The Development of a Novel Flexible Electrospun Hollow Fibre Membrane for the use in 3D Tissue Culture Bioreactors

Lead Research Organisation: University of Oxford
Department Name: Engineering Science

Abstract

This research aims to answer the questions:

1. Can hollow fibre (HF) membranes be fabricated by electrospinning in a reproducible way so that they mimic the structure and capability of capillary vasculature in vivo to:

a. supply nutrients to cellular tissue through convective transport, in both mechanically static and dynamic culture conditions
b. be routed in non-linear configurations such that cell growth may be maintained throughout large irregularly shaped three-dimensional (3D) cultures?

2. If such HFs can be produced and characterised, can they be used as a substrate for biomedical research and potentially for the production of biomaterials for therapeutic application?
In recent years there has been a surge in interest in three-dimensional (3D) tissue culture techniques, capable of exhaustively mimicking the cellular microenvironments found in vivo in a way that cannot be achieved by traditional two dimensional tissue culture techniques (Mortera-Blanco, 2008). The application of these 3D culture techniques has however been limited by the short effective range of diffusive mass transfer, reportedly limiting viable cell growth to only 10-4 m from the surface of 3D culture substrate (Carrier et al., 2002). In vivo, a complex capillary network enables bulk convective mass transport, without disrupting adjacent sensitive cellular microenvironments, thereby overcoming this issue by ensuring that cellular proximity to capillaries rarely exceeds 20-4 m (Eghbali et al., 2016).
HF membranes traditionally used in filtration, reverse osmosis and gas separation have more recently been applied in the context of biomedical engineering. Within tissue engineering, HFs have been used as selective barriers upon which, or around, cell may be seeded, thereby acting analogously to capillaries in 3D culture systems. The suitability of HF membranes used to date, however, has been limited by the lack of their physiologically mimetic nano-structure and rigidity of the membranes. This rigidity limits the routeing potential of fibres used, constraining HF bioreactor configurations to regularly shaped mechanically static configurations thereby hindering physical cues which may be imparted on the system(Diban and Stamatialis, 2014).

Electrospinning, a versatile technique enabling the drawing of nano-fibres from polymer solutions or melts, has enabled the development of bioactive materials which mimic the fibrous structure of the extracellular matrix (ECM) (Abhari, Carr and Mouthuy, 2018). Through the utilisation of this technique, short sections of cylindrical scaffold for the culture of vascular tissues have been produced (Lee et al., 2008; Ju et al., 2010). While this demonstrates the possibility of producing HF membranes through the use of electrospinning, the method employed to make these scaffolds only yielded short sections. The constraint in length of sections produced thereby limits the use of these membranes in their current state in the wider context of tissue engineering. Subsequently, electrospinning has also been implemented in the production of long flexible filaments with similar mechanical properties to that of tendon(Mouthuy et al., 2015). The development of this second electrospinning technique thereby overcomes the limitation of short lengths of electrospun material.

In light of these collective developments, this DPhil research project proposes to investigate a combination of the electrospinning techniques, described above, for the development of novel flexible, elastic, bioactive HF membranes which mimic the nano-structure of the ECM and may be produced in quantities relevant for bioreactor construction.

This project falls within the EPSRC Health Care Technologies research area, specifically towards the development of biomaterials and tissue engineering.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509711/1 01/10/2016 30/09/2021
2116587 Studentship EP/N509711/1 01/10/2018 30/09/2021 Risto John Martin