Glycosaminoglycan functionalization of electrospun scaffolds enhances Schwann cell activity

Statement of Significance

Nerve fibers of the peripheral nervous system (PNS) have a remarkable ability to regenerate up to an almost complete recovery of normal function following a crush or a Sunderland Type II injury. This process is governed by glial cells, known as Schwann cells, through their unique capacity to dedifferentiate into cells that drive the healing process. Despite that many progresses have occurred in restorative medicine and microsurgery, the regenerative process after a severe lesion of a major nerve trunk (e.g., Sunderland Types III-V) is often incomplete and functional recovery is unsatisfactory. In this aspect, it is known that glycosaminoglycans (GAGs) of the extracellular matrix are involved in proliferation, synaptogenesis, neural plasticity, and regeneration of the PNS. Here, we developed poly(caprolactone) (PCL) fibrous scaffolds functionalized with GAGs, which allowed us to assess their influence on the adhesion, proliferation, and differentiation of Schwann cells. We found that both aligned and random fiber scaffolds functionalized with GAGs resulted in increased cell proliferation on day 1. In addition, aligned functionalized scaffolds also resulted in increased GAG presence on day 1, probably because of cell extracellular matrix (ECM) formation and an increased syndecan-4 expression on day 7. A different modification and activation of Schwann cells in the presence of GAG versus no-GAG scaffolds was underlined by proteomic comparative analysis, where a general downregulation of the expression of intracellular/structural and synthetic proteins was shown on day 7 for GAG-functionalized scaffolds with regard to the nonfunctionalized ones. In conclusion, we have shown that GAG-functionalized scaffolds are effective in modulating Schwann cell behavior in terms of adhesion, proliferation, and differentiation and should be considered in strategies to improve PNS repair.