Novel soft alginate hydrogel strongly supports neurite growth and protects neurons against oxidative stress

Neural tissue engineering focuses on development of biomaterials that could support regeneration of neurons after trauma as well as injury caused by degenerative diseases. In this work we describe novel soft alginate hydrogels, which provide an adhesive matrix for rat and human neurons and facilitate neurite outgrowth. Only soft hydrogels, prepared with sub-stoichiometric concentrations of Ca²⁺, Ba²⁺, and Sr²⁺ cations by cross-linking with no >10% of all potentially available gelation sites in alginate, facilitated rapid and abundant neurite outgrowth in primary neuronal monolayer cultures, neural spheroids, and neurons derived from rat and human neural stem cells. To support neurite growth, hydrogels did not require modification by any extracellular matrix components and were prepared from high as well as low viscous alginates of different origin. In addition, neurons cultured on soft hydrogels were resistant to oxidative stress injury induced by hydrogen peroxide. These findings, which apply both to rat and human neurons, go beyond the well-described role of alginates as inert materials for cell encapsulation. Such soft alginate hydrogels may be useful for the preparation of pharmaceutical compositions for prophylaxis and treatment of neurodegenerative disorders, for promoting neuronal regeneration in the peripheral and central nervous system and for neural tissue engineering applications.