Poly(Trimethylene Carbonate-co-ε-Caprolactone) Promotes Axonal Growth

Abstract

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(ε-caprolactone), poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) (11∶89 mol%) and poly(trimethylene carbonate) - with the final goal of using these materials in the development of conduits to promote spinal cord regeneration. Poly(L-lysine) (PLL) coated polymeric films were tested for neuronal cell adhesion and neurite outgrowth. At similar PLL film area coverage conditions, neuronal polarization and axonal elongation was significantly higher on P(TMC-CL) films. Furthermore, cortical neurons cultured on P(TMC-CL) were able to extend neurites even when seeded onto myelin. This effect was found to be mediated by the glycogen synthase kinase 3β (GSK3β) signaling pathway with impact on the collapsin response mediator protein 4 (CRMP4), suggesting that besides surface topography, 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, overcoming myelin inhibition.

The role of the surface on microglia function: implications for central nervous system tissue engineering

“…Interface 12: 20141224 of the surface on the response of microglia to myelin debris. These results, along with our previous findings reporting that P(TMC-CL) has suitable properties for neuronal growth [24,25], put forward P(TMC-CL) as a supportive material for tissue regeneration in the context of an injury of the CNS.…”

“…It is noteworthy that P(TMC-CL) has been shown to stimulate cortical neuron polarization and promote axonal elongation. Moreover, even in the presence of myelin, cortical neurons cultured on P(TMC-CL) films were found to extend more neurites, demonstrating the ability of P(TMC-CL) to tame myelin inhibition in a CNS lesion scenario [25]. Here we investigate the response of microglia to P(TMC-CL) surfaces prepared either by electrospinning or by solvent cast in order to gather important clues towards the design of instructive scaffolds that can contribute to the challenging process of CNS regeneration.…”

“…The preparation of fibres of this biodegradable polymer by electrospinning was previously reported [22], as were its remarkable properties in the context of tissue engineering for regeneration of the peripheral [23,24] and the central nervous system [25]. It is noteworthy that P(TMC-CL) has been shown to stimulate cortical neuron polarization and promote axonal elongation.…”

Biodegradable poly(lactic‐acid)/poly(trimethylene‐carbonate)/laponite composite film: development and application to the packaging of mushrooms (Agaricus bisporus)

“…Poly(trimethylene carbonate) (PTMC) is a biodegradable amorphous polymer with a low glass transition temperature ( T g ) between −14°C and −25°C. High‐molecular‐weight PTMC holds elastic properties at ambient temperature . Qin et al .…”

Recent advances in synthetic polymer based hydrogels for spinal cord repair

“…Other recent studies on aliphatic polyester-based biomaterials for spinal cord repair consist of increasing polymer flexibility through introduction of trimethylene carbonate (TMC) units along aliphatic polyesters [78]. In a further study, it was demonstated that a poly(trimethylene carbonate-co-3-caprolactone) (P(TMC-CL)) copolymer significantly promote axonal growth [79]. Interestingly, Xing et al showed the possibility of chemical derivatization of the TMC monomer with bioactive molecules, such as acetylcholine analog.…”