DEVELOPMENT OF NOVEL ELECTRICALLY CONDUCTIVE SCAFFOLDS BASED ON SILK FIBROIN WITH ELECTRICAL STIMULATION FOR PERIPHERAL NERVE REGENERATION

Abstract

Electrically conductive materials represent a new generation of biomedical materials for tissue engineering and regenerative medicine, particularly for peripheral nerve regeneration. The use of an electrically conductive scaffold with electrical stimulation (ES) has the potential to facilitate regeneration of the fully functional nerve. Herein, non-woven mats of silk fibroin (SF) with fibre diameters of ~200 nm are fabricated by electrospinning for use as an acellular peripheral nerve scaffold. The electrospinning SF solution is prepared via a dialysis free protocol, which is far less time-consuming in comparison to conventional methods. The double layer electrospun SF mat consisting of random fibres as the base and aligned fibres as the top surface is designed to improve processability and handling of the scaffold and support the unidirectional alignment of neurites on the mat, respectively. Electrical properties are then imparted to the electrospun SF mat by post-modification using an interpenetrating polymer network (IPN) of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) with various molar ratios (α) of PSS and EDOT monomers. In vitro, the IPN (α = 2.3) mat is non-toxic and evidences many promising results to promote neurite outgrowth following the alignment of fibres and has potential for ES application. In addition, the neurite outgrowth on fibre mats under the influence of electrical regime is considered here in a preliminary study. Direct ES with the monophasic pulse of 1 V amplitude, 2 ms pulse width, 100 ms pulse cycle, and 24 h/day was applied to differentiated cells in culture for 3 days. Although the neuronal cells can grow as expected on the IPN (α = 2.3) mat with ES, the lengths of neurites have no significant difference from the control without ES. However, further investigation of electrical parameters optimisation may give more favourable results on neurite outgrowth. Without ES, the IPN (α = 2.3) mat can promote longer neurite extension length compared to the pristine electrospun SF mat, especially for those without laminin coating. This study provides a platform for the use of electrically conductive material based on SF as scaffolds for peripheral nerve regeneration, which has potential for integration with ES therapy towards realising fully functional tissue recovery.

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Sarah Cartmell (Supervisor) & Jonny Blaker (Supervisor)