Abstract
Development of tissue engineering scaffolds with native-like biology and microarchitectures is a prerequisite for stem cell mediated generation of off-the-shelf-tissues. So far, the field of tissue engineering has not full-filled its grand potential of engineering such combinatorial scaffolds for engineering functional tissues. This is primarily due to the many challenges associated with finding the right microarchitectures and ECM compositions for optimal tissue regeneration. Here, we have developed a new microgel array to address this grand challenge through robotic printing of complex stem cell-laden microgel arrays. The developed microgel array platform consisted of various microgel environments that where composed of native-like cellular microarchitectures resembling vascularized and bone marrow tissue architectures. The feasibility of our array system was demonstrated through localized cell spreading and osteogenic differentiation of human mesenchymal stem cells (hMSCs) into complex tissue-like structures. In summary, we have developed a tissue-like microgel array for evaluating stem cell differentiation within complex and heterogeneous cell microenvironments. We anticipate that the developed platform will be used for high-throughput identification of combinatorial and native-like scaffolds for tissue engineering of functional organs.
Highlights
To print cell-laden hydrogel bioinks with tissue-like architectures
Prepolymer solutions consisting of human mesenchymal stem cells (hMSCs) were deposited on functionalized glass slides (25 mm × 75 mm) (Fig. 1)
The cell-laden prepolymer gelatin methacrylate (GelMA) microdrops were crosslinked through free radical polymerization mediated by UV irradiation in presence of photoinitiator (Irgacure-2959)
Summary
To print cell-laden hydrogel bioinks with tissue-like architectures. It is expected that through this technology it is possible to evaluate a range of biomaterials with different physical, biological, geometrical and cellular heterogeneities. A range of studies has demonstrated the application of layer-by-layer printing techniques for engineering complex tissue constructs[27,28,29] None of these microprinting technologies have been shown to generate structurally complex cell-laden microgel arrays. It is our expectation that by generating arrays of complex tissue structure it is possible to understand effect of structural, cellular and microenvironmental heterogeneity on human mesenchymal stem cells (hMSCs) differentiation. To our knowledge this is the first approach to demonstrate the application of microprinting technology for the manufacture of microgel arrays with tissue-like architectures. It is expected that this technology can be used to understand cellular behavior within multi-component tissue constructs in a high-throughput approach
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