Parallelization remains a key challenge in advancing 3D bioprinting from a prototyping method to a practical tool for true high-throughput screening (HTS). The ability to fabricate many tissue substitutes simultaneously is essential for studying cell–material interactions and drug responses across the ever-growing libraries required in disease modeling and drug discovery. HTS of tissue substitutes requires models in culture that remain viable under long-term immersion in liquid. However, existing fabrication approaches are fundamentally limited by a trade-off between physiological relevance and throughput. Two-dimensional cultures on liquid-compartmentalization platforms enable HTS but lack physiological accuracy, while 3D cultures provide physiological relevance at the expanse of speed and scalability. 3D bioprinting methods on traditional liquid compartmentalization platforms are inherently serial, resulting in sequential fabrication of models, which scale unfavorably with increasing array sizes required for HTS.
Here, we present a 3D bioprinting solution that integrates digital light processing (DLP) stereolithography with a patterned slippery liquid infused porous surface droplet microarray (SLIPS-DMA). This wall-less compartmentalization platform repels gelatin methacrylate (GelMA) inks, maintains stable droplet boundaries and enables complete immersion of printed hydrogel 3D structures. By eliminating inter-compartment travel for material deposition, the process decouples fabrication time from array size, achieving true parallelization.
Using optimized printing parameters, we demonstrate high-fidelity parallel 3D printing of tens to hundreds of GelMA structures in under ten minutes, while preserving cell viability and subsequent complete structure immersion in stable compartmentalized droplets. The process supports immobilization of cells or cell-aggregates within individual 3D hydrogel structures of an array on the platform for downstream assays.
By combining parallel 3D printing with a solid wall-less compartmentalization platform, this technology overcomes the serial bottleneck of existing approaches. This technology represents a significant advance, effectively bridging the gap between arrays of high-fidelity 3D tissue models and the fabrication speed required for HTS. The developed parallel 3D printing-SLIPS-DMA approach establishes a flexible high-throughput system-on-a-chip for 3D cell culture in separate, miniaturized liquid environments. It thereby enables scalable multi-condition HTS for investigation of cell–material–drug interactions.