Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair

Bingkun K. Chen; Andrew M. Knight; Nicolas N. Madigan; Lou Ann Gross; Mahrokh Dadsetan; Jarred J. Nesbitt; Gemma E. Rooney; Bradford L. Currier; Michael J. Yaszemski; Robert J. Spinner; Anthony J. Windebank

doi:10.1016/j.biomaterials.2011.07.029

Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair

Bingkun K. Chen, Andrew M. Knight, Nicolas N. Madigan, Lou Ann Gross, Mahrokh Dadsetan, Jarred J. Nesbitt, Gemma E. Rooney, Bradford L. Currier, Michael J. Yaszemski, Robert J. Spinner, Anthony J. Windebank

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

The transected rat thoracic (T _9/10) spinal cord model is a platform for quantitatively comparing biodegradable polymer scaffolds. Schwann cell-loaded scaffolds constructed from poly (lactic co-glycolic acid) (PLGA), poly(e{open}-caprolactone fumarate) (PCLF), oligo(polyethylene glycol) fumarate (OPF) hydrogel or positively charged OPF (OPF+) hydrogel were implanted into the model. We demonstrated that the mechanical properties (3-point bending and stiffness) of OPF and OPF + hydrogels closely resembled rat spinal cord. After one month, tissues were harvested and analyzed by morphometry of neurofilament-stained sections at rostral, midlevel, and caudal scaffold. All polymers supported axonal growth. Significantly higher numbers of axons were found in PCLF (P < 0.01) and OPF+ (P < 0.05) groups, compared to that of the PLGA group. OPF + polymers showed more centrally distributed axonal regeneration within the channels while other polymers (PLGA, PCLF and OPF) tended to show more evenly dispersed axons within the channels. The centralized distribution was associated with significantly more axons regenerating (P < 0.05). Volume of scar and cyst rostral and caudal to the implanted scaffold was measured and compared. There were significantly smaller cyst volumes in PLGA compared to PCLF groups. The model provides a quantitative basis for assessing individual and combined tissue engineering strategies.

Original language	English (US)
Pages (from-to)	8077-8086
Number of pages	10
Journal	Biomaterials
Volume	32
Issue number	32
DOIs	https://doi.org/10.1016/j.biomaterials.2011.07.029
State	Published - Nov 2011

Keywords

Axon regeneration
OPF
PCLF
PLGA
Schwann cell
Spinal cord injury

ASJC Scopus subject areas

Mechanics of Materials
Ceramics and Composites
Bioengineering
Biophysics
Biomaterials

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10.1016/j.biomaterials.2011.07.029

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Chen, B. K., Knight, A. M., Madigan, N. N., Gross, L. A., Dadsetan, M., Nesbitt, J. J., Rooney, G. E., Currier, B. L., Yaszemski, M. J., Spinner, R. J., & Windebank, A. J. (2011). Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair. Biomaterials, 32(32), 8077-8086. https://doi.org/10.1016/j.biomaterials.2011.07.029

Chen, BK, Knight, AM, Madigan, NN, Gross, LA, Dadsetan, M, Nesbitt, JJ, Rooney, GE, Currier, BL, Yaszemski, MJ, Spinner, RJ & Windebank, AJ 2011, 'Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair', Biomaterials, vol. 32, no. 32, pp. 8077-8086. https://doi.org/10.1016/j.biomaterials.2011.07.029

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title = "Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair",

abstract = "The transected rat thoracic (T 9/10) spinal cord model is a platform for quantitatively comparing biodegradable polymer scaffolds. Schwann cell-loaded scaffolds constructed from poly (lactic co-glycolic acid) (PLGA), poly(e{open}-caprolactone fumarate) (PCLF), oligo(polyethylene glycol) fumarate (OPF) hydrogel or positively charged OPF (OPF+) hydrogel were implanted into the model. We demonstrated that the mechanical properties (3-point bending and stiffness) of OPF and OPF + hydrogels closely resembled rat spinal cord. After one month, tissues were harvested and analyzed by morphometry of neurofilament-stained sections at rostral, midlevel, and caudal scaffold. All polymers supported axonal growth. Significantly higher numbers of axons were found in PCLF (P < 0.01) and OPF+ (P < 0.05) groups, compared to that of the PLGA group. OPF + polymers showed more centrally distributed axonal regeneration within the channels while other polymers (PLGA, PCLF and OPF) tended to show more evenly dispersed axons within the channels. The centralized distribution was associated with significantly more axons regenerating (P < 0.05). Volume of scar and cyst rostral and caudal to the implanted scaffold was measured and compared. There were significantly smaller cyst volumes in PLGA compared to PCLF groups. The model provides a quantitative basis for assessing individual and combined tissue engineering strategies.",

