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Bioengineering of a 3D gut model for drug permeation research

   Department of Materials

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  Prof Jian Lu, Dr Jiashen Li, Dr Jeff Penny  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 The intestine represents the interface between the body and food and drink we consume. It mediates the uptake of nutrients and bioactives, including therapeutics, and acts as the line of defence for removing toxins, mutagens and carcinogens ingested. Because of the huge complexity involved, it is essential to undertake as much lab based model research as possible before any animal studies are considered (NC3Rs). However, current gut model research heavily relies on the Transwell culture of Caco-2 cell monolayers. This model, and other similar ones, lack structural and morphological complexity, making them unsuitable for studying efflux transport and metabolic enzymes expressed in the intestinal epithelium.

The aim of this PhD project is to harness recent advances in the design and fabrication of nano-porous conducting composite fibre materials from Dr Jiashen Li’s lab, the recently developed short peptide self-assembled bionanomaterials with antimicrobial release capability from Prof Jian R Lu’s group to construct functional cell sheets as a more physiologically-complex 3D model of the human small intestine. Lu and Penny have developed a Transwell culture based 3D gut model in which the underlying fibroblasts were grown in a collagen scaffold (DOI: 10.1080/09637486.2019.1700940), but there are shortcomings with the scaffold concerning its instability during cell growth implicated by hydrolysis and hydration. In a more recent study using poly(L-lactic acid) (PLLA) and poly (lactic acid)-poly(lactic- glycolic acid) (PLA-PLGA) micro- and nanoporous fibre membrane scaffolds, cell growth was substantially improved, evident from transepithelial electrical resistance (TEER) and permeation behaviour (Carter J, in preparation).

Main questions to be answered:

The core part of this project is to extend previous work by demonstrating the consistency and reproducibility in the fabrication of the gut model, focusing on the design and production of the porous fibre membrane scaffolds, evaluation of their structure, stability and functionality for further improvement. The novelty and the central focus of this project is to explore how nanoporous polymeric PLLA and PLA-PLGA membrane scaffolds fabricated from electrospinning and subsequent processing can be further transformed by incorporating conducting polymers such as polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) with and without infusion of self-assembled short peptide bionanomaterials – the questions to be asked are:

  1. How will the conducting polymers affect the integrity and stability of the new composite fibres and their conducting and permeation?
  2. How can the composite membrane scaffolds be fabricated reproducibly?
  3. How do the new composites affect cell growth?
  4. How does conductivity affect transmembrane permeation of model drugs?
  5. How does incorporation of ECM mimicry peptides affect biocompatibility?
  6. How can antimicrobial peptides (AMPs), once loaded, be manipulated by applying small external current and voltage?
  7. How do AMPs affect cell growth?
  8. Would AMPs selectively target bacteria in a co-culture with the gut model?

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

University of Sheffield, Department of Materials Science and Engineering, 7 PhD Projects Available

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