TY - JOUR
T1 - Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord
AU - Krych, Aaron J.
AU - Rooney, Gemma E.
AU - Chen, Bingkun
AU - Schermerhorn, Thomas C.
AU - Ameenuddin, Syed
AU - Gross, Lou Ann
AU - Moore, Michael J.
AU - Currier, Bradford L.
AU - Spinner, Robert J.
AU - Friedman, Jonathan A.
AU - Yaszemski, Michael J.
AU - Windebank, Anthony J.
N1 - Funding Information:
Funding support was provided in part by the Mayo Foundation and the National Institutes of Health through Grants EB02390 to Dr. Windebank’s laboratory.
PY - 2009/9
Y1 - 2009/9
N2 - Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450 μm (n = 19) or 660 μm in diameter (n = 14). Animals were sacrificed after 1, 2 and 3 months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450 μm scaffolds had significantly greater axon fibers per channel at the 1 month (186 ± 37) and 3 month (78 ± 11) endpoints than the 660 μm scaffolds (90 ± 19 and 40 ± 6, respectively) (p = 0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660 μm channels was most pronounced at the 1 month endpoint, at 28,046 ± 6551 and 58,633 ± 7063 μm2, respectively (p = 0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.
AB - Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450 μm (n = 19) or 660 μm in diameter (n = 14). Animals were sacrificed after 1, 2 and 3 months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450 μm scaffolds had significantly greater axon fibers per channel at the 1 month (186 ± 37) and 3 month (78 ± 11) endpoints than the 660 μm scaffolds (90 ± 19 and 40 ± 6, respectively) (p = 0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660 μm channels was most pronounced at the 1 month endpoint, at 28,046 ± 6551 and 58,633 ± 7063 μm2, respectively (p = 0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.
KW - Biomedical engineering
KW - Central nervous system
KW - Polymeric scaffolds
KW - Tissue development and growth
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U2 - 10.1016/j.actbio.2009.03.021
DO - 10.1016/j.actbio.2009.03.021
M3 - Article
C2 - 19409869
AN - SCOPUS:68949140667
SN - 1742-7061
VL - 5
SP - 2551
EP - 2559
JO - Acta Biomaterialia
JF - Acta Biomaterialia
IS - 7
ER -