Rapid Magnetically Directed Assembly of Pre-Patterned Capillary-Scale Microvessels

Abstract

Capillary scale vascularization is critical to the survival of engineered 3D tissues and remains an outstanding challenge for the field of tissue engineering. Current methods to generate micro-scale vasculatures such as 3D printing, two photon hydrogel ablation, angiogenesis, and vasculogenic assembly face challenges in rapidly creating organized, highly vascularized tissues at capillary length-scales. Within metabolically demanding tissues, native capillary beds are highly organized and densely packed to achieve adequate delivery of nutrients and oxygen and efficient waste removal. Here, two existing techniques are adopted to fabricate lattices composed of sacrificial microfibers that can be efficiently and uniformly seeded with endothelial cells (ECs) by magnetizing both lattices and ECs. Ferromagnetic microparticles are incorporated into microfibers produced by solution electrowriting and fiber electropulling. By loading ECs with superparamagnetic iron oxide nanoparticles, the cells could be seeded onto magnetized microfiber lattices. Following encapsulation in a hydrogel, the capillary templating lattice is selectively degraded by a bacterial lipase that does not impact mammalian cell viability or function. This study introduces a novel approach to rapidly producing organized capillary networks within metabolically demanding engineered tissue constructs which should have broad utility in the fields of tissue engineering and regenerative medicine.