Fabrication of Short Polymeric μFibers as Building Blocks for Anisotropic High-Throughput Compatible 3D Tissue Models

Modeling the 3D microenvironment and cell growth of natively anisotropic human tissues in vitro constitutes a significant challenge in tissue engineering and biofabrication. Short polymeric fibers gain growing attention in this field due to their applicability as pipettable or injectable anisometric building blocks in 3D hydrogel-based cell culture systems or bioinks. However, the production of monodisperse short fibers with high production rates suitable for screening remains challenging. In this study, short, quasi-monodisperse, magneto-responsive, fluorescent poly({varepsilon}-caprolactone) {micro}fibers with variable dimensions in the micrometer range are produced in a scalable, semi-continuous two-step fabrication process combining controlled wet-dry spinning with subsequent cryosectioning. Influences of the spinning process parameters on fiber properties and process features, as well as boundary spinning conditions and upscaling potential, are explored using Design of Experiments approaches. Further, magnetic alignment of the {micro}fibers in a weak magnetic field and incorporation of nile red as fluorescent dye for facile analysis in 3D are demonstrated. Implementation of aligned {micro}fibers into a hydrogel-based 3D vasculogenesis model, produced in a high-throughput automated manner, is shown to stimulate oriented cell growth. This highlights the potential of our {micro}fibers as guiding elements inside tissue and disease models and their suitability for automated high-throughput applications.