3D biofabrication and characterization of vascularized tissue constructs have developed as an effective tool for advancements in tissue engineering and regenerative medicine. Successful 3D tissue fabrication requires bioink formulation, anatomically informed designs with the inclusion of the innate vasculatures, and new analytical techniques for efficient and continuous monitoring of the biofabricated tissue. Gelatin methacryloyl (GelMa) is one of the most favored hydrogel used for 3D bioprinting and in vitro prototyping. Extremely sensitive rheological properties and a narrow solgel transition temperature range has been the main challenge in using GelMa as a biomaterial carrier which results in poor process control and undesired prints. We present a wholesome solution for successful bioink formulation, 3D tissue bioprinting, cell-conditioning and monitoring. We have tailored a hydrogel composite using GelMa, glycerol and hyaluronic acid (HA) to create a bioink which is independent of temperature induced viscosity changes during the bioprinting process. We have optimized extrusion-based printing parameters to create vascularized cardiac tissue scaffolds with complex geometries comprising of co-cultures of cardiac-derived cells. These bioprinted constructs were operate in a custom bioreactor comprising of an electrical stimulation system integrated with microfluidic flow sensing. This bioreactor setup was used to simultaneously apply pulsed electrical stimulus and to monitor the pulsatile perfusion induced angiogenic response. Future efforts will include optimization of the microvascular patterns to mimic in vivo anatomy and investigation of frequency, amplitude, waveform shape and polarity of the electrical pulses to mimic the complex in vivo cell signaling environment and facilitate generational vascularization in 3D bioprinted tissues.

3D Bioprinting and Continuous Monitoring of Vascularized Cardiac Tissue Constructs Using Electrical Actuation and Flow Sensing Systems

ACS Fall 2021

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