Over the recent years, various materials have been introduced as potential 3D cell culture scaffolds. These include protein extracts, peptide amphiphiles, and synthetic polymers. Hydrogel scaffolds without human or animal borne components or added bioactive components are preferred from the immunological point of view. Here we demonstrate that native nanofibrillar cellulose (NFC) hydrogels derived from the abundant plant sources provide the desired functionalities. We show 1) rheological properties that allow formation of a 3D scaffold in-situ after facile injection, 2) cellular biocompatibility without added growth factors, 3) cellular polarization, and 4) differentiation of human hepatic cell lines HepaRG and HepG2. At high shear stress, the aqueous NFC has small viscosity that supports injectability, whereas at low shear stress conditions the material is converted to an elastic gel. Due to the inherent biocompatibility without any additives, we conclude that NFC generates a feasible and sustained microenvironment for 3D cell culture for potential applications, such as drug and chemical testing, tissue engineering, and cell therapy.

Cellulose nanofibrils show remarkable properties with applications in several fields of materials science, such as for composites, hydrogels, aerogels, foams, and coatings. Cellulose nanofibrils are typically produced by mechanical and enzymatic processing leading to fibrils having a width in the nanometer range and very high aspect ratios. The formation of percolating networks and interactions between fibrils lead to useful properties in for example gel formation and composites. In this work we studied how the residual xylan that is found in cellulose nanofibrils that have been produced from hardwood pulp affects these properties. We used enzymatic hydrolysis to specifically remove xylan and studied rheological properties, morphological features, and properties of paper-like films of cellulose nanofibrils. We found that removal of xylan enhances the formation of fibril networks, resulting in both stiffer gels and stronger films. However xylan also stabilizes the fibrils against flocculation. Also the history of processing of the preparations affects the results significantly.