Recent advances in Organ-on-a-Chip models: How precision engineering integrates cutting edge technologies in fabrication and characterization

•OoC tech shifts from animals for human-like models.•Novel tech: 3D printing, microfluidics, biomaterials.•Sensors, AI, ML enhance OoC monitoring.•Precision meets variation for personalized medicine.•Aim: Replace or complement animal models. There is an increasing need for better preclinical therapeutic development models suitable for the human body. As a result, there has been a shift from traditional animal models to Organ-on-a-Chip (OoC) technologies. This transition is driven by the realization that conventional animal models have limited use in predicting human clinical outcomes, especially in biological therapies designed with human-specific molecular structures. These treatments make increasingly significant proportions of pharmaceutical developmental pipelines requiring preclinical models that are physiologically similar to humans to verify their efficacy and safety before being implemented into clinical trials. Novel fabrication techniques and precision engineering have revolutionized the OoC field by providing an alternative approach to animal experiments by mimicking the complex biological functions of human organ devices on microscale platforms. This review highlights the potential of using emerging technologies, like 3D bioprinting, microfluidics, advanced biomaterials, and surface engineering to make OoC models. With these technologies, it is possible to make tissue-like microenvironments that mimic the natural cues found in tissues of human beings. Secondly, the incorporation of microscale sensors, artificial intelligence (AI), and machine learning (ML) enables the development of OoC devices with improved real-time monitoring and analytics capabilities that would be instrumental for personalized medicine applications and accurate modeling of genetic disorders. The OoC model's fidelity to human physiology will increase or be enhanced by these technologies' mergers, and at the same time, this converges with precision medicine, which acknowledges genetic variation and environmental factors that differ among different patients. This review aims to chart the field's future directions by discussing the roles and integration challenges of these technologies in OoC development. This technology must reach a stage where it can either substitute or be used alongside animal models for preclinical studies, thereby transforming clinical trial design and hastening the personalized drug discovery process. [Display omitted]