Large-diameter Fibers Research Articles

Ytterbium-doped all glass leakage channel fibers with highly fluorine-doped silica pump cladding

All glass leakage channel fibers have been demonstrated to be a potential practical solution for power scaling in fiber lasers beyond the nonlinear limits in conventional large mode area fibers. The all glass nature with absence of any air holes is especially useful for allowing the fibers to be used and fabricated much like conventional fibers. Previously, double clad active all glass leakage channel fibers used low index polymer as a pump guide with the drawbacks of being less reliable at high pump powers and not being able to change fiber outer diameter independent of pump guide dimension. In this work, we demonstrate, for the first time, ytterbium-doped double clad all glass leakage channel fibers with highly fluorine-doped silica as pump cladding. The new all glass leakage channel fibers have no polymer in the pump path and have independent control of fiber outer diameters and pump cladding dimension, and, therefore, enable designs with smaller pump guide for high pump absorption and, at the same time, with large fiber diameters to minimize micro and macro bending effects, a much desired features for large core fibers where intermodal coupling can be an issue due to a much increased mode density. An ytterbium-doped double clad PM fiber with core diameter of 80 microm is also reported, which can be coiled in 76 cm diameter coils.

Tailoring Fiber Diameter in Electrospun Poly(ɛ-Caprolactone) Scaffolds for Optimal Cellular Infiltration in Cardiovascular Tissue Engineering

Despite the attractive features of nanofibrous scaffolds for cell attachment in tissue-engineering (TE) applications, impeded cell ingrowth has been reported in electrospun scaffolds. Previous findings have shown that the scaffold can function as a sieve, keeping cells on the scaffold surface, and that cell migration into the scaffold does not occur in time. Because fiber diameter is directly related to the pore size of an electrospun scaffold, the objective of this study was to systematically evaluate how cell delivery can be optimized by tailoring the fiber diameter of electrospun poly(epsilon-caprolactone) (PCL) scaffolds. Five groups of electrospun PCL scaffolds with increasing average fiber diameters (3.4-12.1 microm) were seeded with human venous myofibroblasts. Cell distribution was analyzed after 3 days of culture. Cell penetration increased proportionally with increasing fiber diameter. Unobstructed delivery of cells was observed exclusively in the scaffold with the largest fiber diameter (12.1 microm). This scaffold was subsequently evaluated in a 4-week TE experiment and compared with a poly(glycolic acid)-poly(4-hydroxybutyrate) scaffold, a standard scaffold used successfully in cardiovascular tissue engineering applications. The PCL constructs showed homogeneous tissue formation and sufficient matrix deposition. In conclusion, fiber diameter is a crucial parameter to allow for homogeneous cell delivery in electrospun scaffolds. The optimal electrospun scaffold geometry, however, is not generic and should be adjusted to cell size.

Structure–function relationships and source-to-ground distance in electrospun polycaprolactone

The strength of electrospun scaffolds has direct relevance to their function within tissue engineering. We characterized the effects of source-to-ground distance on the mechanical properties of electrospun poly(ε-caprolactone) (PCL). Source-to-ground distances of 10, 15 and 20 cm, solids concentrations of 12 and 18 wt.% and mandrel rotation surface speeds of 0–12 m s −1 were utilized. Tensile tests evaluated elastic modulus, tensile strength and elongation at failure. Scanning electron microscopy provided morphology and quantified fiber alignment. Increased source-to-ground distance yielded a microstructure allowing greater fiber rearrangement under load, tripling the observed tensile strength. Increases in rotational speed generally increased fiber alignment and strength at high but not low to moderate speeds. As fiber is quickly pulled out of a comparatively gentle falling process, collision with neighboring fibers moving at different speeds and in different directions can occur. The source-to-ground distance influences these collisions and thus has critical implications for microstructure and biocompatibility. In larger diameter (18 wt.% PCL), heavily point-bonded fibers (produced using a shorter, 10 cm source-to-ground distance), elongation at failure in the aligned direction increases dramatically due to severe localized necking. These specimens show only half of the tensile strength (from 2.6 to 4.5 MPa) and a dramatic increase (from 94% to 503%) in elongation at failure vs. a longer 20 cm source-to-ground distance. Strains of several hundred per cent are accompanied by periodic necking of large-diameter fibers in which microstructural failure appears to occur in a sequential manner involving an equilibrium between localized strain in the tensile direction and anisotropic point bonding that locally resists strain.

