To apply for this programme, please visit www.advanced-biomedical-materials-cdt.manchester.ac.uk. Informal enquiries are welcome, to [Email Address Removed]
ABM CDT There is a critical need of effective regenerative therapies for various clinical conditions where our biological regenerative capabilities fall short in restoring diseased organs. Examples include gastrointestinal diseases, such as long-gap esophageal atresia and short bowel in which up to two thirds of the organ is missing. Additionally, due to high unmet demand of organ transplantation, advanced tissue engineering techniques are also needed.
Tissue regeneration is a complex, long-term, dynamic, physiologically and metabolically demanding process. Effective therapies will be those which respond to these dynamic processes with the appropriate combination of therapeutic remedies. It has been shown that mechanical stimulation has significant influence upon cells’ fate, e.g., proliferation, differentiation, and apoptosis. This effect has been leveraged in the pervasive use of bioreactors. However the mechanical stimulation provided by off-the-shelf and state-of-the-art bioreactors have typically preprogrammed stimulation waveforms and little sensitivity to the evolving tissue construct. Additionally once the tissue construct is implanted inside the body it is deprived of much of the prior stimulation leaving it with limited guidance and control.
Our group has pioneered robotic technologies that apply mechanical stimulation in a responsive way depending on the tissue’s evolving mechanical properties. This technology has been demonstrated in vivo with swine where we showed that we can grow 77% de novo tissue in 9 days. We also demonstrated the technology in vitro with fibroblast-seeded PGSM scaffolds, showing we could advance the features of current bioreactors.
The aim of this proposed research is to realise physical-biological devices in the form of robotic scaffold interfaces which allow responsive tissue regeneration in a complex and dynamic biological environment. The scaffold is sensorised and provides responsive spatiotemporal control of mechanical stimulation to tissue constructs in vitro.
Main questions to be answered:
This underlying questions that we will seek to answer through this project are the following:
- Can we realise a tissue construct with a cellular arrangement and peristaltic-like response similar to the intestinal muscle (for both longitudinal and radial layers) by applying both strain and compressive cues allowed by the technology developed during this project? Strain will be applied by our in-lab robotic bioreactor, while compression will be transferred by the robotic scaffold interface, using realistic physiological motility parameters.
- What are the most promising mechanostimulation regimens which could create a biomechanically-functionalised (muscle) structure of the gastrointestinal tract (bowel or/and esophagus)? The real-time optimisation of the tissue growth via mechanostimulation patterns produced by the proposed technology is done not only depending on the physiologically-realistic spatiotemporal parameters but also on the dynamic state of the tissue (e.g., its stiffness) at a given moment in the evolution of the tissue (construct).
- How are the diverse applied mechanostimulation patterns contributing to the cellular composition, e.g., cell proliferation, ECM production, of the tissue construct? We will seek to understand how to precisely control the cellular responses and use this knowledge as a guideline for future in vivo mechanostimulation toward accelerating tissue growth and minimising the fibrotic response to implantable devices. We will culture myoblasts initially and smooth muscle cells in the advanced phases of this project, on PGSM scaffolds. For the robotic scaffold interface we will explore moldable biocompatible materials, e.g., MED-4805 and MDX4-4210, and hydrogels.
University of Manchester, Department of Materials - 19 PhD Projects Available
University of Sheffield, Department of Materials Science and Engineering, 7 PhD Projects Available