Abstract
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.
Highlights
Microparticles, known as microcarriers, have gained signifi cance as building blocks for tissue engineering strategies, in bioinks for three-dimensional (3D) bioprinting and for large-scale expansion of anchorage-dependent cells [1]
Our studies have demonstrated that both micropar ticle and dimple sizes were dependent on polymer concentration and polymer/fusidic acid (FA) ratio (Fig. 1C–D, Table S1 and Fig. S1B)
poly(lactic-co-glycolic acid) (PLGA)-based microparticles displayed uniform dimpled morphologies, degradation was rapid, and the dimpled morphology was not preserved after days in culture media (Fig. S1F)
Summary
Microparticles, known as microcarriers, have gained signifi cance as building blocks for tissue engineering strategies, in bioinks for three-dimensional (3D) bioprinting and for large-scale expansion of anchorage-dependent cells [1]. Since they allow the formation of interconnected porous scaffolds and spatiotemporal release of bioactive factors, microparticles are an attractive tool for engineering complex tissues and biological interfaces. We demonstrate the potential of capitalizing on cell-substrate in teractions to develop cell-instructive microparticles, whereby tailored microparticle design can allow control over stem cell fate. To test the capability of topo graphical designs on microparticles to induce osteogenesis, a range of viability and osteo-specific gene, protein and mineralization assays were performed using primary human mesenchymal stem cells (hMSCs) in vitro, and within non-healing murine radial bone defects in vivo
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