Microfiber-Templated Porogel Bioinks Enable Tubular Interfaces and Microvascularization Down to the Building Blocks for 3D Bioprinting

Abstract

Vascularization is key to the biofabrication of large-scale tissues. Despite the progress, there remain some outstanding challenges, such as limited vessel density, difficulty in fabricating microvasculatures, and inhomogeneity of post-seeding cells. Here, we introduce a new form of bioink called microfiber-templated porogel (FTP) bioink to engineer vasculatures down to the filament building blocks of 3D bioprinted hydrogels. The cell-laden sacrificial microfibers (diameter ranges from 50-150 m) are embedded in the bioink to template tubular voids and deliver endothelial cells for in-situ endothelialization. The inclusion of softening hydrogel microfibers retains the desirable rheological properties of the bioink for extrusion-based bioprinting. Such bioinks can be printed into a well-defined 3D structure with tunable tubular porosities up to 55%. Compared to the conventional bulk bioink counterpart, the FTP bioink supports the significant growth and spread of endothelial cells either embedded in the matrix or sacrificial fibers, free of the post-cell seeding procedure. Furthermore, the bioprinted scaffolds based on FTP bioink are seen to significantly promote the in-growth of blood vessels and native tissues in vivo. The FTP bioink approach enables the engineering of tubular bio-interfaces within the building blocks and contributes to the in-situ endothelialization of microvasculatures, providing a versatile tool for the construction of customized vascularized tissue models.