Multiple-channel scaffolds to promote spinal cord axon regeneration.
As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic-co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments. Injection molding with rapid solvent evaporation resulted in scaffolds with a plurality of distinct channels running parallel along the length of the scaffolds. The feasibility of creating scaffolds with various channel sizes and geometries was demonstrated. Walls separating open channels were found to possess void fractions as high as 89%, with accessible void fractions as high as 90% through connections 220 microm or larger. Scaffolds degraded in vitro over a period of 30 weeks, over which time-sustained delivery of a surrogate drug was observed for 12 weeks. Primary neonatal Schwann cells were distributed in the channels of the scaffold and remained viable in tissue culture for at least 48 h. Schwann-cell containing scaffolds implanted into transected adult rat spinal cords contained regenerating axons at one month post-operation. Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections.
Moore
Michael J
MJ
Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Friedman
Jonathan A
JA
Lewellyn
Eric B
EB
Mantila
Sara M
SM
Krych
Aaron J
AJ
Ameenuddin
Syed
S
Knight
Andrew M
AM
Lu
Lichun
L
Currier
Bradford L
BL
Spinner
Robert J
RJ
Marsh
Richard W
RW
Windebank
Anthony J
AJ
Yaszemski
Michael J
MJ
D020341:Absorbable Implants; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D003692:Delayed-Action Preparations / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000235:genetics; D048091:Guided Tissue Regeneration / Q000379:methods*; D020007:Implants, Experimental; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008752:Methylene Chloride / Q000737:chemistry; D009416:Nerve Regeneration; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000637:transplantation; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000628:therapy; D023822:Tissue Engineering / Q000379:methods; D014057:Tomography, X-Ray Computed
D003692:Delayed-Action Preparations; D003911:Dextrans; D011108:Polymers; C015219:fluorescein isothiocyanate dextran; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008752:Methylene Chloride; D016650:Fluorescein-5-isothiocyanate