Integration of Alginate Hydrogels with Microfluidic Devices for use in Tissue-on-Chip Applications
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The use of hydrogels in tissue engineering together with the emerging applications of tissue- on-chip technology is an expanding research field. Hydrogels have been widely used as cell scaffolds in order to replicate the extracellular environment, and tissue-on-chip technology, combined with microfluidics, presents the possibility to more accurately replicate in vivo conditions and miniaturize the experimental scale. Therefore, the successful integration of hydrogels with microfluidic devices is very attractive and is thus the focus of this study.In this research project, an approach using two different crosslinking strategies to make alginate hydrogels were used in an attempt to integrate the hydrogel with the channel of a microfluidic device. In order to achieve this, surface modification using a carboxyl silane covalently linked to poly-L-lysine was used to increase adhesion between the channel and the hydrogel. The two crosslinking strategies used were ionic crosslinking and photocrosslinking. Ionic crosslinks were attained with calcium ions, which could be reversed with exposure to a calcium chelator, and photocrosslinking was achieved under ultraviolet light, using methacrylated alginate and a photoinitiator. To control the spatial arrangement of the hydrogel, a photolithography approach using a photomask was used with the aim to introduce photocrosslinks in determined parts of the hydrogel embedded in the channel, and then retrieve the non-photocrosslinked material, by using a calcium chelator for calcium alginate and water for non-crosslinked alginate.A decrease in adhesion was observed with methacrylated alginate compared to non- modified alginate, resulting in gel destruction. This may be attributed to a reduced interac- tion between poly-L-lysine and methacrylated alginate. However, an integration was achieved after incorporating photocrosslinks in a selected part of the hydrogel inside the channel and thereafter, applying low flow rate to pump out the non-photocrosslinked alginate solution.Preliminary diffusion studies were performed using fluorescence imaging to measure the intensity signal of different diffusing species into the hydrogel. In ionically crosslinked alginate (LF10/60) dextran showed to diffuse the fastest into the hydrogel, IgG diffused slower and IgM did not appear to permeate the hydrogel. In ionically and photocrosslinked methacry- lated alginate, diffusion of all species was detected, which is probably attributed to a de- creased gel strength, and thus crosslink density, that these samples presented.This study has been acellular but cells could be easily incorporated into the system by mixing with the alginate solution prior to gelation. However, further studies evaluating cell viability and cytotoxicity under UV exposure would be necessary to fulfill the aim of achieving a tissue-on-chip platform.