Microfluidic direct writer with integrated declogging mechanism for fabricating cell-laden hydrogel constructs
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Cell distribution and nutrient supply in 3D cell-laden hydrogel scaffolds are critical and should mimic the in vivo cellular environment, but been difficult to control with conventional fabrication methods. Here, we present a microfluidic direct writer (MFDW) to construct 3D cell-laden hydrogel structures with openings permitting media exchange. The MFDW comprises a monolithic microfluidic head, which delivers coaxial streams of cell-laden sodium alginate and calcium chloride solutions to form hydrogel fibers. Fiber diameter is controlled by adjusting the ratio of the volumetric flow rates. The MFDW head is mounted on a motorized stage, which is automatically controlled and moves at a speed synchronized with the speed of fiber fabrication. Head geometry, flow rates, and viscosity of the writing solutions were optimized to prevent the occurrence of curling and bulging. For continuous use, a highly reliable process is needed, which was accomplished with the integration of a declogging conduit supplying a solvent to dissolve the clogging gel. The MFDW was used for layer-by-layer fabrication of simple 3D structures with encapsulated cells. Assembly of 3D structures with distinct fibers is demonstrated by alternatively delivering two different alginate gel solutions. The MFDW head can be built rapidly and easily, and will allow 3D constructs for tissue engineering to be fabricated with multiple hydrogels and cell types.
KeywordsMicrofluidic coaxial flow Direct writing Cell-laden constructs Calcium alginate Tissue engineering 3D cell scaffold
We acknowledge funding from Natural Sciences and Engineering Research Council of Canada (NSERC), The Canadian Institutes of Health Research (CIHR), Certified Human Resources Professional (CHRP), Genome Canada, Genome Quebec, and Canada Foundation for Innovation (CFI.) M.A.Q. acknowledges Alexander Graham Bell Canada Graduate Scholarship (CGSD), M.A and A. T. acknowledge NSERC Postdoctoral fellowships, and D.J. acknowledges support from a Canada Research Chair. The authors thank Adiel Malik, Veronique Laforte, Sebastien Bergeron, and Kate Turner for critical reading of the manuscript.
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