Project related news and papers

Project related news and papers (83)

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.

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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.

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Novel bioabsorbable polymeric porous tubes for tissue engineering nerve growth are disclosed. The tubes are made from a bioabsorbable polymeric foam material and have a gradient of pore sizes across the wall thickness of the tubes such that cell growth occurs into the wall of the tubes from the inner surface, while cell growth or entry is not permitted through the outer wall into the tubular wall. The wall is permeable inwardly and outwardly to fluids. A novel method of manufacturing porous nerve tubes is also disclosed.

Polymeric fibers are of increasing interest to regenerative medicine, as materials made from these fibers are porous, allowing for cell infiltration, influx of nutrients, and efflux of waste products. Recently, multilayered coextrusion has emerged as a scalable and rapid fabrication method to yield microscale to submicron fibers. In this report, we describe the multilayered coextrusion of aligned poly(ε-caprolactone) (PCL) fibers, followed by a simple photochemical patterning to create surface-immobilized gradients onto the polymer fibers. PCL fibers were photochemically decorated with a linear gradient of propargyl benzophenone using a gradient photomask to control light source intensity. The pendant alkynes were then able to undergo the copper-catalyzed azide–alkyne cycloaddition reaction with an azide-modified IKVAV peptide to further functionalize the surface. Gradient-modified IKVAV fibers were evaluated for neural cell adhesion and neural differentiation, using PC-12 cells cultured onto the fibers. The aligned gradient fibers provided directional cues for neurite outgrowth and alignment of neural cells, as observed by cellular elongation, neurite differentiation, and orientation. The work presented herein describes a scalable fiber system combined with simple chemical patterning to generate aligned fibers with controlled surface gradients as cell-seeding scaffolds.

 

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Abstract

  • The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair peripheral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good histocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration (2-8 weeks), the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objective and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury.

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Abstract

  • The peripheral nervous system has a limited innate capacity for self-repair following injury, and surgical intervention is often required. For injuries greater than a few millimeters autografting is standard practice although it is associated with donor site morbidity and is limited in its availability. Because of this, nerve guidance conduits (NGCs) can be viewed as an advantageous alternative, but currently have limited efficacy for short and large injury gaps in comparison to autograft. Current commercially available NGC designs rely on existing regulatory approved materials and traditional production methods, limiting improvement of their design. The aim of this study was to establish a novel method for NGC manufacture using a custom built laser-based microstereolithography (μSL) setup that incorporated a 405 nm laser source to produce 3D constructs with ∼50 μm resolution from a photocurable poly(ethylene glycol) resin. These were evaluated by SEM, in vitro neuronal, Schwann and dorsal root ganglion culture and in vivo using a thy-1-YFP-H mouse common fibular nerve injury model. NGCs with dimensions of 1 mm internal diameter × 5 mm length with a wall thickness of 250 μm were fabricated and capable of supporting re-innervation across a 3 mm injury gap after 21 days, with results close to that of an autograft control. The study provides a technology platform for the rapid microfabrication of biocompatible materials, a novel method for in vivo evaluation, and a benchmark for future development in more advanced NGC designs, biodegradable and larger device sizes, and longer-term implantation studies.

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Scientists at Sheffield University are doing work in additive manufacturing and 3D printing that pushes the boundaries of the technology to the limit, and their most recent announcement is very much in keeping with their previous breakthroughs.

 

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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.

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Abstract

  • Peripheral nerve injuries are often associated with loss of nerve tissue and require a graft to bridge the gap. Autologous nerve grafts are still the 'gold standard' in reconstructive surgery but have several disadvantages, such as sacrifice of a functional nerve, neuroma formation and loss of sensation at the donor site. Bioengineered grafts represent a promising approach to address this problem. In this study, poly-3-hydroxybutyrate (PHB) strips were used to bridge a 10 mm rat sciatic nerve gap and their effects on long-term (12 weeks) nerve regeneration were compared. PHB strips were seeded with different cell types, either primary Schwann cells (SCs) or SC-like differentiated adipose-derived stem cells (dASCs) suspended in a fibrin glue matrix. The control group was PHB and fibrin matrix without cells. Functional and morphological properties of the regenerated nerve were assessed using walking track analysis, EMGs, muscle weight ratios and muscle and nerve histology. The animals treated with PHB strips seeded with SCs or dASCs showed significantly better functional ability than the control group. This correlated with less muscle atrophy and greater axon myelination in the cell groups. These findings suggest that the PHB strip seeded with cells provides a beneficial environment for nerve regeneration. Furthermore, dASCs, which are abundant and easily accessible, constitute an attractive cell source for future applications of cell therapy for the clinical repair of traumatic nerve injuries. Copyright © 2014 John Wiley & Sons, Ltd.

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Abstract: 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.

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