Neurofilament light chain polypeptide gene mutations in Charcot–Marie–Tooth disease: nonsense mutation probably causes a recessive phenotype

The neurofilament light chain polypeptide (NEFL) forms the major intermediate filament in neurons and axons. NEFL mutation is a cause of axonal or demyelinating forms of dominant Charcot-Marie-Tooth disease (CMT). We investigated NEFL in 223 Japanese CMT patients who were negative for PMP22, MPZ, GJB1, LITAF, EGR2, GDAP1, MTMR2 and PRX in the demyelinating form and negative for MFN2, MPZ, GJB1, HSP27, HSP22 and GARS in the axonal form. We detected four heterozygous missense mutations--Pro8Leu, Glu90Lys, Asn98Ser and Glu396Lys--in five unrelated patients and a homozygous nonsense mutation, Glu140Stop, in one other patient. All patients had mildly to moderately delayed nerve conduction velocities, possibly caused by a loss of large diameter fibers. This is the first report of a homozygous nonsense mutation of NEFL. Results of our study show that nonsense NEFL mutations probably cause a recessive phenotype, in contrast to missense mutations, which cause a dominant phenotype.

Could Sex Differences in White Matter be Explained by g ratio?

Recent studies with magnetic resonance imaging suggest that age-related changes in white matter during male adolescence may indicate an increase in g ratio wherein the radial growth of an axon outpaces a corresponding increase in myelin thickness. We review the original Rushton (1951) model where a g ratio of ∼0.6 represents an optimal relationship between the axon and fibre diameters vis-à-vis conduction velocity, and point out evidence indicating slightly higher g ratio in large-diameter fibres. We estimate that fibres with a diameter larger than 9.6 μm will have a relatively thinner myelin sheath, and brains with increasingly larger proportions of such large-diameter fibres will have progressively lower concentration of myelin. We conclude by pointing out possible implications of “suboptimal” g ratio for the emergence of “disconnection” disorders, such as schizophrenia, in late adolescence.

Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration

Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study, we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries.

Physiology and Treatment of Pain

Physiology and Treatment of Pain

A model of tight junction function in central nervous system myelinated axons

The insulative properties of myelin sheaths in the central and peripheral nervous systems (CNS and PNS) are widely thought to derive from the high resistance and low capacitance of the constituent membranes. Although this view adequately accounts for myelin function in large diameter fibers, it poorly reflects the behavior of small fibers that are prominent in many regions of the CNS. Herein, we develop a computational model to more accurately represent conduction in small fibers. By incorporating structural features that, hitherto, have not been simulated, we demonstrate that myelin tight junctions (TJs) improve saltatory conduction by reducing current flow through the myelin, limiting axonal membrane depolarization and restraining the activation of ion channels beneath the myelin sheath. Accordingly, our simulations provide a novel view of myelin by which TJs minimize charging of the membrane capacitance and lower the membrane time constant to improve the speed and accuracy of transmission in small diameter fibers. This study establishes possible mechanisms whereby TJs affect conduction in the absence of overt perturbations to myelin architecture and may in part explain the tremor and gait abnormalities observed in Claudin 11-null mice.

Histopathological Findings in Hereditary Motor and Sensory Neuropathy of Axonal Type With Onset in Early Childhood Associated WithMitofusin 2Mutations

Neuropathologic abnormalities can be sufficiently characteristic to suggest the genetic basis of some hereditary neuropathies such as those associated with mutations in MPZ, GJB1, GDAP1, MTMR2, SH3TC2, PRX, FGD4, and LMNA. We analyzed the morphologic features of 9 sural nerve biopsies from 6 patients with mutations of mitofusin 2. All patients presented in early childhood with axonal neuropathies designated as mild or severe motor and sensory neuropathy. In all cases, there was a marked decrease in density of myelinated fibers, mainly of large diameter fibers. These changes were more marked in the second biopsies of 3 patients that were performed from 7 to 19 years after the first biopsies. Neurophysiologic findings were most suggestive of axonal degeneration, but some onion bulbs were present in all cases. Axonal mitochondria were smaller than normal, were round, and were abnormally aggregated. These changes may result from abnormal mitochondrial fusion and fission. The results suggest that these clinical and pathological features may be sufficiently characteristic to suggest the diagnosis of mitofusin 2-related neuropathy.

