3D topographies promote macrophage M2d-Subset differentiation

Stefania C. Carrara*, Amanda Davila-Lezama, Clément Cabriel, Erwin J.W. Berenschot, Silke Krol, J.G.E. Gardeniers, Ignacio Izeddin, Harald Kolmar, Arturo Susarrey-Arce*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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In vitro cellular models denote a crucial part of drug discovery programs as they aid in identifying successful drug
candidates based on their initial efficacy and potency. While tremendous headway has been achieved in improving 2D and 3D culture techniques, there is still a need for physiologically relevant systems that can mimic or alter cellular responses without the addition of external biochemical stimuli. A way forward to alter cellular responses is using physical cues, like 3D topographical inorganic substrates, to differentiate macrophage-like cells. Herein, protein secretion and gene expression markers for various macrophage subsets cultivated on a 3D topographical substrate are investigated. The results show that macrophages differentiate into anti-inflammatory M2-type macrophages, secreting increased IL-10 levels compared to the controls. Remarkably, these macrophage cells are differentiated into the M2d subset, making up the main component of tumour-associated macrophages (TAMs), as measured by upregulated Il-10 and Vegf mRNA. M2d subset differentiation is attributed to the topographical substrates with 3D fractal-like geometries arrayed over the surface, else primarily achieved by tumour-associated factors in vivo. From a broad perspective, this work paves the way for implementing 3D topographical inorganic surfaces for drug discovery programs, harnessing the advantages of in vitro assays without external stimulation and allowing the rapid characterisation of therapeutic modalities in physiologically relevant environments.
Original languageEnglish
Article number100897
Number of pages8
JournalMaterials Today Bio
Early online date6 Dec 2023
Publication statusPublished - Feb 2024


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