Bioengineering of High Cell Density Tissues with Hierarchical Vascular Networks for Ex Vivo Whole Organs

Abstract

The development of tissue‐like structures such as cell sheets, spheroids, and organoids has contributed to progress in regenerative medicine. Simultaneous achievement of scale up and high cell density of these tissues is challenging because sufficient oxygen cannot be supplied to the inside of large, high cell density tissues. Here, in vitro fabrication of vessels to supply oxygen to the inside of millimeter‐sized scaffold‐free tissues whose cell density is ≈200 million cells mL−1, corresponding to those of native tissues, is shown. Hierarchical vascular networks by anastomosis of capillaries and a large vessel are essential for oxygen supply, whereas a large vessel or capillary networks alone make negligible contributions to the supply. The hierarchical vascular networks are formed by a top‐down approach, which offers a new option for ex vivo whole organs without decellularization and 3D‐bioprinting.

Technology for the formation of engineered microvascular network models and their biomedical applications

“…For instance, when utilizing microfabrication techniques such as photolithography that necessitate retention of morphological characteristics even after demolding, harder materials like PDMS are commonly employed [ 40 ]. 3D printing techniques require the material to maintain high fluidity at the start and then quickly become stiffer for sufficient mechanical support of the cells [ 23 ]. The stiffness of the matrix can be modulated through variation in the polymer or crosslinking agent, or by increasing the enzyme cleavage sites [ 151 ].…”

“…Although capillary networks have been extensively utilized in various disciplines and notable advancements have been achieved. Nevertheless, microvascular networks require a different set of design considerations and fabrication techniques due to the intricate geometry and small size of capillaries, compared to those used in large vessel engineering [ 7 , 23 ]. In recent years, scientists have attempted to create microvascular networks in vitro using different biofabrication techniques and have achieved some progress.…”

Vascularized organ bioprinting: From strategy to paradigm

“…This empowers cells to autonomously complete the subsequent development. 2.5D structures in organs‐on‐chips, for example, the AngioChip13,14 and other methods 15 that follow this strategy are especially noteworthy.…”

Engineering vascularized organotypic tissues via module assembly

“…Tissues that possess the required cellular density, microstructure, and function can be achieved using the prevascularized MoA approach (figure 6) [124,125]. For instance, Skylar-Scott et al suggested using the 'sacrificial writing into functional tissue (SWIFT)' method to create huge, organotypic tissues with embedded vascular channels and high cellular density [126].…”