The Hybrid Model and Mechanical Properties of Hybrid Composites Reinforced with Different Diameter Fibers

By using carbon fiber (CF) as small-diameter fiber, SiC fiber (SiCF) or boron fiber (BF) as large-diameter fiber, the SiCF/CF and BF/CF fiber reinforced epoxy resin hybrid composites have been fabricated and investigated. Through SEM micrograph analysis and fiber volume fraction statistics, the hybrid fiber distribution model of bi-diameter hybrid composites has been developed. Compressive and flexural properties of both hybrid composites were tested, and then the damage characteristics and the fracture mechanism of the two kinds of hybrid composites were studied contrastively. The hybrid effect of BF/CF composites is positive, i.e., the hybrid composites have higher compressive and flexural strengths than CFRP and BFRP. In contrast, the compressive and flexural strengths of SiCF/CF composite are both between those of CFRP and SiCFRP. The simple linear addition rule slowly dominates, obviously. The flexural modulus of the two hybrid materials obeys the rule of mixture.

Effects of fiber orientation and diameter on the behavior of human dermal fibroblasts on electrospun PMMA scaffolds

We used the electrospinning technique to produce fibrous scaffolds of poly(methyl methacrylate) (PMMA). Using a rotating drum, we aligned the fibers and formed multilayered structures where both the fiber spacing and pore size could be varied. We then plated adult human dermal fibroblasts and studied the effect of fiber diameter and orientation on the cell conformation, integrin receptor expression, proliferation, and migration. We found that a critical diameter minimum diameter existed, D0 = 0.97 microm for cell orientation to occur. For D < D0, no big difference in aspect ratio was observed relative to the control samples on PMMA thin film. Hence, we could fabricate substrate patterned with fibers of different diameters where different cell conformations coexisted on the same scaffold. On the other hand, staining for vinculin proteins in the cells indicated that on large diameter fibers and on flat surfaces, the integrin receptors followed the cell perimeter. On the very small diameter surfaces, the receptors were distributed uniformly along the cell. Cell dynamics studies indicated that the proliferation and migration were also affected by the fiber orientation.

012 Microvascular Endothelial Cell Migration in Scaffolds of Electrospun Collagen

Electrospinning is a nonmechanical processing strategy that is used to fabricate tissue-engineering scaffolds composed of submicron diameter, banded fibrils of collagen. Fiber diameter and porosity can be manipulated over a wide range simply by regulating the concentration of collagen present in the starting electrospinning solutions (Table). Collagen Concentration Fiber Diameter Pore Area 40 mg/ml TFE 113 ± 51 nm 184 ± 87.6 nm2 60 mg/ml TFE 302 ± 74 nm 1,598 ± 1,272 nm2 80 mg/ml TFE 909 ± 272 nm 4,420 ± 3,193 nm2 100 mg/ml TFE 1,389 ± 446 nm 10,950 ± 9,758 nm2 120 mg/ml TFE 1,533 ± 448 nm 24,032 ± 32,581 nm2 To examine how fiber diameter regulates microvascular endothelial cell migration/infiltration into a tissue engineering scaffold of electrospun collagen, we conducted in vitro migration assays. Electrospun scaffolds were prepared, cut into disks (150–300 microns thick), seeded with human microvascular endothelial cells and recovered at intervals. Varying fiber diameter from 100 to 2000 nm induced the expression of three distinct phenotypes. Scaffolds composed of fibers less than 300 nm in diameter exhibited a confluent layer of flat, stellate-shaped cells at all time points. The bulk of the cells were confined to the scaffold surface. At intermediate fiber diameters (300 nm–900 nm) the cells displayed a more rounded cell shape. By day 3 aggregates of these cells were clustered throughout scaffold in a capillary-like pattern. In scaffolds prepared with large diameter fibers (>1000 nm) the cells displayed an elongated, fusiform cell-shape and appeared to be uniformly scattered throughout the scaffold. These results parallel our in vivo studies that suggest fiber diameters of less than 300 nm reduce, but do not completely suppress, the infiltration of endothelial cells in a full thickness dermal injury model in the guinea pig. US and International Patents Pending and issued.

