Abstract
Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.
Highlights
The development of microengineered in vitro models able to reproduce architecture and functionality of human organs and tissues is expected to boost the drug development field advancement.These models are promising tools for elucidating the biological mechanisms underlying morphogenetic and pathogenetic processes, as well as for investigating cellular mechanisms which are paramount for the improvement of drug screening process [1,2,3].Two-dimensional (2D) cell cultures on Petri dishes or similar standard culture platforms are typically used in pharmaceutical research and development, as they offer multiple advantages, such as simplicity, low cost, and ease of handling
The platform was able to detect a biphasic electrical activity, typical signature of human or murine islets in vivo, as well as in vitro. These results proved that physiological recordings of the islet electrical activity could be obtained within 2 h after seeding, a very short period as compared to several days required for classical multielectrode arrays (MEAs)
These results clearly demonstrated a contribution of the liver metabolism to the drug effects on the cardiac constructs, indicating the strong necessity of integrating multiple tissues inside OoC platforms in drug screening applications
Summary
The development of microengineered in vitro models able to reproduce architecture and functionality of human organs and tissues is expected to boost the drug development field advancement. One of the major limitations of current OoC is the hurdle to collect real-time information about the cells and the surrounding environment in order to monitor online tissue maturation and response to stimuli (e.g., drug administration) Several characterization methods, such as viability assays and biomarker quantification to assess, respectively, cytotoxicity or functionality, still rely on off-chip analysis (i.e., ELISA technology) and imaging techniques for data acquisition and are mostly limited to end-point assays [43]. Multisensor integration within multiorgan platforms will be further reviewed and discussed
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