Biohybrid 3D Printing of a Tissue-Sensor Platform for Wireless, Real-Time, and Continuous Monitoring of Drug-Induced Cardiotoxicity.

Drug-induced cardiotoxicity is regarded as a major hurdle in the early stages of drug development. Although there are various methods for preclinical cardiotoxicity tests, they cannot completely predict the cardiotoxic potential of a compound due to the lack of physiological relevance. Recently, 3D engineered heart tissue (EHT) has been used to investigate cardiac muscle functions as well as pharmacological effects by exhibiting physiological auxotonic contractions. However, there is still no adequate platform for continuous monitoring to test acute and chronic pharmacological effects in vitro. Here, a biohybrid 3D printing method for fabricating a tissue-sensor platform, composed of a bipillar-grafted strain gauge sensor and EHT, is first introduced. Two pillars are three-dimensionally printed as grafts onto a strain gauge-embedded substrate to promote the EHT contractility and guide the self-assembly of the EHTs along with the strain gauge. In addition, the integration of a wireless multi-channel electronic system allows for continuous monitoring of the EHT contractile force by the tissue-sensor platform and, ultimately, for the observation of the acute and chronic drug effects of cardiotoxicants. In summary, biohybrid 3D printing technology is expected to be a potential fabrication method to provide a next-generation tissue-sensor platform for an effective drug development process.

Modular assembly of bioprinted perfusable blood vessel and tracheal epithelium for studying inflammatory respiratory diseases.

In vitroorgan models allow for the creation of precise preclinical models that mimic organ physiology. During a pandemic of a life-threatening acute respiratory disease, an improved trachea model (TM) is required. We fabricated a modular assembly of the blood vessel and TMs using 3D bioprinting technology. First, decellularized extracellular matrix (dECM) were prepared using the porcine trachea and blood vessels. A trachea module was fabricated based on the tracheal mucosa-derived dECM and microporous membrane. Further, a blood vessel module was manufactured using the prepared vascular-tissue-derived dECM. By assembling each manufactured module, a perfusable vascularized TM simulating the interface between the tracheal epithelium and blood vessels was fabricated. This assembled model was manufactured with efficient performance, and it offered respiratory symptoms, such as inflammatory response and allergen-induced asthma exacerbation. These characteristics indicate the possibility of manufacturing a highly functional organ model that mimics a complex organ environment in the future.