Electrophysiological and Functional Effects of Shock Waves on the Sciatic Nerve of Rats

Extracorporeal shockwave therapy (ESWT) has been applied in lithotripsy and treatments of musculoskeletal disorders over the past decade, but its effects on peripheral nerves remain unclear. This study investigated the short-term effects of shockwaves on the sciatic nerve of rats. The nerves were surgically exposed and then stimulated with shockwaves at three intensities. We evaluated the motor nerve conduction velocity (MNCV) of treated sciatic nerves before, immediately after (day 0) and at 1, 4, 7 and 14 d after shockwave treatment. Two functional tests—the sciatic functional index and the withdrawal reflex latency—were evaluated before and at 1, 4, 7 and 14 d after shockwave application. The rats were sacrificed on days 0, 1, 4, 7 and 14 for morphologic observation. The degassed treatment group received high-intensity shockwave treatment using degassed normal saline as the contact medium, and MNCV was measured before and on days 0, 1, 4, 7 and 14. The sham group received the same procedure as the treatment groups ( i.e., the surgical operation to expose the sciatic nerve) but with no shockwave treatment. The control group received no surgical operation or shockwave treatment. The results showed moderate decrease in the MNCV after shockwave treatment and damage to the myelin sheath of large-diameter myelinated fibers. The effect was largest (reduction to 60.9% of baseline MNCV) and of longest duration (7 to 14 d) in the high-intensity group. There were no significant changes in functional tests. These results indicated that direct application of shockwaves can induce reversible segmental demyelination in large-diameter fibers, with the electrophysiological changes being positively correlated with the intensity of the shockwaves. (E-mail: jjluh@ntu.edu.tw)

Nandrolone Decanoate Administration and Skeletal Muscle Recovery from Disuse Atrophy

Skeletal muscle atrophy commonly occurs during periods of disuse. The mouse soleus (SOL) muscle undergoes rapid atrophy during hindlimb suspension (HS). Nandrolone decanoate (ND) is an anabolic steroid known to promote muscle mass accretion. Therefore, ND administration could be an intervention to enhance muscle mass recovery from disuse. PURPOSE: The purpose of this study was to determine the effect of ND administration on the mouse SOL muscle fiber cross-sectional area (CSA) after 7 days of recovery from 10 days of HS-induced disuse. METHODS: Young healthy male C57BL6 mice were divided into four separate day-of-recovery groups: ground control (CON, n = 9), HS with 0 days of recovery (SUS+0, n = 5), HS with 7 days of recovery (SUS+7, n = 4) and HS with 7 days of recovery with ND administration (SUS+7ND, n = 4). ND was administered at the completion of 10 days of HS. SOL muscles were removed, frozen, and cross sectioned (12 μm) at the mid-belly for histological analysis. Type I and type II fibers were identified with myosin ATPase staining and fiber CSA was determined by quantifying a minimum of 120 type I and 80 type II fibers for each muscle. Fiber CSA distribution of small diameter fibers (≤ 750 μm2) and large diameter fibers (≥ 1500 μm2) was examined by a one group chi-square analysis. RESULTS: After 10 days of disuse the percentage of large diameter fibers decreased and small fibers increased in both fiber types. 7 days of recovery had no effect on fiber CSA distribution. However, ND administration with 7 days of recovery increased the percentage of large diameter and decreased the percentage of small diameter type II fibers. There was a trend for a decreased percentage of small diameter type I fibers (p<0.061) with ND and 7 days of recovery. CONCLUSIONS: These data indicate ND administration may be beneficial for muscle recovery from disuse atrophy. Supported by NIH Grant 5R03AR051434-02.

Polyneuropathy after cisplatin treatment

Polyneuropathy developed in 7 of 87 women who had been treated with cis-platinum for ovarian carcinoma. Distal disturbances of sensitivity were clinically prominent, the emphasis being on disturbed vibratory perception and acrognosis. No relevant signs of motor dysfunction were noticed, neither clinically nor neurophysiologically. Sural biopsies taken from two women revealed a primary axonal degeneration, mostly affecting the myelinic fibres of large diameter. In 3 cases mild reversion was seen, and in 4 cases no definite reversion, of the disturbed functions - uncertain gait and clumsiness of the hands - during the follow-up period of 6 to 30 months.

Congenital Axonal Neuropathy and Encephalopathy

Congenital axonal neuropathy associated with encephalopathy appears to be very rare. Only a few cases have been reported in the literature. In the last 25 years, we have seen seven patients affected by congenital axonal neuropathy with encephalopathy. Biopsies of their sural nerves revealed axonal atrophy and loss of large-diameter nerve fibers. All of these patients presented at birth or soon thereafter with hypotonia associated with distal weakness and diffuse areflexia. Central nervous system manifestations included microcephaly, seizures, and developmental delay. Outcomes were poor. Four children died before age 3 years from respiratory insufficiency or aspiration pneumonia. The three surviving patients manifested severe developmental delay. In our most recent patient, Western-blot analysis of snap-frozen specimens of the temporal and cerebellar cortex demonstrated an absence or marked decrease of microtubule-associated protein types 1A and 2, compared with age-matched control subjects. Calloso-splenial hypogenesis and neurofilament swellings were also documented in the deep white matter and adjacent cortex. The absence or hypo-expression of central nervous system microtubule-associated proteins has never been reported in congenital neuropathies, and may represent a new clinicopathologic entity.

