3D cellulose nanofiber scaffold with homogeneous cell population and long-term proliferation
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Tumor-originated and undefined extracellular matrices (ECMs) such as Matrigel™ have been widely used in three-dimensional (3D) cell and tissue culture, but their use is unacceptable in clinical cell therapies. In this study, we proposed a 3D cellulose nanofiber (CNF) hydrogel that has great potential as a defined tissue-engineering scaffold, especially for osteoblast culture. The CNF hydrogel showed attractive features as a cell scaffold material. It exhibited a ~ 1.4-fold higher diffusion coefficient (~ 2.98 × 10−7 cm2/s) of macromolecules such as bovine serum albumin than does Matrigel™ (< 2.2 × 10−7 cm2/s) due to the former’s higher porosity (> 95%) and pore size (~ 310.8 μm). Most pre-osteoblast cells that are encapsulated in the CNF hydrogel were immediately locked without sinking by instant hydrogen bond cross-linking between CNFs, whereas cells encapsulated in Matrigel™ sank to the bottom of the scaffold due to the slow sol–gel transition (> 20 min). The elastic modulus of the cell-encapsulated CNF hydrogel could be reinforced by further calcium-mediated cross-linking without cytotoxicity. As a result, the pre-osteoblast cells in the CNF hydrogels were homogeneously distributed in the 3D structure, proliferated for 3 weeks, and successfully differentiated. Overall, CNFs showed that it has potential to be used in tissue engineering as a defined ECM component.
KeywordsCellulose nanofibers Extracellular matrices Matrigel Shear-dependent viscosity 3D hydrogel scaffolds
We would like to acknowledge the financial support from the Grant the Marine Biotechnology program (Marine BioMaterials Research Center) funded by the Ministry of Oceans and Fisheries of Korea (D11013214H480000110). This work was also supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2016M1A5A1027592 and NRF-2017R1A2B3006354). DXO acknowledges KRICT SI-1809.
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Conflicts of interest
All authors declare that there is no conflict of interest.
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