Freeform printing of thermoresponsive poly(2-cyclopropyl-oxazoline) as cytocompatible and on-demand dissolving template of hollow channel networks in cell-laden hydrogels

Abstract

Conventional additive-manufacturing technologies rely on the vertical stacking of layers, whereas each layer provides the structural integrity for the upcoming one. This inherently gives rise to limitations in freedom of design especially when structures containing large voids or truly 3D pathways for printed filaments are aspired. An especially interesting technique, which overcomes these layer limitations, is freeform printing, where thermoplastic materials are printed in 3D through controlling the temperature profile such that the polymer melt solidifies right when it exits the nozzle. In this study, we introduce freeform printing for thermoresponsive polymers at the example of poly(2-cyclopropyl-oxazoline) (PcycloPrOx). This material is especially interesting for biofabrication, as poly(oxazoline)s are known to provide excellent cytocompatibility. Furthermore, (PcycloPrOx) scaffolds provide adequate stability, so that the printed structures can be embedded in cell-laden hydrogels and sufficient time remains for the gel to form around the scaffold before dissolution via temperature reduction. This ensures accuracy and prevents channel collapse for the creation of cell-laden hydrogels with an embedded three-dimensionally interconnected channel network without the need of any additional processing step such as coating.