3D-Bioprinted Living System for Sensor Development

TECHNOLOGY AREA(S): Human Systems OBJECTIVE: The objective of this program is to develop a three dimensional (3D) bioprinted tissue or organ that recapitulates and simulates human-level architectures, microstructures, and physiological conditions. Successful development of a platform that encompasses functionality of human organ(s) integrated into a single platform would allow for robust analysis human performance with the ease and flexibility in a small, light-weight, and transportable device. The first phase is to develop a 3D-bioprinted tissue with human cells that simulate complex multi-cell functions. The second phase will require integrated, real-time biosensors using chip or other microelectronic technology for sensing and analysis of kinetic biological signals of stress and resiliency. The resultant platform would ultimately provide a capability to respond in a physiologically-relevant manner and continually monitor unique biosignatures from physical stressors (such as extreme temperature or hypoxic environments) or environmental exposures (such as chemicals, particles, or radiation). DESCRIPTION: The development of microfluidic technologies has catalyzed the merging of sensors, fabrication, and tissue engineering on the micro- and nanometer size regime. For example, the organ-on-chip construct allows for the ex vivo design of organ level architectures, microstructures, and physical conditions to bring life-relevant functionality of human organs packaged in devices commonly the size of a quarter. Over the last 5 years, the prevalence of microfluidic manuscripts have sky-rocketed, mainly for the purpose of developing sensing applications. One aspect of photolithography constructed microdevices is that they are prepared layer-by-layer and require sealing, interfacing, and aligning small channels to create passages for cell and matrix seeding, perfusion, and solution delivery. Therefore, due to this planar development process, the configuration of 3D features or cellular structures has been traditionally more difficult. However, using a bioprinter, complex 3D highly organized tissue structures can be rapidly created and integrated with precisely sized channels. The second component of this integrated platform will involve a sensor system that provides real-time, physiologically relevant alerts due to threats from various environmental stressors. PHASE I: Create an integrated platform encompassing a select organ(s). The platform must have the ability to detect, collect, and display information after exposure to environmental stressors. The design concept can include, but is not limited to, microdevices with channels, wells and/or connections that create passages for cell seeding, perfusion, and experimental solution delivery. The resultant integrated platform must be an innovative concept and be associated with a theoretical algorithm or software. The human cells used must be specific to the unique perfusion and cell-types of the selected organ(s). This Phase will demonstrate the feasibility of producing a model capable of simulating an organ with key components, must be connected physically and fluidically to an external stimuli, and produce data that will allow for an understanding of exposure and the potential biosignatures of interest. PHASE II: The second phase will require integration of a sensor system onto a microprocessor, such as a chip) to provide real-time, continual monitoring of biologically-derived signatures. The sensor system will provide electrical, biochemical, photo, and/or physical monitoring outputs in as a response to stimuli. The components of this sensor system need to be fully integrated into the tissue model in a small, 3D configuration in order to ensure portability and ease of use. The biosignatures should be relevant for detecting exposure, threat level, and/or resiliency parameters to maintain Airmen health, performance, and/or cognition. A test-bed validation of known biosignatures within the tissue or organ is necessary for product translation. PHASE III: The portable device will be fully operational for up to 48 hours with ability to detect the health effects of physical stressors or environmental exposures through known biosignatures in real-time. REFERENCES: 1. Jinah Jang, Hee-Gyeong Yi, and Dong-Woo Cho (2016) : 3D Printed Tissue Models: Present and Future; ACS Biomater. Sci. Eng., Publication Date (Web): April 30, 2016 DOI: 10.1021/acsbiomaterials.6b00129; 2. 3D Bioprinting for Tissue and Organ Fabrication. (2016) Zhang YS, et al Ann Biomed Eng. 2016 Apr 28. [Epub ahead of print]; 3. Label-Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes. (2017) Shin SR et al., Adv Sci (Weinh). 6;4(5):1600522. doi: 10.1002/advs.201600522. eCollectionKEYWORDS: 3D Bioprinting, Sensor Development, Biosignatures, Organ On Chip