Dataset Information

Development of Oxidized Polyvinyl Alcohol-Based Nerve Conduits Coupled with the Ciliary Neurotrophic Factor.

ABSTRACT: Functionalized synthetic conduits represent a promising strategy to enhance peripheral nerve regeneration by guiding axon growth while delivering therapeutic neurotrophic factors. In this work, hollow nerve conduits made of polyvinyl alcohol partially oxidized with bromine (OxPVA_Br2) and potassium permanganate (OxPVA_KMnO4) were investigated for their structural/biological properties and ability to absorb/release the ciliary neurotrophic factor (CNTF). Chemical oxidation enhanced water uptake capacity of the polymer, with maximum swelling index of 60.5% ± 2.5%, 71.3% ± 3.6% and 19.5% ± 4.0% for OxPVA_Br2, OxPVA_KMnO4 and PVA, respectively. Accordingly, hydrogel porosity increased from 15.27% ± 1.16% (PVA) to 62.71% ± 8.63% (OxPVA_Br2) or 77.50% ± 3.39% (OxPVA_KMnO4) after oxidation. Besides proving that oxidized PVA conduits exhibited mechanical resistance and a suture holding ability, they did not exert a cytotoxic effect on SH-SY5Y and Schwann cells and biodegraded over time when subjected to enzymatic digestion, functionalization with CNTF was performed. Interestingly, higher amounts of neurotrophic factor were detected in the lumen of OxPVA_Br2 (0.22 ± 0.029 µg) and OxPVA_KMnO4 (0.29 ± 0.033 µg) guides rather than PVA (0.11 ± 0.021 µg) tubular scaffolds. In conclusion, we defined a promising technology to obtain drug delivery conduits based on functionalizable oxidized PVA hydrogels.

SUBMITTER: Porzionato A

PROVIDER: S-EPMC6631399 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of Oxidized Polyvinyl Alcohol-Based Nerve Conduits Coupled with the Ciliary Neurotrophic Factor.

Porzionato Andrea A Barbon Silvia S Stocco Elena E Dalzoppo Daniele D Contran Martina M De Rose Enrico E Parnigotto Pier Paolo PP Macchi Veronica V Grandi Claudio C De Caro Raffaele R

Materials (Basel, Switzerland) 20190621 12

Functionalized synthetic conduits represent a promising strategy to enhance peripheral nerve regeneration by guiding axon growth while delivering therapeutic neurotrophic factors. In this work, hollow nerve conduits made of polyvinyl alcohol partially oxidized with bromine (OxPVA_Br<sub>2</sub>) and potassium permanganate (OxPVA_KMnO<sub>4</sub>) were investigated for their structural/biological properties and ability to absorb/release the ciliary neurotrophic factor (CNTF). Chemical oxidation e ...[more]

PMID: 31234386

Similar Datasets

Project description:Administration of ciliary neurotrophic factor (CNTF) to experimental animals exerts anti-obesity effects by acting on multiple targets. In white adipose tissue CNTF reduces lipid content, promotes fatty acid (FA) oxidation and improves insulin sensitivity. This study was performed to establish whether CNTF exerts similar effects on human white adipocytes. To this end, adipose differentiation was induced in vitro in human multipotent adipose-derived stem (hMADS) cells. CNTF receptor ? (CNTFR?) expression was assessed in hMADS cells and adipocytes by qRT-PCR, Western blotting, and immunocytochemistry. After administration of human recombinant CNTF, signaling pathways and gene expression were evaluated by Western blotting and qRT-PCR. Glucose uptake was assessed by measuring 2-nitrobenzodeoxyglucose uptake with a fluorescence plate reader. Lastly, CNTF-induced anti-inflammatory responses were evaluated in hMADS adipocytes stressed with tumor necrosis factor ? (TNF?) for 24 h. Results showed that CNTFR? protein expression was higher in undifferentiated hMADS cells than in hMADS adipocytes, where it was however clearly detectable. In hMADS adipocytes, 1 nM CNTF strongly activated the JAK-STAT3 (Janus kinase-signaling transducer and activator of transcription 3) pathway and acutely and transiently activated the AMPK (AMP-activated protein kinase) and AKT (protein kinase B) pathways. Acute CNTF treatment for 20 min significantly increased basal glucose uptake and was associated with increased AKT phosphorylation. Longer-term (24 and 48 h) treatment reduced the expression of lipogenic markers (FA synthase and sterol regulatory element-binding protein-1) and increased the expression of lipolytic [hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)] and mitochondrial (peroxisome proliferator-activated receptor ? coactivator-1? and carnitine palmitoyltransferase 1) markers. In TNF?-treated hMADS adipocytes, CNTF significantly reduced the expression of monocyte chemoattractant protein 1 and TNF?-induced AKT inhibition. Collectively, these findings demonstrate for the first time that CNTF plays a role also in human adipocytes, driving their metabolism toward a less lipid-storing and more energy-consuming phenotype.

Project description:BackgroundIt is difficult to repair nerve if proximal stump is unavailable or autogenous nerve grafts are insufficient for reconstructing extensive nerve damage. Therefore, alternative methods have been developed, including lateral anastomosis based on axons' ability to send out collateral sprouts into denervated nerve. The different capacity of a sensory or motor axon to send a sprout is controversial and may be controlled by cytokines and/or neurotrophic factors like ciliary neurotrophic factor (CNTF). The aim of the present study was to quantitatively assess collateral sprouts sent out by intact motor and sensory axons in the end-to-side neurorrhaphy model following intrathecal administration of CNTF in comparison with phosphate buffered saline (vehiculum) and Cerebrolysin. The distal stump of rat transected musculocutaneous nerve (MCN) was attached in an end-to-side fashion with ulnar nerve. CNTF, Cerebrolysin and vehiculum were administered intrathecally for 2 weeks, and all animals were allowed to survive for 2 months from operation. Numbers of spinal motor and dorsal root ganglia neurons were estimated following their retrograde labeling by Fluoro-Ruby and Fluoro-Emerald applied to ulnar and musculocutaneous nerve, respectively. Reinnervation of biceps brachii muscles was assessed by electromyography, behavioral test, and diameter and myelin sheath thickness of regenerated axons.ResultsVehiculum or Cerebrolysin administration resulted in significantly higher numbers of myelinated axons regenerated into the MCN stumps compared with CNTF treatment. By contrast, the mean diameter of the myelinated axons and their myelin sheath thickness in the cases of Cerebrolysin- or CNTF-treated animals were larger than were those for rats treated with vehiculum. CNTF treatment significantly increased the percentage of motoneurons contributing to reinnervation of the MCN stumps (to 17.1%) when compared with vehiculum or Cerebrolysin treatments (at 9.9 or 9.6%, respectively). Reduced numbers of myelinated axons and simultaneously increased numbers of motoneurons contributing to reinnervation of the MCN improved functional reinnervation of the biceps brachii muscle after CNTF treatment.ConclusionThe present experimental study confirms end-to-side neurorrhaphy as an alternative method for reconstructing severed peripheral nerves. CNTF promotes motor reinnervation of the MCN stump after its end-to-side neurorrhaphy with ulnar nerve and improves functional recovery of the biceps brachii muscle.

Dataset Information

Development of Oxidized Polyvinyl Alcohol-Based Nerve Conduits Coupled with the Ciliary Neurotrophic Factor.

Publications

Development of Oxidized Polyvinyl Alcohol-Based Nerve Conduits Coupled with the Ciliary Neurotrophic Factor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets