Abstract
The high failure rate in drug development is largely attributed to the limited physiological relevance of traditional 2D cell cultures and animal models. Organ-on-a-chip (OoC) technology has emerged as a transformative tool, bridging the gap between in vitro assays and clinical outcomes by recapitulating human organ-level functions. A critical challenge in this field has been the integration of functional vascular networks, which are essential for nutrient transport, waste removal, and the simulation of systemic drug delivery. This paper investigates the current state of vascularized OoC models specifically designed for high-throughput screening (HTS) and toxicity assessment as of March 2024. We evaluate the methodologies for constructing perfusable microvessels, including bioprinting and self-assembly, and their application across various organ systems such as the liver, kidney, and colon. Our synthesis of recent data demonstrates that vascularized models provide significantly more accurate toxicokinetic profiles compared to non-vascularized counterparts, particularly in assessing drug-induced organ injury. Key metrics such as trans-endothelial electrical resistance (TEER) and metabolic clearance rates were analyzed across multiple platforms. The results indicate that incorporating vascular interfaces enhances the predictive power of HTS platforms, though challenges remain regarding the standardization of materials and the complexity of multi-organ integration. This review concludes that while the technology is maturing, the transition toward fully automated, multi-sensor integrated systems is necessary for widespread adoption in the pharmaceutical industry.