TY - JOUR
T1 - Discovery of synergistic material-topography combinations to achieve immunomodulatory osteoinductive biomaterials using a novel in vitro screening method
T2 - The ChemoTopoChip
AU - Burroughs, Laurence
AU - Amer, Mahetab H.
AU - Vassey, Matthew
AU - Koch, Britta
AU - Figueredo, Grazziela P.
AU - Mukonoweshuro, Blessing
AU - Mikulskis, Paulius
AU - Vasilevich, Aliaksei
AU - Vermeulen, Steven
AU - Dryden, Ian L.
AU - Winkler, David A.
AU - Ghaemmaghami, Amir M.
AU - Rose, Felicity R. A. J.
AU - de Boer, Jan
AU - Alexander, Morgan R.
N1 - Funding Information:
This research is supported by funding from the UK's Engineering Physical Sciences Research Council ( EPSRC ) under the Programme Grant Next Generation Biomaterials Discovery EP/N006615/1 . AV and JdB are funded by the European Union's Seventh Framework Programme ( FP7/2007-2013 ) under grant agreement no 289720. AV acknowledge the financial contribution of the Province of Limburg. SV acknowledges the financial support of the European Union's Horizon 2020 Programme (H2020-MSCA- ITN-2015; Grant agreement 676338 ).
Publisher Copyright:
© 2021 The Authors
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Biomaterials
KW - Macrophages
KW - Mesenchymal stem cells
KW - Regenerative medicine
KW - CELLS
KW - OSTEOBLAST DIFFERENTIATION
KW - RECEPTOR
KW - CULTURE
KW - HYDROGEL
KW - SUBSTRATE
KW - FOREIGN-BODY RESPONSE
KW - POLYMER
KW - CHEMISTRY
U2 - 10.1016/j.biomaterials.2021.120740
DO - 10.1016/j.biomaterials.2021.120740
M3 - Article
C2 - 33714019
SN - 0142-9612
VL - 271
JO - Biomaterials
JF - Biomaterials
M1 - 120740
ER -