BIOMATERIAL COMPRISING POLY(TRIMETHYLENE CARBONATE-CO-E-CAPROLACTONE) FOR PROMOTING AXONALL GROWTH AND NEURONAL REGENERATION

摘要

Mammalian central nervous system (CNS) neurons do not regenerate after injury due to the inhibitory environment formed by the glial scar, largely constituted by myelin debris. The use of biomaterials to bridge the lesion area and the creation of an environment favoring axonal regeneration is an appealing approach, currently under investigation. This work aimed at assessing the suitability of three candidate polymers - poly(?-caprolactone), poly(trimethylene carbonate-co- ?-caprolactone) (P(TMC-CL)) (11:89 mol%) and poly(trimethylene carbonate) - with the final goal of using these materials in medicine, namely in the development of conduits to promote spinal cord regeneration. Cortical neurons cultured on P(TMC-CL) in the presence of myelin were able to tame myelin inhibition in comparison with the control condition (glass substrate). This effect was found to be mediated by the glycogen synthase kinase 3p (GSK3p) signaling pathway with impact on the collapsin response mediator protein 4 (CRMP4), suggesting that nanomechanical properties were implicated in this process. The obtained results indicate P(TMC-CL) as a promising material for CNS regenerative applications as it promotes axonal growth, taming myelin inhibition.