Vascularization remains a critical challenge in tissue engineering, limiting graft survival, integration, and clinical translation. Although bioprinting enables spatial control over vascular architectures, many existing approaches prioritize geometric precision over biological performance. Bioprinted vasculature can be understood as a dynamic and time-dependent system that requires tissue-specific maturation. Within this framework, hydrogel systems act as active microenvironments rather than passive scaffolds. Hydrogel platforms vary from natural matrices and synthetic polymers to bioinspired or stimuli-responsive systems, each offering tunable control over stiffness, degradation, and biochemical signaling needed for vascular maturation. The design requirements of large and small vessels differ in terms of mechanical demands, remodeling capacity, and host integration. A key limitation in current models is the absence of time-resolved evaluation, as critical processes such as lumen formation, pericyte recruitment, and flow-induced remodeling occur progressively and are not captured by static endpoints. Advancements in bioprinting technologies are evaluated based on their capacity to support hydrogel-mediated vascularization across varying length scales and structural complexities. A framework for functional assessment is proposed, and translational challenges related to immunogenicity, scalability, and regulatory requirements are discussed. Such integration of hydrogel-driven biological cues and bioprinting fidelity is critical to advancing vascularized constructs toward clinical translation.

Pre-vascularization has been receiving significant attention for developing implantable engineered 3D tissues. While various pre-vascularization techniques have been developed to improve graft vascularization, the effect of pre-vascularized patterns on in vivo neo-vessel formation has not been studied. In this study, we developed a functional pre-vascularized construct that significantly promotes graft vascularization and conducted in vivo evaluations of the micro-vascular patterns (μVPs) in various printed designs. μVP formation, composed of high-density capillaries, was induced by the co-printing of endothelial cells and adipose-derived stem cells (ADSC). We implanted the printed constructs with various μVP designs into a murine femoral arteriovenous bundle model and evaluated graft vascularization via 3D visualization and immune-histological analysis of the neo-vessels. The μVP-distal group (μVP located away from the host vessel) showed approximately two-fold improved neo-vascularization compared to the μVP-proximal group (μVP located near the host vessel). Additionally, we confirmed that the μVP-distal group can generate the angiogenic factor gradient spatial environment for graft vascularization via computational simulations. Based on these results, the ADSC mono pattern (AMP), which secretes four times higher angiogenic factors than μVP, was added to the μVP + AMP group design. The μVP + AMP group showed approximately 1.5- and 1.9-fold higher total sprouted neo-vessel volume than the μVP only and AMP only groups, respectively. In immunohistochemical staining analysis, the μVP + AMP group showed two-fold improved density and diameter of the matured neo-vessels. To summarize, these findings demonstrate graft vascularization accelerated due to design optimization of our pre-vascularized constructs. We believe that the developed pre-vascularization printing technique will facilitate new possibilities for the upscaling of implantable engineered tissues/organs.

The authors would like to make the following corrections to