Photo-crosslinked poly(ε-caprolactone fumarate) networks for guided peripheral nerve regeneration: Material properties and preliminary biological evaluations

Abstract

In an effort of achieving suitable biomaterials for peripheral nerve regeneration, we present a material design strategy of combining a crystallite-based physical network and a crosslink-based chemical network. Biodegradable polymer disks and conduits have been fabricated by photo-crosslinking three poly(ε-caprolactone fumarate)s (PCLF530, PCLF1250, and PCLF2000), which were synthesized from the precursor poly(ε-caprolactone) (PCL) diols with nominal molecular weights of 530, 1250, and 2000 g.mol −1 , respectively. Thermal properties such as glass transition temperature (T g ), melting temperature (T m ), and crystallinity of photo-crosslinked PCLFs were examined and correlated with their rheological and mechanical properties. Furthermore, in vitro degradation of uncrosslinked and crosslinked PCLFs in PBS crosslinked PCLFs in 1 N NaOH aqueous solution at 37 °C was studied. In vitro cytocompatibility, attachment, and proliferation of Schwann cell precursor line SPL201 cells on three PCLF networks were investigated. Crosslinked PCLF2000 with the highest crystallinity and mechanical properties was found to best support cell attachment and proliferation. Using a new photocrosslinking method, single-lumen crosslinked PCLF nerve conduits without defects were fabricated in a glass mold. Crosslinked PCLF2000 nerve conduits were selected for evaluation in a 1-cm gap rat sciatic nerve model. Histological evaluation demonstrated that the material was biocompatible with sufficient strength to hold sutures in place after 6 and 17 weeks of implantation. Nerve cable with myelinated axons was found in the crosslinked PCLF2000 nerve conduit.

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

“…Numerous forms of surface modifications have been used with both synthetic biodegradable materials ( polycaprolactone (PCL), PLA and PLLA) and numerous natural materials (collagen, chitosan and fibrin) [36,46,[67][68][69][70][71]. These materials while they exhibit the required structural cues for guided cell growth, SC adhesion and migration, their surface characteristics may not be such as to induce the required effects; these materials tend to be hydrophilic or hydrophobic reducing their applicability for nerve repair [72].…”

A biocompatibility study of injectable poly(caprolactone-trifumarate) for use as a bone substitute material

“…Various modifications, such as the addition of sebacic acid, have been reported to improve its degradation rate (Salgado et al 2012). Similarly, PCL can be modified by cross-linking a functional group such as fumarate, resulting in the synthesis of polycaprolactone fumarate (PCLF) (Wang et al 2009;Salgado et al 2012). However, this semi-crystalline product needs to be heated to a high temperature before it can be injected into any bone defect site.…”

Regeneration and repair of peripheral nerves with different biomaterials: Review

“…The addition a small amount of poly (ethylene oxide) (PEO) was found to stabilize the porous structure of poly (TMC). 44,107,108,169 Chitosan. The nerve conduit material used under the name of ''chitosan'' [(1?4)-2-amino-2-deoxy-ß-D-glucan] is obtained after the crab tendon is separated from the calcium phosphates and proteins.…”

“…105,111,112,178 The synthetic materials include the silicone, polyglycolic acid (PGA), polilactic acid (PLA), poly-L-lactide-co-glicolide (PLGA), poli-e-caprolactone (PCL), poly-lactide-co-caprolactone (PLC) and poly-3-hydroxybutyrate (PHB). 96,87,91,101,107,108,167,169,178 The success rate of autologous vein grafts is minimal especially in the long nerve defects. 178 The reason for this unsuccessful results is it the wall of vein conduit which is thin and has a risk of collapse, and also subjected to the constriction by the surrounding scar tissue.…”