Three-dimensional (3D) in vitro tumor models that can capture the pathophysiology of human tumors are essential for cancer biology and drug development. However, simulating the tumor microenvironment is still challenging because it consists of a heterogeneous mixture of various cellular components and biological factors. In this regard, current extracellular matrix (ECM)-mimicking hydrogels used in tumor tissue engineering lack physical interactions that can keep biological factors released by encapsulated cells within the hydrogel and improve paracrine interactions. Here, we developed a nanoengineered ion-covalent cross-linkable bioink to construct 3D bioprinted organotypic tumor models. The bioink was designed to implement the tumor ECM by creating an interpenetrating network composed of gelatin methacryloyl (GelMA), a light cross-linkable polymer, and synthetic nanosilicate (Laponite) that exhibits a unique ionic charge to improve retention of biological factors released by the encapsulated cells and assist in paracrine signals. The physical properties related to printability were evaluated to analyze the effect of Laponite hydrogel on bioink. Low GelMA (5%) with high Laponite (2.5%–3.5%) composite hydrogels and high GelMA (10%) with low Laponite (1.0%–2.0%) composite hydrogels showed acceptable mechanical properties for 3D printing. However, a low GelMA composite hydrogel with a high Laponite content could not provide acceptable cell viability. Fluorescent cell labeling studies showed that as the proportion of Laponite increased, the cells became more aggregated to form larger 3D tumor structures. Reverse transcription-polymerase chain reaction (RT-qPCR) and western blot experiments showed that an increase in the Laponite ratio induces upregulation of growth factor and tissue remodeling-related genes and proteins in tumor cells. In contrast, cell cycle and proliferation-related genes were downregulated. On the other hand, concerning fibroblasts, the increase in the Laponite ratio indicated an overall upregulation of the mesenchymal phenotype-related genes and proteins. Our study may provide a rationale for using Laponite-based hydrogels in 3D cancer modeling.

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.

Osteochondral defects (OCD) refer to localized injuries affecting both the avascular cartilage and subchondral bone. Current treatments, such as transplantation or microfracture surgery, are hindered by limitations like donor availability and the formation of small, rigid fibrocartilage. Tissue engineering presents a promising alternative, yet challenges arise from limited oxygen and nutrient supply when fabricating human-scale tissue constructs. To address this, we propose assembling engineered micro-scale tissue constructs as building blocks for human-scale constructs. In this study, we aimed to develop bone and cartilage microtissues as building blocks for osteochondral tissue engineering. We fabricated placental stem cell (PSC)-laden microgels, inducing differentiation into osteogenic and chondrogenic microtissues. Utilizing a microfluidics chip platform, these microgels comprised a cell-laden core containing bone-specific and cartilage-specific growth factor-mimetic peptides, respectively, along with an acellular hydrogel shell. Additionally, we investigated the effect of culture conditions on microtissue formation, testing dynamic and static conditions. Results revealed over 85% cell viability within the microgels over 7 d of continuous growth. Under static conditions, approximately 60% of cells migrated from the core to the periphery, while dynamic conditions exhibited evenly distributed cells. Within 4 weeks of differentiation, growth factor-mimetic peptides accelerated PSC differentiation into bone and cartilage microtissues. These findings suggest the potential clinical applicability of our approach in treating OCD.

The authors would like to make the following corrections to