TY - JOUR
T1 - Innate immune cell instruction using micron-scale 3D objects of varied architecture and polymer chemistry
T2 - The ChemoArchiChip
AU - Vassey, Matthew
AU - Ma, Le
AU - Kämmerling, Lisa
AU - Mbadugha, Chidimma
AU - Trindade, Gustavo F.
AU - Figueredo, Grazziela P.
AU - Pappalardo, Francesco
AU - Hutchinson, Jason
AU - Markus, Robert
AU - Rajani, Seema
AU - Hu, Qin
AU - Winkler, David A.
AU - Irvine, Derek J.
AU - Hague, Richard
AU - Ghaemmaghami, Amir M.
AU - Wildman, Ricky
AU - Alexander, Morgan R.
N1 - Funding Information:
We thank Nicola Weston at the Nanoscale and Microscale Research Center (NMRC; University of Nottingham) for technical assistance with electron microscopy. This study was supported by the EPSRC, who are gratefully acknowledged for Next Generation Biomaterials Discovery Program Grant funding (EP/N006615/1) and Enabling Next Generation Additive Manufacturing Program Grant funding (EP/P031684/1) that supported this work. The image analysis for GDGDA was supported by the APEER annotation and segmentation machine learning tool by Carl Zeiss, and L.K. introduced this and its interpretation into the manuscript. Overview schematics were generated in BioRender. M.V. concept, cell culture experiments, data interpretation, image analysis, and writing; L.M. concept, 2PP printing, and writing; L.K. image analysis, data interpretation, and writing; C.M. initial screening and cell culture screening experiments; G.F.T. ToF-SIMS analysis; G.P.F. machine learning; F.P. AFM analysis; J.H. 2PP printing files; R.M. and S.R. image analysis support; Q.H. 2PP proof-of-concept studies; D.A.W. D.J.I. R.H. A.M.G. R.W. and M.R.A. concept, supervision, funding and editing of the manuscript. The authors hold a patent application related to this work (UK Patent Application GB2217458.5).
Funding Information:
We thank Nicola Weston at the Nanoscale and Microscale Research Center (NMRC; University of Nottingham) for technical assistance with electron microscopy. This study was supported by the EPSRC , who are gratefully acknowledged for Next Generation Biomaterials Discovery Program Grant funding ( EP/N006615/1 ) and Enabling Next Generation Additive Manufacturing Program Grant funding ( EP/P031684/1 ) that supported this work. The image analysis for GDGDA was supported by the APEER annotation and segmentation machine learning tool by Carl Zeiss, and L.K. introduced this and its interpretation into the manuscript. Overview schematics were generated in BioRender.
Publisher Copyright:
© 2023 The Authors
PY - 2023/3/1
Y1 - 2023/3/1
N2 - To design effective immunomodulatory implants, innate immune cell interactions at the surface of biomaterials need to be controlled and understood. The architectural design freedom of two-photon polymerization is used to produce arrays of surface-mounted, geometrically diverse 3D polymer objects. This reveals the importance of the interplay between architecture and materials chemistry in determining human macrophage fate in vitro. The ChemoArchiChip identifies key structure-function relationships and design rules from machine learning models to build a mechanistic understanding of cell attachment and polarization. Object shape, vertex/cone angle, and size are key drivers of attachment. Particular shapes are found to heavily modulate pro- or anti-inflammatory cell polarization, while triangular pyramids drastically reduce or even eliminate attachment. Caveola-dependent endocytosis is a principal mechanism by which cells respond to objects with sharp points; i.e., low vertex/cone angles. The discovery of these putative design rules points to surfaces decorated with architectures to augment implant performance.
AB - To design effective immunomodulatory implants, innate immune cell interactions at the surface of biomaterials need to be controlled and understood. The architectural design freedom of two-photon polymerization is used to produce arrays of surface-mounted, geometrically diverse 3D polymer objects. This reveals the importance of the interplay between architecture and materials chemistry in determining human macrophage fate in vitro. The ChemoArchiChip identifies key structure-function relationships and design rules from machine learning models to build a mechanistic understanding of cell attachment and polarization. Object shape, vertex/cone angle, and size are key drivers of attachment. Particular shapes are found to heavily modulate pro- or anti-inflammatory cell polarization, while triangular pyramids drastically reduce or even eliminate attachment. Caveola-dependent endocytosis is a principal mechanism by which cells respond to objects with sharp points; i.e., low vertex/cone angles. The discovery of these putative design rules points to surfaces decorated with architectures to augment implant performance.
KW - 2-photon polymerization
KW - 3D geometries
KW - biomaterials
KW - immune modulation
KW - macrophages
KW - MAP1: Discovery
UR - https://www.scopus.com/pages/publications/85149058732
U2 - 10.1016/j.matt.2023.01.002
DO - 10.1016/j.matt.2023.01.002
M3 - Article
AN - SCOPUS:85149058732
SN - 2590-2393
VL - 6
SP - 887
EP - 906
JO - Matter
JF - Matter
IS - 3
ER -