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Abstract Despite substantial advancements in development of cancer treatments, lack of standardized and physiologically‐relevant in vitro testing platforms limit the early screening of anticancer agents. A major barrier is the complex interplay between the tumor microenvironment and immune response. To tackle this, a dynamic‐flow based 3D bioprinted multi‐scale vascularized breast tumor model, responding to chemo and immunotherapeutics is developed. Heterotypic tumors are precisely bioprinted at pre‐defined distances from a perfused vasculature, exhibit tumor angiogenesis and cancer cell invasion into the perfused vasculature. Bioprinted tumors treated with varying dosages of doxorubicin for 72 h portray a dose‐dependent drug response behavior. More importantly, a cell based immune therapy approach is explored by perfusing HER2‐targeting chimeric antigen receptor (CAR) modified CD8⁺T cells for 24 or 72 h. Extensive CAR‐T cell recruitment to the endothelium, substantial T cell activation and infiltration to the tumor site, resulted in up to ≈70% reduction in tumor volumes. The presented platform paves the way for a robust, precisely fabricated, and physiologically‐relevant tumor model for future translation of anti‐cancer therapies to personalized medicine. 

Abstract Metastatic breast cancer is one of the deadliest forms of malignancy, primarily driven by its characteristic micro‐environment comprising cancer cells interacting with stromal components. These interactions induce genetic and metabolic alterations creating a conducive environment for tumor growth. In this study, a physiologically relevant 3D vascularized breast cancer micro‐environment is developed comprising of metastatic MDA‐MB‐231 cells and human umbilical vein endothelial cells loaded in human dermal fibroblasts laden fibrin, representing the tumor stroma. The matrix, as well as stromal cell density, impacts the transcriptional profile of genes involved in tumor angiogenesis and cancer invasion, which are hallmarks of cancer. Cancer‐specific canonical pathways and activated upstream regulators are also identified by the differential gene expression signatures of these composite cultures. Additionally, a tumor‐associated vascular bed of capillaries is established exhibiting dilated vessel diameters, representative of in vivo tumor physiology. Further, employing aspiration‐assisted bioprinting, cancer–endothelial crosstalk, in the form of collective angiogenesis of tumor spheroids bioprinted at close proximity, is identified. Overall, this bottom–up approach of tumor micro‐environment fabrication provides an insight into the potential of in vitro tumor models and enables the identification of novel therapeutic targets as a preclinical drug screening platform. 

Abstract The heterogeneous and anisotropic articular cartilage is generally studied as a layered structure of “zones” with unique composition and architecture, which is difficult to recapitulate using current approaches. A novel hybrid bioprinting strategy is presented here to generate zonally stratified cartilage. Scaffold‐free tissue strands (TSs) are made of human adipose‐derived stem cells (ADSCs) or predifferentiated ADSCs. Cartilage TSs with predifferentiated ADSCs exhibit improved mechanical properties and upregulated expression of cartilage‐specific markers at both transcription and protein levels as compared to TSs with ADSCs being differentiated in the form of strands and TSs of nontransfected ADSCs. Using the novel hybrid approach integrating new aspiration‐assisted and extrusion‐based bioprinting techniques, the bioprinting of zonally stratified cartilage with vertically aligned TSs at the bottom zone and horizontally aligned TSs at the superficial zone is demonstrated, in which collagen fibers are aligned with designated orientation in each zone imitating the anatomical regions and matrix orientation of native articular cartilage. In addition, mechanical testing study reveals a compression modulus of ≈1.1 MPa, which is similar to that of human articular cartilage. The prominent findings highlight the potential of this novel bioprinting approach for building biologically, mechanically, and histologically relevant cartilage for tissue engineering purposes.