Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

Abstract

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.

An in vitro spinal cord injury model to screen neuroregenerative materials

“…PLA is approved for clinical use by the Food and Drug Administration as it creates non-toxic waste products and has been widely used as a scaffolding material in the tissue engineering research community. Uncoated PLA scaffolds generally exhibit low levels of host neuronal regeneration and typically result in the formation of a gliotic scar at the interface between host tissue and the implant [46][47][48][49]. By contrast, the incorporation of laminin (or a suitable hydrogel e.g.…”

Preparation of the acellular scaffold of the spinal cord and the study of biocompatibility

“…[16][17][18][19] As their pores and channels are artificial, it is difficult to completely simulate the conduction channels of normal spinal cords. Moreover, these scaffold materials have their respective disadvantages, such as degradation products that are unfit for neuronal survival and axonal regeneration; low adhesiveness of cells; and much poorer biological and physical characteristics.…”

Polímeros bioreabsorvíveis na engenharia de tecidos

“…Publicadas na literatura científica (concomitantemente às requisições de patentes nos EUA), as técnicas de preparo de suportes porosos foram descritas em culturas de células específicas, e ainda representam um importante enfoque de desenvolvimentos [41] . Entre as técnicas podemos destacar: fiber bonding [42] , evaporação de solvente com adição e lixiviação de sal (solvent casting -particulate leaching) [43] , inversão de fases [44] , injeção de gás [45] , fused deposition modeling (FDM) [46] , freeze-dried [47] e outras.…”