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Comprehensive research, particularly in evaluating drug efficacy, still heavily relies on the results obtained by the utilization of cell monolayers and animals. However, the inherent limitations of these models such as their physiological disparities from humans pose significant obstacles to acquiring reliable results thus impeding further scientific progression. To address this challenge, 3D in vitro cell culture models emerged as physiologically relevant models having the potential to enhance research and drug discovery. Our study aimed to develop a 3D in vitro cell culture model based on bone-like scaffolds in conjunction with a perfusion bioreactor (“3D Perfuse”, Innovation Center FTM, Belgrade, Serbia) for studying both physiological and pathological (i.e. tumors) bone conditions.

In the past decades, anticancer drug development brought the field of tumor engineering to a new level by the need of robust test systems. Simulating tumor microenvironment in vitro remains a challenge, and osteosarcoma—the most common primary bone cancer—is no exception. The growing evidence points to the inevitable connection between biomechanical stimuli and tumor chemosensitivity and aggressiveness, thus making this component of the microenvironment a mandatory requirement to the developed models. In this review, we addressed the question: is the “in vivo - in vitro” gap in osteosarcoma engineering bridged from the perspective of biomechanical stimuli? The most notable biomechanical cues in the tumor cell microenvironment are observed and compared in the contexts of in vivo conditions and engineered three-dimensional in vitro models.