The construction of an in vitro 3D cellular model to mimic the human liver is highly desired for drug discovery and clinical applications, such as patient‐specific treatment and cell‐based therapy in regenerative medicine. However, current bioprinting strategies are limited in their ability to generate multiple cell‐laden microtissues with biomimetic structures. This study presents a method for producing hepatic‐lobule‐like microtissue spheroids using a bioprinting system incorporating a precursor cartridge and microfluidic emulsification system. The multiple cell‐laden microtissue spheroids can be successfully generated at a speed of approximately 45 spheroids min−1 and with a uniform diameter. Hepatic and endothelial cells are patterned in a microtissue spheroid with the biomimetic structure of a liver lobule. The spheroids allow long‐term culture with high cell viability, and the structural integrity is maintained longer than that of non‐structured spheroids. Furthermore, structured spheroids show high MRP2, albumin, and CD31 expression levels. In addition, the in vivo study reveals that structured microtissue spheroids are stably engrafted. These results demonstrate that the method provides a valuable 3D structured microtissue spheroid model with lobule‐like constructs and liver functions.

Biomedical Applications In article number 2102624, Songwan Jin and co‐workers generate liver spheroids that resemble the in vivo structure of the lobules. The structural integrity is maintained for several days, engendering an increased performance of cellular function. This is achieved thanks to the combination of two cutting edge technologies: preset‐extrusion 3D bioprinting and microfluidics. Moreover, structured microtissues once injected into animals show a better engraftment, bringing to light the importance of phenotypically relevant models not only for drug screening but also regenerative medicine.

Thymosin β-4 is a 43-amino acid intracellular polypeptide that was originally isolated from bovine thymus. Of the 16 known thymosin families, thymosin β-4 is the most common type found in all tissues. Thymosin β-4 regulates angiogenesis, cell differentiation, morphogenesis, migration, and organogenesis and is linked to a dynamic equilibrium between G-actin and F-actin. In particular, thymosin β-4 is well-known for its angiogenic and anti-apoptotic functions. In this study, we synthesized thymosin β-4 linked with the well-known cell-penetrating peptide TAT (YGRKKRRRQRRR). TAT-thymosin β-4 promotes angiogenesis and cell migration in vitro via the VEGFR2 signaling pathway and reduces apoptosis. To examine angiogenic potential in vivo, a Matrigel Plus assay was conducted that revealed the angiogenic effect of TAT-thymosin β-4. In conclusion, TAT-thymosin β-4 promotes blood vessels and is expected to be applicable in regenerative medicine for all organs requiring blood vessels.