Engineering\nBiomimetic Microvascular Capillary Networks\nin Hydrogel Fibrous Scaffolds via Microfluidics-Assisted Co-Axial\nWet-Spinning

The microvascular\nbed plays a crucial role in establishing nutrient\nexchange and waste removal, as well as maintaining tissue metabolic\nactivity in the human body. However, achieving microvascularization\nof engineered 3D tissue constructs is still an unsolved challenge.\nIn this work, we developed biomimetic cell-laden hydrogel microfibers\nrecapitulating oriented microvascular capillary-like networks by using\na 3D bioprinting technique combined with microfluidics-assisted coaxial\nwet-spinning. Highly packed and aligned bundles embedding a coculture\nof human bone marrow-derived mesenchymal stem cells (MSCs) and human\numbilical vein endothelial cells (HUVECs) were produced by simultaneously\nextruding two different bioinks. To this aim, core–shell fibers\nwere wet-spun in a coagulation bath to collect the scaffolds later\non a rotary drum. Initially, the versatility of the proposed system\nwas assessed for the extrusion of multimaterial core–shell\nhydrogel fibers. Subsequently, the platform was validated for the <i>in vitro</i> biofabrication of samples promoting optimal cell\nalignment along the fiber axis. After 3 weeks of culture, such fiber\nconfiguration resulted in the development of an oriented capillary-like\nnetwork within the fibrin-based core and in the endothelial-specific\nCD31 marker expression upon MSC/HUVEC maturation. Synergistically,\nthe vertical arrangement of the coaxial nozzle coupled with the rotation\nof the fiber collector facilitated the rapid creation of tightly packed\nbundles characterized by a dense, oriented, and extensively branched\ncapillary network. Notably, such findings suggest that the proposed\nbiofabrication strategy can be used for the microvascularization of\ntissue-specific 3D constructs.