The potential of TEMPO-oxidized nanofibrillar cellulose beads for cell delivery applications

Abstract

The advanced development of cell carriers for regenerative medicine and cell therapy demands materials able to sustain cell viability prior to their delivery to the target tissue, ability which can be controlled via the shape/size and degradability of the matrix. TEMPO-oxidized nanofibrillar cellulose (ToNFC) macromolecules are negatively charged and therefore can be easily formulated by ionotropic gelation into beads of varying sizes that can release their payload through an erosion-controlled process. We report here for the first time on the preparation of ToNFC beads via ionic gelation using CaCl2 and on their loading with OSTEO-1 rat bone cells, with a view to examine their capacity of sustaining the cell viability and of releasing the bone cells in a controlled manner. The initial results obtained demonstrate that ToNFC is able to protect the OSTEO-1 cells and to maintain their viability for at least two weeks; following gradual disintegration of the beads, a significant cell release and subsequent proliferation was observed after 7 days. These results indicate the considerable potential of nanofibrillar cellulose (ToNFC) for applications in cell therapy and regenerative medicine.

TEMPO-Nanocellulose/Ca2+ Hydrogels: Ibuprofen Drug Diffusion and In Vitro Cytocompatibility

“…The high percentage of viable cells in C1 proves the possibility of embedding viable cells in TOUS-CNFs/Ca 2+ hydrogels, even though the percentage number of viable cells embedded in C1 was lower (p < 0.05) compared to those embedded in alginate and those seeded on TCPS. The percentage of viable cells in C1 at the different considered time points (i.e., 1 vs. 3 vs. 7 days), did not evidence a statistical difference (p > 0.05), thus proving the possibility of culturing viable cells, as demonstrated by other authors who used TOUS-CNFs microbeads to release viable encapsulated cells [63,64]. Moreover, after 1 and 3 days of culture, L929 cells were qualitatively characterized by a spherical morphology when embedded and cultured either in C1 or in alginate/Ca 2+ hydrogels [65].…”

TEMPO-Oxidized Cellulose with High Degree of Oxidation

“…For example, through a series of oxidation reaction, aldehyde, carboxyl, and ketone groups can be attached to the cellulose molecular chain, and the modified cellulose exhibits novel functional properties. In particular, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation can produce oxidized cellulose for valuable polyelectrolytes and intermediates, and has attracted a number of investigations [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. This technique converts hydroxyl groups at the C6-position of the d -glucose unit into charged carboxyl entities region-selectively.…”

TEMPO-Oxidized Cellulose Hydrogel Fiber Cell Load, a Cell Support System Proof of Concept&nbsp;

“…The oxidation of CNF hydroxyls to carboxyl groups using 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO catalyst) is one of the most used methods to introduce negative charges on cellulose bers which increases cellulose hydrophilicity (Saito et al 2006) and giving rise to concentration-dependent viscosity hydrogel formed by individualized nano brils (Saito et al 2006) (Singh et al 1982) (Weishaupt et al 2015). Carboxylate groups are also appropriate to crosslink cellulose by ionic complexation (Carvalho et al 2016) (Grande et al 2017), which may be used as a bottom-up approach to obtain exible scaffolds with superior cell distribution. TEMPO oxidized cellulose nano bers (ToCNF) derivative can be assembled into beads with 0.5-3 mm diameter (Carvalho et al, 2016) or bers with 0.2 mm diameter (Grande et al, 2017) by ionic complexation.…”

“…Carboxylate groups are also appropriate to crosslink cellulose by ionic complexation (Carvalho et al 2016) (Grande et al 2017), which may be used as a bottom-up approach to obtain exible scaffolds with superior cell distribution. TEMPO oxidized cellulose nano bers (ToCNF) derivative can be assembled into beads with 0.5-3 mm diameter (Carvalho et al, 2016) or bers with 0.2 mm diameter (Grande et al, 2017) by ionic complexation. Several tissues are naturally organized in ber shape, including the nervous system and the striated muscle, the most challenging tissues to be repaired.…”