Abstract

Biomimetic Vascular Constructs Using Three-Dimensionally (3D) Printed Porous Molds

Michinao Hashimoto, Associate Professor, Singapore University of Technology and Design,

We present a method to fabricate anatomically relevant vascular models using 3D-printed molds. Advanced biofabrication methods—sacrificial molding, direct ink writing, coaxial bioprinting, and embedded bioprinting—have enabled the fabrication of vascular models with intricate 3D architecture. Despite their advances, however, achieving full anatomical mimicry of native vasculature (such as freestanding, branching, multilayered, perfusable, and mechanically stretchable) remains to be challenging. In this work, we demonstrated an alternative biofabrication method for freestanding cell-laden vascular constructs with complex 3D architecture. The fabrication is achieved by employing a two-part mold consisting of porous hydrogels. The diffusion of calcium chloride (Ca2+) ions from the mold prompted dynamic crosslinking of the alginate-containing hydrogels in the radially inward direction to form a tubular construct. The same approach was extended to employing molds with complex shapes to achieve intricate 3D vascular architecture. The fabricated vascular models may be laden with smooth muscle cells (SMCs) and endothelial cells (ECs) in the multilayered arrangement. Lastly, vascular constructs with anatomically accurate geometries (e.g., constructions, bifurcation) and mechanical stress (e.g., cyclical motion) were readily fabricated. These vasculature models with increased biomimicry should benefit future research in mechanistic understanding of cardiovascular diseases and their therapeutic intervention.