric generator (STEG) employing human body as the conduit, making the applications of STEG in portable electronics much more practical and leading to a significant output improvement. The STEG with micro-patterned polydimethylsiloxane surface achieved an output voltage of over 200 V with a current density of 4.7 μA/cm{sup 2}. With human body conduit, the output current increased by 39% and the amount of charge that transferred increased by 34% compared to the results with grounded electrode. A larger increment of 210% and 81% was obtained in the case of STEG with a large-size flat polyethylene terephthalate surface.

  9. Biological performance of a novel biodegradable polyamidoamine hydrogel as guide for peripheral nerve regeneration.

    PubMed

    Magnaghi, Valerio; Conte, Vincenzo; Procacci, Patrizia; Pivato, Giorgio; Cortese, Paolo; Cavalli, Erika; Pajardi, Giorgio; Ranucci, Elisabetta; Fenili, Fabio; Manfredi, Amedea; Ferruti, Paolo

    2011-07-01

    Polyamidoamines (PAAs) are a well-known family of synthetic biocompatible and biodegradable polymers, which can be prepared as soft hydrogels characterized by low interfacial tension and tunable elasticity. For the first time we report here on the in vivo performance of a PAA hydrogel implant as scaffold for tissue engineering. In particular, an amphoteric agmatine-deriving PAA hydrogel shaped as small tubing was obtained by radical polymerization of a soluble functional oligomeric precursor and used as conduit for nerve regeneration in a rat sciatic nerve cut model. The animals were analyzed at 30, 90, and 180 days post-surgery. PAA tubing proved to facilitate nerve regeneration. Good surgical outcomes were achieved with no signs of inflammation or neuroma. Moreover, nerve regeneration was morphologically sound and the quality of functional recovery satisfactory. In conclusion, PAA hydrogel scaffolds may represent a novel and promising material for peripheral nerve regeneration.

  10. A new type of Schwann cell graft transplantation to promote optic nerve regeneration in adult rats.

    PubMed

    Fang, Yuan; Mo, Xiaofen; Guo, Wenyi; Zhang, Meng; Zhang, Peihua; Wang, Yan; Rong, Xianfang; Tian, Jie; Sun, Xinghuai

    2010-12-01

    Like other parts of the central nervous system, the adult mammalian optic nerve is difficult to regenerate after injury. Transplantation of the peripheral nerve or a Schwann cell (SC) graft can promote injured axonal regrowth. We tried to develop a new type of tissue-engineered SC graft that consisted of SCs seeded onto a poly(lactic-co-glycolic acid)/chitosan conduit. Meanwhile, SCs were transfected along the ciliary neurotrophic factor (CNTF) gene in vitro by electroporation to increase their neurotrophic effect. Four weeks after transplantation, GAP-43 labelled regenerating axons were found in the SC grafts, and axons in the CNTF-SC graft were longer than those in the SC graft. Tissue-engineered SC grafts can provide a feasible environment for optic nerve regeneration and may become an alternative for bridging damaged nerves and repairing nerve defects in the future.

  11. Tracking dynamics of magma migration in open-conduit systems

    NASA Astrophysics Data System (ADS)

    Valade, Sébastien; Lacanna, Giorgio; Coppola, Diego; Laiolo, Marco; Pistolesi, Marco; Donne, Dario Delle; Genco, Riccardo; Marchetti, Emanuele; Ulivieri, Giacomo; Allocca, Carmine; Cigolini, Corrado; Nishimura, Takeshi; Poggi, Pasquale; Ripepe, Maurizio

    2016-11-01

    Open-conduit volcanic systems are typically characterized by unsealed volcanic conduits feeding permanent or quasi-permanent volcanic activity. This persistent activity limits our ability to read changes in the monitored parameters, making the assessment of possible eruptive crises more difficult. We show how an integrated approach to monitoring can solve this problem, opening a new way to data interpretation. The increasing rate of explosive transients, tremor amplitude, thermal emissions of ejected tephra, and rise of the very-long-period (VLP) seismic source towards the surface are interpreted as indicating an upward migration of the magma column in response to an increased magma input rate. During the 2014 flank eruption of Stromboli, this magma input preceded the effusive eruption by several months. When the new lateral effusive vent opened on the Sciara del Fuoco slope, the effusion was accompanied by a large ground deflation, a deepening of the VLP seismic source, and the cessation of summit explosive activity. Such observations suggest the drainage of a superficial magma reservoir confined between the crater terrace and the effusive vent. We show how this model successfully reproduces the measured rate of effusion, the observed rate of ground deflation, and the deepening of the VLP seismic source. This study also demonstrates the ability of the geophysical network to detect superficial magma recharge within an open-conduit system and to track magma drainage during the effusive crisis, with a great impact on hazard assessment.

  12. Parastomal hernias after radical cystectomy and ileal conduit diversion

    PubMed Central

    Donahue, Timothy F.

    2016-01-01

    Parastomal hernia, defined as an "incisional hernia related to an abdominal wall stoma", is a frequent complication after conduit urinary diversion that can negatively impact quality of life and present a clinically significant problem for many patients. Parastomal hernia (PH) rates may be as high as 65% and while many patients are asymptomatic, in some series up to 30% of patients require surgical intervention due to pain, leakage, ostomy appliance problems, urinary obstruction, and rarely bowel obstruction or strangulation. Local tissue repair, stoma relocation, and mesh repairs have been performed to correct PH, however, long-term results have been disappointing with recurrence rates of 30%–76% reported after these techniques. Due to high recurrence rates and the potential morbidity of PH repair, efforts have been made to prevent PH development at the time of the initial surgery. Randomized trials of circumstomal prophylactic mesh placement at the time of colostomy and ileostomy stoma formation have shown significant reductions in PH rates with acceptably low complication profiles. We have placed prophylactic mesh at the time of ileal conduit creation in patients at high risk for PH development and found it to be safe and effective in reducing the PH rates over the short-term. In this review, we describe the clinical and radiographic definitions of PH, the clinical impact and risk factors associated with its development, and the use of prophylactic mesh placement for patients undergoing ileal conduit urinary diversion with the intent of reducing PH rates. PMID:27437533

  13. Methods of measuring pumpage through closed-conduit irrigation systems

    USGS Publications Warehouse

    Kjelstrom, L.C.

    1991-01-01

    Methods of measuring volumes of water withdrawn from the Snake River and its tributaries and pumped through closed-conduit irrigation systems were needed for equitable management of and resolution of conflicts over water use. On the basis of evaluations and field tests by researchers from the University of Idaho, Water Resources Research Institute, Moscow, Idaho, an impeller meter was selected to monitor pumpage through closed-conduit systems. In 1988, impeller meters were installed at 20 pumping stations along the Snake River between the Upper Salmon Falls and C.J. Strike Dams. Impeller-derived pumpage data were adjusted if they differed substantially from ultrasonic flow-meter- or current-meter-derived values. Comparisons of pumpage data obtained by ultrasonic flow-meter and current-meter measurements indicated that the ultrasonic flow meter was a reliable means to check operation of impeller meters. The equipment generally performed satisfactorily, and reliable pumpage data could be obtained using impeller meters in closed-conduit irrigation systems. Many pumping stations that divert water from the Snake River for irrigation remain unmeasured; however, regression analyses indicate that total pumpage can be reasonably estimated on the basis of electrical power consumption data, an approximation of total head at a pumping station, and a derived coefficient.

  14. MMP19 expression in the human optic nerve

    PubMed Central

    Chirco, Kathleen R.; Hazlewood, Ralph J.; Miller, Kathy; Workalemahu, Grefachew; Jampol, Lee M.; Lesser, G. Robert; Mullins, Robert F.; Kuehn, Markus H.; Fingert, John H.

    2016-01-01

    Purpose The defining feature of glaucoma is excavation of the optic nerve head; however, the mechanism of this loss of tissue is not well understood. We recently discovered a copy number variation upstream of matrix metalloproteinase 19 (MMP19) in a large, autosomal dominant pedigree with a congenital malformation of the optic disc called cavitary optic disc anomaly (CODA). Patients with CODA have abnormal optic discs that exhibit an excavated shape similar to cupping seen in glaucoma. The goal of this study is to characterize the localization of MMP19 within the human optic nerve. Methods The MMP19 protein in the optic nerve was evaluated with western blot analysis and with immunohistochemistry in sagittal and en face/cross sections of optic nerves obtained from healthy human donor eyes. Results The MMP19 protein was detected in the human optic nerve, retina, and RPE/choroid with western blot analysis, with highest expression in the retina and the optic nerve. Using immunohistochemistry, MMP19 was localized within the optic nerve to the extracellular space within the septa that separate bundles of optic nerve axons into fascicles. The presence of MMP19 within the optic nerve septa was further confirmed by the colocalization of MMP19 to this structure with type IV collagen. Strong labeling of MMP19 was also detected in the arachnoid layer of the optic nerve sheath. Finally, immunohistochemistry of the optic nerve cross sections demonstrated that MMP19 shows a peripheral to central gradient, with more abundant labeling along the edges of the optic nerve and in the arachnoid layer than in the center of the nerve. Conclusions Abundant MMP19 was detected in the optic nerve head, the primary site of pathology in patients with CODA. The localization of MMP19 to the optic nerve septa is consistent with its predicted secretion and accumulation within the extracellular spaces of this tissue. Moreover, the lateral localization of MMP19 observed in the optic nerve cross

  15. WARP interacts with collagen VI-containing microfibrils in the pericellular matrix of human chondrocytes.

    PubMed

    Hansen, Uwe; Allen, Justin M; White, Rachel; Moscibrocki, Cathleen; Bruckner, Peter; Bateman, John F; Fitzgerald, Jamie

    2012-01-01

    Collagen VI and WARP are extracellular structural macromolecules present in cartilage and associated with BM suprastructures in non-skeletal tissues. We have previously shown that in WARP-deficient mice, collagen VI is specifically reduced in regions of the peripheral nerve ECM where WARP is expressed, suggesting that both macromolecules are part of the same suprastructure. The object of this study was to conduct a detailed analysis of WARP-collagen VI interactions in vitro in cartilage, a tissue rich in WARP and collagen VI. Immunohistochemical analysis of mouse and human articular cartilage showed that WARP and collagen VI co-localize in the pericellular matrix of superficial zone articular chondrocytes. EM analysis on extracts of human articular cartilage showed that WARP associates closely with collagen VI-containing suprastructures. Additional evidence of an interaction is provided by immunogold EM and immunoblot analysis showing that WARP was present in collagen VI-containing networks isolated from cartilage. Further characterization were done by solid phase binding studies and reconstitution experiments using purified recombinant WARP and isolated collagen VI. Collagen VI binds to WARP with an apparent K(d) of approximately 22 nM and the binding site(s) for WARP resides within the triple helical domain since WARP binds to both intact collagen VI tetramers and pepsinized collagen VI. Together, these data confirm and extend our previous findings by demonstrating that WARP and collagen VI form high affinity associations in vivo in cartilage. We conclude that WARP is ideally placed to function as an adapter protein in the cartilage pericellular matrix.

  16. Frictional melting and stick-slip behavior in volcanic conduits

    NASA Astrophysics Data System (ADS)

    Kendrick, Jackie Evan; Lavallee, Yan; Hirose, Takehiro; di Toro, Giulio; Hornby, Adrian Jakob; Hess, Kai-Uwe; Dingwell, Donald Bruce

    2013-04-01

    Dome-building eruptions have catastrophic potential, with dome collapse leading to devastating pyroclastic flows with almost no precursory warning. During dome growth, the driving forces of the buoyant magma may be superseded by controls along conduit margins; where brittle fracture and sliding can lead to formation of lubricating cataclasite and gouge. Under extreme friction, pseudotachylyte may form at the conduit margin. Understanding the conduit margin processes is vital to understanding the continuation of an eruption and we postulate that pseudotachylyte generation could be the underlying cause of stick-slip motion and associated seismic "drumbeats", which are so commonly observed at dome-building volcanoes. This view is supported by field evidence in the form of pseudotachylytes identified in lava dome products at Soufrière Hills (Montserrat) and Mount St. Helens (USA). Both eruptions were characterised by repetitive, periodic seismicity and lava spine extrusion of highly viscous magma. High velocity rotary shear (HVR) experiments demonstrate the propensity for melting of the andesitic and dacitic material (from Soufrière Hills and Mount St. Helens respectively) at upper conduit stress conditions (<10 MPa). Starting from room temperature, frictional melting of the magmas occurs in under 1 s (<< 1 m) at 1.5 m/s (a speed that is achievable during stick-slip motion). At lower velocities melting occurs comparatively later due to dissipation of heat from the slip zone (e.g. 8-15 m at 0.1 m/s). Hence, given the ease with which melting is achieved in volcanic rocks, and considering the high ambient temperatures in volcanic conduits, frictional melting may thus be an inevitable consequence of viscous magma ascent. The shear resistance of the slip zone during the experiment is also monitored. Frictional melting induces a higher resistance to sliding than rock on rock, and viscous processes control the slip zone properties. Variable-rate HVR experiments which mimic

  17. UV damage of collagen: insights from model collagen peptides.

    PubMed

    Jariashvili, Ketevan; Madhan, Balaraman; Brodsky, Barbara; Kuchava, Ana; Namicheishvili, Louisa; Metreveli, Nunu

    2012-03-01

    Fibrils of Type I collagen in the skin are exposed to ultraviolet (UV) light and there have been claims that collagen photo-degradation leads to wrinkles and may contribute to skin cancers. To understand the effects of UV radiation on collagen, Type I collagen solutions were exposed to the UV-C wavelength of 254 nm for defined lengths of time at 4°C. Circular dichroism (CD) experiments show that irradiation of collagen leads to high loss of triple helical content with a new lower thermal stability peak and SDS-gel electrophoresis indicates breakdown of collagen chains. To better define the effects of UV radiation on the collagen triple-helix, the studies were extended to peptides which model the collagen sequence and conformation. CD studies showed irradiation for days led to lower magnitudes of the triple-helix maximum at 225 nm and lower thermal stabilities for two peptides containing multiple Gly-Pro-Hyp triplets. In contrast, the highest radiation exposure led to little change in the T(m) values of (Gly-Pro-Pro)(10) and (Ala-Hyp-Gly)(10) , although (Gly-Pro-Pro)(10) did show a significant decrease in triple helix intensity. Mass spectroscopy indicated preferential cleavage sites within the peptides, and identification of some of the most susceptible sites of cleavage. The effect of radiation on these well defined peptides gives insight into the sequence and conformational specificity of photo-degradation of collagen.

  18. Heterogeneity of collagens in rabbit cornea: type VI collagen

    SciTech Connect

    Cintron, C.; Hong, B.S.

    1988-05-01

    Normal adult rabbit corneas were digested with 5% pepsin and their collagens extracted with acetic acid. Collagen extracts were fractionated by differential salt precipitation. The 2.5 M NaCl fraction was then redissolved with tris buffer and precipitated with sodium acetate. The precipitate contained a high-molecular-weight disulfide-bonded aggregate which, upon reduction with mercaptoethanol, was converted into three distinct polypeptides having molecular weights between 45 and 66 Kd. These physical characteristics, together with the susceptibility of these polypeptides to collagenase and their amino acid composition, identified the high molecular weight aggregate as type VI collagen. Corneas from neonate rabbits and adult corneas containing 2-week-old scars were organ cultured in the presence of (/sup 14/C) glycine to incorporate radiolabel into collagen. Tissues were digested with 0.02% pepsin and their collagens extracted with formic acid. The total radioactivity of the extracts and tissue residues was determined before the collagens were separated by SDS-polyacrylamide slab gel electrophoresis. Radioactive collagen polypeptides bands were then stained with Coomassie blue, processed for fluorography, and analyzed by densitometry. The results show that: (1) type VI collagen is synthesized by neonate corneas and healing adult corneas; (2) it is not readily solubilized from either corneal tissue by 0.02% pepsin digestion and formic acid extraction; and (3) the proportion of type VI collagen deposited in scar tissue is markedly lower than that found in neonate corneas.

  19. Heterogeneity of collagens in rabbit cornea: type III collagen

    SciTech Connect

    Cintron, C.; Hong, B.S.; Covington, H.I.; Macarak, E.J.

    1988-05-01

    Whole neonate rabbit corneas and adult corneas containing 2-week-old scars were incubated in the presence of (/sup 14/C) glycine. Radiolabeled collagen extracted from the corneas and scar tissue were analyzed by sodium dodecylsulfate/polyacrylamide gel electrophoresis and fluorography to determine the types and relative quantity of collagen polypeptides present and synthesized by these tissues. In addition to other collagen types, type III was found in both neonate cornea and scar tissue from adult cornea, albeit in relatively small quantities. Type III collagen in normal cornea was associated with the residue after pepsin digestion and formic acid extraction of the tissue, and the same type of collagen was extracted from scar tissue after similar treatment. Type III collagen-specific monoclonal antibody bound to developing normal corneas and healing adult tissue sections, as determined by immunofluorescence. Antibody binding was localized to the endothelium and growing Descemet's membrane in fetal and neonate corneas, and restricted to the most posterior region of the corneal scar tissue. Although monoclonal antibody to keratan sulfate, used as a marker for stromal fibroblasts, bound to most of the scar tissue, the antibody failed to bind to the posterior scar tissue positive for type III collagen. We conclude that endothelial cells from fetal and neonate rabbit cornea and endothelium-derived fibroblasts from healing wounds of adult cornea synthesize and deposit type III collagen. Moreover, this collagen appears to be incorporated into the growing Descemet's membrane of normal corneas and narrow posterior portion of the scar tissue.

  20. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  1. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  2. Collagenous colitis: an unrecognised entity.

    PubMed Central

    Bogomoletz, W V; Adnet, J J; Birembaut, P; Feydy, P; Dupont, P

    1980-01-01

    A patient is reported with chronic abdominal pain, diarrhoea, and associated radiological and endoscopic abnormalities of the sigmoid colon. Light and electron microscopic study of colorectal mucosa showed abnormal collagenous thickening of the subepithelial basement membrane. The authors felt that the clinical and morphological features justified a diagnosis of collagenous colitis. Review of the literature suggested that collagenous colitis was still an unrecognised entity. Images Fig. 1 Fig. 2 Fig. 3 PMID:7380341

  3. Second harmonic generation in collagen

    NASA Astrophysics Data System (ADS)

    Reiser, Karen M.; Stoller, Patrick; Celliers, Peter; Rubenchik, Alexander; Bratton, Clay; Yankelevich, Diego

    2003-11-01

    Collagen possesses a strong second order nonlinear susceptibility; when it is irradiated with intense laser light, some of the reflected and transmitted light will have twice the frequency of the incident beam, a phenomenon known as second harmonic generation (SHG). Polarization modulation of an ultra-short pulse laser beam can be used to simultaneously measure collagen fiber orientation, SHG intensity, and a parameter related to the second order non-linear susceptibility. This technique has made it possible to discriminate among patterns of fibrillar orientation in many tissues. In the present study the role that organizational complexity plays in the relationship between nonlinear optical properties and collagen structure is investigated. As a component of tissues and organs, collagen"s structure and function is inextricably intertwined with that of the many other matrix components; to what extent do these noncollagenous components affect its nonlinear properties? To answer this, we investigated SHG in two different collagenous tissues, liver and cartilage; in addition we looked at the effect of progressive pathological changes in these tissues on SHG. At the other end of the spectrum, we studied collagen organized at the minimal level of complexity necessary for SHG detection: fibrils generated from solutions containing only a single type of collagen. Data obtained from these studies suggest that collagen"s strong nonlinear susceptibility, a property no other biologically significant macromolecule shares to the same degree, may serve as more than the basis of a novel imaging device for soft tissue. Collagen"s nonlinear optical properties in conjunction with its vast capacity for self-initiated conformational change--through self-assembly, site recognition, post-translational modification, and the like -make it an attractive candidate molecule for any of several demanding engineering applications, such as nanopatterning.

  4. Cells that emerge from embryonic explants produce fibers of type IV collagen

    PubMed Central

    1985-01-01

    Double immunofluorescence staining experiments designed to examine the synthesis and deposition of collagen types I and IV in cultured explants of embryonic mouse lung revealed the presence of connective tissue-like fibers that were immunoreactive with anti-type IV collagen antibodies. This observation is contrary to the widely accepted belief that type IV collagen is found only in sheet-like arrangements beneath epithelia or as a sheath-like layer enveloping bundles of nerve or muscle cells. The extracellular matrix produced by cells that migrate from embryonic mouse lung rudiments in vitro was examined by double indirect immunofluorescence microscopy. Affinity-purified monospecific polyclonal antibodies were used to examine cells after growth on glass or native collagen substrata. The data show that embryonic mesenchymal cells can produce organized fibers of type IV collagen that are not contained within a basement membrane, and that embryonic epithelial cells deposit fibers and strands of type IV collagen beneath their basal surface when grown on glass; however, when grown on a rat tail collagen substratum the epithelial cells produce a fine meshwork. To our knowledge this work represents the first report that type IV collagen can be organized by cells into a fibrous extracellular matrix that is not a basement membrane. PMID:3900085

  5. Optic Nerve Pit

    MedlinePlus

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Pit What is optic nerve pit? An optic nerve pit is a ... may be seen in both eyes. How is optic pit diagnosed? If the pit is not affecting ...

  6. The effects of gradients of nerve growth factor immobilized PCLA scaffolds on neurite outgrowth in vitro and peripheral nerve regeneration in rats.

    PubMed

    Tang, Shuo; Zhu, Jixiang; Xu, Yangbin; Xiang, Andy Peng; Jiang, Mei Hua; Quan, Daping

    2013-09-01

    Introducing concentration gradients of nerve growth factor (NGF) into conduits for repairing of peripheral nerve injury is crucial for nerve regeneration and guidance. Herein, combining differential adsorption of NGF/silk fibroin (SF) coating, the gradient of NGF-immobilized membranes (G-Ms) and nanofibrous nerve conduits (G-nNCs) were successfully fabricated. The efficacy of NGF gradients was confirmed by a quantitative comparison of dorsal root ganglia (DRG) neurite outgrowth on the G-Ms or uniform NGF-immobilized membranes (U-Ms). Significantly, the neurite turning ratio was 0.48 ± 0.11 for G-M group, but it was close to zero for U-M group. The neurite length of DRGs in the middle of the G-Ms was significantly longer than that of U-M group, even though the average NGF concentration was approximated. Furthermore, 12 weeks after implantation in rats with a 14 mm gap of sciatic nerve injury, G-nNCs achieved satisfying outcomes of nerve regeneration associated with morphological and functional improvements, which was superior to that of the uniform NGF-immobilized nNCs (U-nNCs). Sciatic function index (SFI), compound muscle action potentials (CMAPs), total number of myelinated nerve fibers, thickness of myelin sheath were similar for the G-nNCs and autografts, with the G-nNCs having a higher density of axons than the autografts. Our results demonstrated the significant role of introducing NGF gradients into scaffolds in promoting nerve regeneration.

  7. Conduit speed limit promotes formation of explosive `super slugs'

    NASA Astrophysics Data System (ADS)

    Llewellin, E. W.; Burton, M. R.; Mader, H. M.; Polacci, M.

