Rapid 3D bioprinting of biomimetic vascularized tissue constructs

University Of California, San Diego, La Jolla CA

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Abstract

PROJECT SUMMARY Recent advances in rapid prototyping methods including stereolithography and nozzle-based bioprinting have enabled manufacturing of complex structures with controlled architectures and tunable properties. With their capability of patient-specific design and precision engineering, these technologies have impacted many areas such as tissue engineering and regenerative medicine. In tissue engineering, the fabrication of highly organized, functional three-dimensional (3D) constructs that mimic the complex architecture of various organs is of great importance. Towards this goal, different rapid prototyping strategies based on stereolithography and bioprinting have been demonstrated. Despite significant advances, however, the following key challenges for bioprinting biomimetic tissue constructs still remain: a) Current methods for fabricating 3D cell-laden constructs with clinically-relevant precision require time-scales that induce cell death. b) Multicomponent/multicellular tissue constructs with biologically-relevant architectures and characteristics are difficult or impossible to bioprint at present. To address both of these challenges simultaneously, we plan to develop a Rapid, Multimaterial Bioprinting (RMB) technology. The novel RMB approach is significantly faster than conventional 3D bioprinting and produces multicomponent complex architectures using diverse cell-laden biomaterials continuously. Therefore, this novel 3D bioprinting system can be used to build biomimetic tissues, such as pre-vascularized cardiac tissue with blood vessels ranging from larger anastomosable vessels to smaller capillaries. We will integrate a programmable microfluidic system with a dynamic optical printing method to deliver different cell types and gel precursors to mimic the biomechanical characteristics and compositions of the cardiac tissue. Specifically, we will incorporate iPS cell-derived human cardiomyocytes (iCMs) and endothelial cells (ECs) with designed spatial distributions in the engineered tissue constructs. We will then assess the maturation of the pre- vascularized cardiac tissues in vitro and examine the biocompatibility and functionality of the bioprinted vascular networks in a subcutaneous implantation model in nude rats. The completion of this work will be a paradigm shift and a landmark achievement in efforts towards clinical treatments of vascularized cardiac tissue.