Automated and scalable fabrication of scaffolded spheroids as building blocks for modular tissue engineering
Current tissue engineering approaches typically utilize either scaffold-based or scaffold-free strategies. Recently, a third approach has emerged, offering a synergistic method that leverages the benefits of both approaches while avoiding their usual drawbacks. In this strategy, spheroids are formed within highly porous microscaffolds, which subsequently serve as building blocks for larger tissue constructs produced through self-assembly. This study demonstrates the automated fabrication of large numbers of these building blocks, tested in vessels of up to 1,536-well plates. To achieve this, we first developed a microfluidic device capable of sorting highly porous microscaffolds, each 300 µm in diameter, at high flow speeds of up to 300 mm/s. A fluorescent detection system was integrated to identify only intact microscaffolds and deposit them individually into separate wells of cell culture plates. Subsequently, the system automatically dispensed culture medium containing suspended human adipose-derived stem cells into each well. Spheroids were formed within 24 hours of culture with a formation efficiency of 95%. This study presents the development of an automated microfluidic device capable of depositing single microscaffolds and the cells required to form scaffolded spheroids. By enabling large-scale, high-throughput production, this approach advances the third strategy of tissue engineering and supports applications in both screening and clinical translation.

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