    2014-12-01

    Strombolian activity - characterized by discrete, impulsive explosions - is common at basaltic volcanoes. The explosions are caused by the arrival, at the volcanic vent, of over-pressured `slugs' of magmatic gas, which have ascended the volcanic conduit. We present data from large-scale analogue experiments which reveal a previously-undescribed process which promotes the formation of large, highly over-pressured `super slugs'. We propose that these large slugs may drive the most violent Strombolian eruptions. Experiments were performed at the Large Analogue Volcano Apparatus at Durham University, UK, which comprises a 13m tall, 24cm diameter transparent conduit, surmounting a reservoir of analogue magma held at constant pressure. We simulate a vesiculation event deep in the sub-volcanic plumbing system by fluxing gas into the reservoir. Magma analogues with a range of viscosities are used, giving slug Reynolds numbers in the range 16 to 140,000. At moderate-to-high Reynolds number, we find that the gas rapidly self-organizes to form a conduit-filling lead slug; this slug ascends the column slowly, at a velocity limited by the flux of the falling film of liquid around it. Trailing bubbles, which ascend through the wake of the lead slug, rise much more rapidly. As they catch and coalesce with the lead slug, it grows and becomes increasingly over-pressured. This mechanism causes large slugs to form rapidly and we propose that it underpins the formation of the very large slugs that are responsible for the most explosive strombolian eruptions.

  8. Migrating quake swarm may indicate magma conduit clog

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2014-03-01

    On 13 January 2006, Augustine Volcano, a towering volcano offshore from the Alaska Peninsula, erupted explosively. In the days leading up to the eruption, a series of explosions and earthquake swarms had warned of the impending activity. On 12 January, 36 hours before the first magmatic explosions, a swarm of 54 earthquakes was detected across the 13-station seismic network on Augustine Island. Analyzing the seismic waves produced by the earthquakes, Buurman and West found that the earthquakes were being triggered from point sources within the magma conduit itself.

  9. Imaging of platelets in right-sided extracardiac conduits in humans

    SciTech Connect

    Agarwal, K.C.; Wahner, H.W.; Dewanjee, M.K.; Fuster, V.; Puga, F.J.; Danielson, G.K.; Chesebro, J.H.; Feldt, R.H.

    1982-04-01

    As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with /sup 111/In-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth postoperative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

  10. Imaging of platelets in right-sided extracardiac conduits in humans

    SciTech Connect

    Agarwal, K.C.; Wahner, H.W.; Dewanjee, M.K.; Fuster, V.; Puga, F.J.; Danielson, G.K.; Chesebro, J.H.; Feldt, R.H.

    1982-04-01

    As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with In-111-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth post-operative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

  11. Optic Nerve Elongation

    PubMed Central

    Alvi, Aijaz; Janecka, Ivo P.; Kapadia, Silloo; Johnson, Bruce L.; McVay, William

    1996-01-01

    The length of the optic nerves is a reflection of normal postnatal cranio-orbital development. Unilateral elongation of an optic nerve has been observed in two patients with orbital and skull base neoplasms. In the first case as compared to the patient's opposite, normal optic nerve, an elongated length of the involved optic nerve of 45 mm was present. The involved optic nerve in the second patient was 10 mm longer than the normal opposite optic nerve. The visual and extraocular function was preserved in the second patient. The first patient had only light perception in the affected eye. In this paper, the embryology, anatomy, and physiology of the optic nerve and its mechanisms of stretch and repair are discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 13 PMID:17170975

  12. Photo-crosslinked poly(epsilon-caprolactone fumarate) networks for guided peripheral nerve regeneration: material properties and preliminary biological evaluations.

    PubMed

    Wang, Shanfeng; Yaszemski, Michael J; Knight, Andrew M; Gruetzmacher, James A; Windebank, Anthony J; Lu, Lichun

    2009-06-01

    In an effort to achieve suitable biomaterials for peripheral nerve regeneration, we present a material design strategy of combining a crystallite-based physical network and a crosslink-based chemical network. Biodegradable polymer disks and conduits have been fabricated by photo-crosslinking three poly(epsilon-caprolactone fumarate)s (PCLF530, PCLF1250, and PCLF2000), which were synthesized from the precursor poly(epsilon-caprolactone) (PCL) diols with nominal molecular weights of 530, 1250, and 2000 g mol(-1), respectively. Thermal properties such as glass transition temperature (T(g)), melting temperature (T(m)), and crystallinity of photo-crosslinked PCLFs were examined and correlated with their rheological and mechanical properties. Furthermore, in vitro degradation of uncrosslinked and crosslinked PCLFs in PBS crosslinked PCLFs in 1 N NaOH aqueous solution at 37 degrees C was studied. In vitro cytocompatibility, attachment, and proliferation of Schwann cell precursor line SPL201 cells on three PCLF networks were investigated. Crosslinked PCLF2000 with the highest crystallinity and mechanical properties was found to best support cell attachment and proliferation. Using a new photo-crosslinking method, single-lumen crosslinked PCLF nerve conduits without defects were fabricated in a glass mold. Crosslinked PCLF2000 nerve conduits were selected for evaluation in a 1cm gap rat sciatic nerve model. Histological evaluation demonstrated that the material was biocompatible with sufficient strength to hold sutures in place after 6 and 17 weeks of implantation. Nerve cable with myelinated axons was found in the crosslinked PCLF2000 nerve conduit.

  13. The nerve: A fragile balance between physiology and pathophysiology.

    PubMed

    Estebe, Jean-Pierre; Atchabahian, Arthur

    2017-03-01

    Regarding nerves as simple cables and electrical conduits is a gross error that does not allow us to understand the anomalies and disorders observed postoperatively. Instead, nerves should be seen as a living tissue of which physiological regulation is as complex as that of the blood-brain barrier. This review describes the basic structure and functions of this blood-nerve barrier and highlights the mechanisms of its breakdown and the resultant disorders. For clinical practice, it is important to note that the diffusion of molecules from the perineurium or from the blood is very limited, and so the blood-nerve barrier is a major pharmacologic barrier. Any stress upon neural physiological balance, particularly the terminal vascular blood supply, will induce the classic inflammatory cascade. Due to the complexity of the vascular system, nerve ischaemia will occur more quickly when the terminal blood supply is compromised. This blood supply can adapt in a variety of ways but when these possibilities of adaptation are exceeded, tissue ischaemia may be more extensive. Also, even after the initial injury has subsided, inflammation can cause a secondary insult. This could be particularly important in some patients with subclinical neuropathy.

  14. APICAL LEFT VENTRICULAR-ABDOMINAL AORTIC COMPOSITE CONDUITS FOR LEFT VENTRICULAR OUTFLOW OBSTRUCTIONS

    PubMed Central

    Cooley, Denton A.; Norman, John C.

    1978-01-01

    Certain problems related to the left ventricular outflow tract are not amenable to conventional surgical methods, but may be solved with the creation of a double outlet left ventricle by using a composite rigid pyrolite left ventricular apex outlet prosthesis and a fabric valve-containing conduit. Low porosity woven Dacron tube grafts are used for the conduit. Twenty-three patients who have undergone apico-aortic bypass with this conduit are reported here, with gratifying results in eighteen. PMID:15216062

  15. Assessment of nerve morphology in nerve activation during electrical stimulation

    NASA Astrophysics Data System (ADS)

    Gomez-Tames, Jose; Yu, Wenwei

    2013-10-01

    The distance between nerve and stimulation electrode is fundamental for nerve activation in Transcutaneous Electrical Stimulation (TES). However, it is not clear the need to have an approximate representation of the morphology of peripheral nerves in simulation models and its influence in the nerve activation. In this work, depth and curvature of a nerve are investigated around the middle thigh. As preliminary result, the curvature of the nerve helps to reduce the simulation amplitude necessary for nerve activation from far field stimulation.

  16. Collagen for bone tissue regeneration.

    PubMed

    Ferreira, Ana Marina; Gentile, Piergiorgio; Chiono, Valeria; Ciardelli, Gianluca

    2012-09-01

    In the last decades, increased knowledge about the organization, structure and properties of collagen (particularly concerning interactions between cells and collagen-based materials) has inspired scientists and engineers to design innovative collagen-based biomaterials and to develop novel tissue-engineering products. The design of resorbable collagen-based medical implants requires understanding the tissue/organ anatomy and biological function as well as the role of collagen's physicochemical properties and structure in tissue/organ regeneration. Bone is a complex tissue that plays a critical role in diverse metabolic processes mediated by calcium delivery as well as in hematopoiesis whilst maintaining skeleton strength. A wide variety of collagen-based scaffolds have been proposed for different tissue engineering applications. These scaffolds are designed to promote a biological response, such as cell interaction, and to work as artificial biomimetic extracellular matrices that guide tissue regeneration. This paper critically reviews the current understanding of the complex hierarchical structure and properties of native collagen molecules, and describes the scientific challenge of manufacturing collagen-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of innovative techniques for scaffold and material manufacturing that are currently opening the way to the preparation of biomimetic substrates that modulate cell interaction for improved substitution, restoration, retention or enhancement of bone tissue function.

  17. Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

    NASA Astrophysics Data System (ADS)

    Sharma, Anup Dutt

    Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

  18. Environmental tracers as indicators of karst conduits in groundwater in South Dakota, USA

    USGS Publications Warehouse

    Long, A.J.; Sawyer, J.F.; Putnam, L.D.

    2008-01-01

    Environmental tracers sampled from the carbonate Madison aquifer on the eastern flank of the Black Hills, South Dakota, USA indicated the approximate locations of four major karst conduits. Contamination issues are a major concern because these conduits are characterized by direct connections to sinking streams, high groundwater velocities, and proximity to public water supplies. Objectives of the study were to estimate approximate conduit locations and assess possible anthropogenic influences associated with conduits. Anomalies of young groundwater based on chlorofluorocarbons (CFCs), tritium, and electrical conductivity (EC) indicated fast moving, focused flow and thus the likely presence of conduits. ??18O was useful for determining sources of recharge for each conduit, and nitrate was a useful tracer for assessing flow paths for anthropogenic influences. Two of the four conduits terminate at or near a large spring complex. CFC apparent ages ranged from 15 years near conduits to >50 years in other areas. Nitrate-N concentrations >0.4 mg/L in groundwater were associated with each of the four conduits compared with concentrations ranging from <0.1 to 0.4 mg/L in other areas. These higher nitrate-N concentrations probably do not result from sinking streams but rather from other areas of infiltration. ?? Springer-Verlag 2007.

  19. System and method for bidirectional flow and controlling fluid flow in a conduit

    DOEpatents

    Ortiz, M.G.

    1999-03-23

    A system for measuring bidirectional flow, including backflow, of fluid in a conduit is disclosed. The system utilizes a structural mechanism to create a pressure differential in the conduit. Pressure sensors are positioned upstream from the mechanism, at the mechanism, and downstream from the mechanism. Data from the pressure sensors are transmitted to a microprocessor or computer, and pressure differential detected between the pressure sensors is then used to calculate the backflow. Control signals may then be generated by the microprocessor or computer to shut off valves located in the conduit, upon the occurrence of backflow, or to control flow, total material dispersed, etc. in the conduit. 3 figs.

  20. System and method for bidirectional flow and controlling fluid flow in a conduit

    DOEpatents

    Ortiz, Marcos German

    1999-01-01

    A system for measuring bidirectional flow, including backflow, of fluid in a conduit. The system utilizes a structural mechanism to create a pressure differential in the conduit. Pressure sensors are positioned upstream from the mechanism, at the mechanism, and downstream from the mechanism. Data from the pressure sensors are transmitted to a microprocessor or computer, and pressure differential detected between the pressure sensors is then used to calculate the backflow. Control signals may then be generated by the microprocessor or computer to shut off valves located in the conduit, upon the occurrence of backflow, or to control flow, total material dispersed, etc. in the conduit.

  1. Development of a new lacrimal drainage conduit using POSS nanocomposite.

    PubMed

    Chaloupka, Karla; Motwani, Meghna; Seifalian, Alexander Marcus

    2011-01-01

    Lacrimal surgery in cases of severely obstructed or missing canalicular ducts is highly challenging. In these cases, the placement of a bypass tube is currently the only option to restore the drainage of tears into the nose and reduce the symptomatic watery eye. Different approaches to achieve functional drainage have been tried using blood vessels or artificial implants. The implantation of the rigid Lester Jones tube is, since its introduction in the late 1960s, the gold standard. The functional success is satisfactory. However, complication rates are high and remain, even with many modifications of the original design, a major problem. These complications include mainly the displacement and blockage of the tube, requiring regular checkups, as well as irritation of the surrounding tissue including the nose and the eye. The objective of this study was to develop a new lacrimal duct conduit (LDC) to restore structural and functional integrity of the lacrimal drainage system. The conduit is constructed with a novel polymer, polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU), that offers biocompatibility. We exploit nanotopography to evade the problems associated with current applications. A number of extrusion techniques were investigated for this purpose: ultrasonic atomization spraying, electrohydrodynamic atomization spraying/spinning, extrusion-coagulation, and high-pressure coagulation by autoclave and casting. Finally, the coagulation and cast technique were selected to construct an LDC superior to its predecessors, and its advantages highlighted.

  2. Conduit for high temperature transfer of molten semiconductor crystalline material

    NASA Technical Reports Server (NTRS)

    Fiegl, George (Inventor); Torbet, Walter (Inventor)

    1983-01-01

    A conduit for high temperature transfer of molten semiconductor crystalline material consists of a composite structure incorporating a quartz transfer tube as the innermost member, with an outer thermally insulating layer designed to serve the dual purposes of minimizing heat losses from the quartz tube and maintaining mechanical strength and rigidity of the conduit at the elevated temperatures encountered. The composite structure ensures that the molten semiconductor material only comes in contact with a material (quartz) with which it is compatible, while the outer layer structure reinforces the quartz tube, which becomes somewhat soft at molten semiconductor temperatures. To further aid in preventing cooling of the molten semiconductor, a distributed, electric resistance heater is in contact with the surface of the quartz tube over most of its length. The quartz tube has short end portions which extend through the surface of the semiconductor melt and which are lef bare of the thermal insulation. The heater is designed to provide an increased heat input per unit area in the region adjacent these end portions.

  3. Documentation of a Conduit Flow Process (CFP) for MODFLOW-2005

    USGS Publications Warehouse

    Shoemaker, W. Barclay; Kuniansky, Eve L.; Birk, Steffen; Bauer, Sebastian; Swain, Eric D.

    2007-01-01

    This report documents the Conduit Flow Process (CFP) for the modular finite-difference ground-water flow model, MODFLOW-2005. The CFP has the ability to simulate turbulent ground-water flow conditions by: (1) coupling the traditional ground-water flow equation with formulations for a discrete network of cylindrical pipes (Mode 1), (2) inserting a high-conductivity flow layer that can switch between laminar and turbulent flow (Mode 2), or (3) simultaneously coupling a discrete pipe network while inserting a high-conductivity flow layer that can switch between laminar and turbulent flow (Mode 3). Conduit flow pipes (Mode 1) may represent dissolution or biological burrowing features in carbonate aquifers, voids in fractured rock, and (or) lava tubes in basaltic aquifers and can be fully or partially saturated under laminar or turbulent flow conditions. Preferential flow layers (Mode 2) may represent: (1) a porous media where turbulent flow is suspected to occur under the observed hydraulic gradients; (2) a single secondary porosity subsurface feature, such as a well-defined laterally extensive underground cave; or (3) a horizontal preferential flow layer consisting of many interconnected voids. In this second case, the input data are effective parameters, such as a very high hydraulic conductivity, representing multiple features. Data preparation is more complex for CFP Mode 1 (CFPM1) than for CFP Mode 2 (CFPM2). Specifically for CFPM1, conduit pipe locations, lengths, diameters, tortuosity, internal roughness, critical Reynolds numbers (NRe), and exchange conductances are required. CFPM1, however, solves the pipe network equations in a matrix that is independent of the porous media equation matrix, which may mitigate numerical instability associated with solution of dual flow components within the same matrix. CFPM2 requires less hydraulic information and knowledge about the specific location and hydraulic properties of conduits, and turbulent flow is approximated by

  4. Type I Collagen and Collagen Mimetics as Angiogenesis Promoting Superpolymers

    SciTech Connect

    Twardowski, T.; Fertala, A.; Orgel, J.P.R.O.; San Antonio, J.D.

    2008-07-18

    Angiogenesis, the development of blood vessels from the pre-existing vasculature, is a key component of embryogenesis and tissue regeneration. Angiogenesis also drives pathologies such as tumor growth and metastasis, and hemangioma development in newborns. On the other hand, promotion of angiogenesis is needed in tissues with vascular insufficiencies, and in bioengineering, to endow tissue substitutes with appropriate microvasculatures. Therefore, much research has focused on defining mechanisms of angiogenesis, and identifying pro- and anti-angiogenic molecules. Type I collagen, the most abundant protein in humans, potently stimulates angiogenesis in vitro and in vivo. Crucial to its angiogenic activity appears to be ligation and possibly clustering of endothelial cell (EC) surface {alpha}1{beta}1/{alpha}2{beta}1 integrin receptors by the GFPGER502-507 sequence of the collagen fibril. However, additional aspects of collagen structure and function that may modulate its angiogenic properties are discussed. Moreover, type I collagen and fibrin, another angiogenic polymer, share several structural features. These observations suggest strategies for creating 'angiogenic superpolymers', including: modifying type I collagen to influence its biological half-life, immunogenicity, and integrin binding capacity; genetically engineering fibrillar collagens to include additional integrin binding sites or angiogenic determinants, and remove unnecessary or deleterious sequences without compromising fibril integrity; and exploring the suitability of poly(ortho ester), PEG-lysine copolymer, tubulin, and cholesteric cuticle as collagen mimetics, and suggesting means of modifying them to display ideal angiogenic properties. The collagenous and collagen mimetic angiogenic superpolymers described here may someday prove useful for many applications in tissue engineering and human medicine.

  5. Erosion processes in volcanic conduits and application to the AD 79 eruption of Vesuvius

    NASA Astrophysics Data System (ADS)

    Macedonio, Giovanni; Dobran, Flavio; Neri, Augusto

    1994-01-01

    The flow of gas, magma and pyroclasts through a volcanic conduit produces erosion of the conduit wall. Erosion may be produced by the impact of pyroclasts on the conduit wall, fluid shear stress at the wall, conduit wall collapse, and volcanic tremor. Using a two-phase flow non-equilibrium model of magma ascent along the volcanic conduits demonstrated that the erosion due to the impact of particles on the wall can occur only above the magma fragmentation level of the conduit where the particles or pyroclasts remove the wall material by an abrasion process. This abrasion process was found to be the largest near the conduit exit where the gas-magma velocities are the largest. The erosion due to the fluid shear stress at the wall can be produced along the entire length of a conduit, depending on the wall roughness and yield strength of wall rocks. This shear stress is the largest near the magma fragmentation level where the gas-magma viscosity and velocity gradients are very large. The collapse of conduit wall due to the difference between the gas-magma and lithostatic pressures can occur below and above the magma fragmentation level, causing the production of lithics directly when the wall collapses inward, and indirectly when the wall collapses outward. The effectiveness of different erosion mechanisms was tested with the magma characteristics, conduit geometry, and wall rock properties pertaining to the AD 79 eruption of Vesuvius. It was found that during the white and gray magma plinian eruption phases the lithics should have come from the deep as well as from the shallow regions of the conduit. The conclusions from erosion modeling are also consistent with the limited field data whereby the gray magma phase deposits are associated with larger lithic content and larger proportion of deep limestone fragments.

  6. Ultrastructure of type VI collagen in human skin and cartilage suggests an anchoring function for this filamentous network

    PubMed Central

    1988-01-01

    An mAb was used in conjunction with immunoelectron microscopy to study the ultrastructure and distribution of the type VI collagen network. Type VI collagen in femoral head and costal cartilage was found distributed throughout the matrix but concentrated in areas surrounding chondrocytes. Three-dimensional information gained from high voltage stereo pair electron microscopy showed that the type VI collagen network in skin was organized into a highly branched, open, filamentous network that encircled interstitial collagen fibers, but did not appear to interact directly with them. Type VI collagen was also found concentrated near basement membranes of nerves, blood vessels, and fat cells although in a less organized state. Labeling was conspicuously reduced close to the epithelial basement membrane in the region of the anchoring fibrils. No labeling of basement membranes was seen. Based on these observations it is suggested that the type VI collagen forms a flexible network that anchors large interstitial structures such as nerves, blood vessels, and collagen fibers into surrounding connective tissues. PMID:3182942

  7. Silicic magma differentiation in ascent conduits. Experimental constraints

    NASA Astrophysics Data System (ADS)

    Rodríguez, Carmen; Castro, Antonio

    2017-02-01

    Crystallization of water-bearing silicic magmas in a dynamic thermal boundary layer is reproduced experimentally by using the intrinsic thermal gradient of piston-cylinder assemblies. The standard AGV2 andesite under water-undersaturated conditions is set to crystallize in a dynamic thermal gradient of about 35 °C/mm in 10 mm length capsules. In the hotter area of the capsule, the temperature is initially set at 1200 °C and decreases by programmed cooling at two distinct rates of 0.6 and 9.6 °C/h. Experiments are conducted in horizontally arranged assemblies in a piston cylinder apparatus to avoid any effect of gravity settling and compaction of crystals in long duration runs. The results are conclusive about the effect of water-rich fluids that are expelled out the crystal-rich zone (mush), where water saturation is reached by second boiling in the interstitial liquid. Expelled fluids migrate to the magma ahead of the solidification front contributing to a progressive enrichment in the fluxed components SiO2, K2O and H2O. The composition of water-rich fluids is modelled by mass balance using the chemical composition of glasses (quenched melt). The results are the basis for a model of granite magma differentiation in thermally-zoned conduits with application of in-situ crystallization equations. The intriguing textural and compositional features of the typical autoliths, accompanying granodiorite-tonalite batholiths, can be explained following the results of this study, by critical phenomena leading to splitting of an initially homogeneous magma into two magma systems with sharp boundaries. Magma splitting in thermal boundary layers, formed at the margins of ascent conduits, may operate for several km distances during magma transport from deep sources at the lower crust or upper mantle. Accordingly, conduits may work as chromatographic columns contributing to increase the silica content of ascending magmas and, at the same time, leave behind residual mushes that

  8. Collagen binding to Staphylococcus aureus

    SciTech Connect

    Holderbaum, D.; Hall, G.S.; Ehrhart, L.A.

    1986-11-01

    Staphylococcus aureus can bind soluble collagen in a specific, saturable manner. We have previously shown that some variability exists in the degree of collagen binding between different strains of heat-killed, formaldehyde-fixed S. aureus which are commercially available as immunologic reagents. The present study demonstrates that live S. aureus of the Cowan 1 strain binds amounts of collagen per organism equivalent to those demonstrated previously in heat-killed, formaldehyde-fixed bacteria but has an affinity over 100 times greater, with Kd values of 9.7 X 10(-11) M and 4.3 X 10(-8) M for live and heat-killed organisms, respectively. Studies were also carried out with S. aureus killed by ionizing radiation, since this method of killing the organism seemed less likely to alter the binding moieties on the surface than did heat killing. Bacteria killed by exposure to gamma radiation bound collagen in a manner essentially indistinguishable from that of live organisms. Binding of collagen to irradiated cells of the Cowan 1 strain was rapid, with equilibrium reached by 30 min at 22 degrees C, and was fully reversible. The binding was not inhibited by fibronectin, fibrinogen, C1q, or immunoglobulin G, suggesting a binding site for collagen distinct from those for these proteins. Collagen binding was virtually eliminated in trypsin-treated organisms, indicating that the binding site has a protein component. Of four strains examined, Cowan 1 and S. aureus ATCC 25923 showed saturable, specific binding, while strains Woods and S4 showed a complete lack of binding. These results suggest that some strains of S. aureus contain high-affinity binding sites for collagen. While the number of binding sites per bacterium varied sixfold in the two collagen-binding strains, the apparent affinity was similar.

