AVS2018 Session IPF+AS+BI+NS-MoM: Biofabrication: From Tissue to Organ

Bioprinting refers to the co-deposition of cells alongside scaffolding materials to build two- and three-dimensional constructs for tissue engineering applications. The technology faces several limitations that present interesting engineering opportunities. The nature and scope of the problems will be discussed in the context of the fabrication of microvasculature. The current tissue-engineering paradigm is that successfully engineered thick tissues must include vasculature. Studies of membrane properties of thermal inkjet printed cells by evaluating showed normal electrophysiology, but short-term membrane disruptions, which allow small molecular weight molecules to enter. Cell viability was high and apoptotic behavior was not upregulated. Alginate (1%) and gelatin type B (2.5%) constructs or scaffolds were prepared by bioprinting of a crosslinker with endothelial and endothelial / β cells. Control scaffolds were manually pipetted with the same cells and without any cells.Upon implantation the bioprinted endothelial cell constructs showed a nearly ten-fold increase in blood vessels was observed (p= 0.009), a dose response was observed but the β cells seemed to inhibit vessel formation. The explanted implants show large complete vascular features on the H&E and CD31 stains; Immunohistochemistry showed the tissue were regenerated with the human cells that made up a large part of the vasculature. Further insights into how the inkjet printing process activated endothelial cells will be presented. Understanding these processes will improve bioprinting and may eventually lead to creating fully vascularized large soft tissues, which have not been successfully grown thus far.

Engineered tissues have emerged as promising new approaches to repair damaged tissues as well as to provide useful platforms for drug testing and disease modeling. Outstanding challenges remain in 1) the lack of well-defined and mature cell sources to facilitate translational outcomes and 2) the lack of control over vascular structure and perfusion efficiency in engineered 3D tissue constructs, preventing large-scale tissue fabrication, and leading to insufficient perfusion after implantation in vivo. In this talk, I will present recent progress in my lab in engineering microvasculature from human pluripotent stem cell derived endothelial cells, and their anastomosis in vitro and infarcted heart in vivo. The eventual goal of this drive is to use the single cell source to derive organ-specific vascular cells and tissue for regeneration. Next I will discuss our work in understanding the human microvascular endothelial cell heterogeneity from four major organs, heart, lung, liver and kidney and describe their distinct structure and function. I will show an example of using human kidney-specific microvascular cells to model kidney specific injury. Finally I will discuss challenges and future perspectives towards engineering human organ-specific tissue models.

Tissue engineering and regenerative medicine has emerged as an innovative scientific field that focuses on developing new approaches to repairing cells, tissues and organs. Over the years, various engineering strategies have been developed to build functional tissues and organs for clinical applications. However, challenges still exist in developing complex tissue systems. In recent years, 3D bioprinting has emerged as an innovative tool that enables rapid construction of complex 3D tissue structures with precision and reproducibility. This developing field promises to revolutionize the field of medicine addressing the dire need for tissues and organs suitable for surgical reconstruction. In this session novel and versatile approaches to building tissue structures using 3D printing technology will be discussed. Clinical perspectives unique to 3D printed structures will also be discussed.