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

Melt-extruded guides for peripheral nerve repair
based on poly(epsilon-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.