Bio-inspired electroconductive scaffolds for spinal cord injury repair

Background: Spinal cord injury (SCI) is a debilitating disorder which often results in the loss of motor and sensory function of the patient, as well as paralysis at or below the injury site. Currently there is no effective treatment for SCI. A recent trend in tissue engineered (TE) scaffolding materials for SCI has emerged in the form of conductive materials. Various conductive additives have been combined with hydrogels to infer electroconductivity, though the major drawbacks of using these conductive additives arise from low conductivity in neutral pH, insolubility in water and poor biocompatibility.

Methods: The central research question of this thesis centres on the development and characterisation of novel hybrid biomaterials which can be processed into scaffolds for use in SCI repair strategies. The main objective is the replication of the spinal cord's native extracellular matrix by utilising biomaterials such as alginate, gelatin and/or hyaluronic acid. This objective was furthered through the incorporation of novel electroconductive additives such as carbon nanofibers (CNFs), and novel Poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy) submicron particles (MPs) synthetised via the mini-emulsion method. Techniques used to characterise these electroconductive materials included compression, FTIR, swelling studies, rheology, in-vitro, and in-vivo biocompatibility studies.

Results: Chemical crosslinking of gelatin and hyaluronic acid with N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC): N?hydroxysuccinimide (NHS) resulted in mechanical properties which matched that of the native spinal cord at 1.2±0.2 MPa. Incorporation of the conductive additives increased the conductivities to 4.1×10-4±2×10-5 , 4.3×10-6±1.1×10-6 and 8.3×10-4±8.1×10-5 S/cm for the CNF, PPy MP and PEDOT MP scaffolds respectively. In-vitro studies showed the scaffolds are cytocompatible. In-vivo assessment in a rat SCI lesion model with a PEDOT MP scaffold showed decreased levels of inflammation at the site of injury with glial fibrillary acidic protein (GFAP), macrophage and microglia staining, as well as increased axon migration towards the scaffold observed.

Conclusions: The incorporation of conductive additives into biomaterial scaffolds enhances not only the conductive capabilities of the material, but also the provision of a healing environment. Hence, conductive scaffolds are a promising TE option for stimulating regeneration following SCI.