A continuous model for mode mixing in graded-index multimode fibres with random imperfections

This article investigates the evolution of the distribution of propagating modes in a graded-index multimode fibre with random imperfections. These perturbations may be microscopic random bends and ellipticity, or an index of refraction fluctuations, introduced during manufacture. For large-diameter fibres (with respect to a typical electromagnetic wavelength), the number of guided modes becomes large, and so we can regard the discrete set as a continuum in which the mode number is treated as a continuous variable. The theory is applied to the propagation of guided optical modes in round fibres with a parabolic refractive index profile. This continuous model offers the great advantage of elucidating the relevant physical parameters that participate in the mode mixing dynamics, and leads to a numerically tractable problem. Numerical results are presented for the specific problem of random micro-bends, demonstrating that the theoretically predicted behaviour is achieved.

Factors influencing the properties of reconstituted collagen fibers prior to self‐assembly: Animal species and collagen extraction method

This research work allows a direct comparison between collagen solutions of equal concentration derived from the two widely used collagen sources: bovine Achilles tendon (BAT) and rat tail tendon (RTT), and extraction methods: acid (AS) and pepsin (PS) solubilization on the properties of extruded collagen fibers. Scanning electron microscopy revealed that the substructure of the collagen fibers was the same independent of the treatment. Transmission electron microscopy revealed that the AS collagen-derived fibers were comprised of thick quarter-staggered fibrils, while the coexistence of thin nonbanded and thick banded fibrils was apparent for the PS collagen-derived fibers. The BAT-derived fibers demonstrated higher denaturation temperature than the RTT-derived ones (p < 0.05). The extraction method had no influence on the thermal characteristics of the fibers produced (p > 0.05). ASBAT collagen was of higher viscosity than both ASRTT and PSBAT (p < 0.002), and therefore larger diameter fibers were obtained (p < 0.001). An inversely proportional relationship between dry-fiber diameter and stress at break was observed within the treatments. The PS yielded 10 times more soluble collagen from BAT and the derived fibers were of similar tensile strength, stiffness, and elongation (p > 0.05) as those derived from the AS collagen. No significant difference was observed for the stress at break for the ASBAT and the ASRTT, while significant difference was observed for the elongation and modulus values (p < 0.005). Overall, reconstituted collagen fibers were produced with properties similar to native or synthetic fibers to suit a wide range of tissue engineering applications.

Aciniform Spidroin, a Constituent of Egg Case Sacs and Wrapping Silk Fibers from the Black Widow Spider Latrodectus hesperus

Spiders produce high performance fibers with diverse mechanical properties and biological functions. Molecular and biochemical studies of spider egg case silk have revealed that the main constituent of the large diameter fiber contains the fibroin TuSp1. Here we demonstrate by SDS-PAGE and protein silver staining the presence of a distinct approximately 300-kDa polypeptide that is found in solubilized egg case sacs. Combining matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry and reverse genetics, we have isolated a novel gene called AcSp1-like and demonstrate that its protein product is assembled into the small diameter fibers of egg case sacs and wrapping silks from the black widow spider, Latrodectus hesperus. BLAST searches of the NCBInr protein data base using the amino acid sequence of AcSp1-like revealed similarity to AcSp1, an inferred protein proposed to be a component of wrapping silk. However, the AcSp1-like protein was found to display more nonuniformity in its internal iterated repeat modules than the putative AcSp1 fibroin. Real time quantitative PCR analysis demonstrates that the AcSp1-like gene displays an aciniform gland-restricted pattern of expression. The amino acid composition of the fibroins extracted from the luminal contents of the aciniform glands was remarkably similar to the predicted amino acid composition of the AcSp1-like protein, which supports the assertion that AcSp1-like protein represents the major constituent stored within the aciniform gland. Collectively, our findings provide the first direct molecular evidence for the involvement of the aciniform gland in the production of a common fibroin that is assembled into the small diameter threads of egg case and wrapping silk of cob weavers.

Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization

Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.