hPL-human adipose-derived stem cells in IKVAV-functionalised hydrogel conduit (Biogelx): an innovative delivery strategy to improve peripheral nerve repair

Abstract

AbstractBackground.Adipose-derived stem cells (ADSC) are nowadays one of the most exploited cells in regenerative medicine. They are fast growing, capable of enhancing axonal elongation, support and locally stimulate Schwann cells (SC) and protect de-innervated muscles from atrophy after a peripheral nerve injury.Methods.With the aim of developing a bio-safe, clinically translatable cell-therapy, we assessed the effect of ADSC pre-expanded with human platelet lysate (hPL) in anin vivorat model, delivering the cells into a 15 mm critical-size sciatic nerve defect embedded within a laminin-peptide-functionalised hydrogel (Biogelx-IKVAV) wrapped by a poly--caprolactone (PCL) nerve conduit.Results.ADSC retained their stemness, their immunophenotype and proliferative activity when testedin vitro. At six weeks post implantation, robust regeneration was observed across the critical-size gap as evaluated by both the axonal elongation (anti-NF 200) and SC proliferation (anti-S100) within the Biogelx-IKVAV filled PCL conduit. All the other experimental groups manifested significantly lower levels of growth cone elongation. The histological gastrocnemius muscle analysis was comparable with no quantitative significant differences among the experimental groups.Conclusion.Taken together, these results suggest that ADSC encapsulated in Biogelx-IKVAV are a potential path to improve the efficacy of nerve regeneration. New perspectives can be pursued for the development of a fully synthetic bioengineered nerve graft for the treatment of peripheral nerve injury.