Trueman, Ryan P.; (2024) Organic semiconductor-based bioelectronics for peripheral nerve regeneration. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Electrical stimulation has shown promise in clinical studies to treat less severe peripheral nerve injuries, such as crush type injuries. However, there is an unmet clinical need for the treatment of traumatic nerve injuries that result in a large gap, with cell laden, biomaterial-based constructs presenting an attractive solution to bridging the nerve gap. This work aims to first assess if the repair capabilities of Schwann cells, the glial cells of the peripheral nervous system, can be enhanced using electrical stimulation. After fabricating a novel electrical stimulation platform, experiments investigated the expression of genes associated to the repair phenotype of Schwann cells. Key genes were upregulated following a single application of electrical stimulation. Electrical stimulation of Schwann cells was shown to enhance the neurite extension of a model cell line within a coculture and conditioned media experiment. To translate these effects of electrical stimulation towards nerve regeneration scenarios, 3D aligned conductive constructs comprised of collagen and polypyrrole (PPy) nanoparticles were designed and fabricated. The bioelectronic constructs provided good biocompatibility to both Schwann cells and primary rat neurons when electrically stimulated in vitro. The PPy loaded constructs supported a 1.7-fold increase in neurite length in comparison to control collagen constructs. Furthermore, upon electrical stimulation of the PPy-collagen construct, a 1.8-fold increase in neurite length was shown. The final chapter of this work details a novel strategy to improve the biointerfacing capabilities of novel organic semiconducting polymers, in this instance DPP3T. Through the introduction of dopants (FeCl3 & Magic Blue) to organic semiconducting films, it is possible to alter the cell behaviour on the surfaces of the thin films and improve the biological interfacing capability of novel materials. This thesis illustrates the potential of organic semiconductor-based bioelectronics for neural tissue engineering and lays the groundwork for the development of novel bioelectronic materials for neural interfacing applications.

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