Microfluidic Approach to Generate a Tadpole-Egg-Shaped Alginate Fiber and Its Application in Tissue Engineering

Herein, we introduce a facile microfluidic technique to produce a hybrid alginate fiber with a tadpole-egg shape. A triple-flow polydimethylsiloxane microfluidic device was constructed to allow the formation of oil droplets inside the alginate stream and was instantaneously gelated with the coaxially adjacent CaCl₂. The fiber entrapping the uniform oil droplets was dehydrated, leading to the formation of a distinct tadpole-egg-shaped structure. A series of diverse fiber architectures was fabricated in a controlled manner based on the flow rates of the relevant flows. The tadpole-egg-shaped alginate fibers were employed as building blocks to create a three-dimensional microwell template for cell cultures. First, the tadpole-egg-shaped alginate fibers containing the oil droplets were half-dipped into a melted agarose solution. After the solidification of the agarose gel, the alginate fibers were degraded by an ethylenediaminetetraacetic acid (EDTA) solution to generate the hemispherical microwells. Mesenchymal stem cells (MSCs) were cultured in the microwells to generate spheroids, which were induced into chondrocytes using transforming growth factor-β3. The formed MSC spheroids exhibited a relatively high ratio of cell viability with more than 95% live cells after 14 days of culture. The success of the chondrogenic differentiation was proven based on staining (Safranin O) and the glycosaminoglycan levels. The latter was significantly higher in spheroids that were induced to form chondrocytes compared to those that were not induced after 21 days of differentiation. Second, we investigated the potential of the tadpole-egg-shaped alginate fibers as microcarriers for applications in drug delivery and implantable technologies. It was revealed that the degradation of the Ca-alginate wall of the hybrid fibers to release the oil droplets required an EDTA solution with a concentration of 500 mM for a 15 min period. This result can be used to further develop the tadpole-egg-shaped alginate fibers as uniform microcarriers with multiple compartments.