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    Designing topographically textured microparticles for induction and modulation of osteogenesis in mesenchymal stem cell engineering

    Year: 2021

    Journal: Biomaterials, Volume 266, JAN

    Authors: Amer, Mahetab H.; Alvarez-Paino, Marta; McLaren, Jane; Pappalardo, Francesco; Trujillo, Sara; Wong, Jing Qian; Shrestha, Sumana; Abdelrazig, Salah; Stevens, Lee A.; Lee, Jong Bong; Kim, Dong-Hyun; Gonzalez-Garcia, Cristina; Needham, David; Salmeron-Sanchez, Manuel; Shakesheff, Kevin M.; Alexander, Morgan R.; Alexander, Cameron; Rose, Felicity R. A. J.

    Organizations: Engineering and Physical Sciences Research Council (EPSRC) [EP/N006615/1]; EPSRC Programme Grant Engineering growth factor microenvironments - a new therapeutic paradigm for regenerative medicine [EP/P001114/1]; BBSRC [BB/L013827/1] Funding Source: UKRI; EPSRC [EP/N006615/1] Funding Source: UKRI

    Keywords: Microcarriers; Mesenchymal stem cells; Osteogenic differentiation; Osteoinductive; Topography; 3D

    Mesenchymal stem cells are the focus of intense research in bone development and regeneration. The potential of microparticles as modulating moieties of osteogenic response by utilizing their architectural features is demonstrated herein. Topographically textured microparticles of varying microscale features are produced by exploiting phase-separation of a readily soluble sacrificial component from polylactic acid. The influence of varying topographical features on primary human mesenchymal stem cell attachment, proliferation and markers of osteogenesis is investigated. In the absence of osteoinductive supplements, cells cultured on textured microparticles exhibit notably increased expression of osteogenic markers relative to conventional smooth microparticles. They also exhibit varying morphological, attachment and proliferation responses. Significantly altered gene expression and metabolic profiles are observed, with varying histological characteristics in vivo. This study highlights how tailoring topographical design offers cell-instructive 3D microenvironments which allow manipulation of stem cell fate by eliciting the desired downstream response without use of exogenous osteoinductive factors.
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