Melt-extruded guides for peripheral nerve regeneration. Part I: Poly(ε-caprolactone)

Abstract

Melt-extruded guides for peripheral nerve repair based on poly(ε-caprolactone) (PCL) were realised and their physico-chemical properties were evaluated. Preliminarily, PCL cast films were found to support the attachment and proliferation of Neonatal Olfactory Bulb Ensheating Cells (NOBEC). S5Y5 neuroblastoma cells were cultured inside PCL guides in their uncoated form or coated with a non-specific adhesion protein (gelatin) and a specific peptide for nerve regeneration (poly(L-lysine)). Coating increased cell density (gelatin) and/or the cell density rate on substrates (poly(L-lysine); gelatin) as compared to uncoated guides. Various in vivo tests were carried out for the repair of small (0.5 cm), medium (1.5 cm) and long (4.5 cm) size defects in the peripheral nerves of Wistar rats. For the small nerve defects, uncoated and coated PCL guides were tested. Results from in vivo tests were subjected to histological examination after 45 days, 6 and 8 months postoperative for small, medium and large defects, respectively. Regeneration was found for small and medium size defects. For 0.5 cm defects, the coating did not affect regeneration significantly. Grip-tests also evidenced functional recovery for the 1.5 cm-long defects treated with PCL guides, after 6 months from implantation. On the other hand, mechanical stiffness of PCL conduits impaired the repair of 4.5 cm-long defects in 8-month period: the lack of flexibility of the guide to rat movements caused its detachment from the implant site. The research showed that PCL guides can be used for the successful repair of small and medium size nerve defects, with possible improvements by suitable bio-mimetic coatings.