Conductive hydrogels based on agarose/alginate/chitosan for neural disorder therapy

Abstract

Electroactive scaffolds derived from carbohydrate hydrogels were synthesized, resulting in a large shift in the conductivity of chitosan (CS) from 10^-6 S/cm to about 10^-3 S/cm, assigned to CS-oligoaniline. Several analyses including UV-vis spectroscopy and cyclic voltammetry were performed, before examining the carbohydrate-based scaffolds for their ability to recapitulate the neural tissue microenvironment. Good conductivity and resemblance of the modulus to soft tissue of the optimized hydrogels led to appropriate cellular activity and neural regeneration. The loss of dopaminergic neurons as the prominent source of dopamine in the central nervous system results in the deterioration of multiple brain functions such as voluntary movement and behavioral processes. To overcome this, olfactory ecto-mesenchymal stem cells (OE-MSCs) were induced to differentiate into dopaminergic neuron-like cells on hydrogels through a monolayer arrangement cell culture by using cocktail neurotrophic factors including sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). The differentiation capacity of a series of OE-MSCs on the conductive hydrogel was evaluated by real-time PCR, immunocytochemistry and flow cytometry, and the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) neural and dopaminergic markers. The results of this study represent the first steps in designing and implementing advanced platforms based on conductive polysaccharide hydrogels for neural disorder therapies, such as the treatment of Parkinson's disease.

Keywords: Carbohydrates; Dopaminergic neuron differentiation; Polysaccharides; Stem cells.