keywords = "Axon regeneration, OPF, PCLF, PLGA, Schwann cell, Spinal cord injury",

author = "Chen, {Bingkun K.} and Knight, {Andrew M.} and Madigan, {Nicolas N.} and Gross, {Lou Ann} and Mahrokh Dadsetan and Nesbitt, {Jarred J.} and Rooney, {Gemma E.} and Currier, {Bradford L.} and Yaszemski, {Michael J.} and Spinner, {Robert J.} and Windebank, {Anthony J.}",

note = "Funding Information: We thank James Tarara for his critical help in imaging of the axon counting and measure of the scar and cyst formation. We thank Jane Meyer for her administrative role in manuscript preparation. This work was supported by a grant from the NIH ( EB02390 ) and the Wilson, Morton, Neilsen and Mayo Foundations (AJW).",

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AU - Madigan, Nicolas N.

AU - Gross, Lou Ann

AU - Dadsetan, Mahrokh

AU - Nesbitt, Jarred J.

AU - Rooney, Gemma E.

AU - Currier, Bradford L.

AU - Yaszemski, Michael J.

AU - Spinner, Robert J.

AU - Windebank, Anthony J.

N1 - Funding Information: We thank James Tarara for his critical help in imaging of the axon counting and measure of the scar and cyst formation. We thank Jane Meyer for her administrative role in manuscript preparation. This work was supported by a grant from the NIH ( EB02390 ) and the Wilson, Morton, Neilsen and Mayo Foundations (AJW).

PY - 2011/11

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N2 - The transected rat thoracic (T 9/10) spinal cord model is a platform for quantitatively comparing biodegradable polymer scaffolds. Schwann cell-loaded scaffolds constructed from poly (lactic co-glycolic acid) (PLGA), poly(e{open}-caprolactone fumarate) (PCLF), oligo(polyethylene glycol) fumarate (OPF) hydrogel or positively charged OPF (OPF+) hydrogel were implanted into the model. We demonstrated that the mechanical properties (3-point bending and stiffness) of OPF and OPF + hydrogels closely resembled rat spinal cord. After one month, tissues were harvested and analyzed by morphometry of neurofilament-stained sections at rostral, midlevel, and caudal scaffold. All polymers supported axonal growth. Significantly higher numbers of axons were found in PCLF (P < 0.01) and OPF+ (P < 0.05) groups, compared to that of the PLGA group. OPF + polymers showed more centrally distributed axonal regeneration within the channels while other polymers (PLGA, PCLF and OPF) tended to show more evenly dispersed axons within the channels. The centralized distribution was associated with significantly more axons regenerating (P < 0.05). Volume of scar and cyst rostral and caudal to the implanted scaffold was measured and compared. There were significantly smaller cyst volumes in PLGA compared to PCLF groups. The model provides a quantitative basis for assessing individual and combined tissue engineering strategies.

AB - The transected rat thoracic (T 9/10) spinal cord model is a platform for quantitatively comparing biodegradable polymer scaffolds. Schwann cell-loaded scaffolds constructed from poly (lactic co-glycolic acid) (PLGA), poly(e{open}-caprolactone fumarate) (PCLF), oligo(polyethylene glycol) fumarate (OPF) hydrogel or positively charged OPF (OPF+) hydrogel were implanted into the model. We demonstrated that the mechanical properties (3-point bending and stiffness) of OPF and OPF + hydrogels closely resembled rat spinal cord. After one month, tissues were harvested and analyzed by morphometry of neurofilament-stained sections at rostral, midlevel, and caudal scaffold. All polymers supported axonal growth. Significantly higher numbers of axons were found in PCLF (P < 0.01) and OPF+ (P < 0.05) groups, compared to that of the PLGA group. OPF + polymers showed more centrally distributed axonal regeneration within the channels while other polymers (PLGA, PCLF and OPF) tended to show more evenly dispersed axons within the channels. The centralized distribution was associated with significantly more axons regenerating (P < 0.05). Volume of scar and cyst rostral and caudal to the implanted scaffold was measured and compared. There were significantly smaller cyst volumes in PLGA compared to PCLF groups. The model provides a quantitative basis for assessing individual and combined tissue engineering strategies.

KW - Axon regeneration

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KW - PCLF

KW - PLGA

KW - Schwann cell

KW - Spinal cord injury

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Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair

Abstract

Keywords

ASJC Scopus subject areas

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