One-step rapid fabrication of cell-only living fibers

Abstract

Cellular aggregates are used as relevant regenerative building blocks, tissue models, and cell delivery platforms. Biomaterial-free structures are often assembled either as 2D cell sheets or spherical microaggregates, both incompatible with free-form deposition, and dependent on challenging processes for macroscale 3D upscaling. The continuous and elongated nature of fiber-shaped materials enables their deposition in unrestricted multiple directions. Cellular fiber fabrication has often required exogenously provided support proteins and/or the use of biomaterial-based sacrificial templates. Here, the rapid (<24 h) assembly of fiberoids is reported: living centimeter-long scaffold-free fibers of cells produced in the absence of exogenous materials or supplements. Adipose-derived mesenchymal stem cell fiberoids can be easily modulated into complex multidimensional geometries and show tissue-invasive properties while keeping the secretion of trophic factors. Proangiogenic properties studied on a chick chorioallantoic membrane in an ovo model are observed for heterotypic fiberoids containing endothelial cells. These micro-to-macrotissues may find application as morphogenic therapeutic and tissue-mimetic building blocks, with the ability to integrate 3D and 4D full biological materials.