Nanocellulose Grafted with Poly(2-alkyl-2-oxazoline): Thermoresponsive Hydrogels for Biomedical Applications

Nanocellulose has gained significant attention as a sustainable nanomaterial for developing responsive nanocomposites, particularly in combination with synthetic polymers. Its exceptional mechanical strength, stiffness, biocompatibility, high surface area, and gel-forming capability make it an attractive alternative to fossil-based materials. Sourced from renewable and biodegradable resources such as agricultural waste and wood, nanocellulose offers an eco-friendly solution for advanced material design. When integrated with thermoresponsive polymers like poly(2-alkyl-2-oxazoline)s, it enables the fabrication of intelligent materials that respond to temperature variations, with promising applications in controlled drug release and tissue engineering.

In this study, nanocellulose derived from sugarcane bagasse, an abundant agricultural residue in Brazil, was obtained through both chemical and physical methods: cellulose nanocrystals (CNC) were produced via acid hydrolysis, while cellulose nanofibrils (CNF) were generated through fibrillation using a Masuko Ultragrinder. Both types of nanocelluloses were further modified via TEMPO-mediated oxidation. The functionalization of CNC and CNF was carried out using a grafting-to approach, where amine-terminated poly(2-alkyl-2-oxazoline)s were covalently attached to oxidized nanocellulose. The coupling between primary amine and carboxylate groups was facilitated by EDC/NHS chemistry, ensuring a stable polymer-nanocellulose attachment. After centrifugation to remove unbound polymer, the resulting nanocomposites exhibited self-assembling behavior, forming thermoresponsive hydrogels. These hydrogels demonstrated a reversible sol-gel transition at approximately 50°C, highlighting their potential for smart material applications.

Additionally, poly(2-alkyl-2-oxazoline) synthesis was optimized to achieve low polydispersity index (PDI) and tunable lower critical solution temperature (LCST) by adjusting the polymer molar mass and alkyl side chains. Monomers including 2-methyl-, 2-ethyl-, 2-n-propyl-, and 2-isopropyl-2-oxazoline were used, yielding polymers ranging from 2.5 kDa to 10 kDa. Given that poly(2-alkyl-2-oxazoline)s can be used as precursors to poly(ethyleneimine), a polycation widely employed in gene delivery, these materials hold significant promise for biomedical applications. To further enhance the biomedical potential of the hydrogels, block copolymers of poly(2-ethyl-2-oxazoline)-b-(ethyleneimine) were synthesized.

Future studies will focus on optimizing the rheological properties and biocompatibility of these hydrogels to improve their performance in drug delivery and tissue engineering applications.