Despite advances in microsurgical techniques, treatment options to restore prior
function following major peripheral nerve injury remain unavailable. In the presence of a nerve gap, autologous nerve grafting remains the therapy of choice. Much recent experimental work has focused on the development of artificial constructs incorporating novel smart biomaterials and stem cells, aspiring to match and improve the outcomes of nerve autografting. Human Adipose-derived Stem Cells (dhASC) can be chemically stimulated in vitro to produce essential growth factors able to improve nerve regeneration outcomes; however, these properties are lost when the chemical stimulation is withdrawn and survival rate upon transplantation is low. Our aim was to exploit the properties of novel, fully synthetic hydrogel matrices to retain and improve the neurotrophic characteristics of dhASC, with a view to delivering stem cell therapies for nerve repair. dhASC were cultured on PeptiGel®-Alpha 1 and PeptiGel®-Alpha 2 self-assembling peptide hydrogels showing comparable viability to Collagen I gels used as controls. Alpha 2 substrates allowed long-term dhASC cultures (up to 3 weeks), and retained mechanical properties comparable to peripheral nerve tissues. Culturing dhASC on Alpha 1 and Alpha 2 substrates allowed the maintenance of neurotrophic features, such as the expression of growth factors and several neuroglial markers. Both Alpha 1 and Alpha 2 substrates were suitable for the culture of peripheral sensory neurons, permitting the sprouting of neuronal extensions without the need of biological extracellular matrices, and preserving neuronal function. We propose Alpha 1 and Alpha 2 substrates loaded with hdASC as promising candidates for the development of tissue engineering therapies for the repair of peripheral nerve injuries.