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Regeneration and functional recovery after peripheral nerve damage still remain a significant clinical problem. In this study, alginate/chitosan (alg/chit) hydrogel was used for the transplantation of olfactory ectomesenchymal stem cells (OE‐MSCs) to promote peripheral nerve regeneration. The OE‐MSCs were isolated from olfactory mucosa biopsies and evaluated by different cell surface markers and differentiation capacity. After creating sciatic nerve injury in a rat model, OE‐MSCs were transplanted to the injured area with alg/chit hydrogel which was prepared and well‐characterized. The prepared hydrogel had the porosity of 91.3 ± 1.27%, the swelling ratio of 379% after 240 min, weight loss percentages of 80 ± 5.56% after 14 days, and good blood compatibility. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, 4′,6‐diamidino‐2‐phenylindole, and LIVE/DEAD staining were done to assay the behavior of OE‐MSCs on alg/chit hydrogel and the results confirmed that the hydrogel can provide a suitable substrate for cell survival. For functional analysis, alg/chit hydrogel with and without OE‐ MSCs was injected into a 3‐mm sciatic nerve defect of Wistar rats. The results of the sciatic functional index, hot plate latency, electrophysiological assessment, weight‐loss percentage of wet gastrocnemius muscle, and histopathological examination using hematoxylin–eosin and Luxol fast blue staining showed that utilizing alg/chit hydrogel with OE‐MSCs to the sciatic nerve defect enhance regeneration compared to the control group and hydrogel without cells.

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Conductive hydrogel based on chitosan-aniline pentamer/gelatin/agarose significantly promoted motor neuron-like cells differentiation of human olfactory ecto-mesenchymal stem cells.

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