Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord.
The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use of poly(D,L-lactic acid) foams, with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response.
Patist
Carla M
CM
The Miami Project to Cure Paralysis, University of Miami School of Medicine, PO Box 016960, R-48, Miami, FL 33136, USA.
Mulder
Mascha Borgerhoff
MB
Gautier
Sandrine E
SE
Maquet
Véronique
V
Jérôme
Robert
R
Oudega
Martin
M
D020341:Absorbable Implants; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D019544:Equipment Failure Analysis; D005260:Female; D005612:Freeze Drying; D008567:Membranes, Artificial; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000502:physiology*; D011091:Polyesters / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D011916:Rats, Inbred F344; D013119:Spinal Cord Injuries / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D013904:Thoracic Vertebrae / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
D019208:Brain-Derived Neurotrophic Factor; D020099:Coated Materials, Biocompatible; D008567:Membranes, Artificial; D011091:Polyesters; C033616:poly(lactide)