Photocross-Linkable and Shape-Memory Biomaterial Hydrogel Based on Methacrylated Cellulose Nanofibres

Abstract

In the context of three-dimensional (3D) cell culture and tissue engineering, 3D printing is a powerful tool for customizing in vitro 3D cell culture models that are critical for understanding the cell−matrix and cell−cell interactions. Cellulose nanofibril (CNF) hydrogels are emerging in constructing scaffolds able to imitate tissue in a microenvironment. A direct modification of the methacryloyl (MA) group onto CNF is an appealing approach to synthesize photocross-linkable building blocks in formulating CNF-based bioinks for light-assisted 3D printing; however, it faces the challenge of the low efficiency of heterogenous surface modification. Here, a multistep approach yields CNF methacrylate (CNF-MA) with a decent degree of substitution while maintaining a highly dispersible CNF hydrogel, and CNF-MA is further formulated and copolymerized with monomeric acrylamide (AA) to form a super transparent hydrogel with tuneable mechanical strength (compression modulus, approximately 5−15 kPa). The resulting photocurable hydrogel shows good printability in direct ink writing and good cytocompatibility with HeLa and human dermal fibroblast cell lines. Moreover, the hydrogel reswells in water and expands to all directions to restore its original dimension after being air-dried, with further enhanced mechanical properties, for example, Young's modulus of a 1.1% CNF-MA/1% PAA hydrogel after reswelling in water increases to 10.3 kPa from 5.5 kPa.

Methacrylated Cellulose Nanocrystals as Fillers for the Development of Photo-Cross-Linkable Cytocompatible Biosourced Formulations Targeting 3D Printing

“…These results clearly demonstrate the potential of mCNC addition in photo-cross-linkable and 3D-printable formulations for reducing the printing time. These results are in good agreement with the gel time value of 30 s recently reported by Brusentsev et al for a 1.1 wt % methacrylated cellulose nanofibrils (DS = 2%), 1% acrylamide, and 0.4 wt % Irgacure 2959 formulation …”

“…Similarly, the DS decreased rapidly in the first 2 h (32%) and then more slowly up to 24 h. This evolution of DS was explained by the amount of NaOH added over time. To avoid the loss of sulfates and the consequent detrimental effect on the colloidal stability of mCNCs in water, the grafting of carboxylates on the CNC surface, for example, through TEMPO-mediated oxidation, could be envisioned. , However, we rather made the choice to make a compromise between DM and DS values by choosing conditions when DS was still high enough to ensure colloidal stability and DM was high enough to enable efficient cross-linking. Accordingly, a 30 min reaction using a N MA / N OH(surf) of 3.0, yielding mCNC with a DM of 0.83 ± 0.040% and a DS of 2.9% was selected.…”

“…Pore size should be increased to achieve applications such as hydrogels dedicated to extracellular matrix or scaffolds for soft tissue engineering where cell growth is required. , In this prospect, the present work shows formulations that could be printed by additive manufacturing, such as vat photopolymerization, to modulate the pore size. Nonetheless, these promising cryogels could find applications in drug delivery systems. , Alternatively, to overcome the adhesion and proliferation issues, the cytotoxicity study could be done directly on hydrogels, as shown by Brusentsev et al on mCNF/acrylamide hydrogels with HeLa and HDF cells …”

“…Once all the C6 hydroxyls are consumed, esterification should continue on the secondary alcohols. As a comparison with CNFs, Kelly et al only obtained a maximum of 0.07 methacrylate group per anhydroglucose (DM = 7%) after methacrylation with MA in aqueous medium, whereas Brusentsev et al obtained a DM = 2% in DMF. The only example of the application of such a methacrylation protocol to CNCs was reported by Ma et al Unfortunately, the authors did not provide any information about the obtained DM.…”

“…In this context, many cellulose derivatives with various characteristics have already been investigated for 3D printing applications. − Among these, carboxymethylcellulose (CMC) is probably one of the most studied biosourced polymers for biomedical applications thanks to its water solubility , and ability to be chemically modified with (meth)­acrylate groups by reaction with methacrylic anhydride to make it photo-cross-linkable. − …”