  9. Influence of cross-linking degree of a biodegradable genipin-cross-linked gelatin guide on peripheral nerve regeneration.

    PubMed

    Lu, Ming-Chin; Hsiang, Shih-Wei; Lai, Tung-Yuan; Yao, Chun-Hsu; Lin, Li-Yu; Chen, Yueh-Sheng

    2007-01-01

    We evaluated peripheral nerve regeneration using biodegradable genipin-cross-linked gelatin nerve conduits (GGCs) with three different cross-linking degrees, 24, 36 and 51%. Biocompatibility and biodegradability of the GGC and its efficiency as a guidance channel were examined based on the repair process of a 10-mm gap in the rat sciatic nerve. From this pilot study we concluded that GGCs with a mean cross-linking degree of 36% can ensure nerve regeneration with a more mature structure, as demonstrated by better developed epineural and perineural organisation and axonal development, as well as better-recovered electrophysiology with a relatively positive sciatic functional index and a shorter latency of the muscle action potential curve. Regenerated nerves in the GGCs with mean cross-linking degrees of 24 and 51% were less favourable, due to irritation caused by degradation material and compression by the remaining tube walls, respectively.

  10. In vivo evaluation of polysialic acid as part of tissue-engineered nerve transplants.

    PubMed

    Haastert-Talini, Kirsten; Schaper-Rinkel, Janett; Schmitte, Ruth; Bastian, Rode; Mühlenhoff, Martina; Schwarzer, David; Draeger, Gerald; Su, Yi; Scheper, Thomas; Gerardy-Schahn, Rita; Grothe, Claudia

    2010-10-01

    With the aim to develop new biomaterials for peripheral nerve grafts, the current study used bioidentical polysialic acid (polySia) as complement in synthetic conduits. polySia provides an important guidance cue during nervous system development and regeneration. First in vivo results on the use of cell-free and Schwann cell-containing synthetic peripheral nerve grafts complemented with soluble exogenous K1-polySia are presented. Reconstructing 10 mm rat sciatic nerve gaps, K1-polySia complementation significantly improved structural nerve regeneration in comparison to cell-free and K1-polySia-free grafts. Subsequently, long nerve gaps (13 mm) were reconstructed by Schwann cell transplants plus K1-polySia and compared to nerve autotransplantation. Structural but also functional regeneration could be observed using K1-polySia transplants; however, autotransplantation was still significantly more successful. Overall, the current study demonstrates that exogenous K1-polySia has no negative but rather regeneration promoting effects. This is important novel evidence on the applicability of exogenous polySia in vivo. Further studies are required to develop solid three-dimensional polySia-based scaffolds for nerve tissue engineering. Biocompatible and assessable biodegrading materials will ensure long-lasting presence of polySia to allow its applicability and prolonged efficacy in the slow regenerating scenario of human peripheral nerve reconstruction.

  11. Electrostatic effects in collagen fibrillization

    NASA Astrophysics Data System (ADS)

    Morozova, Svetlana; Muthukumar, Murugappan

    2014-03-01

    Using light scattering and AFM techniques, we have measured the kinetics of fibrillization of collagen (pertinent to the vitreous of human eye) as a function of pH and ionic strength. At higher and lower pH, collagen triple-peptides remain stable in solution without fibrillization. At neutral pH, the fibrillization occurs and its growth kinetics is slowed upon either an increase in ionic strength or a decrease in temperature. We present a model, based on polymer crystallization theory, to describe the observed electrostatic nature of collagen assembly.

  12. Optimization and stability of a cable-in-conduit superconductor

    SciTech Connect

    Schauer, F.

    1996-07-01

    The optimization process for strand number and diameter, cable void fraction, and Cu/NbTi-ratio of the cable-in-conduit conductor for the superconducting magnet system of the planned stellarator fusion experiment Wendelstein 7-X is presented. Main optimization criteria are stability and cable cooling requirements, taking into account transient disturbances and losses. A simple stability criterion regarding transient disturbances is used which is derived from cable compression experiments. The resulting data for the 16 kA, 6 T cable are: cable and strand diameter {approx}11.5 mm and {approx}0.57 mm, respectively, strand number {approx}250, void {approx}36%, and Cu/sc-ratio {approx}2.7.

  13. 26 CFR 1.58-2 - General rules for conduit entities; partnerships and partners.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and partners. 1.58-2 Section 1.58-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Tax Preference Regulations § 1.58-2 General rules for conduit entities; partnerships and partners. (a) General rules for conduit entities. Sections 1.58-3 through 1.58-6 provide...

  14. 26 CFR 1.58-2 - General rules for conduit entities; partnerships and partners.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and partners. 1.58-2 Section 1.58-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Tax Preference Regulations § 1.58-2 General rules for conduit entities; partnerships and partners. (a) General rules for conduit entities. Sections 1.58-3 through 1.58-6 provide...

  15. 26 CFR 1.58-2 - General rules for conduit entities; partnerships and partners.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and partners. 1.58-2 Section 1.58-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Tax Preference Regulations § 1.58-2 General rules for conduit entities; partnerships and partners. (a) General rules for conduit entities. Sections 1.58-3 through 1.58-6 provide...

  16. 78 FR 69403 - South Tahoe Public Utility District; Notice of Preliminary Determination of a Qualifying Conduit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ... a Qualifying Conduit Hydropower Facility and Soliciting Comments and Motions To Intervene On... qualifying conduit hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the Hydropower Regulatory Efficiency Act of 2013 (HREA). The CHYDRO Project would be...

  17. 78 FR 69847 - North Side Canal Company; Notice of Preliminary Determination of a Qualifying Conduit Hydropower...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-21

    ... Qualifying Conduit Hydropower Facility and Soliciting Comments and Motions To Intervene On November 5, 2013, North Side Canal Company, filed a notice of intent to construct a qualifying conduit hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the Hydropower...

  18. 78 FR 61987 - Corbett Water District; Notice of Preliminary Determination of a Qualifying Conduit Hydropower...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-09

    ... Conduit Hydropower Facility and Soliciting Comments and Motions To Intervene On September 23, 2013, Corbett Water District filed a notice of intent to construct a qualifying conduit hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the Hydropower...

  19. 78 FR 61985 - City of Astoria, Oregon; Notice of Preliminary Determination of a Qualifying Conduit Hydropower...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-09

    ... Conduit Hydropower Facility and Soliciting Comments and Motions To Intervene On September 24, 2013, City of Astoria, Oregon (Astoria) filed a notice of intent to construct a qualifying conduit hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the...

  20. 78 FR 61986 - City of Santa Barbara, California; Notice of Preliminary Determination of a Qualifying Conduit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-09

    ... Qualifying Conduit Hydropower Facility and Soliciting Comments and Motions To Intervene On September 24, 2013... hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the Hydropower Regulatory Efficiency Act of 2013 (HREA). The Gibraltar Conduit Hydroelectric Project would...

  1. 78 FR 56872 - City of Barre, Vermont; Notice of Preliminary Determination of a Qualifying Conduit Hydropower...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-16

    ... Conduit Hydropower Facility and Soliciting Comments and Motions To Intervene On August 29, 2013, City of Barre, Vermont filed a notice of intent to construct a qualifying conduit hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the Hydropower...

  2. 78 FR 66355 - Pleasant Grove City, UT; Notice of Preliminary Determination of a Qualifying Conduit Hydropower...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    ... Conduit Hydropower Facility and Soliciting Comments and Motions To Intervene On October 22, 2013, as... a qualifying conduit hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the Hydropower Regulatory Efficiency Act of 2013 (HREA). The 120 kW Battle...

  3. A one-dimensional heat-transport model for conduit flow in karst aquifers

    USGS Publications Warehouse

    Long, A.J.; Gilcrease, P.C.

    2009-01-01

    A one-dimensional heat-transport model for conduit flow in karst aquifers is presented as an alternative to two or three-dimensional distributed-parameter models, which are data intensive and require knowledge of conduit locations. This model can be applied for cases where water temperature in a well or spring receives all or part of its water from a phreatic conduit. Heat transport in the conduit is simulated by using a physically-based heat-transport equation that accounts for inflow of diffuse flow from smaller openings and fissures in the surrounding aquifer during periods of low recharge. Additional diffuse flow that is within the zone of influence of the well or spring but has not interacted with the conduit is accounted for with a binary mixing equation to proportion these different water sources. The estimation of this proportion through inverse modeling is useful for the assessment of contaminant vulnerability and well-head or spring protection. The model was applied to 7 months of continuous temperature data for a sinking stream that recharges a conduit and a pumped well open to the Madison aquifer in western South Dakota. The simulated conduit-flow fraction to the well ranged from 2% to 31% of total flow, and simulated conduit velocity ranged from 44 to 353 m/d.

  4. Sedimentary roles on hyporheic exchange in karst conduits at low Reynolds numbers by laboratory experiments

    NASA Astrophysics Data System (ADS)

    Wu, Yuexia; Hunkeler, Daniel

    2017-01-01

    The relative roles of the sediment grain size/permeability, conduit flow rate and conduit geometry/angle on the hyporheic exchange between a karst conduit and its underlying sediments under low Reynolds numbers (Re) were investigated by means of laboratory experiments and numerical simulations. Two laboratory analogues consisting of siphon structured glass tubes (with bend angles of 15 and 45°) were used for the experimental studies. Tracer experiments were performed in each analogue with sediments of variable grain size (0.45 mm, 0.4-0.7 mm, 1 mm) to characterize the transport properties of contaminants originating from the sediments. Numerical simulations were used to probe the exchange flow patterns and exchange flux magnitudes between the conduit and sediment. Tracer experiments demonstrated a zone of forward flow and a zone of reverse flow in the sediments that were independent of grain size, which were reproduced well by numerical simulations. The exchange flux ranged from 0.02% for fine grains to 2% for coarse grains under the experimental flow conditions. A linear relationship between the exchange flux and the conduit Re value, which was independent of the conduit geometry and sediment grain size, was established with numerical simulations. This study demonstrated that sediment grain size/permeability has no influence on the exchange flow patterns; however, relative to the conduit flow rate and conduit geometry/angle, sediment permeability has a much stronger influence on the exchange rate of hyporheic flow.

  5. Nanostructured Guidance for Peripheral Nerve Injuries: A Review with a Perspective in the Oral and Maxillofacial Area

    PubMed Central

    Sivolella, Stefano; Brunello, Giulia; Ferrarese, Nadia; Puppa, Alessandro Della; D’Avella, Domenico; Bressan, Eriberto; Zavan, Barbara

    2014-01-01

    Injury to peripheral nerves can occur as a result of various surgical procedures, including oral and maxillofacial surgery. In the case of nerve transaction, the gold standard treatment is the end-to-end reconnection of the two nerve stumps. When it cannot be performed, the actual strategies consist of the positioning of a nerve graft between the two stumps. Guided nerve regeneration using nano-structured scaffolds is a promising strategy to promote axon regeneration. Biodegradable electrospun conduits composed of aligned nanofibers is a new class of devices used to improve neurite extension and axon outgrowth. Self assembled peptide nanofibrous scaffolds (SAPNSs) demonstrated promising results in animal models for central nervous system injuries, and, more recently, for peripheral nerve injury. Aims of this work are (1) to review electrospun and self-assembled nanofibrous scaffolds use in vitro and in vivo for peripheral nerve regeneration; and (2) its application in peripheral nerve injuries treatment. The review focused on nanofibrous scaffolds with a diameter of less than approximately 250 nm. The conjugation in a nano scale of a natural bioactive factor with a resorbable synthetic or natural material may represent the best compromise providing both biological and mechanical cues for guided nerve regeneration. Injured peripheral nerves, such as trigeminal and facial, may benefit from these treatments. PMID:24562333

  6. An integrated model of magma chamber, conduit and column for the analysis of sustained explosive eruptions

    NASA Astrophysics Data System (ADS)

    Colucci, S.; de'Michieli Vitturi, M.; Neri, A.; Palladino, D. M.

    2014-10-01

    Explosive volcanic eruptions comprise a complex series of processes involving withdrawal from the magma chamber, magma ascent along the conduit and eruption column dynamics. Numerous studies have modeled the different sub-domains of a volcanic system, but their interplay has seldom been analyzed. To this end, we developed C3 (C-cubed, that stands for Chamber, Conduit and Column), a new integrated model that describes the dynamics of an explosive eruption as a series of steady state regimes and as a function of geometry and initial conditions of the magma reservoir. We used Global Sensitivity Analysis to quantify the role of the relevant model parameters and describe the interplay between the different volcanic sub-domains. In particular, we analyzed the evolution of a sustained explosive eruption in order to identify the conditions for buoyant, super-buoyant and collapsing columns. Input data were based on field reconstructions of Quaternary explosive eruptions in the Vulsini Volcanic District (Roman Province, central Italy). Model results show that: 1) the column regime, although affected by complex interactions among several factors, mostly depends on the conduit radius, the volatile content (i.e. supersaturation concentration at the top of the chamber) and length of the conduit, in decreasing level of importance; 2) the amount of mass erupted is independent of the conduit radius and depends mostly on volatile supersaturation, the radius of the magma chamber, the length of the conduit and the overpressure at the conduit inlet; 3) the mass flow-rate, column height and duration of the eruption are largely controlled by the conduit radius; 4) the flow pressure and density at the conduit exit are mostly controlled by the conduit inlet overpressure at the onset of the eruption, and by the length of the conduit at the end of the eruption; 5) the exit velocity from the conduit is mostly controlled by the volatile content, the length of the conduit and the inlet

  7. Large-scale tests of insulated conduit for the ITER CS coil

    NASA Astrophysics Data System (ADS)

    Reed, R. P.; Walsh, R. P.; Schutz, J. B.

    Compression-fatigue tests at 77 K were conducted on test modules of insulated Incoloy 908 conduit. To replicate the operating conditions for the ITER central solenoid (CS) full-scale coil, fatigue loads up to 3.6 MN were applied for 10 5 cycles; no mechanical breakdowns occurred. The conduits were insulated with a preimpregnated resin system, a tetraglycidyl diaminodiphenyl methane (TGDM) epoxy cured with DDS aromatic amine. The conduits were joined by vacuum-pressure impregnation with a diglycidyl ether of bisphenol-F epoxy/anhydride-cured resin system. In the 4×4 stacked-conduit test modules, the layer insulation (a high-pressure laminate of TGDM epoxy cured with DDS aromatic amine) was inserted. Periodically during the tests, breakdown voltage was measured across the conduits of both turn and layer insulation; throughout the test, breakdown voltages were at least 46 kV. The addition of a barrier increased structural and electrical reliability.

  8. Clinical uses of collagen shields.

    PubMed

    Poland, D E; Kaufman, H E

    1988-09-01

    Collagen shields immersed in tobramycin solution for one minute were applied to one eye each of 60 patients who had had cataract extraction, penetrating keratoplasty, or epikeratophakia or who had nonsurgical epithelial healing problems. The shields were well tolerated; one patient had the shield removed and one patient lost the shield in the early postoperative period. The surgical patients showed more rapid healing of epithelial defects after surgery with the use of the collagen shield. Patients with acute nonsurgical epithelial problems, such as contact lens abrasions and recurrent erosion, responded to the use of the collagen shield with improved healing. Patients with chronic epithelial defects responded poorly, presumably because underlying abnormalities in Bowman's layer prevented epithelial growth in the area of the defect. No infections were noted in any of the patients. The collagen shields appear to promote enhanced healing in patients with postsurgical and acute epithelial defects and to provide adequate antibiotic prophylaxis against infection in these vulnerable eyes.

  9. (-)-Epigallocatechin-3-gallate (EGCG) attenuates peripheral nerve degeneration in rat sciatic nerve crush injury.

    PubMed

    Renno, Waleed M; Al-Maghrebi, May; Alshammari, Ahmad; George, Preethi

    2013-02-01

    Recently, we have shown that green tea (GT) consumption improves both reflexes and sensation in unilateral chronic constriction injury to the sciatic nerve. Considering the substantial neuroprotective properties of GT polyphenols, we sought to investigate whether (-)-epigallocatechin-3-gallate (EGCG) could protect the sciatic nerve and improve functional impairments induced by a crushing injury. We also examined whether neuronal cell apoptosis induced by the crushing injury is affected by EGCG treatment. Histological examination of sciatic nerves from EGCG-treated (50mg/kg; i.p.) showed that axonotmized rats had a remarkable axonal and myelin regeneration with significant decrease in the number of myelinated axonal fibers compared to vehicle-treated crush group. Similarly, ultrastructural evaluation of EGCG-treated nerves displayed normal unmyelinated and myelinated axons with regular myelin sheath thickness and normalized appearance of Schmidt-Lantermann clefts. Extracellular matrix displayed normal collagen fibers appearance with distinctively organized distribution similar to sham animals. Analysis of foot position and extensor postural thrust test showed a progressive and faster recovery in the EGCG-treated group compared to vehicle-treated animals. EGCG-treated rats showed significant increase in paw withdrawal thresholds to mechanical stimulation compared to vehicle-treated crush group. EGCG treatment also restored the mRNA expression of Bax, Bcl-2 and survivin but not that of p53 to sham levels on days 3 and 7 post-injury. Our results demonstrate that EGCG treatment enhanced functional recovery, advanced morphological nerve rescue and accelerated nerve regeneration following crush injury partly due to the down regulation of apoptosis related genes.

  10. Human collagen produced in plants

    PubMed Central

    Shoseyov, Oded; Posen, Yehudit; Grynspan, Frida

    2014-01-01

    Consequential to its essential role as a mechanical support and affinity regulator in extracellular matrices, collagen constitutes a highly sought after scaffolding material for regeneration and healing applications. However, substantiated concerns have been raised with regard to quality and safety of animal tissue-extracted collagen, particularly in relation to its immunogenicity, risk of disease transmission and overall quality and consistency. In parallel, contamination with undesirable cellular factors can significantly impair its bioactivity, vis-a-vis its impact on cell recruitment, proliferation and differentiation. High-scale production of recombinant human collagen Type I (rhCOL1) in the tobacco plant provides a source of an homogenic, heterotrimeric, thermally stable “virgin” collagen which self assembles to fine homogenous fibrils displaying intact binding sites and has been applied to form numerous functional scaffolds for tissue engineering and regenerative medicine. In addition, rhCOL1 can form liquid crystal structures, yielding a well-organized and mechanically strong membrane, two properties indispensable to extracellular matrix (ECM) mimicry. Overall, the shortcomings of animal- and cadaver-derived collagens arising from their source diversity and recycled nature are fully overcome in the plant setting, constituting a collagen source ideal for tissue engineering and regenerative medicine applications. PMID:23941988

  11. Promoting central nervous system regeneration: lessons from cranial nerve I.

    PubMed

    Ruitenberg, Marc J; Vukovic, Jana

    2008-01-01

    The olfactory nerve differs from cranial nerves III-XII in that it contains a specialised type of glial cell, called 'olfactory ensheathing cell' (OEC), rather than Schwann cells. In addition, functional neurogenesis persists postnatally in the olfactory system, i.e. the primary olfactory pathway continuously rebuilds itself throughout adult life. The presence of OECs in the olfactory nerve is thought to be critical to this continuous growth process. Because of this intrinsic capacity for self-repair, the mammalian olfactory system has proved as a useful model in neuroregeneration studies. In addition, OECs have been used in transplantation studies to promote pathway regeneration elsewhere in the nervous system. Here, we have reviewed the parameters that allow for repair within the primary olfactory pathway and the role that OECs are thought to play in this process. We conclude that, in addition to intrinsic growth potential, the presence of an aligned substrate to the target structure is a fundamental prerequisite for appropriate restoration of connectivity with the olfactory bulb. Hence, strategies to promote regrowth of injured nerve pathways should incorporate usage of aligned, oriented substrates of OECs or other cellular conduits with additional intervention to boost neuronal cell body responses to injury and/or neutralisation of putative inhibitors.

  12. Peripheral nerve surgery.

    PubMed

    McQuarrie, I G

    1985-05-01

    In treating the three main surgical problems of peripheral nerves--nerve sheath tumors, entrapment neuropathies, and acute nerve injuries--the overriding consideration is the preservation and restoration of neurologic function. Because of this, certain other principles may need to be compromised. These include achieving a gross total excision of benign tumors, employing conservative therapy as long as a disease process is not clearly progressing, and delaying repair of a nerve transection until the skin wound has healed. Only three pathophysiologic processes need be considered: neurapraxia (focal segmental dymyelination), axonotmesis (wallerian degeneration caused by a lesion that does not disrupt fascicles of nerve fibers), and neurotmesis (wallerian degeneration caused by a lesion that interrupts fascicles). With nerve sheath tumors and entrapment neuropathies, the goal is minimize the extent to which neurapraxia progresses to axonotmesis. The compressive force is relieved without carrying out internal neurolysis, a procedure that is poorly tolerated, presumably because a degree of nerve ischemia exists with any long-standing compression. When the nerve has sustained blunt trauma (through acute compression, percussion, or traction), the result can be a total loss of function and an extensive neuroma-in-continuity (scarring within the nerve). However, the neural pathophysiology may amount to nothing more than axonotmesis. Although this lesion, in time, leads to full and spontaneous recovery, it must be differentiated from the neuroma-in-continuity that contains disrupted fascicles requiring surgery. Finally, with open nerve transection, the priority is to match the fascicles of the proximal stump with those of the distal stump, a goal that is best achieved if primary neurorrhaphy is carried out.

  13. Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

    PubMed

    Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

    2015-12-01

    During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure.

