Enzymatically cross-linked hyaluronic acid/graphene oxide nanocomposite hydrogel with pH-responsive release

Abstract

Hyaluronic acid (HA) is made up of repeating disaccharide units (β-1,4-d-glucuronic acid and β-1,3-N-acetyl-d-glucosamine) and is a major constituent of the extracellular matrix. HA and its derivatives which possess excellent biocompatibility and physiochemical properties have been studied in drug delivery and tissue engineering applications. Tyramine-based HA hydrogel with good compatibility to cell and tissue has been reported recently. However, inferior mechanical property may limit the biomedical application of the HA hydrogel. In this study, HA/graphene oxide (GO) nanocomposite (NC) hydrogel was prepared through a horseradish peroxidase catalyzed in situ cross-linking process. As compared with pure HA hydrogels, incorporation of GO to the HA matrix could significantly enhance the mechanical properties (storage moduli 1800 Pa) of the hydrogel and prolong the release of rhodamine B (RB) as the model drug from the hydrogel (33 h) as well. In addition, due to the multiple interactions between GO and RB, the NC hydrogels showed excellent pH-responsive release behavior. The release of RB from the NC hydrogel was prolonged at low pH (pH 4.0) in the presence of GO, which could be attributed to the enhanced interactions between GO and HA as well as with RB. In situ three-dimensional encapsulation of mouse embryonic fibroblasts (BALB 3T3 cells) in the NC hydrogels and cytotoxicity results indicated the cytocompatibility of both the enzymatic cross-linking process and HA/GO NC hydrogels (cell viability 90.6 ± 4.25%). The enzymatically catalyzed fabrication of NC hydrogels proved to be an easy and mild approach, and had great potential in the construction of both tissue engineering scaffolds and stimuli-responsive drug release matrices.

Drug Carriers Based on Graphene Oxide and Hydrogel: Opportunities and Challenges in Infection Control Tested by Amoxicillin Release

“…The combination of GO with hydrogels was described previously in another drug delivery context. GO-based hydrogels present functional properties, for instance, pH-responsiveness, good mechanical properties, and thermal stabilities [60]. Thus this combination was tested, i.e., in curing bacterial infections in the gastrointestinal tract [61,62].…”

Hyaluronic Acid-Conjugated Carbon Nanomaterials for Enhanced Tumour Targeting Ability

“…Graphene and its derivatives have attracted considerable interest due to their unique 2-D structure that provides a large surface area for π–π stacking [ 83 , 84 , 85 , 86 ]. The functional groups attached to GO sheets such as epoxy, hydroxyl, and carboxylic acid facilitate easy modification [ 87 ] and facilitate the dispersion of GO in specific polymer matrices or polar monomers during in situ polymerization [ 88 ].…”

Soft-Nanocomposites of Nanoparticles and Nanocarbons with Supramolecular and Polymer Gels and Their Applications

“…Song et al employed another biomolecule hyaluronic acid to prepare nanocomposite hydrogel with GO through horseradish peroxidase catalyzed in situ cross-linking process. 399 Compared to pure hyaluronic acid hydrogel, mechanical stability of the composite gel was Several other groups have also reported potential dye removal application of GO-based gel-nanocomposites. Li et al reported functionalization of poly(vinyl alcohol) (PVA) hydrogels with GO for dye removal applications.…”