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The formation of multiscale vascular networks is essential for the in vitro construction of large-scale biomimetic cardiac tissues/organs. Although a variety of bioprinting processes have been developed to achieve the construction of mesoscale and large-scale blood vessels, the formation of microvascular networks still mainly depends on the self-assembly behavior of endothelial cells (ECs), which is inefficient and demanding without appropriate stimulus. To address this problem, the elongation and connection of endothelial cells in engineered cardiac tissue (ECT) are sought to promote by electrical stimulation (ES) to achieve vascularization. As proof of the concept, bio-inks are composed of GelMA/fibrin hydrogel, human pluripotent stem cells induced cardiomyocytes (iPSC-CM), and human umbilical vein endothelial cells (HUVEC) are used for the bioprinting of ECTs. It is demonstrated that electrical stimulation significantly promotes the elongation, migration, and interconnection of HUVECs in ECT and increases the expression of related genes. Moreover, ES also enhances the secretion of signal factors interacting between CMs and HUVECs. It seems that the HUVECs further strengthen the contractility of cardiac tissue. Taken together, electrical stimulation promotes vascularization and CMs functionalization in ECT, which has important application potential in the fabrication of vascularized ECT and its clinical transplantation., (© 2023 Wiley-VCH GmbH.)

Creating functional tissues and organs in vitro on demand is a major goal in biofabrication, but the ability to replicate the external geometry of specific organs and their internal structures such as blood vessels simultaneously remains one of the greatest impediments. Here, this limitation is addressed by developing a generalizable bioprinting strategy of sequential printing in a reversible ink template (SPIRIT). It is demonstrated that this microgel-based biphasic (MB) bioink can be used as both an excellent bioink and a suspension medium that supports embedded 3D printing due to its shear-thinning and self-healing behavior. When encapsulating human-induced pluripotent stem cells, the MB bioink is 3D printed to generate cardiac tissues and organoids by extensive stem cell proliferation and cardiac differentiation. By incorporating MB bioink, the SPIRIT strategy enables the effective printing of a ventricle model with a perfusable vascular network, which is not possible to fabricate using extant 3D printing strategies. This SPIRIT technique offers an unparalleled bioprinting capability to replicate the complex organ geometry and internal structure in a faster manner, which will accelerate the biofabrication and therapeutic applications of tissue and organ constructs., (© 2023 Wiley-VCH GmbH.)

Despite progress in engineering both vascularized tissues and oriented tissues, the fabrication of 3D vascularized oriented tissues remains a challenge due to an inability to successfully integrate vascular and anisotropic structures that can support mass transfer and guide cell alignment, respectively. More importantly, there is a lack of an effective approach to guiding the scaffold design bearing both structural features. Here, an approach is presented to optimize the bifurcated channels within an anisotropic scaffold based on oxygen transport simulation and biological experiments. The oxygen transport simulation is performed using the experimentally measured effective oxygen diffusion coefficient and hydraulic permeability of the anisotropic scaffolds, which are also seeded with muscle precursor cells and cultured in a custom-made perfusion bioreactor. Symmetric bifurcation model is used as fractal unit to design the channel network based on biomimetic principles. The bifurcation level of channel network is further optimized based on the oxygen transport simulation, which is then validated by DNA quantification assay and pimonidazole immunostaining. This study provides a practical guide to optimizing bifurcated channels in anisotropic scaffolds for oriented tissue engineering., (© 2020 Wiley-VCH GmbH.)