Abstract
Mesenchymal stromal/stem cells (MSC) have been studied extensively for their potential use in the generation of connective tissues for both therapeutics and biomedical research. Here, using the NovoGen™bioprinting platform and osteogenic differentiation media discovered with the high throughput combinatorial platform CombiCult®, we report the rapid fabrication of, and efficient osteogenesis in, 3D, scaffold‐free, bioprinted tissue constructs containing adipose‐derived MSC (aMSC) or aMSC and endothelial cells (EC). Constructs were bioprinted in multi‐well tissue culture vessels enabling rapid generation of replicate tissues for interrogation with standard laboratory assays. Bioprinted constructs cultured in media used for aMSC propagation showed no signs of osteogenesis. Evaluation of bioprinted 3D tissue constructs maintained in CombiCult® (OsteoMax‐XF™, EMD Millipore) differentiation media revealed marked evidence of osteogenic differentiation. By 5d post‐printing, aMSC‐containing tissue constructs exposed to CombiCult® were found to contain osteopontin‐ and alkaline phosphatase‐positive cells and mineralization was confirmed by Alizarin Red S staining. Osteogenesis was associated with elevated levels of IL‐1α, IL‐6, IL‐8, CCL2 and CXCL1. Experiments were repeated with multiple lots of commercially‐sourced aMSC implicating utility of this model for a variety of MSC sources.
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