  14. Mutual attraction between emigrant cells from transected denervated nerve.

    PubMed Central

    Abernethy, D A; Thomas, P K; Rud, A; King, R H

    1994-01-01

    It is known that regenerating axons emerging from the proximal stump of a transected nerve are attracted towards the distal stump. It is not certain whether this neurotropic effect is on the axons themselves or whether it is on supporting cells such as Schwann cells that the axons then follow. In order to investigate this question in rats, segments of the sciatic nerve were either isolated or removed and reinserted as grafts, and then sutured into the opposing ends of double-Y silicone tubes. In these tubes, a central conduit was formed by connecting the centrally facing limb of each Y tube. The nerve segments were sutured into one of the limbs at either end. The third limbs of the Y tubes formed side arms, one of which was left open; a plug of mobilised fatty connective tissue was sutured into the other. A gap of 6 mm was left between the cut ends and the fat pads (or openings from the side arms). After 2-3 wk a significantly greater outgrowth (P < 0.001) was found to link the nerve segments than to invade the side arms. The major cell component in the outgrowth was Schwann cells, supported by fibroblasts and capillaries and surrounded by a lamellated layer of flattened fibroblasts. The growth into the side arms had a looser cellular architecture and contained considerably fewer Schwann cells. The results strongly suggest the existence of mutual attraction between emigrant Schwann cells, or possibly endoneurial fibroblasts, from the 2 cut ends of transected nerves. This conclusion has implications for the guidance of axons across gaps in nerves. It does not exclude an additional neurotropic effect from the distal stump on axons. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8014117

  15. Nanomechanics of Type I Collagen.

    PubMed

    Varma, Sameer; Orgel, Joseph P R O; Schieber, Jay D

    2016-07-12

    Type I collagen is the predominant collagen in mature tendons and ligaments, where it gives them their load-bearing mechanical properties. Fibrils of type I collagen are formed by the packing of polypeptide triple helices. Higher-order structures like fibril bundles and fibers are assembled from fibrils in the presence of other collagenous molecules and noncollagenous molecules. Curiously, however, experiments show that fibrils/fibril bundles are less resistant to axial stress compared to their constituent triple helices-the Young's moduli of fibrils/fibril bundles are an order-of-magnitude smaller than the Young's moduli of triple helices. Given the sensitivity of the Young's moduli of triple helices to solvation environment, a plausible explanation is that the packing of triple helices into fibrils perhaps reduces the Young's modulus of an individual triple helix, which results in fibrils having smaller Young's moduli. We find, however, from molecular dynamics and accelerated conformational sampling simulations that the Young's modulus of the buried core of the fibril is of the same order as that of a triple helix in aqueous phase. These simulations, therefore, suggest that the lower Young's moduli of fibrils/fibril bundles cannot be attributed to the specific packing of triple helices in the fibril core. It is not the fibril core that yields initially to axial stress. Rather, it must be the portion of the fibril exposed to the solvent and/or the fibril-fibril interface that bears the initial strain. Overall, this work provides estimates of Young's moduli and persistence lengths at two levels of collagen's structural assembly, which are necessary to quantitatively investigate the response of various biological factors on collagen mechanics, including congenital mutations, posttranslational modifications and ligand binding, and also engineer new collagen-based materials.

  16. Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair.

    PubMed

    Kingham, Paul J; Kolar, Mallappa K; Novikova, Liudmila N; Novikov, Lev N; Wiberg, Mikael

    2014-04-01

    In future, adipose-derived stem cells (ASC) might be used to treat neurological disorders. In this study, the neurotrophic and angiogenic properties of human ASC were evaluated, and their effects in a peripheral nerve injury model were determined. In vitro growth factor stimulation of the cells resulted in increased secretion of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor-A (VEGF-A), and angiopoietin-1 proteins. Conditioned medium from stimulated cells increased neurite outgrowth of dorsal root ganglia (DRG) neurons. Similarly, stimulated cells showed an enhanced ability to induce capillary-like tube formation in an in vitro angiogenesis assay. ASC were seeded into a fibrin conduit that was used to bridge a 10 mm rat nerve gap. After 2 weeks, the animals treated with control or stimulated ASC showed an enhanced axon regeneration distance. Stimulated cells evoked more total axon growth. Analysis of regeneration and apoptosis-related gene expression showed that both ASC and stimulated ASC enhanced GAP-43 and activating transcription factor 3 (ATF-3) expression in the spinal cord and reduced c-jun expression in the DRG. Caspase-3 expression in the DRG was reduced by stimulated ASC. Both ASC and stimulated ASC also increased the vascularity of the fibrin nerve conduits. Thus, ASC produce functional neurotrophic and angiogenic factors, creating a more desirable microenvironment for nerve regeneration.

  17. Modeling the closure of volcanic conduits with an application to Mount Vesuvius

    NASA Astrophysics Data System (ADS)

    Quareni, Francesca; Mulargia, Francesco

    1993-03-01

    The eruptive activity of a volcano is controlled by the opening and closure of conduits through which magma ascends to the surface. We develop a model to study the deformation of a cylindrical conduit surrounded by a viscoelastic cylindrical region in an infinite, elastic, homogeneous space. The viscoelastic behavior of the zone around the conduit is due to heat conduction from the hot magma, which raises the temperature beyond the brittle-ductile transition point. The effect of a tectonic regional stress which favors (compressive) or acts against (tensile) conduit closure is taken into account. Conduit closure is found to be ruled essentially by the extension of the viscoelastic region and by the ratio between its rigidity and the rigidity of the surrounding elastic medium, while tectonic stress is much less important. The model is applied to the last eruptive cycle of Mount Vesuvius. We find that an open conduit condition has been possible from 1631 to 1944, while the quiescence from 1944 on implies a closed conduit state.

  18. Enhanced stabilization of collagen by furfural.

    PubMed

    Lakra, Rachita; Kiran, Manikantan Syamala; Usha, Ramamoorthy; Mohan, Ranganathan; Sundaresan, Raja; Korrapati, Purna Sai

    2014-04-01

    Furfural (2-furancarboxaldehyde), a product derived from plant pentosans, has been investigated for its interaction with collagen. Introduction of furfural during fibril formation enhanced the thermal and mechanical stability of collagen. Collagen films treated with furfural exhibited higher denaturation temperature (Td) (p<0.04) and showed a 3-fold increase in Young's modulus (p<0.04) at higher concentration. Furfural and furfural treated collagen films did not have any cytotoxic effect. Rheological characterization showed an increase in shear stress and shear viscosity with increasing shear rate for treated collagen. Circular dichroism (CD) studies indicated that the furfural did not have any impact on triple helical structure of collagen. Scanning electron microscopy (SEM) of furfural treated collagen exhibited small sized porous structure in comparison with untreated collagen. Thus this study provides an alternate ecologically safe crosslinking agent for improving the stability of collagen for biomedical and industrial applications.

  19. Effect of mutated defensin NP-1 on sciatic nerve regeneration after transection--A pivot study.

    PubMed

    Xu, Chungui; Bai, Lili; Chen, Yuhong; Fan, Chengming; Hu, Zanmin; Xu, Hailin; Jiang, Baoguo

    2016-03-23

    Defensins are small cationic peptides that constitute the first line of defense against pathogens and are involved in immune regulation. In this study, their role in peripheral nerve regeneration was investigated. Rat sciatic nerves were transected and the two nerve stumps were bridged by a chitin conduit with a gap of 5mm between the stumps. The animals were injected intramuscularly with mutated rabbit neutrophil peptide 1 (defensin mNP-1), the positive control nerve growth factor (NGF) or the negative control saline, for 7 consecutive days after repair. After 6 weeks, the sciatic functional index (SFI), MNCV (motor nerve conductive velocity) and morphological parameters including myelinated fiber amounts, fiber diameter, axon diameter, myelin thickness and G-ratio were measured. Compared to the SFI of saline group, the NGF and mNP-1 groups had an increase of 18.3% and 18.8%, respectively. The numbers of myelinated fibers in the distal nerve of NGF and mNP-1 groups were 1.45- and 1.32-fold higher than in the saline group. The MNCVs of NGF and mNP-1 groups were 7.3 and 4.4 times of that of saline group. Fiber diameter, axon diameter, myelin thickness and G-ratio in the NGF and mNP-1 groups were also significantly higher than those of saline group. Our results demonstrate that, like NGF, the defensin mNP-1 can promote regeneration after a peripheral nerve cut.

  20. Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.

    PubMed

    Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

    2012-06-29

    The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone.

  1. Hydroperoxide formation in model collagens and collagen type I.

    PubMed

    Madison, S A; McCallum, J E B; Rojas Wahl, R U

    2002-02-01

    Protein hydroperoxides represent a relatively new concept in understanding biological oxidation chemistry. Here, we show with post-column-chemiluminescence that this sometimes remarkably stable and yet reactive species can be formed in collagen models and collagen type I when submitted to oxidative stress as exemplified by the Fenton reaction. These findings are supported by mass spectrometry and iodometry. Using (Proline-hydroxyproline-glycine)(10) (POG)(10), those hydroperoxides are stable for hours at room temperature and can give rise to free radicals in the presence of ferrous sulphate, as evidenced by EPR spin trapping with DMPO. Possible implications for biological systems are discussed with emphasis on collagen in the extracellular matrix in skin as a major type of connective tissue.

  2. Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

    DTIC Science & Technology

    2013-01-01

    there was any dose response to the nanofibers, by varying the density of nanofibers per unit area of conduit by electrospinning for different lengths...the films with nanofibers by electrospinning directly upon them, requiring the films to be sufficiently strong to not break when rotated at over 1000...within the conduits. Next, we will use the electrospinning parameters optimized over the last year to spin larger and smaller fibers (1200 nm and

  3. Glossopharyngeal Nerve Schwannoma

    PubMed Central

    Puzzilli, F.; Mastronardi, L.; Agrillo, U.; Nardi, P.

    1999-01-01

    Complete resection with conservation of cranial nerves is the primary goal of contemporary surgery for lower cranial nerve tumors. We describe the case of a patient with a schwannoma of the left glossopharyngeal nerve, operated on in our Neurosurgical Unit. The far lateral approach combined with laminectomy of the posterior arch of C1 was done in two steps. The procedure allowed total tumor resection and was found to be better than classic unilateral suboccipital or combined supra- and infratentorial approaches. The advantages and disadvantages of the far lateral transcondylar approach, compared to the other more common approaches, are discussed. ImagesFigure 1Figure 2 PMID:17171083

  4. The Role of Collagen Quaternary Structure in the Platelet:Collagen Interaction

    PubMed Central

    Brass, Lawrence F.; Bensusan, Howard B.

    1974-01-01

    We have investigated whether collagen queternary structure is required for the platelet: collagen interaction. Quaternary structure refers to the assembly of collagen monomers (tropocollagen) into polymers (native-type fibrils). Purified monomeric collagen was prepared from acetic acid extracts of fetal calfskin. Polymeric collagen was prepared by dispersion of bovine Achilles tendon collagen and by incubation of monomeric collagen at 37°C and pH 7.4. The state of polymerization was confirmed by electron microscopy. Release of platelet serotonin in the absence of platelet aggregation was used to determine the effectiveness of the platelet: collagen interaction. All forms of collagen produced serotonin release only after a lag period, but polymeric collagen gave a shorter lag period than did monomeric collagen. Monomeric collagen was also quanidinated selectively to convert collagen lysine groups to homoarginine, while leaving the arrangement of polar groups intact. Guanidination of monomeric collagen increased the rate of polymerization and reduced the lag time in serotonin release. Glucosamine (17 mM) retarded polymerization and inhibited the release of platelet serotonin by monomeric collagen but had little effect on release produced by thrombin or polymeric collagen. At the same concentration, glucosamine did not reduce the sensitivity of platelets to stimulation by collagen or block the platelet: collagen interaction. The only effect of glucosamine was on the collagen: collagen interaction. Galactosamine had a similar effect, but glucose, galactose, and N-acetylglycosamine had no effect. We conclude from this data that collagen monomers cannot effectively interact with platelets and that, therefore, collagen quaternary structure has a role in the recognition of collagen by platelets. PMID:4215825

  5. Structure of a Bacterial Cell Surface Decaheme Electron Conduit

    SciTech Connect

    Clarke, Thomas A.; Edwards, Marcus; Gates, Andrew J.; Hall, Andrea; White, Gaye; Bradley, Justin; Reardon, Catherine L.; Shi, Liang; Beliaev, Alex S.; Marshall, Matthew J.; Wang, Zheming; Watmough, Nicholas; Fredrickson, Jim K.; Zachara, John M.; Butt, Julea N.; Richardson, David J.

    2011-05-23

    Some bacterial species are able to utilize extracellular mineral forms of iron and manganese as respiratory electron acceptors. In Shewanella oneidensis this involves deca-heme cytochromes that are located on the bacterial cell surface at the termini of trans-outermembrane (OM) electron transfer conduits. The cell surface cytochromes can potentially play multiple roles in mediating electron transfer directly to insoluble electron sinks, catalyzing electron exchange with flavin electron shuttles or participating in extracellular inter-cytochrome electron exchange along ‘nanowire’ appendages. We present a 3.2 Å crystal structure of one of these deca-heme cytochromes, MtrF, that allows the spatial organization of the ten hemes to be visualized for the first time. The hemes are organized across four domains in a unique crossed conformation, in which a staggered 65 Å octa-heme chain transects the length of the protein and is bisected by a planar 45 Å tetra-heme chain that connects two extended Greek key split β-barrel domains. The structure provides molecular insight into how reduction of insoluble substrate (e.g. minerals), soluble substrates (e.g. flavins) and cytochrome redox partners might be possible in tandem at different termini of a trifurcated electron transport chain on the cell surface.

  6. A conduit dilation model of methane venting from lake sediments

    USGS Publications Warehouse

    Scandella, B.P.; Varadharajan, C.; Hemond, Harold F.; Ruppel, C.; Juanes, R.

    2011-01-01

    Methane is a potent greenhouse gas, but its effects on Earth's climate remain poorly constrained, in part due to uncertainties in global methane fluxes to the atmosphere. An important source of atmospheric methane is the methane generated in organic-rich sediments underlying surface water bodies, including lakes, wetlands, and the ocean. The fraction of the methane that reaches the atmosphere depends critically on the mode and spatiotemporal characteristics of free-gas venting from the underlying sediments. Here we propose that methane transport in lake sediments is controlled by dynamic conduits, which dilate and release gas as the falling hydrostatic pressure reduces the effective stress below the tensile strength of the sediments. We test our model against a four-month record of hydrostatic load and methane flux in Upper Mystic Lake, Mass., USA, and show that it captures the complex episodicity of methane ebullition. Our quantitative conceptualization opens the door to integrated modeling of methane transport to constrain global methane release from lakes and other shallow-water, organic-rich sediment systems, and to assess its climate feedbacks.

  7. Structure of a bacterial cell surface decaheme electron conduit.

    PubMed

    Clarke, Thomas A; Edwards, Marcus J; Gates, Andrew J; Hall, Andrea; White, Gaye F; Bradley, Justin; Reardon, Catherine L; Shi, Liang; Beliaev, Alexander S; Marshall, Matthew J; Wang, Zheming; Watmough, Nicholas J; Fredrickson, James K; Zachara, John M; Butt, Julea N; Richardson, David J

    2011-06-07

    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. The cell surface cytochromes can potentially play multiple roles in mediating electron transfer directly to insoluble electron sinks, catalyzing electron exchange with flavin electron shuttles or participating in extracellular intercytochrome electron exchange along "nanowire" appendages. We present a 3.2-Å crystal structure of one of these decaheme cytochromes, MtrF, that allows the spatial organization of the 10 hemes to be visualized for the first time. The hemes are organized across four domains in a unique crossed conformation, in which a staggered 65-Å octaheme chain transects the length of the protein and is bisected by a planar 45-Å tetraheme chain that connects two extended Greek key split β-barrel domains. The structure provides molecular insight into how reduction of insoluble substrate (e.g., minerals), soluble substrates (e.g., flavins), and cytochrome redox partners might be possible in tandem at different termini of a trifurcated electron transport chain on the cell surface.

  8. Mapping the Hawaiian plume conduit with converted seismic waves

    PubMed

    Li; Kind; Priestley; Sobolev; Tilmann; Yuan; Weber

    2000-06-22

    The volcanic edifice of the Hawaiian islands and seamounts, as well as the surrounding area of shallow sea floor known as the Hawaiian swell, are believed to result from the passage of the oceanic lithosphere over a mantle hotspot. Although geochemical and gravity observations indicate the existence of a mantle thermal plume beneath Hawaii, no direct seismic evidence for such a plume in the upper mantle has yet been found. Here we present an analysis of compressional-to-shear (P-to-S) converted seismic phases, recorded on seismograph stations on the Hawaiian islands, that indicate a zone of very low shear-wave velocity (< 4 km s(-1)) starting at 130-140 km depth beneath the central part of the island of Hawaii and extending deeper into the upper mantle. We also find that the upper-mantle transition zone (410-660 km depth) appears to be thinned by up to 40-50 km to the south-southwest of the island of Hawaii. We interpret these observations as localized effects of the Hawaiian plume conduit in the asthenosphere and mantle transition zone with excess temperature of approximately 300 degrees C. Large variations in the transition-zone thickness suggest a lower-mantle origin of the Hawaiian plume similar to the Iceland plume, but our results indicate a 100 degrees C higher temperature for the Hawaiian plume.

  9. A conduit dilation model of methane venting from lake sediments

    NASA Astrophysics Data System (ADS)

    Scandella, Benjamin P.; Varadharajan, Charuleka; Hemond, Harold F.; Ruppel, Carolyn; Juanes, Ruben

    2011-03-01

    Methane is a potent greenhouse gas, but its effects on Earth's climate remain poorly constrained, in part due to uncertainties in global methane fluxes to the atmosphere. An important source of atmospheric methane is the methane generated in organic-rich sediments underlying surface water bodies, including lakes, wetlands, and the ocean. The fraction of the methane that reaches the atmosphere depends critically on the mode and spatiotemporal characteristics of free-gas venting from the underlying sediments. Here we propose that methane transport in lake sediments is controlled by dynamic conduits, which dilate and release gas as the falling hydrostatic pressure reduces the effective stress below the tensile strength of the sediments. We test our model against a four-month record of hydrostatic load and methane flux in Upper Mystic Lake, Mass., USA, and show that it captures the complex episodicity of methane ebullition. Our quantitative conceptualization opens the door to integrated modeling of methane transport to constrain global methane release from lakes and other shallow-water, organic-rich sediment systems, and to assess its climate feedbacks.

  10. Linear ordered collagen scaffolds loaded with collagen-binding neurotrophin-3 promote axonal regeneration and partial functional recovery after complete spinal cord transection.

    PubMed

    Fan, Juan; Xiao, Zhifeng; Zhang, Hongtian; Chen, Bing; Tang, Guoqiang; Hou, Xianglin; Ding, Wenyong; Wang, Bin; Zhang, Peng; Dai, Jianwu; Xu, Ruxiang

    2010-09-01

    Neurotrophin-3 (NT3) is an important neurotrophic factor for spinal cord injury (SCI) repair. However, constant exchange of cerebrospinal fluid often decreases the effective dosage of NT3 at the targeted injury site. In the present study, a recombinant collagen-binding NT3 (CBD-NT3), consisting of a collagen-binding domain (CBD) and native NT3, was constructed. Linear rat-tail collagen (LRTC) was used as a physical carrier for CBD-NT3 to construct a LRTC/C3 system. The collagen-binding ability of CBD-NT3 was verified, and the bioactivity of CBD-NT3 was assayed with neurite outgrowth of dorsal root ganglia (DRG) explants and DRG cells in vitro. After complete spinal cord transection in rats, LRTC/CBD-NT3 or the LRTC/NT3 system was transplanted into the injury site. Hindlimb locomotion recovery was closely observed using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale and the grid walk test. Significant improvement was observed in the LRTC/CBD-NT3 group. The results of regenerating nerve fiber and anterograde tracing of biotinylated dextran amine (BDA)-labeled corticospinal tract (CST) fibers demonstrated axonal regeneration of LRTC/CBD-NT3 in the injured spinal cord. Serotonin fiber regrowth also illustrated the effectiveness of LRTC/CBD-NT3. Thus, collagen-binding NT3 with LRTC may provide an effective method for treating SCI.

  11. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  12. Optic Nerve Imaging

    MedlinePlus

    ... machines can help monitor and detect loss of optic nerve fibers. The Heidelberg Retina Tomograph (HRT) is a special ... keeping organized, you can establish a routine that works for you. Read more » Are You at Risk ...

  13. Axillary nerve dysfunction

    MedlinePlus

    ... Causes Axillary nerve dysfunction is a form of peripheral neuropathy . It occurs when there is damage to the ... Multiple mononeuropathy Muscle function loss Numbness and tingling Peripheral neuropathy Systemic Review Date 2/3/2015 Updated by: ...

  14. Tibial nerve dysfunction

    MedlinePlus

    ... Tibial nerve dysfunction is an unusual form of peripheral neuropathy . It occurs when there is damage to the ... PA: Elsevier Saunders; 2012:chap 76. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman-Cecil ...

  15. Vagus Nerve Stimulation.

    PubMed

    Howland, Robert H

    2014-06-01

    The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality.

  16. Ulnar nerve damage (image)

    MedlinePlus

    ... is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near the surface of the body where it crosses the elbow, so prolonged pressure on the elbow or entrapment ...

  17. Optic Nerve Disorders

    MedlinePlus

    ... of optic nerve disorders, including: Glaucoma is a group of diseases that are the leading cause of blindness in the United States. Glaucoma usually happens when the fluid pressure inside the eyes slowly rises and damages the ...

  18. Nerve Damage (Diabetic Neuropathies)

    MedlinePlus

    ... may include numbness or insensitivity to pain or temperature a tingling, burning, or prickling sensation sharp pains ... from working properly, the body cannot regulate its temperature as it should. Nerve damage can also cause ...

  19. Diabetes and nerve damage

    MedlinePlus

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  20. Vagus Nerve Stimulation

    PubMed Central

    Howland, Robert H.

    2014-01-01

    The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality. PMID:24834378

  1. Diabetic Nerve Problems

    MedlinePlus

    ... at the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get it. ... you change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. Controlling ...

  2. Effects of Local Administration of Platelet Rich Plasma on Functional Recovery after Bridging Sciatic Nerve Defect Using Silicone Rubber Chamber; An Experimental Study

    PubMed Central

    Abbasipour-Dalivand, Sedighe; Mohammadi, Rahim; Mohammadi, Vahid

    2015-01-01

    Objective: To determine the effects of local administration of platelet rich plasma (PRP) on peripheral nerve regeneration in rat sciatic nerve transection model. Methods: Forty-five male white Wistar rats were randomized into three experimental groups (n=15): Normal control group (NC), silicon group (SIL), PRP treated group (SIL/PRP). In NC group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In SIL group left sciatic nerve was exposed the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone conduit and filled with 10 µL phosphate buffered solution. In SIL/PRP group silicon conduit was filled with 20 µL PRP. Each group was subdivided into three subgroups of five animals each and were studied 4, 8, 12 weeks after surgery. Results: The animals were comparable regarding the baseline characteristics. Behavioral testing, sciatic nerve functional study and gastrocnemius muscle mass showed earlier regeneration of axons in SIL/PRP than in SIL group. Conclusion: Local administration of PRP combined with silicon grafting could accelerate functional recovery of peripheral nerve.  Easily available growth factors and bioactive proteins present in PRP may have clinical implications for the surgical management of patients after nerve transection. PMID:27162893

  3. Nerves and Tissue Repair.

    DTIC Science & Technology

    1992-05-21

    complete dependence on nerves. Organ culture of sciatic nerves, combined with an assay for axolotl transferrin developed earlier, allows quantitative study...axonal release of various unknown proteins. Combining this approach with the ELISA for quantitative measurement of axolotl transferrin developed with...light microscope autoradiographic analysis following binding of radiolabelled Tf. Studies of Tf synthesis will employ cDNA probes for axolotl Tf mRNA

  4. Traumatic facial nerve injury.

    PubMed

    Lee, Linda N; Lyford-Pike, Sofia; Boahene, Kofi Derek O

    2013-10-01

    Facial nerve trauma can be a devastating injury resulting in functional deficits and psychological distress. Deciding on the optimal course of treatment for patients with traumatic facial nerve injuries can be challenging, as there are many critical factors to be considered for each patient. Choosing from the great array of therapeutic options available can become overwhelming to both patients and physicians, and in this article, the authors present a systematic approach to help organize the physician's thought process.

