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Discovery of synergistic material-topography combinations to achieve immunomodulatory osteoinductive biomaterials using a novel in vitro screening method: The ChemoTopoChip

Burroughs, Laurence; Amer, Mahetab; Vassey, Matthew; Koch, Britta; Figueredo, Grazziela; Mukonoweshuro, Blessing; Mikulskis, Paulius; Vasilevich, Aliaksei; Vermeulen, Steven; Dryden, Ian L; Winkler, David A; Ghaemmaghami, Amir M; Rose, Felicity R. A. J.; de Boer, Jan; Alexander, Morgan R

Discovery of synergistic material-topography combinations to achieve immunomodulatory osteoinductive biomaterials using a novel in vitro screening method: The ChemoTopoChip Thumbnail


Authors

Laurence Burroughs

Mahetab Amer

Matthew Vassey

Britta Koch

Blessing Mukonoweshuro

Paulius Mikulskis

Aliaksei Vasilevich

Steven Vermeulen

IAN DRYDEN IAN.DRYDEN@NOTTINGHAM.AC.UK
Professor of Statistics

David A Winkler

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FELICITY ROSE FELICITY.ROSE@NOTTINGHAM.AC.UK
Professor of Biomaterials and Tissue Engineering

Jan de Boer

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MORGAN ALEXANDER MORGAN.ALEXANDER@NOTTINGHAM.AC.UK
Professor of Biomedical Surfaces



Abstract

© 2021 The Authors Human mesenchymal stem cells (hMSCs) are widely represented in regenerative medicine clinical strategies due to their compatibility with autologous implantation. Effective bone regeneration involves crosstalk between macrophages and hMSCs, with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to simultaneously direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-topography screening platform, the ChemoTopoChip, is used here to identify materials suitable for bone regeneration by screening 1008 combinations in each experiment for human immortalized mesenchymal stem cell (hiMSCs) and human macrophage response. The osteoinduction achieved in hiMSCs cultured on the “hit” materials in basal media is comparable to that seen when cells are cultured in osteogenic media, illustrating that these materials offer a materials-induced alternative to osteo-inductive supplements in bone-regeneration. Some of these same chemistry-microtopography combinations also exhibit immunomodulatory stimuli, polarizing macrophages towards a pro-healing phenotype. Maximum control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large combinatorial library allows us for the first time to probe the relative cell-instructive roles of microtopography and material chemistry which we find to provide similar ranges of cell modulation for both cues. Machine learning is used to generate structure-activity relationships that identify key chemical and topographical features enhancing the response of both cell types, providing a basis for a better understanding of cell response to micro topographically patterned polymers.

Journal Article Type Article
Acceptance Date Feb 25, 2021
Online Publication Date Mar 1, 2021
Publication Date Apr 1, 2021
Deposit Date Mar 5, 2021
Publicly Available Date Mar 2, 2022
Journal Biomaterials
Print ISSN 0142-9612
Electronic ISSN 1878-5905
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 271
Article Number 120740
DOI https://doi.org/10.1016/j.biomaterials.2021.120740
Public URL https://nottingham-repository.worktribe.com/output/4373431
Publisher URL https://www.sciencedirect.com/science/article/pii/S0142961221000922