Although metastatic melanoma can be managed with chemotherapy, its heterogeneity and resistance to therapy remain poorly understood. In addition to the spread of melanoma in the bloodstream, melanoma‐stroma interaction and the lymphatic system play active roles in said heterogeneity and resistance, leading to its progression and metastasis. Reproducing the complexities of the melanoma microenvironment in vitro will help understanding its progression and enhance the translatability of potential cancer therapeutics. A blood‐lymphatic integrated system with heterogeneous melanoma spheroids (BLISH) using the in‐bath bioprinting process is developed. The process uniformly prints size‐controllable metastatic melanoma spheroids along with biomimetic blood and lymphatic vessels (LVs). The system reproduces hallmark events of metastatic melanoma, such as tumor stroma interaction, melanoma invasion, and intravasation. The application of the system to investigate the anticancer effect of combinational targeted therapy suggests that it can be used to study the pathophysiology of melanoma and improve the accuracy of drug response monitoring in skin cancer.
The adipose tissue is a crucial endocrine organ that coordinates with other organs, playing a key role in metabolic regulation. However, it remains challenging to recreate the morphology of native adipose tissue with fully packed adipogenic lipid droplets, mainly because of immature adipogenesis caused by the low cell density of current adipose constructs. This study suggests environmentally controlled in-bath 3D bioprinting to create fully-mature densely packed adipose tissue (DPAT) in vitro. As a bath suspension, a hybrid bioink composed of 1% alginate and 1.5% adipose-derived decellularized matrix is developed for selective and compact cell proliferation. In the hybrid bath suspension, the construct printed at a high cell density (>10 7 cells ml −1 ) proliferates within the predefined area without unwanted cell migration throughout the bath suspension, forming a densely packed cellular microenvironment. After adipogenesis for 4 weeks, the results demonstrate that selectively proliferated preadipocytes can differentiate into lipid-accumulating mature adipocytes. The resulting in vivo-like DPAT is successfully engineered in vitro. The DPAT construct shows the physiological changes associated with obesity under the relevant conditions found in obese patients. The recapitulation of obesity-induced inflamed adipose tissue through co-culture with monocytes reveals the potency of the proposed strategy as a promising solution to overcome obesity-related complications.
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