SuRyon Shin1

1, The Brigham and Womens Hospital, Inc, Harvard Medical School, Cambridge, Massachusetts, United States

Tissue engineering holds great promise as an alternative therapy by creating functional tissue constructs that can reestablish the structure and function of injured tissue. However, a major challenge in tissue engineering is recapitulating the in vitro, three-dimensional (3D) hierarchical microarchitecture comprised of multiple cell types and the extracellular matrix (ECM) components of native tissues, along with achievement of continuous function and viability of engineered tissues after implantation. Specifically, survival of implanted cell-laden scaffolds is fully dependent on the oxygenation derived by its connection to blood circulation of the host body. The physiological process of angiogenesis is time-consuming, which results in the failure of clinically sized implants due to starvation-induced cell death, especially in thick and large constructs. Therefore, the incorporation of functional vasculature is important for maintaining thick and large complex tissue constructs, particularly in cardiac and skeletal muscle tissues that require highly vascularized networks to support the large metabolically activity in muscle cells. To address these challenges, 3D bioprinting is emerging as a powerful technique for the development of highly organized and complex 3D constructs. To achieve in vivo-like biological functions in 3D tissue constructs, ECM-based biomaterials are required to mimic biological and physical properties that will enhance the resulting tissue function. Furthermore, the bioprinted 3D tissue constructs can be used for toxicity assays based on organs-on-a-chip platforms, which have become increasingly important for drug discovery. The organs-on-a-chip system allows for the testing of cytotoxic effects of pharmaceutical compounds and nanomaterials on physiologically relevant human tissue models prior to moving forward with animal testing or clinical trials. To successfully establish organs-on-a-chip platforms, it is important to monitor the dynamic behaviors of human organ models interacting with drugs in situ for a long time. Furthermore, efficient methods for accurate analysis of the dynamic behaviors of human organ models are in urgent demand for improving the effectiveness of clinical predictions of human disease responses to different therapeutics. We introduce a microfluidic, label-free, biosensing technology combined with a 3D bioprinted human organ-on-a-chip system, which jointly allows for long-term and accurate measurements of the concentrations of the biomarkers secreted by tissues in response to drugs. The electrochemical biosensing chip will demonstrate a capability for regenerating its sensor surface, allowing for continual kinetic studies over extended periods of time. We believe that this novel platform technology may be further extended to a wide variety of applications in academia and pharmaceutics for personalized screenings of drug toxicity, efficacy, and pharmacokinetics in the future.