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Growing biohybrid scaffolds in the lab: Controlling the culture environment to create biohybrid scaffolds with pre-determined compositions and functionalities

   Department of Materials Science and Engineering

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  Dr N Green, Prof Fred Claeyssens, Dr D Damian  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

To apply for this programme, please visit Informal enquiries are welcome, to [Email Address Removed].

ABM CDT To facilitate widespread clinical use of tissue engineering it is important to create off-the-shelf scaffolds with the correct architecture, biological and mechanical properties. Synthetic scaffolds, natural polymers and decellularized tissues have drawbacks in functionality, mechanical properties, availability, or effective removal of cellular material that limit their success.

Biohybrid scaffolds combine the advantages of biological components with synthetic scaffolds to avoid these drawbacks. Biohybrid scaffolds generated by culturing ECM-producing cells in vitro on synthetic scaffolds and then decellularizing the resulting construct also have the potential to replicate the complexity of native tissue. However, there is little attention placed on optimising and controlling the quantity and structure of the ECM or the conditions required to promote the generation of specific formulations of biomolecules. Furthermore, most decellularization processes were developed for ex vivo tissues. The impact of these processes on the individual components of lab grown and less mature ECM is poorly characterised and requires significant optimisation.

It has been shown that matrix structure and composition have significant influences upon many cell behaviours including migration, differentiation, adhesion, proliferation, and gene expression in vivo. It is therefore important to the clinical success of these materials that the biological components of the scaffolds are defined and controlled during the production process. However, gaps in current knowledge mean that it is not possible to create biomimetic biohybrid scaffolds on demand with pre-defined compositions and biological functionalities for specific clinical uses. The project aims to resolve this with the capability to generate range of pre-determined biohybrid scaffolds.

Main questions to be answered:

This project aims to generate a range of off-the-shelf biohybrid scaffolds, with enhanced functionality and will seek to answer:-

  1. Can the synthetic scaffold modulate the formation of specific ECM components? Synthetic polymer scaffolds will be created by electrospinning or additive manufacture to generate a range of porosities, topographies, chemistries, and mechanical properties. Fibroblasts will be cultured on them and the impact of these variables on the resulting ECM composition, density and organisation will be ascertained through histological or fluorescent staining, imaging techniques, FTIR and biochemical assays.
  2. Can the culture environment be manipulated to control biohybrid scaffold composition? Cultures will be supplemented with factors to promote matrix formation, e.g. TGF-β and PDGF. Mechanical stimulation through in-house and commercial bioreactors will promote cell proliferation, enhance levels of specific matrix components, and control their organisation. This will be assessed as in question 1
  3. What is the most effective decellularization technique for these scaffolds? Chemical and physical decellularization methods will be assessed and the impact on cells and matrix evaluated. The mechanical properties of the resulting biohybrid scaffolds will be evaluated via tensile testing. The biological functionality of the scaffolds will be assessed in vitro and compared to synthetic only scaffolds.

University of Manchester, Department of Materials - 19 PhD Projects Available

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