  5. Lower cranial nerves.

    PubMed

    Soldatos, Theodoros; Batra, Kiran; Blitz, Ari M; Chhabra, Avneesh

    2014-02-01

    Imaging evaluation of cranial neuropathies requires thorough knowledge of the anatomic, physiologic, and pathologic features of the cranial nerves, as well as detailed clinical information, which is necessary for tailoring the examinations, locating the abnormalities, and interpreting the imaging findings. This article provides clinical, anatomic, and radiological information on lower (7th to 12th) cranial nerves, along with high-resolution magnetic resonance images as a guide for optimal imaging technique, so as to improve the diagnosis of cranial neuropathy.

  6. Mandibular Cartilage Collagen Network Nanostructure

    PubMed Central

    Vanden Berg-Foels, Wendy S.

    2015-01-01

    Background Mandibular condyle cartilage (MCC) has a unique structure among articular cartilages; however, little is known about its nanoscale collagen network architecture, hampering design of regeneration therapies and rigorous evaluation of regeneration experiment outcomes in preclinical research. Helium ion microscopy is a novel technology with a long depth of field that is uniquely suited to imaging open 3D collagen networks at multiple scales without obscuring conductive coatings. Objective The objective of this research was to image, at the micro- and nanoscales, the depth-dependent MCC collagen network architecture. Design MCC was collected from New Zealand white rabbits. Images of MCC zones were acquired using helium ion, transmission electron, and light microscopy. Network fibril and canal diameters were measured. Results For the first time, the MCC was visualized as a 3D collagen fibril structure at the nanoscale, the length scale of network assembly. Fibril diameters ranged from 7 to 110 nm and varied by zone. The articular surface was composed of a fine mesh that was woven through thin layers of larger fibrils. The fibrous zone was composed of approximately orthogonal lamellae of aligned fibrils. Fibrocyte processes surrounded collagen bundles forming extracellular compartments. The proliferative, mature, and hypertrophic zones were composed of a branched network that was progressively remodeled to accommodate chondrocyte hypertrophy. Osteoid fibrils were woven around osteoblast cytoplasmic processes to create numerous canals similar in size to canaliculi of mature bone. Conclusion This multiscale investigation advances our foundational understanding of the complex, layered 3D architecture of the MCC collagen network. PMID:27375843

  7. Mice lacking the extracellular matrix protein WARP develop normally but have compromised peripheral nerve structure and function.

    PubMed

    Allen, Justin M; Zamurs, Laura; Brachvogel, Bent; Schlötzer-Schrehardt, Ursula; Hansen, Uwe; Lamandé, Shireen R; Rowley, Lynn; Fitzgerald, Jamie; Bateman, John F

    2009-05-01

    WARP is a recently identified extracellular matrix molecule with restricted expression in permanent cartilages and a distinct subset of basement membranes in peripheral nerves, muscle, and the central nervous system vasculature. WARP interacts with perlecan, and we also demonstrate here that WARP binds type VI collagen, suggesting a function in bridging connective tissue structures. To understand the in vivo function of WARP, we generated a WARP-deficient mouse strain. WARP-null mice were healthy, viable, and fertile with no overt abnormalities. Motor function and behavioral testing demonstrated that WARP-null mice exhibited a significantly delayed response to acute painful stimulus and impaired fine motor coordination, although general motor function was not affected, suggesting compromised peripheral nerve function. Immunostaining of WARP-interacting ligands demonstrated that the collagen VI microfibrillar matrix was severely reduced and mislocalized in peripheral nerves of WARP-null mice. Further ultrastructural analysis revealed reduced fibrillar collagen deposition within the peripheral nerve extracellular matrix and abnormal partial fusing of adjacent Schwann cell basement membranes, suggesting an important function for WARP in stabilizing the association of the collagenous interstitial matrix with the Schwann cell basement membrane. In contrast, other WARP-deficient tissues such as articular cartilage, intervertebral discs, and skeletal muscle showed no detectable abnormalities, and basement membranes formed normally. Our data demonstrate that although WARP is not essential for basement membrane formation or musculoskeletal development, it has critical roles in the structure and function of peripheral nerves.

  8. Short- and long-term peripheral nerve regeneration using a poly-lactic-co-glycolic-acid scaffold containing nerve growth factor and glial cell line-derived neurotrophic factor releasing microspheres.

    PubMed

    de Boer, Ralph; Borntraeger, Andreas; Knight, Andrew M; Hébert-Blouin, Marie-Noëlle; Spinner, Robert J; Malessy, Martijn J A; Yaszemski, Michael J; Windebank, Anthony J

    2012-08-01

    Addition of neural growth factors to bioengineered scaffolds may improve peripheral nerve regeneration. The aim of this study is to evaluate the short- and long term effect of microsphere delivered nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF) in the 10 mm rat sciatic nerve gap. Eighty-four rats were assigned to seven groups (n = 6) at two endpoints (6 and 16 weeks): saline, saline NGF, saline NGF-microspheres, saline GDNF, saline GDNF-microspheres, saline blank microspheres, and autologous nerve graft. Total fascicular area and total number of myelinated fibers at mid-tube increased in all conduit groups between 6 and 16 weeks. Autologous, saline NGF-microsphere and saline GDNF-microsphere groups reached maximal histomorphometric values by 6 weeks (p < 0.05). Compound muscle action potentials returned after 6 weeks for the autologous graft and continued to increase to a level of 3.6 ± 1.9 mV at endpoint. No significant differences were found between study groups as measured by ankle angle. These experiments show an initial beneficial effect of incorporation of NGF- or GDNF-microspheres in a PLGA 85/15 nerve conduit, since histomorphometric values reached their maximum by 6 weeks compared to control groups. These results do not yet extrapolate into improved electrophysiological or functional improvement.

  9. Optic nerve aspergillosis.

    PubMed

    Yuan, Lisi; Prayson, Richard A

    2015-07-01

    We report a 55-year-old woman with optic nerve Aspergillosis. Aspergillus is an ubiquitous airborne saprophytic fungus. Inhaled Aspergillus conidia are normally eliminated in the immunocompetent host by innate immune mechanisms; however, in immunosuppressed patients, they can cause disease. The woman had a past medical history of hypertension and migraines. She presented 1 year prior to death with a new onset headache behind the left eye and later developed blurred vision and scotoma. A left temporal artery biopsy was negative for giant cell arteritis. One month prior to the current admission, she had an MRI showing optic nerve thickening with no other findings. Because of the visual loss and a positive antinuclear antibody test, she was given a trial of high dose steroids and while it significantly improved her headache, her vision did not improve. At autopsy, the left optic nerve at the level of the cavernous sinus and extending into the optic chiasm was enlarged in diameter and there was a 1.3 cm firm nodule surrounding the left optic nerve. Histologically, an abscess surrounded and involved the left optic nerve. Acute angle branching, angioinvasive fungal hyphae were identified on Grocott's methenamine silver stained sections, consistent with Aspergillus spp. No gross or microscopic evidence of systemic vasculitis or infection was identified in the body. The literature on optic nerve Aspergillosis is reviewed.

  10. Cranial nerves in the Australian lungfish, Neoceratodus forsteri, and in fossil relatives (Osteichthyes: Dipnoi).

    PubMed

    Kemp, A

    2017-02-01

    Three systems, two sensory and one protective, are present in the skin of the living Australian lungfish, Neoceratodus forsteri, and in fossil lungfish, and the arrangement and innervation of the sense organs is peculiar to lungfish. Peripheral branches of nerves that innervate the sense organs are slender and unprotected, and form before any skeletal structures appear. When the olfactory capsule develops, it traps some of the anterior branches of cranial nerve V, which emerged from the chondrocranium from the lateral sphenotic foramen. Cranial nerve I innervates the olfactory organ enclosed within the olfactory capsule and cranial nerve II innervates the eye. Cranial nerve V innervates the sense organs of the snout and upper lip, and, in conjunction with nerve IX and X, the sense organs of the posterior and lateral head. Cranial nerve VII is primarily a motor nerve, and a single branch innervates sense organs in the mandible. There are no connections between nerves V and VII, although both emerge from the brain close to each other. The third associated system consists of lymphatic vessels covered by an extracellular matrix of collagen, mineralised as tubules in fossils. Innervation of the sensory organs is separate from the lymphatic system and from the tubule system of fossil lungfish.

  11. In vivo visualization of microneedle conduits in human skin using laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Bal, S.; Kruithof, A. C.; Liebl, H.; Tomerius, M.; Bouwstra, J.; Lademann, J.; Meinke, M.

    2010-03-01

    Solid microneedles enhance the penetration of drugs into the viable skin but little is known about the geometry of the conduits in vivo. Therefore, laser scanning microscopy was used to visualize the conduits of a microneedle system with needles at a length of 300 μm in 6 healthy subjects over a period of time. The model drug, a fluorescent dye was applied before and after piercing. Laser scanning microscopy was evaluated as being an excellent method to monitor the geometry and closure of the conduits over time. The used microneedle system was evaluated as suitable to enhance the transport of model drugs into the viable epidermis without bleeding and a short closure time of the conduits at the skin surface.

  12. The evolution of fibrillar collagens: a sea-pen collagen shares common features with vertebrate type V collagen.

    PubMed

    Tillet, E; Franc, J M; Franc, S; Garrone, R

    1996-02-01

    The extracellular matrix of marine primitive invertebrates (sponges, polyps and jellyfishes) contains collagen fibrils with narrow diameters. From various data, it has been hypothesized that these primitive collagens could represent ancestral forms of the vertebrate minor collagens, i.e., types V or XI. Recently we have isolated a primitive collagen from the soft tissues of the sea-pen Veretillum cynomorium. This report examines whether the sea-pen collagen shares some features with vertebrate type V collagen. Rotary shadowed images of acid-soluble collagen molecules extracted from beta-APN treated animals, positive staining of segment-long-spacing crystallites precipitated from pepsinized collagen, Western blots of the pepsinized alpha1 and alpha2 chains with antibodies to vertebrate types I, III and V collagens, and in situ gold immunolabeling of ECM collagen fibrils were examined. Our results showed that the tissue form of the sea-pen collagen is a 340-nm threadlike molecule, which is close to the vertebrate type V collagen with its voluminous terminal globular domain, the distribution of most of its polar amino-acid residues, and its antigenic properties.

  13. Collagen XIII secures pre- and postsynaptic integrity of the neuromuscular synapse.

    PubMed

    Härönen, Heli; Zainul, Zarin; Tu, Hongmin; Naumenko, Nikolay; Sormunen, Raija; Miinalainen, Ilkka; Shakirzyanova, Anastasia; Oikarainen, Tuomo; Abdullin, Azat; Martin, Paula; Santoleri, Sabrina; Koistinaho, Jari; Silmanl, Israel; Giniatullin, Rashid; Fox, Michael A; Heikkinen, Anne; Pihlajaniemi, Taina

    2017-03-24

    Both transmembrane and extracellular cues, one of which is collagen XIII, regulate formation and function of the neuromuscular synapse, and their absence results in myasthenia. We show that the phenotypical changes in collagen XIII knock-out mice are milder than symptoms in human patients, but the Col13a1-/- mice recapitulate major muscle findings of congenital myasthenic syndrome type 19 and serve as a disease model. In the lack of collagen XIII neuromuscular synapses do not reach full size, alignment, complexity and function resulting in reduced muscle strength. Collagen XIII is particularly important for the preterminal integrity, and when absent, destabilization of the motor nerves results in muscle regeneration and in atrophy especially in the case of slow muscle fibers. Collagen XIII was found to affect synaptic integrity through binding the ColQ tail of acetylcholine esterase. Although collagen XIII is a muscle-bound transmembrane molecule it also undergoes ectodomain shedding to become, a synaptic basal lamina component. We investigated the two forms' roles by novel Col13a1tm/tm mice in which ectodomain shedding is impaired. While postsynaptic maturation, terminal branching and neurotransmission was exaggerated in the Col13a1tm/tm mice, the transmembrane form's presence sufficed to prevent defects in transsynaptic adhesion, Schwann cell invagination/retraction, vesicle accumulation and acetylcholine receptor clustering and acetylcholinesterase dispersion seen in the Col13a1-/- mice, pointing to the transmembrane form as the major conductor of collagen XIII effects. Altogether, collagen XIII secures postsynaptic, synaptic and presynaptic integrity, and it is required for gaining and maintaining normal size, complexity and functional capacity of the neuromuscular synapse.

  14. Can one identify karst conduit networks geometry and properties from hydraulic and tracer test data?

    NASA Astrophysics Data System (ADS)

    Borghi, Andrea; Renard, Philippe; Cornaton, Fabien

    2016-04-01

    Karst aquifers are characterized by extreme heterogeneity due to the presence of karst conduits embedded in a fractured matrix having a much lower hydraulic conductivity. The resulting contrast in the physical properties of the system implies that the system reacts very rapidly to some changes in the boundary conditions and that numerical models are extremely sensitive to small modifications in properties or positions of the conduits. Furthermore, one major issue in all those models is that the location and size of the conduits is generally unknown. For all those reasons, estimating karst network geometry and their properties by solving an inverse problem is a particularly difficult problem. In this paper, two numerical experiments are described. In the first one, 18,000 flow and transport simulations have been computed and used in a systematic manner to assess statistically if one can retrieve the parameters of a model (geometry and radius of the conduits, hydraulic conductivity of the conduits) from head and tracer data. When two tracer test data sets are available, the solution of the inverse problems indicate with high certainty that there are indeed two conduits and not more. The radius of the conduits are usually well identified but not the properties of the matrix. If more conduits are present in the system, but only two tracer test data sets are available, the inverse problem is still able to identify the true solution as the most probable but it also indicates that the data are insufficient to conclude with high certainty. In the second experiment, a more complex model (including non linear flow equations in conduits) is considered. In this example, gradient-based optimization techniques are proved to be efficient for estimating the radius of the conduits and the hydraulic conductivity of the matrix in a promising and efficient manner. These results suggest that, despite the numerical difficulties, inverse methods should be used to constrain numerical

  15. Collagen crosslinks in chondromalacia of the patella.

    PubMed

    Väätäinen, U; Kiviranta, I; Jaroma, H; Arokosi, J; Tammi, M; Kovanen, V

    1998-02-01

    The aim of the study was to determine collagen concentration and collagen crosslinks in cartilage samples from chondromalacia of the patella. To study the extracellular matrix alterations associated to chondromalacia, we determined the concentration of collagen (hydroxyproline) and its hydroxylysylpyridinoline and lysylpyridinoline crosslinks from chondromalacia foci of the patellae in 12 patients and 7 controls from apparently normal cadavers. The structure of the collagen network in 8 samples of grades II-IV chondromalacia was examined under polarized light microscopy. The full-thickness cartilage samples taken with a surgical knife from chondromalacia lesions did not show changes in collagen, hydroxylysylpyridinoline and lysylpyridinoline concentration as compared with the controls. Polarized light microscopy showed decreased birefringence in the superficial cartilage of chondromalacia lesions, indicating disorganization or disappearance of collagen fibers in this zone. It is concluded that the collagen network shows gradual disorganization with the severity of chondromalacia lesion of the patella without changes in the concentration or crosslinks of collagen.

  16. [Disc electrophoresis of collagen protein (author's transl)].

    PubMed

    Reitmayr, P; Verzár, F

    1975-01-01

    The composition of proteins extracted from tendon collagen is investigated by disc electrophoresis. No qualitative differences can be demonstrated between young and old collagen. The action of formaldehyde and methionine on the tendons has no effect on the electrophoretic picture.

  17. [New treatment for peripheral nerve defects: nerve elongation].

    PubMed

    Kou, Y H; Jiang, B G

    2016-10-18

    Peripheral nerve defects are still a major challenge in clinical practice, and the most commonly used method of treatment for peripheral nerve defects is nerve transplantation, which has certain limitations and shortcomings, so new repair methods and techniques are needed. The peripheral nerve is elongated in limb lengthening surgery without injury, from which we got inspirations and proposed a new method to repair peripheral nerve defects: peripheral nerve elongation. The peripheral nerve could beelongated by a certain percent, but the physiological change and the maximum elongation range were still unknown. This study discussed the endurance, the physiological and pathological change of peripheral nerve elongation in detail, and got a lot of useful data. First, we developed peripheral nerve extender which could match the slow and even extension of peripheral nerve. Then, our animal experiment result confirmed that the peripheral nerve had better endurance for chronic elongation than that of acute elongation and cleared the extensibility of peripheral nerve and the range of repair for peripheral nerve defects. Our result also revealed the histological basis and changed the rule for pathological physiology of peripheral nerve elongation: the most important structure foundation of peripheral nerve elongation was Fontana band, which was the coiling of nerve fibers under the epineurium, so peripheral nerve could be stretched for 8.5%-10.0% without injury because of the Fontana band. We confirmed that peripheral nerve extending technology could have the same repair effect as traditional nerve transplantation through animal experiments. Finally, we compared the clinical outcomes between nerve elongation and performance of the conventional method in the repair of short-distance transection injuries in human elbows, and the post-operative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the

  18. Effects of dynamically variable saturation and matrix-conduit coupling of flow in karst aquifers

    USGS Publications Warehouse

    Reimann, T.; Geyer, T.; Shoemaker, W.B.; Liedl, R.; Sauter, M.

    2011-01-01

    Well-developed karst aquifers consist of highly conductive conduits and a relatively low permeability fractured and/or porous rock matrix and therefore behave as a dual-hydraulic system. Groundwater flow within highly permeable strata is rapid and transient and depends on local flow conditions, i.e., pressurized or nonpressurized flow. The characterization of karst aquifers is a necessary and challenging task because information about hydraulic and spatial conduit properties is poorly defined or unknown. To investigate karst aquifers, hydraulic stresses such as large recharge events can be simulated with hybrid (coupled discrete continuum) models. Since existing hybrid models are simplifications of the system dynamics, a new karst model (ModBraC) is presented that accounts for unsteady and nonuniform discrete flow in variably saturated conduits employing the Saint-Venant equations. Model performance tests indicate that ModBraC is able to simulate (1) unsteady and nonuniform flow in variably filled conduits, (2) draining and refilling of conduits with stable transition between free-surface and pressurized flow and correct storage representation, (3) water exchange between matrix and variably filled conduits, and (4) discharge routing through branched and intermeshed conduit networks. Subsequently, ModBraC is applied to an idealized catchment to investigate the significance of free-surface flow representation. A parameter study is conducted with two different initial conditions: (1) pressurized flow and (2) free-surface flow. If free-surface flow prevails, the systems is characterized by (1) a time lag for signal transmission, (2) a typical spring discharge pattern representing the transition from pressurized to free-surface flow, and (3) a reduced conduit-matrix interaction during free-surface flow. Copyright 2011 by the American Geophysical Union.

  19. Conduit Magma Storage during the 800 BP Quilotoa Eruption, Ecuador

    NASA Astrophysics Data System (ADS)

    Ort, M. H.; Cashman, K. V.; Di Muro, A.; Best, J. A.; Rosi, M.; Mothes, P. A.; Bustillos, J.

    2013-12-01

    The 800 BP eruption of Quilotoa produced two large ignimbrites, U1 (~5.8 km3 DRE) and U3 (~1.8 km3 DRE). These eruptions were separated by a series of much smaller eruptions over one to several weeks, as inferred from 1) the intercalation of secondary pyroclastic and debris flow deposits between U1 and U3, 2) deposits from phreatic explosions from the U1 ignimbrite surface, 3) oxidation of the upper 2 m of U1, and 4) a lack of erosion of the U1 surface. Why did the main phase of the eruption (U1) stall when eruptable magma was available? How did explosive activity stop and restart? We address these questions by examining deposits (U2) emplaced during the 'hiatus' that provide information on the conditions in the conduit and vent area between explosive episodes. The lowest sub-unit, U2a, forms a series of pumiceous surge deposits found only within 5 km of the crater rim. U2b is a vitric-poor, crystal- and lithic-rich fall deposit distributed to about 15 km from the crater. U2c is a thin gray fine ash containing 2-5-mm-diameter rhyolite lapilli that is present within 6 km of the vent. Similar lapilli also occur in the lowermost few centimeters of U3 and appear to be from a dome that exploded as the new magma arrived at the surface; their presence as small ballistic fragments ties U2c to lowermost U3 in time. U2a appears to have been emplaced by episodic surges and weak fallout plumes, whereas U2b and U2c were deposited from a series of sustained eruption columns. Moreover, the lack of U2b grain-size variation with distance suggests that the grain size was determined at the vent, not by transport. FTIR analysis of CO2 and H2O in melt inclusions (MIs) indicates that a deep magma chamber (>400 MPa; ~12 km) fed U1. U2a and U2b MIs plot along vapor isopleths, suggesting equilibration at pressures to about 300 MPa as CO2 outgassed. U2b MIs have lower CO2 than U2a, perhaps indicating continued degassing during the 'hiatus'. MIs from the lower few centimeters of U3 lie along

  20. Biofabrication and testing of a fully cellular nerve graft.

    PubMed

    Owens, Christopher M; Marga, Francoise; Forgacs, Gabor; Heesch, Cheryl M

    2013-12-01

    Rupture of a nerve is a debilitating injury with devastating consequences for the individual's quality of life. The gold standard of repair is the use of an autologous graft to bridge the severed nerve ends. Such repair however involves risks due to secondary surgery at the donor site and may result in morbidity and infection. Thus the clinical approach to repair often involves non-cellular solutions, grafts composed of synthetic or natural materials. Here we report on a novel approach to biofabricate fully biological grafts composed exclusively of cells and cell secreted material. To reproducibly and reliably build such grafts of composite geometry we use bioprinting. We test our grafts in a rat sciatic nerve injury model for both motor and sensory function. In particular we compare the regenerative capacity of the biofabricated grafts with that of autologous grafts and grafts made of hollow collagen tubes by measuring the compound action potential (for motor function) and the change in mean arterial blood pressure as consequence of electrically eliciting the somatic pressor reflex. Our results provide evidence that bioprinting is a promising approach to nerve graft fabrication and as a consequence to nerve regeneration.

  1. Polytetrafluoroethylene pulmonary valve conduit implantation for chronic pulmonary insufficiency.

    PubMed

    Quintessenza, James A

    2014-12-01

    Pulmonary valve replacement in patients with congenital cardiac disease is now being performed with more liberal indications in light of the data that chronic pulmonary insufficiency is not a benign lesion. The beneficial effects of valve replacement with low operative mortality and morbidity support this approach. Many options exist for a pulmonary valve prosthesis, which underscores the fact that there is no ideal valve available. Our efforts are focussed around a synthetic valve that avoids the bio-degeneration of a bio-prosthesis and avoids the need for life-long coumadin. We developed a bicuspid (bileaflet) polytetrafluoroethylene valve design, which has now gone through three major revisions in >200 patients over 14 years. We began the experience utilising a polytetrafluoroethylene hand-sewn bicuspid valve in the right ventricular outflow tract, initially using 0.6 mm and more recently 0.1 mm polytetrafluoroethylene. The 0.1 mm thickness material functions well as a leaflet, maintaining a relatively thin and flexible nature. It does not calcify or initiate thromboses at least for the first several years. We identified issues with dehiscence of the leaflet from the right ventricular outflow tract muscle, especially in the larger, potentially expansive right ventricular outflow tracts, and this prompted our latest design change to place the valve within a polytetrafluoroethylene tube. This current version of the polytetrafluoroethylene valve conduit has excellent short-to-intermediate-term function. Further follow-up is necessary to determine late durability and life-long valve-related procedural risk for our patients.

  2. Fluid dynamics of active heterogeneities in a mantle plume conduit

    NASA Astrophysics Data System (ADS)

    Farnetani, C. G.; Limare, A.; Hofmann, A. W.

