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Previous studies have developed vascularized tumor spheroid models to demonstrate the impact of intravascular flow on tumor progression and treatment. However, these models have not been widely adopted so the vascularization of tumor spheroids in vitro is generally lower than vascularized tumor tissues in vivo. To improve the tumor vascularization level, a new strategy is introduced to form tumor spheroids by adding fibroblasts (FBs) sequentially to a pre-formed tumor spheroid and demonstrate this method with tumor cell lines from kidney, lung, and ovary cancer. Tumor spheroids made with the new strategy have higher FB densities on the periphery of the tumor spheroid, which tend to enhance vascularization. The vessels close to the tumor spheroid made with this new strategy are more perfusable than the ones made with other methods. Finally, chimeric antigen receptor (CAR) T cells are perfused under continuous flow into vascularized tumor spheroids to demonstrate immunotherapy evaluation using vascularized tumor-on-a-chip model. This new strategy for establishing tumor spheroids leads to increased vascularization in vitro, allowing for the examination of immune, endothelial, stromal, and tumor cell responses under static or flow conditions.

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Development of accurate and sensitive dental imaging technologies is a top priority in the pursuit of high-quality dental care. However, while early dental caries detection and routine monitoring of treatment progress are crucial for effective long-term results, current radiographic technologies fall short of this objective due to low sensitivity for small lesions and use of ionizing radiation which is unsuitable for frequent monitoring. Here we demonstrate the first application of enhanced Truncated Correlation-Photothermal Coherence Tomography (eTC-PCT) to dental imaging. eTC-PCT is non-invasive and non-ionizing, operates well below the maximum permissible exposure (MPE) limit, and features 3D subsurface imaging capability with operator controlled axial resolution. We explore the potential of this method for dental applications and demonstrate its capability for depth-resolved tomographic 3D reconstructions of the details and subsurface extent of a variety of dental defects. To this end, in this proof-of-concept study, dental eTC-PCT imaging results, and its sensitivity to dental caries, are discussed in comparison with visual examination, x-rays and micro-CT imaging.