They engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top. In this 3D-oBRB model, a fully-polarized RPE monolayer provides barrier resistance, induces choriocapillaris fenestration, and supports the formation of Bruch’s-membrane-like structure by inducing changes in gene expression in cells of the choroid. Complement activation in the 3D-oBRB triggers dry AMD phenotypes (including subRPE lipid-rich deposits called drusen and choriocapillaris degeneration), and HIF-α stabilization or STAT3 overactivation induce choriocapillaris neovascularization and type-I wet AMD phenotype. The 3D-oBRB provides a physiologically relevant model to studying RPE–choriocapillaris interactions under healthy and diseased conditions.
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Heart disease — the leading cause of death in the U.S. — is so deadly in part because the heart, unlike other organs, cannot repair itself after injury. That is why tissue engineering, ultimately including the wholesale fabrication of an entire human heart for transplant, is so important for the future of cardiac medicine.
To build a human heart from the ground up, researchers need to replicate the unique structures that make up the heart. This includes recreating helical geometries, which create a twisting motion as the heart beats. It’s been long theorized that this twisting motion is critical for pumping blood at high volumes, but proving that has been difficult, in part because creating hearts with different geometries and alignments has been challenging.
Helical alignments within the heart’s musculature have been speculated to be important in achieving physiological pumping efficiencies. Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the heart’s musculature using current techniques.
For the first time, bioengineers have developed the first biohybrid model of human ventricles with helically aligned beating cardiac cells, and have shown that muscle alignment does, in fact, dramatically increase how much blood the ventricle can pump with each contraction. In this study, they report focused rotary jet spinning (FRJS), an additive manufacturing approach that enables rapid fabrication of micro/nanofiber scaffolds with programmable alignments in three-dimensional geometries. Seeding these scaffolds with cardiomyocytes enabled the biofabrication of tissue-engineered ventricles, with helically aligned models displaying more uniform deformations, greater apical shortening, and increased ejection fractions compared with circumferential alignments. The ability of FRJS to control fiber arrangements in three dimensions offers a streamlined approach to fabricating tissues and organs, with this work demonstrating how helical architectures contribute to cardiac performance.
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