Hemicellulose-based nanoaggregate-incorporated biocompatible hydrogels with enhanced mechanical properties and...

Local drug delivery has generated considerable interest due to its controlled and sustained drug release at the target site on demand. Nanoaggregate-incorporated composite hydrogels are desirable as local drug delivery systems; however, it is difficult to achieve sustained and controlled hydrophobic drug release and superior mechanical properties in one system. Herein, a "smart" composite hydrogel was synthesized by incorporating hemicellulose-based nanoaggregates into a double network consisting of alginate/Ca²⁺ and polyacrylic acid-co-dimethylaminoethyl methacrylate [P(AA-co-DMAEMA)]. Hemicellulose-based nanoaggregates were assembled from xylan-rich hemicellulose laurate methacrylate (XH-LA-MA) polymers and entrapped into the hydrogel framework via chemical fixation. Another composite hydrogel with physically embedded hemicellulose laurate (XH-LA) nanoaggregates was prepared as a comparison. Accordingly, covalently cross-linked XH-LA-MA nanoaggregates in hydrogels resulted in a denser pore structure and reinforced mechanical properties. Nanoaggregate diffusion analysis revealed that covalent bonding between the nanoaggregates and the hydrogel framework contributed to prolonged diffusion behavior. Curcumin (Cur)-loaded XH-LA-MA composite hydrogels enabled sustained Cur release in simulated body fluid and showed stimulus responsiveness toward ethylenediaminetetraacetic acid (EDTA) and/or glutathione (GSH). All the composite hydrogels were biocompatible, as verified by Cell Counting Kit-8 (CCK-8) assay against NIH/3T3 cells. These composite hydrogels hold great potential as a promising dosage form for biomedical applications.