3D bioprinting of nerve constructs

Abstract

The peripheral nervous system (PNS) refers to nerves that branch out from the brain and spinal cord, which are responsible for movement control, sensation, and coordinate functions. PNS is a fragile structure that can be damaged by traumas such as traffic accidents, tumour removal, and the adverse medical effects of surgery. Currently, there are limited therapies to address peripheral nerve injury, such as autologous nerve grafts, which are limited by donor-site morbidity, commercial nerve conduits have poor functional outcomes and cannot repair large-gap peripheral nerve injuries. This thesis presents the relevant aspects of design, fabrication and characterisation of nerve guidance conduits based on tissue engineering principles and the use of additive manufacturing, providing new possibilities for repairing damaged peripheral nerve tissues. An up-to-date literature review is provided, which discusses the latest strategies in peripheral nerve tissue engineering, biomaterials, additive manufacturing, and topographical guidance cues. The thesis uses additive manufacturing as an enabling technology to explore the possible application of topographic guidance and bioinks in nerve guidance conduits. Stereolithography was used to fabricate high resolution microgroove moulds. The master moulds with different sizes of microgrooves, the PCL, PCL/PLA microgroove thin films and corresponding conduits were successfully fabricated to evaluate the topographical guidance of the nerve guidance conduits. Comprehensive experimental studies including mechanical, wettability, thermal, degradation, and biological studies were carried out to understand the properties. Biological assays showed that cells can maintain high viability and elongate along the microgrooves on the polymer films which satisfies the properties of nerve cells that need to grow directionally to transmit signals. To provide cell encapsulation filler different bioinks including GelMA, GelMA/PEGDA, GelMA/MC, GelMA/MCMA were developed. The mechanical, swelling, rheological, printing, and biological properties of the hydrogels were evaluated. Additionally, suspension printing allows complex structures to be fabricated with the potential for NGCs. This thesis demonstrates the development of a microgroove polymer thin conduit and bioinks that allow cells to survive and spread with promising attributes for application in nerve tissue engineering.

Date of Award	25 Oct 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Otto Jan Bakker (Co Supervisor), Paul Mativenga (Main Supervisor) & Weiguang Wang (Co Supervisor)