    2015-12-01

    Laboratory experiments and numerical simulations indicate that the flow of a purely thermal plume preserves the azimuthal zonation of the source region, thus providing a framework to attribute a deep origin to the isotopic zonation of Hawaiian lavas. However, previous studies were limited to passive heterogeneities not affecting the flow. We go beyond this simplification by considering active heterogeneities which are compositionally denser, or more viscous, and we address the following questions: (1) How do active heterogeneities modify the axially symmetric velocity field of the plume conduit? (2) Under which conditions is the azimuthal zonation of the source region no longer preserved in the plume stem? (3) How do active heterogeneities deform during upwelling and what is their shape once at sublithospheric depths? We conducted both laboratory experiments, using a Particle Image Velocimetry (PIV) to calculate the velocity field, and high resolution three-dimensional simulations where millions of tracers keep track of the heterogeneous fluid. For compositionally denser heterogeneities we cover a range of buoyancy ratios 0

  3. Biology, chemistry and pathology of collagen

    SciTech Connect

    Fleischmajer, R.; Olsen, B.R.; Kuhn, K.

    1985-01-01

    This book consists of five parts and a section of poster papers. Some of the articles are: Structure of the Type II Collagen Gene; Structural and Functional Analysis of the Genes for ..cap alpha..2(1) and ..cap alpha..1(III) collagens; Structure and Expression of the Collagen Genes of C. Elegans; Molecular Basis of Clinical Heterogeneity in the Ehlers-Danlos Syndrome; and Normal and Mutant Human Collagen Genes.

  4. Comparison of a karst groundwater model with and without discrete conduit flow

    NASA Astrophysics Data System (ADS)

    Saller, Stephen P.; Ronayne, Michael J.; Long, Andrew J.

    2013-11-01

    Karst aquifers exhibit a dual flow system characterized by interacting conduit and matrix domains. This study evaluated the coupled continuum pipe-flow framework for modeling karst groundwater flow in the Madison aquifer of western South Dakota (USA). Coupled conduit and matrix flow was simulated within a regional finite-difference model over a 10-year transient period. An existing equivalent porous medium (EPM) model was modified to include major conduit networks whose locations were constrained by dye-tracing data and environmental tracer analysis. Model calibration data included measured hydraulic heads at observation wells and estimates of discharge at four karst springs. Relative to the EPM model, the match to observation well hydraulic heads was substantially improved with the addition of conduits. The inclusion of conduit flow allowed for a simpler hydraulic conductivity distribution in the matrix continuum. Two of the high-conductivity zones in the EPM model, which were required to indirectly simulate the effects of conduits, were eliminated from the new model. This work demonstrates the utility of the coupled continuum pipe-flow method and illustrates how karst aquifer model parameterization is dependent on the physical processes that are simulated.

  5. An Approach to Simulation of the Turbulent Multifield/Multiphase Dynamics of Volcanic Conduits and Plumes

    NASA Astrophysics Data System (ADS)

    Ogden, D. E.; Wohletz, K. H.; Glatzmaier, G. A.

    2004-12-01

    The shape and size of volcanic eruption conduits play a large role in determining the character of eruption phenomena. Conduits for explosive eruptions evolve with time during the eruption greatly affecting mass fluxes and the fate of degassed volatile constituents. Previous modeling has focused on compressible fluid dynamics of gas and solid particle mixtures moving within a cylindrical conduit and expanding into the atmosphere. However, it is clear that evolution of the conduit itself is influenced by the erupting mixture and the flow field of the mixture is controlled in part by the conduit. In order to address this important aspect of eruption dynamics, both compressible fluid flow and solid mechanics must be solved simultaneously. Two different three-dimensional state of the art computer codes have been developed at Los Alamos National Laboratories that are capable of simulating these dynamics together, CFDLib and SAGE. CFDLib is a compilation of well-tested computational fluid dynamics approaches suited for a wide range of fluid and solid dynamics, using well-known Marker-And-Cell (MAC) and Implicit Continuous-fluid Eulerian (ICE) techniques. SAGE employs adaptive grid Eulerian techniques to provide local areas of high resolution for dynamics of complex materials. We are benchmarking and validating these codes for geophysical application as a preliminary step toward modeling the three-dimensional dynamics of volcanic conduits.

  6. In Vitro Evaluation of Carbon-Nanotube-Reinforced Bioprintable Vascular Conduits

    PubMed Central

    Dolati, Farzaneh; Yu, Yin; Zhang, Yahui; De Jesus, Aribet M; Sander, Edward A.; Ozbolat, Ibrahim T.

    2014-01-01

    Vascularization of thick engineered tissue and organ constructs like the heart, liver, pancreas or kidney remains a major challenge in tissue engineering. Vascularization is needed to supply oxygen and nutrients and remove waste in living tissues and organs through a network that should possess high perfusion ability and significant mechanical strength and elasticity. In this paper, we introduce a fabrication process to print vascular conduits directly, where conduits were reinforced with carbon-nanotubes (CNTs) to enhance their mechanical properties and bioprintability. In vitro evaluation of printed conduits encapsulated in human coronary artery smooth muscle cells (HCASMCs) was performed to characterize the effects of CNT reinforcement on the mechanical, perfusion and biological performance of the conduits. Perfusion and permeability, cell viability, extracellular matrix formation and tissue histology were assessed and discussed, and it was concluded that CNT-reinforced vascular conduits provided a foundation for mechanically appealing constructs where CNTs could be replaced with natural protein nanofibers for further integration of these conduits in large-scale tissue fabrication. PMID:24632802

  7. Assessment of Hemodynamic Conditions in the Aorta Following Root Replacement with Composite Valve-Conduit Graft.

    PubMed

    Cheng, Zhuo; Kidher, Emaddin; Jarral, Omar A; O'Regan, Declan P; Wood, Nigel B; Athanasiou, Thanos; Xu, Xiao Yun

    2016-05-01

    This paper presents the analysis of detailed hemodynamics in the aortas of four patients following replacement with a composite bio-prosthetic valve-conduit. Magnetic resonance image-based computational models were set up for each patient with boundary conditions comprising subject-specific three-dimensional inflow velocity profiles at the aortic root and central pressure waveform at the model outlet. Two normal subjects were also included for comparison. The purpose of the study was to investigate the effects of the valve-conduit on flow in the proximal and distal aorta. The results suggested that following the composite valve-conduit implantation, the vortical flow structure and hemodynamic parameters in the aorta were altered, with slightly reduced helical flow index, elevated wall shear stress and higher non-uniformity in wall shear compared to normal aortas. Inter-individual analysis revealed different hemodynamic conditions among the patients depending on the conduit configuration in the ascending aorta, which is a key factor in determining post-operative aortic flow. Introducing a natural curvature in the conduit to create a smooth transition between the conduit and native aorta may help prevent the occurrence of retrograde and recirculating flow in the aortic arch, which is particularly important when a large portion or the entire ascending aorta needs to be replaced.

  8. In vitro evaluation of carbon-nanotube-reinforced bioprintable vascular conduits

    NASA Astrophysics Data System (ADS)

    Dolati, Farzaneh; Yu, Yin; Zhang, Yahui; De Jesus, Aribet M.; Sander, Edward A.; Ozbolat, Ibrahim T.

    2014-04-01

    Vascularization of thick engineered tissue and organ constructs like the heart, liver, pancreas or kidney remains a major challenge in tissue engineering. Vascularization is needed to supply oxygen and nutrients and remove waste in living tissues and organs through a network that should possess high perfusion ability and significant mechanical strength and elasticity. In this paper, we introduce a fabrication process to print vascular conduits directly, where conduits were reinforced with carbon nanotubes (CNTs) to enhance their mechanical properties and bioprintability. In vitro evaluation of printed conduits encapsulated in human coronary artery smooth muscle cells was performed to characterize the effects of CNT reinforcement on the mechanical, perfusion and biological performance of the conduits. Perfusion and permeability, cell viability, extracellular matrix formation and tissue histology were assessed and discussed, and it was concluded that CNT-reinforced vascular conduits provided a foundation for mechanically appealing constructs where CNTs could be replaced with natural protein nanofibers for further integration of these conduits in large-scale tissue fabrication.

  9. Comparison of a karst groundwater model with and without discrete conduit flow

    USGS Publications Warehouse

    Saller, Stephen P.; Ronayne, Michael J.; Long, Andrew J.

    2013-01-01

    Karst aquifers exhibit a dual flow system characterized by interacting conduit and matrix domains. This study evaluated the coupled continuum pipe-flow framework for modeling karst groundwater flow in the Madison aquifer of western South Dakota (USA). Coupled conduit and matrix flow was simulated within a regional finite-difference model over a 10-year transient period. An existing equivalent porous medium (EPM) model was modified to include major conduit networks whose locations were constrained by dye-tracing data and environmental tracer analysis. Model calibration data included measured hydraulic heads at observation wells and estimates of discharge at four karst springs. Relative to the EPM model, the match to observation well hydraulic heads was substantially improved with the addition of conduits. The inclusion of conduit flow allowed for a simpler hydraulic conductivity distribution in the matrix continuum. Two of the high-conductivity zones in the EPM model, which were required to indirectly simulate the effects of conduits, were eliminated from the new model. This work demonstrates the utility of the coupled continuum pipe-flow method and illustrates how karst aquifer model parameterization is dependent on the physical processes that are simulated.

  10. Exposure to Mimivirus Collagen Promotes Arthritis

    PubMed Central

    Shah, Nikunj; Hülsmeier, Andreas J.; Hochhold, Nina; Neidhart, Michel; Gay, Steffen

    2014-01-01

    Collagens, the most abundant proteins in animals, also occur in some recently described nucleocytoplasmic large DNA viruses such as Mimiviridae, which replicate in amoebae. To clarify the impact of viral collagens on the immune response of animals exposed to Mimiviridae, we have investigated the localization of collagens in Acanthamoeba polyphaga mimivirus particles and the response of mice to immunization with mimivirus particles. Using protein biotinylation, we have first shown that viral collagen encoded by open reading frame L71 is present at the surface of mimivirus particles. Exposure to mimivirus collagens elicited the production of anti-collagen antibodies in DBA/1 mice immunized intradermally with mimivirus protein extracts. This antibody response also targeted mouse collagen type II and was accompanied by T-cell reactivity to collagen and joint inflammation, as observed in collagen-induced arthritis following immunization of mice with bovine collagen type II. The broad distribution of nucleocytoplasmic large DNA viruses in the environment suggests that humans are constantly exposed to such large virus particles. A survey of blood sera from healthy human subjects and from rheumatoid arthritis patients indeed demonstrated that 30% of healthy-subject and 36% of rheumatoid arthritis sera recognized the major mimivirus capsid protein L425. Moreover, whereas 6% of healthy-subject sera recognized the mimivirus collagen protein L71, 22% of rheumatoid arthritis sera were positive for mimivirus L71. Accordingly, our study shows that environmental exposure to mimivirus represents a risk factor in triggering autoimmunity to collagens. PMID:24173233

  11. The materials science of collagen.

    PubMed

    Sherman, Vincent R; Yang, Wen; Meyers, Marc A

    2015-12-01

    Collagen is the principal biopolymer in the extracellular matrix of both vertebrates and invertebrates. It is produced in specialized cells (fibroblasts) and extracted into the body by a series of intra and extracellular steps. It is prevalent in connective tissues, and the arrangement of collagen determines the mechanical response. In biomineralized materials, its fraction and spatial distribution provide the necessary toughness and anisotropy. We review the structure of collagen, with emphasis on its hierarchical arrangement, and present constitutive equations that describe its mechanical response, classified into three groups: hyperelastic macroscopic models based on strain energy in which strain energy functions are developed; macroscopic mathematical fits with a nonlinear constitutive response; structurally and physically based models where a constitutive equation of a linear elastic material is modified by geometric characteristics. Viscoelasticity is incorporated into the existing constitutive models and the effect of hydration is discussed. We illustrate the importance of collagen with descriptions of its organization and properties in skin, fish scales, and bone, focusing on the findings of our group.

  12. Conduit evolution during the Avellinio Plinian eruption (Vesuvius): insights from fieldwork, lithic grain size distributions and modelling

    NASA Astrophysics Data System (ADS)

    Hanson, Jonathan; Rust, Alison; Phillips, Jeremy; Sulpizio, Roberto; Engwell, Samantha; Costa, Antonio

    2016-04-01

    Large-scale explosive eruptions are modulated by a combination of magmatic and conduit processes, including changes in the geometry of the conduit as host rocks are eroded from the conduit walls and vent region. This study of deposits 1-45 km from source of the main, quasi-steady Plinian phases of the 3949 ± 10 yBP Avellino eruption of Vesuvius (EU2 and EU3) demonstrates the potential for measurements of lithics and xenoliths to constrain subsurface eruption processes. The lithics comprise volcanic rocks derived from the upper ˜2700 m of the conduit, carbonates from the lower conduit and magma reservoir wall rocks. The lithics (free clasts) are thought to be incorporated into the erupting mixture by conduit wall implosion around and above the fragmentation depth as well as shallow vent spalling, whilst xenoliths are interpreted to result from viscous shear stresses applied to the conduit walls pre-fragmentation. The lithology of xenoliths indicates that they are sourced from relatively deep in the conduit, and their scarcity indicates that there is only minor conduit erosion below magma fragmentation during the Plinian eruptions. In contrast total lithic volumes calculated for EU2 and EU3 are 0.002 and 0.02 km3, respectively, which corresponds to 8 % and 18 % of the total erupted volume. Lava lithics dominate, making up 69 and 74 % of the total lithic volume for EU2 and EU3, respectively. The majority of conduit erosion occurred above the fragmentation depth, in the upper few kilometers of the conduit, and scales approximately with the increase in mass discharge rate between the two phases. Individual component (total lithic, carbonate, lava) Lithic Total Grain Size Distributions (L-TGSDs) provide insights into rock failure mechanisms. The fractal dimensions of the majority of the L-TGSDs are approximately 2 (grain size in φ against log2 no. of grains), inferred to be the result of conduit implosion modified by initial rock characteristics. The lava lithics from

  13. Histomorphometric measurements in human and dog optic nerve and an estimation of optic nerve pressure gradients in human.

    PubMed

    Balaratnasingam, Chandrakumar; Morgan, William H; Johnstone, Victoria; Pandav, Surinder S; Cringle, Stephen J; Yu, Dao-Yi

    2009-11-01

    mmHg the mean pressure difference across the human pia mater will be 4.8 +/- 2.2 mmHg. If we assume that the pressure difference between the intraocular space and post-laminar tissue falls across the entire thickness of the human lamina cribrosa then an estimate of the trans-laminar pressure gradient is 2.0 +/- 0.8 mmHg/100 mum. If we assume that this pressure difference only occurs across the dense collagenous plates of the posterior lamina cribrosa then a trans-laminar pressure gradient high estimate of 3.3 +/- 1.4 mmHg/100 mum is calculated. Changes in tissue pressure gradients in the optic nerve may be an important factor in the pathogenesis of glaucomatous optic neuropathy.

  14. Geophysical Methods for Locating Karst Conduits in Cane Run Watershed, Central Kentucky

    NASA Astrophysics Data System (ADS)

    Zhu, J.; Paylor, R.; Currens, J. C.; Dinger, J. S.

    2009-12-01

    Cane Run watershed in central Kentucky was listed by the Kentucky Division of Water as one of four focus watersheds for clean-up under the State’s nonpoint-source pollution program. This watershed is degraded by pathogens, nutrients, siltation, and organic enrichment. The sources of pollution include both municipal point sources and nonpoint agricultural and nonagricultural sources. The relative contribution of different parts of the watershed to the contamination is not well understood, however. The geology of Cane Run watershed consists of Ordovician thin-bedded limestone with sparse interbeds of shale. The landscape is dominated by karst features such as sinkholes and springs. Cane Run only flows during times of significant rainfall, usually in the spring of the year. The remainder of the year, most water is recharged to a karst conduit system that leads from Lexington, Ky to Royal Spring, as demonstrated by groundwater tracing. Royal Spring is the major water supply for Georgetown in Scott County, Ky. We attempted to locate the karst conduit so that groundwater flowing through the conduit could be monitored. These monitoring data are essential for assessing the effectiveness of remediation plans. In 2008, based on geology, karst features, and hydrogeology, an initial round of electrical-resistivity and spontaneous-potential geophysical surveys were conducted to help pinpoint the location of the conduit at three sites. Fifteen exploratory boreholes were drilled on the basis of the geophysical results. The boreholes confirmed the geophysical surveys had located minor mud-filled conduits that were interpreted as tributaries to the main conduit. Another round of 2D and 3D electrical resistivity surveys were conducted in 2009 to search for the main conduit. The analysis of this round of surveys resulted in one promising site that is suspected to be in close proximity to the conduit. A time-lapse 2D electrical resistivity survey in conjunction with calcium chlorite

  15. Barriers of the peripheral nerve

    PubMed Central

    Peltonen, Sirkku; Alanne, Maria; Peltonen, Juha

    2013-01-01

    This review introduces the traditionally defined anatomic compartments of the peripheral nerves based on light and electron microscopic topography and then explores the cellular and the most recent molecular basis of the different barrier functions operative in peripheral nerves. We also elucidate where, and how, the homeostasis of the normal human peripheral nerve is controlled in situ and how claudin-containing tight junctions contribute to the barriers of peripheral nerve. Also, the human timeline of the development of the barriers of the peripheral nerve is depicted. Finally, potential future therapeutic modalities interfering with the barriers of the peripheral nerve are discussed. PMID:24665400

  16. Neuromuscular ultrasound of cranial nerves.

    PubMed

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  17. Stem cell-based approaches to improve nerve regeneration: potential implications for reconstructive transplantation?

    PubMed

    Khalifian, Saami; Sarhane, Karim A; Tammia, Markus; Ibrahim, Zuhaib; Mao, Hai-Quan; Cooney, Damon S; Shores, Jaimie T; Lee, W P Andrew; Brandacher, Gerald

    2015-02-01

    Reconstructive transplantation has become a viable option to restore form and function after devastating tissue loss. Functional recovery is a key determinant of overall success and critically depends on the quality and pace of nerve regeneration. Several molecular and cell-based therapies have been postulated and tested in pre-clinical animal models to enhance nerve regeneration. Schwann cells remain the mainstay of research focus providing neurotrophic support and signaling cues for regenerating axons. Alternative cell sources such as mesenchymal stem cells and adipose-derived stromal cells have also been tested in pre-clinical animal models and in clinical trials due to their relative ease of harvest, rapid expansion in vitro, minimal immunogenicity, and capacity to integrate and survive within host tissues, thereby overcoming many of the challenges faced by culturing of human Schwann cells and nerve allografting. Induced pluripotent stem cell-derived Schwann cells are of particular interest since they can provide abundant, patient-specific autologous Schwann cells. The majority of experimental evidence on cell-based therapies, however, has been generated using stem cell-seeded nerve guides that were developed to enhance nerve regeneration across "gaps" in neural repair. Although primary end-to-end repair is the preferred method of neurorrhaphy in reconstructive transplantation, mechanistic studies elucidating the principles of cell-based therapies from nerve guidance conduits will form the foundation of further research employing stem cells in end-to-end repair of donor and recipient nerves. This review presents key components of nerve regeneration in reconstructive transplantation and highlights the pre-clinical studies that utilize stem cells to enhance nerve regeneration.

  18. The collagenous gastroenteritides: similarities and differences.

    PubMed

    Gopal, Purva; McKenna, Barbara J

    2010-10-01

    Collagenous gastritis, collagenous sprue, and collagenous colitis share striking histologic similarities and occur together in some patients. They also share some drug and disease associations. Pediatric cases of collagenous gastritis, however, lack most of these associations. The etiologies of the collagenous gastroenteritides are not known, so it is not clear whether they are similar because they share pathogeneses, or because they indicate a common histologic response to varying injuries. The features, disease and drug associations, and the inquiries into the pathogenesis of these disorders are reviewed.

  19. Collagen I confers gamma radiation resistance.

    PubMed

    Azorin, E; González-Martínez, P R; Azorin, J

    2012-12-01

    The effect of collagen on the response of somatomammotroph tumor cells (GH3) to gamma, radiation therapy was studied in vitro. After incubating confluent GH3 cell monolayers in a serum-free, maintaining medium, either with or without collagen, the monolayers were irradiated with 137Cs, gamma radiation. Collagen reduces cell mortality via ERK1/2 activation, abolishing gamma radiation, cell death, and promotes cell invasion when acting in synergy with collagen and in association with the, MAPK/ERK1/2 signaling pathway activation. The presence of collagen in somatomammotroph tumors, confers resistance to radiation.

  20. Collagen: a network for regenerative medicine

    PubMed Central

    Pawelec, K. M.; Best, S. M.

    2016-01-01

    The basic building block of the extra-cellular matrix in native tissue is collagen. As a structural protein, collagen has an inherent biocompatibility making it an ideal material for regenerative medicine. Cellular response, mediated by integrins, is dictated by the structure and chemistry of the collagen fibers. Fiber formation, via fibrillogenesis, can be controlled in vitro by several factors: pH, ionic strength, and collagen structure. After formation, fibers are stabilized via cross-linking. The final bioactivity of collagen scaffolds is a result of both processes. By considering each step of fabrication, scaffolds can be tailored for the specific needs of each tissue, improving their therapeutic potential. PMID:27928505

  1. Genes and nerves.

    PubMed

    Dieu, Tam; Johnstone, Bruce R; Newgreen, Don F

    2005-04-01

    The unpredictability of a brachial plexus graft, a median nerve repair, or a facial-nerve reconstruction is well known. No matter how precise the technical skills, a perfect recovery from a peripheral-nerve lesion is elusive. To resolve this problem, understanding of the normal development of the peripheral nervous system is needed. Presently, the development of the innervation in the upper limb is complex and not fully understood. However, many of the genes involved in this process are now known, and the link between anatomy and genetics is becoming clearer. This short review aims to acquaint the clinical surgeon with some of the main genes. The principal steps in the establishment of neural circuits will be summarized, in particular, the specification and development of neurons and glia, the pathfinding of cells and axons towards their target, and the downstream molecules that control the circuitry of these neurons.

  2. Investigating degassing dynamics into the shallow conduit through decompression experiments

    NASA Astrophysics Data System (ADS)

    Spina, Laura; Scheu, Bettina; Cimarelli, Corrado; Dingwell, Donald

    2014-05-01

    The history of bubbles' growth and interaction, as well as their spatial distribution in the shallow conduit, is deeply interconnected with the style of the eruptions. According to the fundamental role played by volatiles in the eruptive process, more effort is required in determining how the key factors of volcanic systems (i.e., magma properties, decompression rate) influence the dynamics of degassing. Therefore, our aim is to provide, through the analysis of decompression experiments on analogue materials, insights on such relations. We performed several decompression experiments with a shock-tube apparatus, and using silicon oil as laboratory-analogue for the magmatic melt. The sample was placed in a transparent autoclave, saturated with Argon for an established amount of time under a fixed pressure (up to a maximum of 10 MPa). Successively it was decompressed to atmospheric conditions, by releasing gas through a control valve. The dynamics of gas exsolution processes were recorded by using pressure sensors and a high speed camera. A range of viscosity values (1, 10, 100, 1000 Pa s) was investigated, for the same decompression path. Furthermore, some experiments were carried out with the addition of glass beads, as analogue to crystals, to the pure liquid. The height of the expanding column was monitored, in conjunction with images recorded during the experiments, and the growth rate of bubbles was measured at different times and depth. Finally, bubble size distribution has been evaluated at various stages for some experiments, in order to achieve a spatial map of the ongoing degassing phenomena. Results allowed us to define different regimes occurring during the decompression, whose features and characteristics are strongly affected by fluid viscosity. Indeed, several degassing phases were observed, from bubbly fluid to the eventual buildup of a more or less "foamy" phase, which ultimately experiences periodical oscillations around an average equilibrium level

  3. [Lumbosacral nerve bowstring disease].

