Geometrical control of degradation and cell delivery in 3D printed nanocellulose hydrogels

Abstract

Hydrogels based on cellulose nanofibers are rapidly gaining attention in biomedical applications due to their biocompatibility, exogenous degradation to mammals, and their unique properties and functionalities distinct from molecular cellulose and wood pulp. Among those properties, the mechanical toughness and shear thinning behavior make these hydrogels particularly well suited to be extruded and bioprinted. The recent discovery of their ability to support stem cell growth while preserving their pluripotency adds to their promising use as carriers for the storage and controlled delivery of stem cells. However, the simultaneous stemness preservation and biodegradation dependency on the degree of oxidation avoids their optimization by chemical modifications. Here, those limitations are circumvented by bioprinting nanocellulose hydrogels without additives, enabling geometry-controlled degradation and cell retrieval at a constant degree of oxidation. This approach is demonstrated by tuning cell delivery from hours to days in nanocellulose scaffolds—of both plant and bacterial origin—in similar compositions and volumes but different apparent areas. The results, which are generalizable to other biodegradable polymers, provide a new approach for the encapsulation, storage, and delivery of mammalian cells in cellulose hydrogel, with a direct application in stem cell biology, tissue engineering, and biomedical devices.