Hesperidin promotes peripheral nerve regeneration based on tissue engineering strategy using alginate/chitosan hydrogel: in vitro and in vivo study

About 2.8% of trauma patients suffer from peripheral nerve injury and it becomes a serious challenge in the world. Therefore, various methods and materials have been used for regenerating peripheral nerve damages. The aim of this study is to evaluate the effect of different dosages of Hesperidin on peripheral nerve regeneration. For this purpose, different concentration (0.1%, 1%, and 10% (w/v)) of Hesperidin was loaded into cross-linked alginate/chitosan hydrogel and its characters such as morphology, swelling properties, weight loss, hemo-, and cytocompatibility were evaluated. For functional analysis, the fabricated hydrogels without and with different amounts of hesperidin were administrated after creating sciatic nerve injury in a rat model, and the various experiments like walking-foot-print analysis, Hot plate latency test, gastrocnemius muscle wet weight loss, and histopathological examination were used. Our results indicated that prepared hydrogels contained the porosity of 90%, with the interconnected pores. Biodegradability of fabricated hydrogels was confirmed with weight loss assessment and the weight loss percentage was about 80% after 14 days. Moreover, hydrogels had good blood compatibility and antibacterial properties. The MTT assay indicated that the developed hydrogels do not have toxicity effect and they have ability to increase the proliferation rate of Olfactory Ecto-mesenchymal stem cells (OE-MSCs). The results of in vivo study showed that hesperidin specially the group contained 1% of hesperidin improve sciatic nerve regeneration and hesperidin could be considered as a potential material for peripheral nerve regeneration.