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Nerve guidance conduit design based on self-rolling tubes.

ABSTRACT: The current gold standard in peripheral nerve repair is nerve autografts for bridging gaps larger than a centimeter. However, autografts are associated with a low availability and the loss of function at the donor site. Nerve guidance conduits (NGCs) made of biocompatible and biodegradable materials reflect suitable alternatives. Clinically approved NGCs comprise either wraps that are rolled around the loose ends of the nerve or steady-state tubes; however, both lack internal guidance structures. Here, we established self-rolling NGCs to allow for gentle encapsulation of nerve cells together with supportive microenvironments, such as (1) an inner tube wall coating with a bioactive spider silk film, (2) an inner tube wall lining using an anisotropic spider silk non-woven mat, or (3) a luminal filler using an anisotropic collagen cryogel. Neuronal cells adhered and differentiated inside the modified tubes and formed neurites, which were oriented along the guidance structures provided by the spider silk non-woven mat or by the fibrillary structure of the collagen cryogel. Thus, our size-adaptable NGCs provide several features useful for peripheral nerve repair, and distinct combinations of the used elements might support and enhance the clinical outcome.

SUBMITTER: Aigner TB

PROVIDER: S-EPMC7063334 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Nerve guidance conduit design based on self-rolling tubes.

Aigner T B TB Haynl C C Salehi S S O'Connor A A Scheibel T T

Materials today. Bio 20200127

The current gold standard in peripheral nerve repair is nerve autografts for bridging gaps larger than a centimeter. However, autografts are associated with a low availability and the loss of function at the donor site. Nerve guidance conduits (NGCs) made of biocompatible and biodegradable materials reflect suitable alternatives. Clinically approved NGCs comprise either wraps that are rolled around the loose ends of the nerve or steady-state tubes; however, both lack internal guidance structures ...[more]

PMID: 32159159

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Project description:BackgroundEfficient and stable delivery of neurotrophic factors (NTFs) is crucial to provide suitable microenvironment for peripheral nerve regeneration. Neurotrophin-3 (NT-3) is an important NTF during peripheral nerve regeneration which is scarce in the first few weeks of nerve defect. Exosomes are nanovesicles and have been served as promising candidate for biocarrier. In this work, NT-3 mRNA was encapsulated in adipose-derived stem cell (ADSC)-derived exosomes (ExoNT-3). These engineered exosomes were applied as NT-3 mRNA carrier and then were loaded in nerve guidance conduit (ExoNT-3-NGC) to bridge rat sciatic nerve defect.MethodNT-3 mRNA was encapsulated in exosomes by forcedly expression of NT-3 mRNA in the donor ADSCs. ExoNT-3 were co-cultured with SCs in vitro; after 24 h of culture, the efficiency of NT-3 mRNA delivery was evaluated by qPCR, western blotting and ELISA. Then, ExoNT-3 were loaded in alginate hydrogel to construct the nerve guidance conduits (ExoNT-3-NGC). ExoNT-3-NGC were implanted in vivo to reconstruct 10 mm rat sciatic nerve defect. The expression of NT-3 was measured 2 weeks after the implantation operation. The sciatic nerve functional index (SFI) was examined at 2 and 8 weeks after the operation. Moreover, the therapeutic effect of ExoNT-3-NGC was also evaluated by morphology assay, immunofluorescence staining of regenerated nerves, function evaluation of gastrocnemius muscles after 8 weeks of implantation.ResultsThe engineered exosomes could deliver NT-3 mRNA to the recipient cells efficiently and translated into functional protein. The constructed NGC could realize stable release of exosomes at least for 2 weeks. After NGC implantation in vivo, ExoNT-3-NGC group significantly promote nerve regeneration and improve the function recovery of gastrocnemius muscles compared with control exosomes (Exoempty-NGC) group.ConclusionIn this work, NGC was constructed to allow exosome-mediated NT-3 mRNA delivery. After ExoNT-3-NGC implantation in vivo, the level of NT-3 could restore which enhance the nerve regeneration. Our study provide a potential approach to improve nerve regeneration.

Project description:Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment. Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells (SCs) play critical role in nerve repair, combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration. VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge (HSPS) conduits. When HSPS is mechanically distorted, it still has high durability of strain strength, thus, can accommodate unexpected strain of nerve tissues in motion. A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC (VEGF) conduits, meanwhile the HSPS, HSPS-SC, HSPS-VEGF conduits and autografts were worked as controls. The immunofluorescent co-staining of GFP/VEGF-A, Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation, migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells. The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics, electrophysiology, nerve innervation to gastrocnemius muscle (GM), toluidine blue (TB) staining, transmission electron microscopy (TEM) and NF200/S100 double staining in the regenerated nerve. The results displayed that the effects on the repair of peripheral nerves in HSPS-SC (VEGF) group was the best among the conduits groups and closed to autografts. HSPS-SC (VEGF) group exhibited notably increased CD31+ endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues, which probably contributed to the improved nerve regeneration. Altogether, the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.

Project description:Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo. However, they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far. In this study, a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly (D,L-lactide-co-caprolactone) (PLCL) guidance conduit and its advantages in regeneration of peripheral nerve in vivo. After linear ridges/grooves of 20/40 μm in width are created on the PLCL film, its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups, which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde. The Schwann cells are better aligned along with the stripes, and show a faster migration rate toward the region of higher peptide density. Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate, function recovery and microstructures, and reduction of fibrosis in muscle tissues. Moreover, this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo. Graphical abstract Dual gradient of nerve-affinitive CQAASIKVAV peptides and linear ridges/grooves on the inner surface of biodegradable guidance conduit synergistically promote the regeneration of sciatic nerve in terms of rate, function recovery and microstructures, and reduction of fibrosis in muscle tissues in vivo.Image 1 Highlights • CQAASIKVAV peptide gradient and micropatterns are integrated on inner surface of a nerve regeneration conduit.• Cell alignment and migration are promoted toward the region of a higher peptide density.• The peptide gradient and micropatterns can synergistically accelerate the regeneration of sciatic nerve in vivo.

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Nerve guidance conduit design based on self-rolling tubes.

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Nerve guidance conduit design based on self-rolling tubes.

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