期刊
MOLECULAR PHARMACEUTICS
卷 11, 期 7, 页码 2151-2159出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp400573g
关键词
3D bioprinting; micropatterning; biomimetic tissue platforms; functional tissue models; tissue interfaces; genomic expression analysis
资金
- Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health)
- Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]
- Harvard Catalyst, The Harvard Clinical and Translational Science Center (Harvard University)
- National Science Foundation under NSF CAREER Award [1150733]
- NIH [R21HL112114]
Over the past decade, bioprinting has emerged as a promising patterning strategy to organize cells and extracellular components both in two and three dimensions (2D and 3D) to engineer functional tissue mimicking constructs. So far, tissue printing has neither been used for 3D patterning of mesenchymal stem cells (MSCs) in multiphase growth factor embedded 3D hydrogels nor been investigated phenotypically in terms of simultaneous differentiation into different cell types within the same micro-patterned 3D tissue constructs. Accordingly, we demonstrated a biochemical gradient by bioprinting nanoliter droplets encapsulating human MSCs, bone morphogenetic protein 2 (BMP-2), and transforming growth factor beta 1 (TGF- beta 1), engineering an anisotropic biomimetic fibrocartilage microenvironment. Assessment of the model tissue construct displayed multiphasic anisotropy of the incorporated biochemical factors after patterning. Quantitative real time polymerase chain reaction (qRT-PCR) results suggested genomic expression patterns leading to simultaneous differentiation of MSC populations into osteogenic and chondrogenic phenotype within the multiphasic construct, evidenced by upregulation of osteogenesis and condrogenesis related genes during in vitro culture. Comprehensive phenotypic network and pathway analysis results, which were based on genomic expression data, indicated activation of differentiation related mechanisms, via signaling pathways, including TGF, BMP, and vascular endothelial growth factor.
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