Artificial skins have been used as skin substitutes for wound healing in the clinic, and as in vitro models for safety assessment in cosmetic and pharmaceutical industries. The three-dimensional (3D) bioprinting technique provides a promising strategy in the fabrication of artificial skins. Despite the technological advances, many challenges remain to be conquered, such as the complicated preparation conditions for bio-printed skin and the unavailability of stability and robustness of skin bioprinting. Here, we formulated a novel bio-ink composed of gelatin, sodium alginate and fibrinogen. By optimizing the ratio of components in the bio-ink, the design of the 3D model and the printing conditions, a fibroblasts-containing dermal layer construct was firstly fabricated, on the top of which laminin and keratinocytes were sequentially placed. Through air-liquid interface (ALI) culture by virtue of sterile wire mesh, a full-thickness skin tissue was thus prepared. HE and immunofluorescence staining showed that the bio-printed skin was not only morphologically representative of the human skin, but also expressed the specific markers related to epidermal differentiation and stratum corneum formation. The presented easy and robust preparation of full-thickness skin constructs provides a powerful tool for the establishment of artificial skins, holding critical academic significance and application value. Graphical Abstract

Despite the rapid advances in the liver-on-a-chip platforms, it remains a daunting challenge to construct a biomimetic liver-on-a-chip for in vitro research. This study aimed to reconstruct the tissue-tissue interfaces based on bilayer microspheres and form vascularized liver tissue. Firstly, we designed a tri-vascular liver-on-a-chip (TVLOC) comprising a hepatic artery, a portal vein and a central vein, and theoretically analyzed the distribution of velocity and concentration fields in the culture area. Secondly, we designed a bilayer microsphere generating microsystem based on the coaxial confocal principle, which is primarily used to produce bilayer microspheres containing different kinds of cells. Finally, the bilayer microspheres were co-cultured with endothelial cells in the cell culture area of the TVLOC to form vascularized liver tissue, and the cell viability and vascular network growth were analyzed. The results revealed that the TVLOC designed in this study can provide a substance concentration gradient similar to that of the liver microenvironment, and the bilayer microspheres can form a three-dimensional (3D) orderly liver structure with endothelial cells. Such a liver-on-a-chip is capable of maintaining the function of hepatocytes (HCs) pretty well. This work provides full insights into further simulation of the liver-on-a-chip.

Osteosarcoma is a highly malignant primary bone tumor that predominantly affects adolescents. Despite the widespread application of standard treatment modalities, including surgical resection, chemotherapy, and radiotherapy, the long-term survival rate of patients remains unsatisfactory due to the high metastatic potential and drug resistance of the disease. In recent years, researchers have focused on developing more precise in vitro models that aim to better simulate the tumor microenvironment, thereby enhancing the effectiveness of drug screening and personalized therapy. This review summarizes the latest advances in osteosarcoma in vitro modeling, including the development of conventional two-dimensional culture systems, three-dimensional culture platforms, organoid models, and microfluidic chips designed to mimic the tumor microenvironment. Additionally, this review explores the application value of these models in drug screening, immune coculture systems, and personalized treatment strategies. The integration of multiomics data and artificial intelligence is also discussed as a means to optimize model design and facilitate precision oncology. Biomimetic in vitro models have the potential to more accurately replicate tumor heterogeneity, cell–cell interactions, and the complexity of the tumor microenvironment, thereby increasing the translational value of preclinical drug development. Finally, this review highlights the current challenges in the field, including the lack of standardized protocols, issues with model stability and reproducibility, and the practical integration of these models into preclinical research pipelines.

Current in vitro tumor models often fail to recapitulate the hierarchical vascular architecture and dynamic interactions of the tumor microenvironment, limiting their utility in cancer research. Here, we present a multi-scale vascularized tumor model integrating coaxial bioprinting, inkjet printing, and fused deposition modeling (FDM) to address this challenge. First, coaxial bioprinting enabled the fabrication of dual-layered vasculature with an endothelium layer and a smooth muscle layer. Second, tumor spheroids with precise size control (±10 μm) were generated via inkjet printing by modulating GelMA concentration and valve actuation time. A FDM-printed chip was designed to co-culture these components under perfusion, facilitating the self-organization of a microvascular network around tumor spheroids. During 11 days of dynamic culture, the model demonstrated tumor-driven angiogenic sprouting and early metastatic behavior, validated by the upregulation of metastasis-related genes (CD44, MMP2, N-cadherin) in vascularized cohorts. Drug testing with paclitaxel revealed dose-dependent suppression of tumor proliferation and invasion. This platform not only mimics the TME’s structural and functional complexity but also provides a scalable, physiologically relevant tool for investigating tumor-vascular crosstalk and evaluating anti-cancer therapeutics.