    PubMed

    Shi, J G; Xu, X M; Sun, J C; Wang, Y; Guo, Y F; Yang, H S; Kong, Q J; Yang, Y; Shi, G D; Yuan, W; Jia, L S

    2017-03-21

    Objective: To define a novel disease-lumbosacral nerve bowstring disease, and propose the diagnostic criteria, while capsule surgery was performed and evaluated in the preliminary study. Methods: From June 2016 to December 2016, a total of 30 patients (22 male and 8 female; mean age of 55.1±9.7 years) with lumbosacral nerve bowstring disease were included in Department of Spine Surgery, Changzheng Hospital, the Second Military Medical University.Lumbosacral nerve bowstring disease was defined as axial hypertension of nerve root and spinal cord caused by congenital anomalies, which could be accompanied by other lesions as lumbar disc herniation, spinal cord stenosis or spondylolisthesis, or aggravated by iatrogenic lesions, resulting in neurological symptoms.This phenomenon is similar to a stretched string, the higher tension on each end the louder sound.Meanwhile, the shape of lumbosacral spine looks like a bow, thus, the disease is nominated as lumbosacral nerve bowstring disease.All the patients underwent capsule surgery and filled out Owestry disability index (ODI) and Tempa scale for kinesiophobia (TSK) before and after surgery. Results: The mean surgery time was (155±36) min, (4.3±0.4) segments were performed surgery.The pre-operative VAS, TSK and ODI scores were (7.6±0.8), (52.0±10.3) and (68.4±12.7), respectively.The post-operative VAS, TSK and ODI scores were (3.3±0.4), ( 24.6±5.2) and (32.1±7.4)(P<0.05, respectively), respectively. Conclusion: The definition and diagnostic criteria of lumbosacral nerve bowstring disease was proposed.Capsule surgery was an effective strategy with most patients acquired excellent outcomes as symptoms relieved and quality of life improved.

  4. Collagen interactions: Drug design and delivery.

    PubMed

    An, Bo; Lin, Yu-Shan; Brodsky, Barbara

    2016-02-01

    Collagen is a major component in a wide range of drug delivery systems and biomaterial applications. Its basic physical and structural properties, together with its low immunogenicity and natural turnover, are keys to its biocompatibility and effectiveness. In addition to its material properties, the collagen triple-helix interacts with a large number of molecules that trigger biological events. Collagen interactions with cell surface receptors regulate many cellular processes, while interactions with other ECM components are critical for matrix structure and remodeling. Collagen also interacts with enzymes involved in its biosynthesis and degradation, including matrix metalloproteinases. Over the past decade, much information has been gained about the nature and specificity of collagen interactions with its partners. These studies have defined collagen sequences responsible for binding and the high-resolution structures of triple-helical peptides bound to its natural binding partners. Strategies to target collagen interactions are already being developed, including the use of monoclonal antibodies to interfere with collagen fibril formation and the use of triple-helical peptides to direct liposomes to melanoma cells. The molecular information about collagen interactions will further serve as a foundation for computational studies to design small molecules that can interfere with specific interactions or target tumor cells. Intelligent control of collagen biological interactions within a material context will expand the effectiveness of collagen-based drug delivery.

  5. Complementary Effects of Two Growth Factors in Multifunctionalized Silk Nanofibers for Nerve Reconstruction

    PubMed Central

    Jose, Rodrigo R.; Vigneron, Pascale; Bresson, Damien; Fitzpatrick, Vincent; Marin, Frédéric; Kaplan, David L.; Egles, Christophe

    2014-01-01

    With the aim of forming bioactive guides for peripheral nerve regeneration, silk fibroin was electrospun to obtain aligned nanofibers. These fibers were functionalized by incorporating Nerve Growth Factor (NGF) and Ciliary NeuroTrophic Factor (CNTF) during electrospinning. PC12 cells grown on the fibers confirmed the bioavailability and bioactivity of the NGF, which was not significantly released from the fibers. Primary neurons from rat dorsal root ganglia (DRGs) were grown on the nanofibers and anchored to the fibers and grew in a directional fashion based on the fiber orientation, and as confirmed by growth cone morphology. These biofunctionalized nanofibers led to a 3-fold increase in neurite length at their contact, which was likely due to the NGF. Glial cell growth, alignment and migration were stimulated by the CNTF in the functionalized nanofibers. Organotypic culture of rat fetal DRGs confirmed the complementary effect of both growth factors in multifunctionalized nanofibers, which allowed glial cell migration, alignment and parallel axonal growth in structures resembling the ‘bands of Bungner’ found in situ. Graftable multi-channel conduits based on biofunctionalized aligned silk nanofibers were developed as an organized 3D scaffold. Our bioactive silk tubes thus represent new options for a biological and biocompatible nerve guidance conduit. PMID:25313579

  6. Insights into volcanic conduit flow from an open-source numerical model

    NASA Astrophysics Data System (ADS)

    Mastin, Larry G.

    2002-07-01

    Numerical models that calculate the fluid dynamics of explosive volcanic eruptions have been used with increasing frequency to understand volcanic processes and evaluate volcanic hazards. Yet those who develop such models rarely make them publicly available so that they can be verified, used, and possibly improved by other scientists. In this paper I present a visual, interactive, open-source numerical model that calculates steady state flow of magma and gas in vertical eruptive conduits and contains user-friendly utilities for quickly determining physical, thermodynamic, and transport properties of silicate melts, H2O gases, and melt-gas-crystal mixtures. The model represents an advance over previously published conduit models by incorporating a non-Arrhenian viscosity relation for hydrous silicate melts, a relation between viscosity and volume fraction of gas that depends on Capillary number, and adiabatic temperature changes in the mixture using established thermodynamic relations for melts and H2O gas, respectively. Volcanologists who have not had access to conduit models have frequently approximated conduit flow using an analytical equation for incompressible, laminar, Newtonian pipe flow, which predicts that the mass flux is proportional to the fourth power of conduit radius and inversely proportional to mixture viscosity. The model presented here, which is not much more difficult to use than a back-of-the-envelope calculation, shows that the pipe-flow approximation significantly overestimates the sensitivity of mass flux to both conduit radius and mixture viscosity. Results from the model also show that viscous heating in the lower conduit, which is not considered in most other models, may increase the mass flux of large silicic eruptions by several percent and decrease the viscosity of the mixture at the fragmentation depth by a few tens of percent.

  7. Evolution of karst conduit networks in transition from pressurised flow to free surface flow

    NASA Astrophysics Data System (ADS)

    Perne, M.; Covington, M. D.; Gabrovšek, F.

    2014-06-01

    We present a novel modelling approach to study the evolution of conduit networks in soluble rocks. Unlike the models presented so far, the model allows a transition from pressurised (pipe) flow to a free surface (open channel) flow in evolving discrete conduit networks. It calculates flow, solute transport and dissolutional enlargement within each time step and steps through time until a stable flow pattern establishes. The flow in each time step is calculated by calling the EPA Storm Water Management Model (EPA SWMM), which efficiently solves the 1-D Saint Venant equations in a network of conduits. We present several cases with low dip and sub-vertical networks to demonstrate mechanisms of flow pathway selection. In low dip models the inputs were randomly distributed to several junctions. The evolution of pathways progresses upstream: initially pathways linking outlets to the closest inputs evolve fastest because the gradient along these pathways is largest. When a pathway efficiently drains the available recharge, the head drop along the pathway attracts flow from the neighbouring upstream junctions and new connecting pathways evolve. The mechanism progresses from the output boundary inwards until all inputs are connected to the stable flow system. In the pressurised phase, each junction is drained by at least one conduit, but only one conduit remains active in the vadose phase. The selection depends on the initial geometry of a junction, initial distribution of diameters, the evolution in a pressurised regime, and on the dip of the conduits, which plays an important role in vadose entrenchment. In high dip networks, the vadose zone propagates downwards and inwards from the rim of the massif. When a network with randomly distributed initial diameters is supplied with concentrated recharge from the adjacent area, the sink point regresses up upstream along junctions connected to the prominent pathways. Large conductive structures provide deep penetration of high

  8. Nerve Transfers in Tetraplegia.

    PubMed

    Fox, Ida K

    2016-05-01

    Hand and upper extremity function is instrumental to basic activities of daily living and level of independence in cervical spinal cord injury (SCI). Nerve transfer surgery is a novel and alternate approach for restoring function in SCI. This article discusses the biologic basis of nerve transfers in SCI, patient evaluation, management, and surgical approaches. Although the application of this technique is not new; recent case reports and case series in the literature have increased interest in this field. The challenges are to improve function, achieve maximal gains in function, avoid complications, and to primum non nocere.

  9. Hyaluronan hydration generates three-dimensional meso-scale structure in engineered collagen tissues.

    PubMed

    Anandagoda, Nelomi; Ezra, Daniel G; Cheema, Umber; Bailly, Maryse; Brown, Robert A

    2012-10-07

    Here, we show that the local incorporation of osmotically active hyaluronan into previously compressed collagen constructs results in further rapid dehydration/compression of collagen layers, channel formation and generation of new interfaces; these novel structures, at the nano-micro (i.e. meso-scale) were formed within native collagen gels, in a highly predictable spatial manner and offer important new methods of fabricating scaffolds (e.g. tubes and open-spirals) with potential for use in tissue regeneration such as in peripheral nerves and small vessels. This paper tests the possibility that the local fluid content of a dense collagen network can be controlled by incorporation of an osmotically active (native) macromolecule--hyluronan. This is an exemplar physiological, osmotic swelling agent. Hyaluronan is commonly secreted by cells deep in connective tissues, so is a good candidate for this role in a cell-driven system balancing mechanical compaction of bulk tissue collagen. These constructs may have potential as functional in vitro models representing developmental and pathological processes.

  10. Protocol and cell responses in three-dimensional conductive collagen gel scaffolds with conductive polymer nanofibres for tissue regeneration.

    PubMed

    Sirivisoot, Sirinrath; Pareta, Rajesh; Harrison, Benjamin S

    2014-02-06

    It has been established that nerves and skeletal muscles respond and communicate via electrical signals. In regenerative medicine, there is current emphasis on using conductive nanomaterials to enhance electrical conduction through tissue-engineered scaffolds to increase cell differentiation and tissue regeneration. We investigated the role of chemically synthesized polyaniline (PANI) and poly(3,4-ethylenedioxythiophene) (PEDOT) conductive polymer nanofibres for conductive gels. To mimic a naturally derived extracellular matrix for cell growth, type I collagen gels were reconstituted with conductive polymer nanofibres and cells. Cell viability and proliferation of PC-12 cells and human skeletal muscle cells on these three-dimensional conductive collagen gels were evaluated in vitro. PANI and PEDOT nanofibres were found to be cytocompatible with both cell types and the best results (i.e. cell growth and gel electrical conductivity) were obtained with a low concentration (0.5 wt%) of PANI. After 7 days of culture in the conductive gels, the densities of both cell types were similar and comparable to collagen positive controls. Moreover, PC-12 cells were found to differentiate in the conductive hydrogels without the addition of nerve growth factor or electrical stimulation better than collagen control. Importantly, electrical conductivity of the three-dimensional gel scaffolds increased by more than 400% compared with control. The increased conductivity and injectability of the cell-laden collagen gels to injury sites in order to create an electrically conductive extracellular matrix makes these biomaterials very conducive for the regeneration of tissues.

  11. Activation of hageman factor by collagen

    PubMed Central

    Wilner, G. D.; Nossel, H. L.; LeRoy, E. C.

    1968-01-01

    Purified acid-soluble and insoluble human collagen accelerated the clotting of plateletpoor plasma in silicone-treated tubes. The clot-promoting effect did not appear to be due to thromboplastic activity since the collagen preparations did not activate factor X in the presence of factor VII and calcium. Instead, collagen appeared to accelerate clotting by activating Hageman factor (factor XII) on the basis of the following findings: collagen increased the clot-promoting activity of partially purified Hageman factor but exerted no further effect in the presence of kaolin, a known activator of Hageman factor; clot-promoting eluates were obtained from collagen exposed to normal, hemophilic, or PTC-deficient plasma but not from collagen exposed to Hageman or PTA-deficient plasma. The collagen molecule itself appeared to be required for the clot-promoting activity since digestion with collagenase or thermal denaturation at pH 2.5 (about 35°C) resulted in very marked reduction in clot-promoting activity. Since thermal denaturation is associated with transformation of collagen structure from triple helical to random coil form, it is suggested that the native form of collagen is essential for the ability to activate Hageman factor. Blockage of the free amino groups by treatment with nitrous acid or dinitrofluorobenzene only slightly reduced the clot-promoting activity of collagen. In contrast, since addition of cationic proteins to collagen markedly reduced pro-coagulant activity it is suggested that negatively charged sites on the collagen molecule are critical for Hageman factor activation. This suggestion is supported by the finding that pepsin treatment of collagen, which removes the predominantly negatively charged telopeptides, results in significant decrease in coagulant activity. Esterification of collagen, which neutralizes 80-90% of the free carboxyl groups, reduced coagulant activity by over 90% and it is suggested that the free carboxyl groups of glutamic and

  12. Overview of the Cranial Nerves

    MedlinePlus

    ... and toxins. Some cranial nerve disorders interfere with eye movement. Eye movement is controlled by 3 pairs of muscles. These ... be able to move their eyes normally. How eye movement is affected depends on which nerve is affected. ...

  13. Nerve Injuries of the Upper Extremity

    MedlinePlus

    ... of individual nerve fibers and surrounding outer sheath (“insulation”) Figure 2: Nerve repair with realignment of bundles © ... of individual nerve fibers and surrounding outer sheath insulation Figure 2 - Nerve repair with realignment of bundles ...

  14. Device and method for measuring multi-phase fluid flow in a conduit having an abrupt gradual bend

    DOEpatents

    Ortiz, M.G.

    1998-02-10

    A system is described for measuring fluid flow in a conduit having an abrupt bend. The system includes pressure transducers, one disposed in the conduit at the inside of the bend and one or more disposed in the conduit at the outside of the bend but spaced a distance therefrom. The pressure transducers measure the pressure of fluid in the conduit at the locations of the pressure transducers and this information is used by a computational device to calculate fluid flow rate in the conduit. For multi-phase fluid, the density of the fluid is measured by another pair of pressure transducers, one of which is located in the conduit elevationally above the other. The computation device then uses the density measurement along with the fluid pressure measurements, to calculate fluid flow. 1 fig.

  15. Optic nerve hypoplasia in children.

    PubMed Central

    Zeki, S. M.; Dutton, G. N.

    1990-01-01

    Optic nerve hypoplasia (ONH) is characterised by a diminished number of optic nerve fibres in the optic nerve(s) and until recently was thought to be rare. It may be associated with a wide range of other congenital abnormalities. Its pathology, clinical features, and the conditions associated with it are reviewed. Neuroendocrine disorders should be actively sought in any infant or child with bilateral ONH. Early recognition of the disorder may in some cases be life saving. Images PMID:2191713

  16. Collagen telopeptides (cross-linking sites) play a role in collagen gel lattice contraction

    NASA Technical Reports Server (NTRS)

    Woodley, D. T.; Yamauchi, M.; Wynn, K. C.; Mechanic, G.; Briggaman, R. A.

    1991-01-01

    Solubilized interstitial collagens will form a fibrillar, gel-like lattice when brought to physiologic conditions. In the presence of human dermal fibroblasts the collagen lattice will contract. The rate of contraction can be determined by computer-assisted planemetry. The mechanisms involved in contraction are as yet unknown. Using this system it was found that the rate of contraction was markedly decreased when collagen lacking telopeptides was substituted for native collagen. Histidinohydroxylysinonorleucine (HHL) is a major stable trifunctional collagen cross-link in mature skin that involves a carboxyl terminal, telopeptide site 16c, the sixteenth amino acid residue from the carboxy terminal of the telopeptide region of alpha 1 (I) in type I collagen. Little, if any, HHL was present in native, purified, reconstituted, soluble collagen fibrils from 1% acetic acid-extracted 2-year-old bovine skin. In contrast, HHL cross-links were present (0.22 moles of cross-link per mole of collagen) in lattices of the same collagen contracted by fibroblasts. However, rat tail tendon does not contain HHL cross-links, and collagen lattices made of rat tail tendon collagen are capable of contraction. This suggests that telopeptide sites, and not mature HHL cross-links per se, are essential for fibroblasts to contract collagen lattices. Beta-aminopropionitrile fumarate (BAPN), a potent lathyrogen that perturbs collagen cross-linking by inhibition of lysyl oxidase, also inhibited the rate of lattice cell contraction in lattices composed of native collagen. However, the concentrations of BAPN that were necessary to inhibit the contraction of collagen lattices also inhibited fibroblast growth suggestive of cellular toxicity. In accordance with other studies, we found no inhibition of the rate of lattice contraction when fibronectin-depleted serum was used. Electron microscopy of contracted gels revealed typical collagen fibers with a characteristic axial periodicity. The data

  17. A Combination of Schwann-Cell Grafts and Aerobic Exercise Enhances Sciatic Nerve Regeneration

    PubMed Central

    Souto, Allana; Oliveira, Júlia Teixeira; de Lima, Silmara; Tonda-Turo, Chiara; Marques, Suelen Adriani; de Almeida, Fernanda Martins; Martinez, Ana Maria Blanco

    2014-01-01

    Background Despite the regenerative potential of the peripheral nervous system, severe nerve lesions lead to loss of target-organ innervation, making complete functional recovery a challenge. Few studies have given attention to combining different approaches in order to accelerate the regenerative process. Objective Test the effectiveness of combining Schwann-cells transplantation into a biodegradable conduit, with treadmill training as a therapeutic strategy to improve the outcome of repair after mouse nerve injury. Methods Sciatic nerve transection was performed in adult C57BL/6 mice; the proximal and distal stumps of the nerve were sutured into the conduit. Four groups were analyzed: acellular grafts (DMEM group), Schwann cell grafts (3×105/2 µL; SC group), treadmill training (TMT group), and treadmill training and Schwann cell grafts (TMT + SC group). Locomotor function was assessed weekly by Sciatic Function Index and Global Mobility Test. Animals were anesthetized after eight weeks and dissected for morphological analysis. Results Combined therapies improved nerve regeneration, and increased the number of myelinated fibers and myelin area compared to the DMEM group. Motor recovery was accelerated in the TMT + SC group, which showed significantly better values in sciatic function index and in global mobility test than in the other groups. The TMT + SC group showed increased levels of trophic-factor expression compared to DMEM, contributing to the better functional outcome observed in the former group. The number of neurons in L4 segments was significantly higher in the SC and TMT + SC groups when compared to DMEM group. Counts of dorsal root ganglion sensory neurons revealed that TMT group had a significant increased number of neurons compared to DMEM group, while the SC and TMT + SC groups had a slight but not significant increase in the total number of motor neurons. Conclusion These data provide evidence that this combination of therapeutic strategies can

  18. A Numerical Program for Steady-State Flow of Magma-Gas Mixtures Through Vertical Eruptive Conduits

    DTIC Science & Technology

    2000-01-01

    Numerical Program for Flow in Eruptive Conduits Figure 6: Comparison of results for conduit flow of Mount St. Helens magma using a fragmentation...calculated by independent methods, for a Mount St. Helens magma at 830 C, with 4.6 wt% total water. These plots indicate the accuracy of Conflow in...Nonequilibrium flow in volcanic conduits and application to the eruptions of Mt. St. Helens on May 18, 1980 and Vesuvius in AD 79: Journal of Volcanology and

  19. Femoral nerve dysfunction

    MedlinePlus

    ... Read More Abscess Diabetes Mononeuropathy Multiple mononeuropathy Myelin Peripheral neuropathy Polyarteritis nodosa Systemic Tumor Review Date 1/5/ ... Related MedlinePlus Health Topics Leg Injuries and Disorders Peripheral Nerve Disorders Browse the Encyclopedia A.D.A.M., Inc. ...

  20. Nerves and Tissue Repair.

    DTIC Science & Technology

    1994-07-01

    axolotl limbs are transected the concentration of transferrin in the distal limb tissue declines rapidly and limb regeneration stops. These results...transferrin binding and expression of the transferrin gene in cells of axolotl peripheral nerve indicate that both uptake and synthesis of this factor occur

  1. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  2. Immunostimulation effect of jellyfish collagen.

    PubMed

    Sugahara, Takuya; Ueno, Masashi; Goto, Yoko; Shiraishi, Ryusuke; Doi, Mikiharu; Akiyama, Koichi; Yamauchi, Satoshi

    2006-09-01

    Certain edible large jellyfishes belonging to the order Rhizostomeae are consumed in large quantities in China and Japan. The exumbrella part of the edible jellyfish Stomolophus nomurai was cut and soaked in dilute hydrochloric acid solution (pH 3.0) for 12 h, and heated at 121 degrees C for 20 min. The immunostimulation effects of the jellyfish extract were examined. The jellyfish extract enhanced IgM production of human hybridoma HB4C5 cells 34-fold. IgM and IgG production of human peripheral blood lymphocytes (PBL) were also accelerated, 2.8- and 1.4-fold respectively. Moreover, production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by human PBL was stimulated 100- and 17-fold respectively. Collagenase treatment inactivated the immunostimulation activity of the jellyfish extract. In addition, purified collagen from bovine Achilles' tendon accelerated IgM production of hybridoma cells. These facts mean that collagen has an immunostimulation effect, and that the active substance in jellyfish extract is collagen.

  3. Bioengineered Human and Allogeneic Pulmonary Valve Conduits Chronically Implanted Orthotopically in Baboons: Hemodynamic Performance and Immunological Consequences

    PubMed Central

    Hopkins, Richard A.; Bert, Arthur A.; Hilbert, Stephen L.; Quinn, Rachael W.; Brasky, Kathleen M.; Drake, William B.; Lofland, Gary K.

    2012-01-01

    Objective This study assesses in a baboon model the hemodynamics and HLA immunogenicity of chronically implanted bioengineered (decellularized with collagen conditioning treatments) human and baboon heart valve scaffolds. Methods Fourteen baboons underwent pulmonary valve replacement, eight with decellularized and conditioned (bioengineered) pulmonary valves derived from either allogeneic (N=3) or xenogeneic (human) (N=5) hearts; for comparison, six baboons received clinically relevant reference cryopreserved or porcine valved conduits. Panel reactive serum antibodies (HLA Class I&II), complement fixing antibodies (C1q binding), and C-reactive protein titers were measured serially until elective sacrifice at 10 or 26 weeks. Serial transesophageal echocardiograms (TEE) measured valve function and geometry. Differences were analyzed with Kruskal-Wallis and Wilcoxon Rank Sum. P≤ 0.05 significant. Results All animals survived and thrived, exhibiting excellent immediate implanted valve function by TEE. Over time, reference valves developed smaller indexed effective orifice areas, EOAI=0.84(1.22) cm2/m2 median (range) while all bioengineered valves remained normal, EOAI=2.45 (1.35) cm2/m2; P=0.005. None of the bioengineered valves developed elevated peak transvalvular gradients, 5.5(6.0) versus 12.5(23.0) mmHg, P=0.003. Cryopreserved valves provoked the most intense antibody responses. Two of five human bioengineered and two of three baboon bioengineered valves did not provoke any Class I antibodies. Bioengineered human (but not baboon) scaffolds provoked Class II antibodies. C1q+ antibodies developed in four recipients. Conclusions Valve dysfunction correlated with markers for more intense inflammatory provocation. The tested bioengineering methods reduced antigenicity of both human and baboon valves. Bioengineered replacement valves from both species were hemodynamically equivalent to native valves. PMID:22841171

  4. Decellularized aortic conduits: could their cryopreservation affect post-implantation outcomes? A morpho-functional study on porcine homografts.

