Current Challenges and Future Promise for Use of Extracellular Matrix Scaffold to Achieve the Whole Organ Tissue Engineering Moonshot.

Whole organ tissue engineering encompasses a variety of approaches, including 3D printed tissues, cell-based self-assembly, and cellular incorporation into synthetic or xenogeneic extracellular matrix (ECM) scaffolds. This review article addresses the importance of whole organ tissue engineering for various solid organ applications, focusing on the use of extracellular (ECM) matrix scaffolds in such engineering endeavors. In this work, we focus on the emerging barriers to translation of ECM scaffold-based tissue-engineered organs and highlight potential solutions to overcome the primary challenges in the field. The 3 main factors that are essential for developing ECM scaffold-based whole organs are (1) recapitulation of a functional vascular tree, (2) delivery and orientation of cells into parenchymal void spaces left vacant in the scaffold during the antigen elimination and associated cellular removal processes, and (3) driving differentiation of delivered cells toward the appropriate site-specific lineage. The insights discussed in this review will allow the potential of allogeneic or xenogeneic ECM scaffolds to be fully maximized for future whole organ tissue-engineering efforts.

Three-dimensional printing of cell-laden microporous constructs using blended bioinks.

Hydrogels such as alginate and gelatin have shown potential as biomaterials in various three-dimensional (3D) bioprinting applications. However, parameters such as viscosity, porosity, and printability influence the performance of hydrogel-based biomaterials, and there are limited characterization studies conducted on the behavior of these constructs. In this work, a syringe-based extrusion bioprinter was used to print 3D constructs with bioink composed of various concentrations of alginate and gelatin along with fibrinogen and human umbilical vein endothelial cells. Instead of crosslinking the gelatin, the gelatin was left uncrosslinked to provide microporosity within the system that can impact the cellular response. Mechanical and biochemical characterization was performed to evaluate the structural stability and integrity of the printed constructs along with viability of embedded cells. Bioprinted constructs of a higher total concentration of alginate and gelatin yielded better stability and structural integrity after culture. More importantly, higher amounts of gelatin (i.e., 1:9 instead of 2:3 alginate:gelatin) were shown to improve printability, which is different than most studies that instead use alginate to improve printability. In addition, higher amounts of gelatin impacted the changes in surface morphological features of the constructs after incubation, and ultimately improved biocompatibility with our system. Overall, this study demonstrated that an uncrosslinked gelatin system can provide flexible printing parameters and surface morphologies, but careful control over the printing parameters may be required. The bioink concentration of 10% (w/v) with minimum alginate and higher gelatin concentration exhibited the best printability, cell survival, and viability.