The effect of glycomimetic functionalized collagen on peripheral nerve repair.
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The effect of glycomimetic functionalized collagen on peripheral nerve repair. / Masand, Shirley N; Chen, Jian; Perron, Isaac J; Hammerling, Babette C; Loers, Gabriele; Schachner, Melitta; Shreiber, David I.
in: BIOMATERIALS, Jahrgang 33, Nr. 33, 33, 2012, S. 8353-8362.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The effect of glycomimetic functionalized collagen on peripheral nerve repair.
AU - Masand, Shirley N
AU - Chen, Jian
AU - Perron, Isaac J
AU - Hammerling, Babette C
AU - Loers, Gabriele
AU - Schachner, Melitta
AU - Shreiber, David I
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred C57BL
KW - Hydrogel/chemistry
KW - Carbohydrates/chemistry
KW - Collagen/chemistry
KW - Nerve Regeneration/drug effects/physiology
KW - Peptides/chemistry/therapeutic use
KW - Peripheral Nerve Injuries/drug therapy
KW - Sialic Acids/chemistry
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred C57BL
KW - Hydrogel/chemistry
KW - Carbohydrates/chemistry
KW - Collagen/chemistry
KW - Nerve Regeneration/drug effects/physiology
KW - Peptides/chemistry/therapeutic use
KW - Peripheral Nerve Injuries/drug therapy
KW - Sialic Acids/chemistry
M3 - SCORING: Journal article
VL - 33
SP - 8353
EP - 8362
JO - BIOMATERIALS
JF - BIOMATERIALS
SN - 0142-9612
IS - 33
M1 - 33
ER -
