Hybrid 3D printed and tissue engineered bioreactors - applications to the neuromuscular system

Lead Research Organisation: Loughborough University
Department Name: Sch of Sport Exercise & Health Sciences

Abstract

The peripheral nervous system (PNS) is the conduit for the afferent and efferent signals that control human movement. There are multiple reasons that physiologically-relevant models are vital for the understanding of normal and pathological processes such as motor control (normal) or motor neurone disease (pathological); it is intrinsically difficult to study mechanisms at the cellular level in living organisms hence the need for highly accurate in vitro models. This project builds on over a decade of published and funded expertise in the use of tissue engineering principles to create and use such models stemming from work in skeletal muscle (SkM) that has expanded to include the tissues that SkM interfaces with - including neural systems.

Specifically the project will aim to utilise 3D printing technology to generate a custom "bioreactor" enabling 3D tissue engineered neuromuscular constructs to be integrated in a "plug and play" style. This perfusion system will be automated allowing live biological feedback and optimisation of the perfusion protocol, reducing handling times and ultimately cost, whilst increasing the quality of representative data being generated from each biological condition.

This project lies at the interface of biology and chemistry, and involves design and 3D printing techniques. It is ambitious but aligns with a larger research agenda and will provide the student with an interdisciplinary training regime that will benefit them in the longer term.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509516/1 01/10/2016 30/09/2021
1949295 Studentship EP/N509516/1 01/10/2017 31/03/2021 Kerry Chaplin
 
Description Tissue engineering is the multi-disciplinary field that combines living cells with natural/synthetic scaffolds within a 3D environment, with the aim of recreating the structural, mechanical and functional properties of in vivo tissues. As most tissues in the body rely upon vascular networks to supply the tissue with nutrients/O2 and remove waste products, in vitro maturation of tissues greater in size than 100-200µm requires either tissue vascularisation or provision of regular controlled media perfusion. Consequently, perfusion bioreactors are becoming increasingly utilised to dynamically transport culture media through porous 3D tissues. This research to date has focussed on the development of the design, prototype and manufacture of perfusion bioreactor systems, specifically for the culture and long-term maturation of tissue engineered skeletal muscle. This allows experimental optimisation within an automated culture environment. The most recent body of work in this study has focussed on the development of an in silico model that is able to accurately recreate the specific micro environment within each unique perfusion environment, allowing experimental optimisation to be rapidly characterised and as such create theoretical perfusion system designs that optimise the culture of the in situ tissue. Continuing experimentation is being undertaken to validate this model, and characterise the maturation of the tissues within various perfusion system designs.
Exploitation Route It is envisaged that through the design, manufacture and characterisation of bespoke perfusion systems the possibility for fully automated and high throughput fabrication of in vitro models of musculoskeletal systems will be increased. These models could be used by other groups who wish to replace simplistic monolayer models of skeletal muscle, allowing improved validity of experimental findings for fundamental research questions relating to musculoskeletal health. It is also envisaged that these models would aid in the reduction of the use of animal models for biological and pharmaceutical research.
Sectors Pharmaceuticals and Medical Biotechnology