Manipulating the Immune System's Interaction with Biomaterials to Guide Immunomodulatory Responses for Optimised Therapeutic Interventions

About this opportunity

Initial immune reactions, such as protein adsorption and macrophage activation, significantly impact long-term compatibility and ultimately determine therapeutic success. Studies have shown that biomaterial properties, such as porosity, stiffness, and surface topography, impact immune responses, underscoring the need for tailored material design. Current immune manipulation techniques can guide the behaviour of immune cells, including surface engineering and embedded delivery systems with immunomodulatory cargo. The Immunocompatibility group at the University of Liverpool (UoL) is identifying key biomaterial criteria that influence immune responses, such as inflammasome activation and macrophage polarisation, with a focus on anti-inflammatory strategies. The McDonald Group at UoM brings expertise in synthesising lipid nanoparticles and biomaterials, supported by the Henry Royce Institute’s high-end facilities. This project combines these strengths to create biomaterials with favourable immune profiles, addressing immune response challenges in therapeutic applications.

Objectives.

1. Characterising Immune Responses to Biomaterials. Investigate immune system interactions with different biomaterials, focusing initially on human immune cell lines robustly characterised by the group as valuable models of primary immune cell responses, focusing on cytokine release and cellular activation markers. Profiling inflammatory (e.g., IL-6, TNF-α) and anti-inflammatory (e.g., IL-10) cytokine levels in response to various biomaterials and quantifying recruitment and activation of immune cells, such as neutrophils, dendritic cells, and T cells, to identify immune modulatory effects through measurement of proliferation, functionality, and cellular bioenergetics. Cell line finding s will be compared to those in primary cells by assessing whole blood cytokine responses, multiparametric immune cell profiling via mass cytometry, and differential gene expression analysis. The ability of biomaterials to impact macrophage polarisation and activate complement are two priorities in addressing the biomaterial-immune interface.

2. Identification of Biomaterial Immunomodulatory Factors. Pinpointing material properties (e.g., surface roughness, chemical composition) and immune pathway interactions are critical in modulating immune responses. Using insights from initial characterisations, this phase will focus on identifying the material properties responsible for favourable immune modulation by varying biomaterial properties, including surface topography and chemistry, material stiffness, and biomaterial degradation.
3. Exploration of biomaterial surface modifications. Through the incorporation of bioactive molecules and local delivery of immunomodulators to shift immune responses toward anti-inflammatory and regenerative outcomes. Building on the identified properties, the project will design and synthesise biomaterials with controlled immune responses, focusing on surface functionalisation (incorporating peptides, antibodies, or small molecules on biomaterial surfaces to modulate immune cell adhesion and activation), embedding anti-inflammatory agents (e.g., NSAIDs, corticosteroids, siRNAs targeting immune signalling) within biomaterial matrices to achieve localised immune modulation, and utilising naturally derived materials or biomimetic structures that mimic native tissue properties to facilitate integration.

This project will provide training in state-of-the-art technique and models, working across multidisciplinary teams with a strong track record of collaboration, for the development and translation of biomaterials.

Further reading

1. DAVID, C. A. W., VERMEULEN, J. P., GIORIA, S., VANDEBRIEL, R. J. & LIPTROTT, N. J. 2024. Nano(bio)Materials Do Not Affect Macrophage Phenotype-A Study Conducted by the REFINE Project. Int J Mol Sci, 25.
2. ELKATEB, H., CAULDBECK, H., NIEZABITOWSKA, E., HOGARTH, C., ARNOLD, K., RANNARD, S., & MCDONALD, T. O, 2023. High drug loading solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions for the dual drug delivery of the HIV drugs darunavir and ritonavir, JCIS Open, 2023, 11, 100087.
3. DAVID, C. A. W., DE LA FONTEYNE-BLANKESTIJN, L. J. J., VERMEULEN, J. P., PLANT-HATELY, A. J., VANDEBRIEL, R. J. & LIPTROTT, N. J. 2023. Application of KU812 cells for assessing complement activation related effects by nano(bio)materials. Biomed Pharmacother, 163, 114841.
4. VANDEBRIEL, R. J., DAVID, C. A. W., VERMEULEN, J. P. & LIPTROTT, N. J. 2022. An inter-laboratory comparison of an NLRP3 inflammasome activation assay and dendritic cell maturation assay using a nanostructured lipid carrier and a polymeric nanomedicine as exemplars. Drug Deliv Transl Res, 12, 2225-2242.

LIPTROTT, N. J., GIARDIELLO, M., MCDONALD, T. O., RANNARD, S. P. & OWEN, A. 2018. Assessment of interactions of efavirenz solid drug nanoparticles with human immunological and haematological systems. J Nanobiotechnology, 16, 22

Additional costs

We understand that budgeting for your time at university is important, and we want to make sure you understand any costs that are not covered by your tuition fee. This could include buying a laptop, books, or stationery.

Find out more about the additional study costs that may apply to this project, as well as general student living costs.

Funding your PhD

If you're a UK national, or have settled status in the UK, you may be eligible to apply for a Postgraduate Doctoral Loan worth up to £30,301 to help with course fees and living costs.

There’s also a variety of alternative sources of funding. These include funded research opportunities and financial support from UK research councils, charities and trusts. Your supervisor may be able to help you secure funding.

Contact us

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