Immune Modulation by Design: Using Topography to Control Human Monocyte Attachment and Macrophage Differentiation

Matthew J. Vassey, Grazziela P. Figueredo, David J. Scurr, Aliaksei S. Vasilevich, Steven Vermeulen, Aurélie Carlier, Jeni Luckett, Nick R.M. Beijer, Paul Williams, David A. Winkler, Jan de Boer, Amir M. Ghaemmaghami (Corresponding author), Morgan R. Alexander (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

94 Citations (Scopus)

Abstract

Macrophages play a central role in orchestrating immune responses to foreign materials, which are often responsible for the failure of implanted medical devices. Material topography is known to influence macrophage attachment and phenotype, providing opportunities for the rational design of “immune-instructive” topographies to modulate macrophage function and thus foreign body responses to biomaterials. However, no generalizable understanding of the inter-relationship between topography and cell response exists. A high throughput screening approach is therefore utilized to investigate the relationship between topography and human monocyte–derived macrophage attachment and phenotype, using a diverse library of 2176 micropatterns generated by an algorithm. This reveals that micropillars 5–10 µm in diameter play a dominant role in driving macrophage attachment compared to the many other topographies screened, an observation that aligns with studies of the interaction of macrophages with particles. Combining the pillar size with the micropillar density is found to be key in modulation of cell phenotype from pro to anti-inflammatory states. Machine learning is used to successfully build a model that correlates cell attachment and phenotype with a selection of descriptors, illustrating that materials can potentially be designed to modulate inflammatory responses for future applications in the fight against foreign body rejection of medical devices.

Original languageEnglish
Article number1903392
JournalAdvanced Science
Volume7
Issue number11
DOIs
Publication statusPublished - 1 Jun 2020

Funding

The EPSRC are gratefully acknowledged for the Next Generation Biomaterials Discovery Programme Grant Funding (Grant no. EP/N006615/1) and the Strategic Equipment grant ‘3D OrbiSIMS: Label free chemical imaging of materials, cells and tissues’ funding that supported this work (grant no. EP/P029868/1). S.V. was supported by the European Union's Horizon 2020 Programme (H2020‐MSCA‐ITN‐2015; Grant agreement 676338). AC kindly acknowledges the Dutch province of Limburg in the LINK (FCL67723) (“Limburg INvesteert in haar Kenniseconomie”) knowledge economy project and a VENI grant (number 15075) from the Dutch Science Foundation (NWO). The authors gratefully acknowledge Dr. Chris Gell (University of Nottingham, SLiM) for technical assistance in microscopy as well as Dr Emily F Smith and Dr Craig Stopiello at the Nanoscale and Microscale Research Centre (NMRC University of Nottingham) for acquiring the XPS spectra.

FundersFunder number
Dutch Province of Limburg15075, FCL67723
European Union 's Horizon 2020 - Research and Innovation Framework ProgrammeH2020-MSCA-ITN-2015
Horizon 2020 Framework Programme676338
Engineering and Physical Sciences Research CouncilEP/N006615/1, EP/P029868/1
University of Nottingham
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

    Keywords

    • biomaterials
    • high-throughput screening
    • immune-modulation
    • topography

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