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Cell-surface engineering with polymers: a new strategy for tissue regeneration.

Primary Supervisor: Dr Maria Chiara Arno, School of Chemistry

Secondary supervisors: Prof. Matthew I. Gibson (University of Warwick) and Prof. Alicia El Haj (University of Birmingham)

PhD project title: Cell-surface engineering with polymers: a new strategy for tissue regeneration

University of Registration: University of Birmingham

Project outline:

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer and various types of chronic diseases. Although they remain unclear, the two major potential mechanisms that have been proposed for stem cell transplantation involve the improvement of the microenvironments through paracrine effects and the replacement of functional tissue.

While organ transplantation is safe in humans, its applicability remains limited due to organ availability, failure of donor engraftment, and vulnerability to cryopreservation damage. Stem cell therapy provides an alternative approach to overcome traditional transplant drawbacks, such as the limited number of donors and transplant rejections. However, this methodology is limited by poor cell attachment at the targeted site and poor interaction of stem cells with the host’s extracellular matrix (ECM).

In this project, we will explore how glycans (sugars) present at the cell membrane can be ‘hijacked’ to engineer the surface of stem cells. Through this methodology, which affects how the sugars are processed inside the cell, we can introduce new bio-orthogonal functionality onto the cell surface, which can then be used to selectively decorate the cell membrane with polymer chains that promote stem cells adhesion to the host tissue and enhance cell-ECM interactions.

This exciting and multidisciplinary project combines the fields of polymer chemistry, stem cell biology, and tissue engineering, with potential for real impact. The MIBTP student will acquire multidisciplinary skills in a unique biomaterials’ environment, ranging from polymer synthesis to cell engineering, confocal microscopy and flow cytometry.

Key objectives will include:

  1. Introduction of bio-orthogonal functionalities in the cell membrane through targeted glycan labelling.
  2. Selective conjugation of polymers at the cell membrane.
  • Demonstrate the success of the approach in 2D and 3D cell culture, mimicking the in vivo

This project combines the research expertise of Dr Arno in the field of biomaterials and precision polymer design, Prof. Gibson in the field of cell engineering and glycan labelling, and Prof. El Haj in cell transplant technologies and tissue regeneration. The student will have access to state-of-the-art equipment and expertise at the School of Chemistry (UoB and UoW), Medical School (UoW), and the Healthcare Technology Institute (HTI, UoB).

Dr Arno has expertise in the field of biomaterials, precision polymer design, and cell-materials interactions:

  • Engineering the Mammalian Cell Surface with Synthetic Polymers: Strategies and Applications, Rapid Commun. 2020, 41, 2000302.
  • Exploiting the role of nanoparticle shape in enhancing hydrogel adhesive and mechanical properties, Nat.Commun. 2020, 11, 1420.
  • Precision Epitaxy for Aqueous 1D and 2D Poly(ε-caprolactone) Assemblies, Am. Chem. Soc.2017, 139, 16980.

Prof. Gibson is an expert in cell engineering and glycan labelling at the University of Warwick. The Gibson Group has previously developed nano/polymer systems for advance therapeutics and also shown the proof of principle that we can recruit polymers to cells:

  • Optimization and Stability of Cell-Polymer Hybrids Obtained by “Clicking” Synthetic Polymers to Metabolically Labelled Cell Surface Glycans; Biomacromolecules 2019, 20, 7, 2726-2736.
  • Engineering Cell Surfaces by Covalent Grafting of Synthetic Polymers to Metabolically-Labelled Glycans, ACS Macro Lett. 2018, 7, 11, 1289-129.

Prof. El Haj is a renowned expert in cell transplant technologies and tissue regeneration:

  • Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair. Mater. 2020, in press.
  • Regenerative Medicine: "Are We There Yet?". Tissue Eng Part A. 2019, 15, 1067-1071.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Stem Cells & Systems Biology & Integrated Understanding of Health: Ageing & Regenerative Biology

Techniques that will be undertaken during the project:

The MIBTP student will be trained in cell culture and cell engineering techniques, carbohydrate chemistry, 2D and 3D cell culture (using spheroids and organoids), confocal fluorescence microscopy, and flow cytometry. They will also receive training in a wide range of polymerisation techniques, NMR spectroscopy, mass spectrometry, IR spectroscopy, fluorescence spectroscopy, and size exclusion chromatography for polymer analysis. Overall, the multidisciplinary nature of this project offers the opportunity to learn skills in a wide range of techniques, from developing new materials to exploiting their performance in a biologically relevant environment.

Contact: Dr Maria Chiara Arno, University of Birmingham