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

Abstract

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.

Differential Effects of Coating Materials on Viability and Migration of Schwann Cells

“…Basement proteins such as collagen I, fibronectin and laminin are known to influence cell viability and migration [22,23,24]. Indeed, there is increasing evidence that collagen type I, fibronectin, laminin, lysine and ornithine are among the ECMs that contribute to the microenvironment of SC-induced nerve recovery during Wallerian degeneration [10,13,14,15,25]. When SC viability was assessed for the different surface materials in this in vitro experiment, the highest cell viability was detected for collagen I (Figure 1).…”

“…Amino acids such as poly- l -lysine and poly- l -ornithine are known to be relevant for in vitro SC attachment as well as SC proliferation during the early phase of Wallerian degeneration [14]. Accordingly, the potential of these polymers to facilitate SC migration and viability was as well evaluated [14,25]. Whereas collagen I showed a slightly stimulating effect on SC migration, fibronectin strongly supported migration.…”

Material properties and electrical stimulation regimens of polycaprolactone fumarate–polypyrrole scaffolds as potential conductive nerve conduits

“…However these grafts have several disadvantages, including donor site morbidity, insufficient donor nerve length, mismatch in diameter, limited availability, and the risk of a second surgical intervention. In order to find alternative treatment methods, nerve conduits have been fabricated from many types of synthetic and natural materials including FDA approved poly(lactic-co-glycolic acid) (PLGA)[4], polycaprolactone (PCL)[5] and collagen[6]. In addition to modifying the geometry, mechanical properties, degradation rates, and chemical compositions of the nerve conduits[7–14], the inclusion of biomolecules such as glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in the conduits for controlled release to promote nerve regeneration have been investigated and have shown significant increases in axonal regrowth[15–17].…”

Poly(ester urethane) Guides for Peripheral Nerve Regeneration

“…A wide variety of materials was used for the production of artificial conduits for nerve repair, including biocompatible non‐degradable and degradable materials. Examples of bioresorbable polymers for nerve repair include aliphatic polyesters and copolyesters, such as poly( L ‐lactic acid) (PLLA),4, 5 poly(glycolic acid) (PGA),6 poly[(lactic acid)‐ co ‐( ε ‐caprolactone)],7, 8 poly[( L‐ lactic acid) ‐co‐ (glycolic acid)] (PLGA),9 poly[(1,3‐trimethylenecarbonate)‐ co ‐( ε ‐caprolactone)],10 poly(hydroxybutyrate ‐co‐ hydroxyvalerate) (PHBHV),11 and polycaprolactone (PCL) 12–14…”

“…The current manuscript is part of a series of reports on guides for peripheral nerve repair. The first manuscript was focused on PCL guides 14. The main result arising from the previous report was the assessment of the key role of mechanical properties of nerve guides in the repair of peripheral nerve defects with increasing size: stiff guides may exert tension at the suture sites in response to body movements, impairing nerve regeneration.…”