    PubMed

    Gallo, Michele; Bonetti, Antonella; Poser, Helen; Naso, Filippo; Bottio, Tomaso; Bianco, Roberto; Paolin, Adolfo; Franci, Paolo; Busetto, Roberto; Frigo, Anna Chiara; Buratto, Edward; Spina, Michele; Marchini, Maurizio; Ortolani, Fulvia; Iop, Laura; Gerosa, Gino

    2016-11-01

    Decellularized porcine aortic valve conduits (AVCs) implanted in a Vietnamese Pig (VP) experimental animal model were matched against decellularized and then cryopreserved AVCs to assess the effect of cryopreservation on graft hemodynamic performance and propensity to in vivo repopulation by host's cells. VPs (n = 12) underwent right ventricular outflow tract substitution using AVC allografts and were studied for 15-month follow-up. VPs were randomized into two groups, receiving AVCs treated with decellularization alone (D; n = 6) or decellularization/cryopreservation (DC; n = 6), respectively. Serial echocardiography was carried out to follow up hemodynamic function. All explanted AVCs were processed for light and electron microscopy. No signs of dilatation, progressive stenosis, regurgitation, and macroscopic calcification were echocardiographically observed in both D and DC groups. Explanted D grafts exhibited near-normal features, whereas the presence of calcification, inflammatory infiltrates, and disarray of elastic lamellae occurred in some DC grafts. In the unaltered regions of AVCs from both groups, almost complete re-endothelialization was observed for both valve cusps and aorta walls. In addition, side-by-side repopulation by recipient's fibroblasts, myofibroblasts, and smooth muscle cells was paralleled by ongoing tissue remodeling, as revealed by the ultrastructural identification of typical canals of collagen fibrillogenesis and elastogenesis-related features. Incipient neo-vascularization and re-innervation of medial and adventitial tunicae of grafted aortic walls were also detected for both D and DC groups. Cryopreservation did not affect post-implantation AVC hemodynamic behavior and was topically propensive to cell repopulation and tissue renewal, although graft deterioration including calcification was present in several areas. Thus, these preliminary data provide essential information on feasibility of decellularization and

  5. Device and method for measuring multi-phase fluid flow in a conduit using an elbow flow meter

    DOEpatents

    Ortiz, M.G.; Boucher, T.J.

    1997-06-24

    A system is described for measuring fluid flow in a conduit. The system utilizes pressure transducers disposed generally in line upstream and downstream of the flow of fluid in a bend in the conduit. Data from the pressure transducers is transmitted to a microprocessor or computer. The pressure differential measured by the pressure transducers is then used to calculate the fluid flow rate in the conduit. Control signals may then be generated by the microprocessor or computer to control flow, total fluid dispersed, (in, for example, an irrigation system), area of dispersal or other desired effect based on the fluid flow in the conduit. 2 figs.

  6. Device and method for measuring multi-phase fluid flow in a conduit using an elbow flow meter

    DOEpatents

    Ortiz, Marcos G.; Boucher, Timothy J.

    1997-01-01

    A system for measuring fluid flow in a conduit. The system utilizes pressure transducers disposed generally in line upstream and downstream of the flow of fluid in a bend in the conduit. Data from the pressure transducers is transmitted to a microprocessor or computer. The pressure differential measured by the pressure transducers is then used to calculate the fluid flow rate in the conduit. Control signals may then be generated by the microprocessor or computer to control flow, total fluid dispersed, (in, for example, an irrigation system), area of dispersal or other desired effect based on the fluid flow in the conduit.

  7. Shallow conduit processes of the 1991 Hekla eruption, Iceland

    NASA Astrophysics Data System (ADS)

    Gudnason, J.; Thordarson, T.; Houghton, B. F.

    2013-12-01

    On January 17, 1991 at 17:00 hrs, the 17th eruption of Hekla since 1104AD began. Lasting for almost two months, it produced 0.02 km3 of icelandite tephra and ~0.15km3 of icelandite lava. This eruption was the third of four eruptions since 1980 with a recurrence period of approximately 10 years, as opposed to a recurrence interval of c. 55 years for the eruptions in the period 1104AD to 1947AD. [1] The last four Hekla eruptions are typified by a 0.5-2 hour-long initial phase of subplinian intensity and discharge ranging from 2900-6700 m3/s [2]. In all 4 events the inital phase was followed by a sustained and relatively low-discharge(<20 m3/s) effusive phase, which in the case of Hekla 1991 lasted until the 11th March 1991 [1]. The initial phase of the 1991 event lasted for ~50 minutes and sustained an eruption plume that rose to 11.5 km in about 10 minutes [1]. The plume was dispersed to the NNE at velocities of 60-70 km/hr producing a well-sorted tephra fall covering >20,000 km2. Here we examine the first phase of the Hekla 1991 eruption with focus on vesiculation and fragmentation processes in the shallow conduit and ash production. Samples of the tephra fall were collected on snow immediately after the initial phase at multiple sites providing a representative spatial coverage within the 0.1mm isopach [3]. This set was augmented by samples collected in 2012 to provide tighter coverage of near vent region. Grain size of all samples has been measured down to 1 micron. Density measurements have been conducted on 4 near-vent pumice samples (100 clasts each) and the pumice vesicle size distribution has been determined in a selected subset of clasts. The reconstructed whole deposit grain size distribution exhibits a unimodal, log-normal distribution peaking at -3 phi, typical of dry, magmatic fragmentation. Pumice densities range from 520-880 kg/m3 and exhibit a tight unimodal and log-normal distribution indicating a mean vesicularity of 77% to 79% for the magma

  8. A Novel Functional Role of Collagen Glycosylation

    PubMed Central

    Jürgensen, Henrik J.; Madsen, Daniel H.; Ingvarsen, Signe; Melander, Maria C.; Gårdsvoll, Henrik; Patthy, Laszlo; Engelholm, Lars H.; Behrendt, Niels

    2011-01-01

    Collagens make up the most abundant component of interstitial extracellular matrices and basement membranes. Collagen remodeling is a crucial process in many normal physiological events and in several pathological conditions. Some collagen subtypes contain specific carbohydrate side chains, the function of which is poorly known. The endocytic collagen receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 plays an important role in matrix remodeling through its ability to internalize collagen for lysosomal degradation. uPARAP/Endo180 is a member of the mannose receptor protein family. These proteins all include a fibronectin type II domain and a series of C-type lectin-like domains, of which only a minor part possess carbohydrate recognition activity. At least two of the family members, uPARAP/Endo180 and the mannose receptor, interact with collagens. The molecular basis for this interaction is known to involve the fibronectin type II domain but nothing is known about the function of the lectin domains in this respect. In this study, we have investigated a possible role of the single active lectin domain of uPARAP/Endo180 in the interaction with collagens. By expressing truncated recombinant uPARAP/Endo180 proteins and analyzing their interaction with collagens with high and low levels of glycosylation we demonstrated that this lectin domain interacts directly with glycosylated collagens. This interaction is functionally important because it was found to modulate the endocytic efficiency of the receptor toward highly glycosylated collagens such as basement membrane collagen IV. Surprisingly, this property was not shared by the mannose receptor, which internalized glycosylated collagens independently of its lectin function. This role of modulating its uptake efficiency by a specific receptor is a previously unrecognized function of collagen glycosylation. PMID:21768090

  9. Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats.

    PubMed

    Li, Rui; Wu, Jiang; Lin, Zhenkun; Nangle, Matthew R; Li, Yi; Cai, Pingtao; Liu, Dan; Ye, Libin; Xiao, Zecong; He, Chaochao; Ye, Jingjing; Zhang, Hongyu; Zhao, Yingzheng; Wang, Jian; Li, Xiaokun; He, Yan; Ye, Qingsong; Xiao, Jian

    2017-02-01

    The prototypical neurotrophin, nerve growth factor (NGF), plays an important role in the development and maintenance of many neurons in both the central and peripheral nervous systems, and can promote functional recovery after peripheral nerve injury in adulthood. However, repair of peripheral nerve defects is hampered by the short half-life of NGF in vivo, and treatment with either NGF alone or NGF contained in synthetic nerve conduits is inferior to the use of nerve autografts, the current gold standard. We tested the reparative ability of a single local injection of a polyvalent coacervate containing polycation-poly(ethylene argininylaspartate diglyceride; PEAD), heparin, and NGF, in adult rats following sciatic nerve crush injury, using molecular, histological and behavioral approaches. In vitro assays demonstrated that NGF was loaded into the coacervate at nearly 100% efficiency, and was protected from proteolytic degradation. In vivo, the coacervate enhanced NGF bioavailability, leading to a notable improvement in motor function (track walking analysis) after 30days. The NGF coacervate treatment was also associated with better weight gain and reduction in atrophy of the gastrocnemius muscle. Furthermore, light and electron microscopy showed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in NGF coacervate-treated rats compared with control groups. Expression of markers of neural tissue regeneration (MAP-2, S-100β, MBP and GAP-43), as well as proliferating Schwann cells and myelin-axon relationships (GFAP and NF200), were also increased. These observations suggest that even a single administration of NGF coacervate could have therapeutic value for peripheral nerve regeneration and functional recovery.

  10. Tissue engineering with peripheral blood-derived mesenchymal stem cells promotes the regeneration of injured peripheral nerves.

    PubMed

    Pan, Mengjie; Wang, Xianghai; Chen, Yijing; Cao, Shangtao; Wen, Jinkun; Wu, Guofeng; Li, Yuanyuan; Li, Lixia; Qian, Changhui; Qin, Zhenqi; Li, Zhenlin; Tan, Dandan; Fan, Zhihao; Wu, Wutian; Guo, Jiasong

    2017-03-07

    Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP. Furthermore, iPBMSCs seeded in an artificial nerve conduit to bridge a 10-mm defect in a sciatic nerve achieved significant nerve regeneration outcomes, including axonal regeneration and remyelination, nerve conduction recovery, and restoration of motor function, and attenuated myoatrophy and neuromuscular junction degeneration in the target muscle. Overall, the data from this study indicated that PBMSCs can transdifferentiate towards SC-like cells and have potential as grafting cells for nerve tissue engineering.

  11. Assessment of Neuroprotective Effects of Local Administration of 17- Beta- Estradiol on Peripheral Nerve Regeneration in Ovariectomized Female Rats

    PubMed Central

    Nobakhti-Afshar, Ahmadreza; Najafpour, Alireza; Mohammadi, Rahim; Zarei, Leila

    2016-01-01

    Objective: To assess the neuroprotective effects of local administration of 17- beta- estradiol on nerve regeneration. Methods: Sixty female Wistar rats were overiectomized and divided into four experimental groups (n = 15), randomly: In autograft group a segment of sciatic nerve was transected and re-implanted reversely. In sham-surgery group sciatic nerve was exposed and manipulated. In transected group left sciatic nerve was transected and stumps were fixed in adjacent muscle. In treatment group defect was bridged using a silicon conduit filled with 10 µL (0.1 mg/mL) 17- beta- estradiol. Each group was subdivided into four subgroups of five animals each and nerve fibers were studied in a 12-week period. Results: Behavioral, functional, biomechanical, electrophysiological and gastrocnemius muscle mass findings and morphometric indices confirmed faster recovery of regenerated axons in treatment group than in other groups (p<0.05). Immunohistochemical reactions to S-100 in treatment group were more positive than that in other groups. Conclusion: Local administration of 17-beta-estradiol improved functional recovery and morphometric indices of sciatic nerve. It could have clinical implications for the surgical management of patients after facial nerve transection. PMID:27540548

  12. Genetically modified canine Schwann cells--In vitro and in vivo evaluation of their suitability for peripheral nerve tissue engineering.

    PubMed

    Schmitte, Ruth; Tipold, Andrea; Stein, Veronika M; Schenk, Henning; Flieshardt, Cornelia; Grothe, Claudia; Haastert, Kirsten

    2010-02-15

    After peripheral nerve injury, Schwann cells (SC) guarantee for a regeneration-promoting milieu and are crucially involved in axonal regeneration. For extended nerve defects, bridging with an autologous nerve transplant is the gold standard therapy. Artificial biohybrid nerve transplants which combine a synthetic conduit with autologous SC genetically modified to express regeneration-promoting proteins may provide an alternative therapy to autotransplantation. The dog seems to be an ideal translational animal model for new treatment strategies. In the present study, utilizing a new transfection protocol, we transplanted enhanced green fluorescent protein (EGFP)-expressing adult canine SC (cSC) into a 5mm epineural pouch in the sciatic nerve of adult rats (n=9). The epineurial pouch technique serves as proof of principle to follow the fate of the transplanted cSC for up to 14 days after surgery. Fluorescence microscopy and immunohistochemistry revealed survival and integration of EGFP-expressing cSC into the regenerating host nerve tissue. We demonstrate that transplanted cSC contribute to the formation of bands of Büngner and are located in close vicinity to growth-associated protein-43 (GAP-43) expressing regenerating nerve fibers. This provides first evidence that transplanted genetically modified Schwann cells do successfully integrate into the host tissue where they could actively contribute to the regeneration process.

  13. Modeling magma flow in volcanic conduit with non-equilibrium crystallization

    NASA Astrophysics Data System (ADS)

    Yulia, Tsvetkova

    2010-05-01

    Modeling magma flow in volcanic conduit including with non -equilibrium crystallization There is a set of models of magma flow in volcanic conduits which predicts oscillations in magma discharge during extrusion of lava domes. These models neglect heating of surrounding rocks and use 1D approximation of the flow in the conduit. Here magma flow is investigated with an account of heat exchange between surrounding rocks and magma and different dependences viscosity on temperature and crystal concentration. Stick-slip conditions were applied at the wall. The flow is assumed to be quasi-static and quasi 1D. Only vertical component of velocity vector is present, thus, we do not consider horizontal momentum balance. At the top of the conduit the pressure is assumed to be fixed, chamber pressure changes according with magma influx and outflux. First set of simulation was made for the viscosity that depends on cross-section average crystal concentration and parabolic velocity profile. In earlier models that account for crystal growth kinetics the temperature was allowed to change only due to the release of latent heat of crystallization. Heat transfer leads to cooling of the outer parts of the conduit leading to high crystal contents and high magma viscosities. Changes in viscosity result in changes in discharge rate. For the non-isothermal case there is no motion during most part of the cycle and a portion of magma solidifies at the top of the conduit forming a plug. During repose period chamber pressure is growing due to influx of fresh magma, and magma discharge rate starts to increase. Influx of hot magma into the conduit leads to decrease in friction resulting in a jump in discharge rate that lead to depressurization of magma chamber. Discharge rate decreases and magma solidifies again. For isothermal model with the same parameters discharge rate monotonically tends to the value of Qin. Simulation reveal that crystal content changes significantly across the conduit

  14. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype

    PubMed Central

    Connor, Yamicia; Tekleab, Sarah; Nandakumar, Shyama; Walls, Cherelle; Tekleab, Yonatan; Husain, Amjad; Gadish, Or; Sabbisetti, Venkata; Kaushik, Shelly; Sehrawat, Seema; Kulkarni, Ashish; Dvorak, Harold; Zetter, Bruce; R. Edelman, Elazer; Sengupta, Shiladitya

    2015-01-01

    Metastasis is a major cause of mortality and remains a hurdle in the search for a cure for cancer. Not much is known about metastatic cancer cells and endothelial cross-talk, which occurs at multiple stages during metastasis. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for transfer of microRNAs. The communication between the tumour cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of ‘metastatic hijack': cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in vivo. Targeting these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer. PMID:26669454

  15. Capacitive effect of cavitation in xylem conduits: results from a dynamic model.

    PubMed

    Hölttä, Teemu; Cochard, Herve; Nikinmaa, Eero; Mencuccini, Maurizio

    2009-01-01

    Embolisms decrease plant hydraulic conductance and therefore reduce the ability of the xylem to transport water to leaves provided that embolized conduits are not refilled. However, as a xylem conduit is filled with gas during cavitation, water is freed to the transpiration stream and this transiently increases xylem water potential. This capacitive effect of embolism formation on plant function has not been explicitly quantified in the past. A dynamic model is presented that models xylem water potential, xylem sap flow and cavitation, taking into account both the decreasing hydraulic conductance and the water release effect of xylem embolism. The significance of the capacitive effect increases in relation to the decreasing hydraulic conductance effect when transpiration rate is low in relation to the total amount of water in xylem conduits. This ratio is typically large in large trees and during drought.

  16. Magma fracture and hybrid earthquakes in the conduit of Augustine Volcano

    NASA Astrophysics Data System (ADS)

    Buurman, Helena; West, Michael E.

    2013-12-01

    exploit subtle but systematic shifts in seismic waveforms to examine a 2 h cluster of repeating hybrid volcanic earthquakes preceding the first magmatic explosions at Augustine Volcano in January 2006. We extract differential P wave traveltimes of <0.01 s to determine that the source locations migrated downward by approximately 35 m. Waveform characteristics, GPS observations, and visual reports of lava effusion at the summit suggest that the earthquakes were sourced by fracturing magma in the upper conduit. As the lava cooled and degassed at the surface, the conditions in the upper conduit changed causing the zone in which magma fracture could occur to move downward through the magma column. These changes may also have been the first indicators that the conduit was becoming choked, causing a buildup in pressure that resulted in the large magmatic explosions that followed 36 h later.

  17. Impact of conduit geometry on the performance of typical particulate microchip packings.

    PubMed

    Jung, Stephanie; Höltzel, Alexandra; Ehlert, Steffen; Mora, Jose-Angel; Kraiczek, Karsten; Dittmann, Monika; Rozing, Gerard P; Tallarek, Ulrich

    2009-12-15

    This work investigates the impact of conduit geometry on the chromatographic performance of typical particulate microchip packings. For this purpose, high-performance liquid chromatography (HPLC)/UV-microchips with separation channels of quadratic, trapezoidal, or Gaussian cross section were fabricated by direct laser ablation and lamination of multiple polyimide layers and then slurry-packed with either 3 or 5 microm spherical porous C8-silica particles under optimized packing conditions. Experimentally determined plate height curves for the empty microchannels are compared with dispersion coefficients from theoretical calculations. Packing densities and plate height curves for the various microchip packings are presented and conclusively explained. The 3 microm packings display a high packing density irrespective of their conduit geometries, and their performance reflects the dispersion behavior of the empty channels. Dispersion in 5 microm packings correlates with the achieved packing densities, which are limited by the number and accessibility of corners in a given conduit shape.

  18. Comparison of postoperative acute kidney injury between ileal conduit and neobladder urinary diversions after radical cystectomy

    PubMed Central

    Joung, Kyoung-Woon; Kong, Yu-Gyeong; Yoon, Syn-Hae; Kim, Yeon Ju; Hwang, Jai-Hyun; Hong, Bumsik; Kim, Young-Kug

    2016-01-01

    Abstract Ileal conduit and neobladder urinary diversions are frequently performed after radical cystectomy. However, complications after radical cystectomy may be different according to the type of urinary diversion. Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. This study was performed to compare the incidence of postoperative AKI between ileal conduit and neobladder urinary diversions after radical cystectomy. All consecutive patients who underwent radical cystectomy in 2004 to 2014 in a single tertiary care center were identified. The patients were divided into the ileal conduit and ileal neobladder groups. Preoperative variables, including demographics, cancer-related data and laboratory values, as well as intraoperative data and postoperative outcomes, including AKI, intensive care unit admission rate, and the duration of hospital stay, were evaluated between the groups. Postoperative AKI was defined according to the Kidney Disease: Improving Global Outcome criteria. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences. After performing 1:1 propensity score matching, the ileal conduit and ileal neobladder groups each included 101 patients. The overall incidence of AKI after radical cystectomy was 30.7% (62 out of 202) and the incidences did not significantly differ between the groups (27 [26.7%], ileal conduit group vs 35 [34.7%], ileal neobladder group, P = 0.268). Intraoperative data, intensive care unit admission rate, and the duration of hospital stay were not significantly different between the groups. Postoperative AKI did not significantly differ between ileal conduit and neobladder urinary diversions after radical cystectomy. This finding provides additional information useful for appropriate selection of the urinary diversion type in conjunction with radical cystectomy

  19. Jellyfish collagen scaffolds for cartilage tissue engineering.

    PubMed

    Hoyer, Birgit; Bernhardt, Anne; Lode, Anja; Heinemann, Sascha; Sewing, Judith; Klinger, Matthias; Notbohm, Holger; Gelinsky, Michael

    2014-02-01

    Porous scaffolds were engineered from refibrillized collagen of the jellyfish Rhopilema esculentum for potential application in cartilage regeneration. The influence of collagen concentration, salinity and temperature on fibril formation was evaluated by turbidity measurements and quantification of fibrillized collagen. The formation of collagen fibrils with a typical banding pattern was confirmed by atomic force microscopy and transmission electron microscopy analysis. Porous scaffolds from jellyfish collagen, refibrillized under optimized conditions, were fabricated by freeze-drying and subsequent chemical cross-linking. Scaffolds possessed an open porosity of 98.2%. The samples were stable under cyclic compression and displayed an elastic behavior. Cytotoxicity tests with human mesenchymal stem cells (hMSCs) did not reveal any cytotoxic effects of the material. Chondrogenic markers SOX9, collagen II and aggrecan were upregulated in direct cultures of hMSCs upon chondrogenic stimulation. The formation of typical extracellular matrix components was further confirmed by quantification of sulfated glycosaminoglycans.

  20. Collagen-coated microparticles in drug delivery.

    PubMed

    Sehgal, Praveen Kumar; Srinivasan, Aishwarya

    2009-07-01

    Advantages of drug-incorporated collagen particles have been described for the controlled delivery system for therapeutic actions. The attractiveness of collagen lies in its low immunogenicity and high biocompatibility. It is also recognized by the body as a natural constituent rather than a foreign body. Our research and development efforts are focused towards addressing some of the limitations of collagen, like the high viscosity of an aqueous phase, nondissolution in neutral pH buffers, thermal instability (denaturation) and biodegradability, to make it an ideal material for drug delivery with particular reference to microparticles. These limitations could be overcome by making collagen conjugates with other biomaterials or chemically modifying collagen monomer without affecting its triple helical conformation and maintaining its native properties. This article highlights collagen microparticles' present status as a carrier in drug delivery.

  1. Collagen-Based Biomaterials for Wound Healing

    PubMed Central

    Chattopadhyay, Sayani; Raines, Ronald T.

    2014-01-01

    With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three-dimensional scaffolds that are intrinsically biocompatible, biodegradable, non-toxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wo