Development and evaluation of BDNF-loaded PCL/PVA two-layer nerve guidance conduit with enhanced biomechanical and biological properties for peripheral nerve regeneration

Abstract

The repair of damaged peripheral nerves and the following restoration of functionality remain significant therapeutic challenges. Hollow nerve conduits currently available do not align with the ideal human model. Successfully mending nerve gaps requires incorporating biomimetic and functional features into neural conduit design. In this research, a new two-layer conduit that combines topographic support and controlled growth factor release was developed. We used a two-layered framework to amplify the mechanical reinforcement and reduce the risk of tissue collapse post-grafting. The hollow nerve conduits were fabricated through three-dimensional printing, employing Polycaprolactone (PCL) and a slowly biodegradable nanofiber for the intraluminal brain-derived neurotrophic factors (BDNF)-loaded polyvinyl alcohol (PVA)/PCL core-shell. The contact angle was indicated to show the hydrophilicity properties and degradation rate for biocompatibility. The scanning electron microscope (SEM) images were analyzed to determine the fiber's diameters, structure morphology, and stem cell adhesion. The performance of core-shell conduits was investigated in human dental pulp stem cells (hDPSC) culture and their differentiation into Schwann cells (SCs) invitro. The vitality of samples was assessed using SEM, MTT assay, and differentiation potential with real-time and Immunofluorescence staining techniques. Invitro cumulated BDNF release followed the Korsmeyer-Peppas model, demonstrating a strong correlation coefficient of 0.981. Real-time analysis showed that after 14 days of induction, the expression of S100 increased 5.89-fold. We concluded that core-shell PCL/PVA nerve guidance conduits can encourage the adhesion and proliferation of hDPSCs and create the ideal environment for increasing cell survival. Also, the sustained release of BDNF within conduit walls promoted differentiation toward SC.

Keywords

• BDNF
• Two-layer nerve guidance conduit
• 3D model
• Nanofiber
• Peripheral nerve regeneration