3D Hybrid Bioprinting for Complex Multi-Tissue Engineering

Abstract

3D bioprinting has revolutionized tissue engineering, enabling intricate, physiologically relevant constructs unattainable with conventional techniques, yet it remains limited in integrating soft and rigid multifunctional components for complex multi-tissue applications. In this study, we introduce a 3D hybrid bioprinting approach implementing the Hybprinter platform, which integrates multiple 3D printing modules under optimized conditions for a continuous bioprinting process with multiple soft and hard biomaterials. This approach demonstrates robust biocompatibility and broad tissue engineering potential for modeling and therapeutic applications. The capacity to fabricate multi-hydrogel hybrid constructs is illustrated by representative examples highlighting vascularization, multifunctionality, mechanical robustness, and implant suturability. Notably, compared with commonly fabricated hydrogel-only constructs, the resulting hybrid constructs achieve over a 1000-fold increase in mechanical strength, and demonstrated enhanced osteogenic differentiation, underscoring their suitability for load-bearing musculoskeletal and orthopedic tissue engineering. Additionally, cell-laden hydrogel constructs demonstrated robust chondrogenic differentiation, highlighting the capacity for lineage-specific tissue development in vitro. Beyond these outcomes, the presented hybrid bioprinting approach integrates essential tissue engineering attributes that unites mechanical robustness and suturable capacity with multi-material integration, gradient property design, incorporation of bioactive agents, and support for multi-cell loading. This versatile platform advances complex tissue engineering and holds promise for patient specific, organ-on-demand applications.