Biofabricated hydrogel core-shell microfibers for endothelial-mesenchymal stem cells co-culture and microvascular organization

The engineering of microvascular fibrous scaffolds is crucial for the advancement of tissue-specific constructs that closely mimic native architecture and function. In this work, we introduce a biofabricated, biomimetic wet-spun core-shell hydrogel fiber designed as a platform for encapsulating and supporting either HUVEC-only cultures or HUVEC-hMSC co-cultures. The combined properties of the mechanically supportive alginate shell and the bioactive fibrin core were evaluated in terms of how they shape multicellular organization within hydrogel fiber systems. A comprehensive characterization of the hydrogel precursors and the wet-spinning process parameters underpinning fiber formation is provided, establishing the material and fabrication basis for the subsequent biological assessment. We confirmed that the dual-compartment system was compatible with cellular encapsulation. Cell morphological analyses revealed that the inclusion of hMSC significantly enhanced cell elongation and orientation. Moreover, the co-culture condition improved core volume coverage and surface dynamics, as highlighted by the more pronounced lamellipodia and filopodia over time, when compared to HUVEC-only controls. These findings emphasize the synergistic role of co-culture systems in modulating the endothelial behavior and highlight how biofabricated fiber platforms can bridge material design and cellular functionality. This versatile fiber-based platform offers a promising tool for advancing the development of biomimetic scaffolds for microvascular applications in regenerative medicine, disease modeling, and tissue-specific engineering strategies.