Additive Manufacturing Frontiers · Nov 2026
Scalable bioprinted tissue manufacturing: A three-scale framework for bottlenecks, strategies and application-specific pathways
By Li B, Wang Z, Huang C et al.
Scalability is a central challenge in bioprinting as the field shifts from proof-of-concept constructs to reproducible application-oriented biofabrication. However, scalable bioprinting is generally interpreted as a larger construct or higher throughput, overlooking the interdependence between structural fidelity, biological function, and manufacturing robustness. In contrast to previous reviews that mainly focused on specific bioprinting technologies, bioink systems, vascularized constructs, high-throughput platforms, or individual applications, this review integrates scalability into an application-dependent three-scale framework linking structural construction, functional maturation, and manufacturing robustness. Specifically, the geometrical scale encompasses tissue dimensions, anatomical architectures, and spatial heterogeneity; the functional scale covers cell viability, tissue maturation, and application-relevant functional outputs; and the manufacturing scale represents throughput, reproducibility, process standardization, and quality control. From this perspective, four bottleneck classes emerge: engineering constraints, such as the precision–throughput–cell viability trade-off; bioink and cell limitations arising from printability–biocompatibility conflicts; culture and maturation barriers related to mass transport and insufficient maturation cues; and standardization challenges caused by batch variability and incomplete quality control frameworks. The potential of parallelized high-throughput printing, maturation-oriented auxiliary processes, and cross-scaling strategies to overcome these limitations is discussed. Finally, application-specific scalability distinctions across drug screening, intermediate scenarios, and regenerative medicine, with intermediate scenarios, such as organ-on-a-chip platforms, patient-specific disease models, and functional tissue assays requiring moderate throughput, increased structural and functional complexity, and reproducible functional assessment are discussed. This review provides a three-scale framework to guide the transition of bioprinted tissues from proof-of-concept fabrication to reproducible application-oriented manufacturing.