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The effect of glycomimetic functionalized collagen on peripheral nerve repair.

ABSTRACT: Increasing evidence suggests that the improper synaptic reconnection of regenerating axons is a significant cause of incomplete functional recovery following peripheral nerve injury. In this study, we evaluate the use of collagen hydrogels functionalized with two peptide glycomimetics of naturally occurring carbohydrates-polysialic acid (PSA) and human natural killer cell epitope epitope (HNK-1)-that have been independently shown to encourage nerve regeneration and axonal targeting. Our novel biomaterial was used to bridge a critical gap size (5 mm) in a mouse femoral nerve injury model. Functional recovery was assessed using gait and hind limb extension, and was significantly better in all glycomimetic peptide-coupled collagen conditions versus non-functional scrambled peptide-coupled collagen, native collagen, and saline controls. Analysis of cross-sections of the regenerated nerve demonstrated that hydrogels coupled with the PSA glycomimetic, but not HNK, had significant increases in the number of myelinated axons over controls. Conversely, hydrogels coupled with HNK, but not PSA, showed improvement in myelination. Additionally, significantly more correctly projecting motoneurons were observed in groups containing coupled HNK-1 mimicking peptide, but not PSA mimicking peptide. Given the distinct morphological outcomes between the two glycomimetics, our study indicates that the enhancement of recovery following peripheral nerve injury induced by PSA- and HNK-functionalized collagen hydrogels likely occurs through distinct mechanisms.

SUBMITTER: Masand SN

PROVIDER: S-EPMC3623557 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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The effect of glycomimetic functionalized collagen on peripheral nerve repair.

Masand Shirley N SN Chen Jian J Perron Isaac J IJ Hammerling Babette C BC Loers Gabriele G Schachner Melitta M Shreiber David I DI

Biomaterials 20120820 33

Increasing evidence suggests that the improper synaptic reconnection of regenerating axons is a significant cause of incomplete functional recovery following peripheral nerve injury. In this study, we evaluate the use of collagen hydrogels functionalized with two peptide glycomimetics of naturally occurring carbohydrates-polysialic acid (PSA) and human natural killer cell epitope epitope (HNK-1)-that have been independently shown to encourage nerve regeneration and axonal targeting. Our novel bi ...[more]

PMID: 22917737

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Project description:Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type I collagen nanofiber conduits (biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within 8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy. S-100 (Schwann cell marker) and CD4 (inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type I collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China (La-1031218) on October 2, 2014.

Dataset Information

The effect of glycomimetic functionalized collagen on peripheral nerve repair.

Publications

The effect of glycomimetic functionalized collagen on peripheral nerve repair.

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