930000_Rostam,H_2020.pdf (3.57 MB)
Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo
journal contributionposted on 2021-05-03, 00:00 authored by David WinklerDavid Winkler, HM Rostam, LE Fisher, Andrew L Hook, Laurence Burroughs, JC Luckett, C Mbadugha, ACK Teo, A Latif, L Kämmerling, Dave Barrett, S Elsheikh, Grazziela P Figueredo, M Ilyas, Morgan R Alexander, Amir M Ghaemmaghami
© 2020 The Authors This study explores the hypothesis that simple polymer chemistries can be used to modulate the phenotype of human immune cells. Unbiased high-throughput screening of a large library of polymer chemistries is undertaken, identifying materials able to instruct macrophage attachment and polarization to pro- or anti-inflammatory phenotypes. The bioinstructive polymer function is validated by a murine model in which modulation of the foreign body response is shown. Polymer structure-cell response relationships modeled using machine learning reveal molecular descriptors useful for interpreting the immune-instructive polymers, highlighting the potential to undertake “immune-instructive” rational design. Identifying new polymers with immune-modulatory properties and elucidating the molecular mechanisms involved offer exciting possibilities to create novel bioinstructive materials with numerous clinical applications from implants and vaccine adjuvants to regenerative medicine and drug delivery.
This project was supported by The EPSRC Program grant in Next Generation Biomaterials Discovery (EP/N006615/1) and a Confidence in Concept Medical Research Council grant. The Cambridge Center for Proteomics is acknowledged for the LCMS/MS service analysis of surface-extracted proteins. Ian Ward, Denise McLean, and Christopher Gell from the School of Life Sciences Imaging teamat the University of Nottingham are acknowledged for assistance in histology and imaging and Declan Sculthorpe from the School of Medicine for aid in whole-slide scanning. A.L.H. acknowledges the University of Nottingham for funding his Nottingham Research Fellowship. H.M.R. acknowledges a Human Capacity Development Program PhD scholarship (Kurdistan Regional Government). A.M.G. acknowledges funding from the European Union's Horizon 2020 research and innovation program under grant agreement 760921 (PANBioRA).
Pagination19p. (p. 1564-1581)
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