Coating the cell surface with adhesive polymers: a strategy to enhance cell adhesion

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Developing polymeric coatings for mammalian cells offers the opportunity to tune the chemical and physical environment at the cell surface. This emerging technology has the potential to enable significant advances in the field of cell-based therapies and push forward their clinical application in regenerative medicine. One of the most established methodologies to achieve a polymeric coating around cells relies on the use of materials with an overall positive charge that can interact with the anionic cell surface. However, this approach has been proved to be inadequate for the coating of single cells, as positively charged polymers can disrupt the cell membrane and consequently induce cell death. Similarly, the susceptibility of mammalian cells to mechanical and chemical stress has also limited the covalent conjugation of polymer chains through functionalities already present at the cell surface, hence restricting the chemistry available to achieve a homogeneous and long-lasting cell coating. Nevertheless, recent advances have demonstrated that bio-orthogonal click strategies can be used to introduce exogenous functional groups at the cell surface that can be exploited for polymer conjugation. While these strategies have undoubtedly advanced the field of cell engineering, achieving a homogeneous polymer coating with tuneable properties that is able to control cell behaviour remains an unmet challenge. Importantly, investigating how polymer composition and density of conjugation can be exploited to modulate cell behaviour is essential to fully realise the potential of cell coating strategies in the field of tissue engineering and beyond. This is exactly what this project intends to achieve. By developing robust methodologies for single cell coating, we aim to provide a platform to control cell adhesion with the extracellular matrix and surrounding tissue. This is particularly relevant in tissue regeneration, where cells with regenerative potential (tissue-specific or staminal cells) are injected directly into the target tissue and vasculature to promote tissue growth. Often, cell attachment to the existing tissue is low, mainly as a result of inefficient adhesion of transplanted cells to the surrounding environment, which in turn leads to their programmed death and clearance by the circulatory system. In this project, we will use human liver cells as a model system that will allow us to develop the chemistry and deliver fundamental understanding on the polymer structure, molecular weight, and density of conjugation that are needed to achieve a homogeneous cell coating. This cell type has shown great promise for the development of targeted cell-based therapies for liver regeneration. Using liver as a model, our goal is to develop a versatile coating platform that can be applied to a wide range of cells, advancing the field of cell-based therapies for tissue regeneration.The project represents a priority area for the UK and aligns strongly with the EPSRC's prosperity outcomes (Healthy Nation) and the Healthcare Technologies grand challenges. It also tallies with the United Nations (UN) Sustainable Development Goals, specifically Goal 3: 'Ensure healthy lives and promote well-being for all at all ages.'