title: 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.
authors.affiliation: a College of Chemistry and Molecular Science , Wuhan University , Wuhan, Hubei 430072 , P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Song
authors.forename: Weikang
authors.initials: W
authors.lastname: Hu
authors.forename: Longqiang
authors.initials: L
authors.lastname: Xiao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cao
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Liqiong
authors.initials: L
authors.lastname: Liao
authors.forename: Lijian
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival; D016503:Drug Delivery Systems / Q000295:instrumentation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D006108:Graphite / Q000138:chemical synthesis / Q000737:chemistry*; D006735:Horseradish Peroxidase / Q000737:chemistry; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053761:Nanocomposites / Q000737:chemistry*; D010087:Oxides / Q000138:chemical synthesis / Q000737:chemistry*; D012235:Rhodamines / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D005456:Fluorescent Dyes; D020100:Hydrogels; D010087:Oxides; D012235:Rhodamines; D006108:Graphite; D006820:Hyaluronic Acid; D006735:Horseradish Peroxidase; C029773:rhodamine B
keywords: graphene oxide; hyaluronic acid; pH responsive; release