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dc.contributor.authorAlexander, Morgan R.
dc.contributor.otherBurroughs, Laurence
dc.contributor.otherAmer, Mahetab H.
dc.contributor.otherVassey, Matthew
dc.contributor.otherKoch, Britta
dc.contributor.otherFigueredo, Grazziela P.
dc.contributor.otherMukonoweshuro, Blessing
dc.contributor.otherMikulskis, Paulius
dc.contributor.otherVasilevich, Aliaksei
dc.contributor.otherVermeulen, Steven
dc.contributor.otherDryden, Ian L.
dc.contributor.otherWinkler, David A
dc.contributor.otherGhaemmaghami, Amir M
dc.contributor.otherRose, Felicity R. A. J.
dc.contributor.otherde Boer, Jan
dc.date.accessioned2020-09-18T07:28:35Z
dc.date.available2020-09-18T07:28:35Z
dc.date.issued2020-09-18
dc.identifier.urihttps://rdmc.nottingham.ac.uk/handle/internal/8614
dc.description.abstractHuman 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 with human immortalized mesenchymal stem cells (hiMSCs) and human macrophages. 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-micro topography 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.en_UK
dc.language.isoen_USen_UK
dc.publisherThe University of Nottinghamen_UK
dc.rightsCC-BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.lcshBiomedical materialsen_UK
dc.subject.lcshMesenchymal stem cellsen_UK
dc.subject.lcshMacrophagesen_UK
dc.subject.lcshRegenerative medicineen_UK
dc.subject.meshBiocompatible Materialsen_UK
dc.subject.meshMesenchymal Stem Cellsen_UK
dc.subject.meshMacrophagesen_UK
dc.subject.meshRegenerative Medicineen_UK
dc.titleSynergistic Material-Topography Combinations to Achieve Immunomodulatory Osteoinductive Biomaterialsen_UK
dc.identifier.doihttp://doi.org/10.17639/nott.7080
dc.subject.freebiomaterials, mesenchymal stem cells, macrophages, regenerative medicineen_UK
dc.subject.jacsPhysical sciencesen_UK
dc.subject.jacsBiological Sciencesen_UK
dc.subject.lcQ Scienceen_UK
dc.subject.lcR Medicineen_UK
dc.date.collection2017-2019en_UK
uon.divisionUniversity of Nottingham, UK Campusen_UK
uon.funder.controlledEngineering & Physical Sciences Research Councilen_UK
uon.datatypeMicroscope images, processed image data, topographical descriptors, image processing pipelinesen_UK
uon.grantEP/N006615/1en_UK
uon.collectionmethodOptical microscopy, fluorescence microscopy, CellProfiler image analysis software processingen_UK
uon.institutes-centresUniversity of Nottingham, UK Campusen_UK


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