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Synergistic material topography combinations to achieve immunomodulatory osteogenic biomaterials
journal contributionposted on 01.02.2021, 05:49 authored by David WinklerDavid Winkler, Laurence Burroughs, M Amer, Matthew Vassaey, Brita Koch, Grazziela Figueredo, Morgan Alexander, Jan de Boer, al et
This is a preliminary report that has not been peer-reviewed. It should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.
Abstract: Human mesenchymal stem cells (hMSCs) are widely represented in ongoing regenerative medicine clinical trials due to their ease of autologous implantation. In bone regeneration, crosstalk between macrophages and hMSCs is critical with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to both direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-microtopography screening platform, the ChemoTopoChip, is used 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 in bone-regenerative applications. These also exhibit immunomodulatory effects, concurrently polarizing macrophages towards a pro-healing phenotype. Control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large library of materials reveals that the relative roles of microtopography and material chemistry are similar, and machine learning identifies key material and topographical features for cell-instruction.