title: Relationship between structure and cytocompatibility of divinyl sulfone cross-linked hyaluronic acid.
abstract: Hyaluronic acid (HA), a carbohydrate polymer naturally found in the eye, has been chemically modified by cross-linking to enhance its performance as a drug carrier. Although the treatment of HA with divinyl sulfone (DVS) is reported, the effects of cross-linker concentration on the biomaterial-mediated retinal pigment epithelial (RPE) cellular responses are yet to be investigated. This paper explores, for the first time, the relationship between molecular structure and cytocompatibility of HA hydrogels cross-linked with DVS of varying concentrations (0-100mM). The results showed that with increasing DVS concentration, the sulfur content and sulfonyl-bis-ethyl cross-link amount are increased and the mechanical stability and resistance against enzymatic degradation are enhanced, indicating the crucial role of cross-linker in the alteration of structure and property of this polysaccharide biomaterial. The cell viability, pro-inflammatory gene and cytokine expression, and glutamate uptake were suggested to be indicative of cytocompatibility and found to be strongly dependent on the cross-linker concentration.
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan, ROC; Biomedical Engineering Research Center, Chang Gung University, Taoyuan 33302, Taiwan, ROC; Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan, ROC. Electronic address: jylai@mail.cgu.edu.tw.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Lai
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D008422:Materials Testing; D055595:Mechanical Phenomena; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D004337:Drug Carriers; D013450:Sulfones; D018698:Glutamic Acid; C009873:divinyl sulfone; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase
keywords: Cross-linker concentration; Cytocompatibility; Divinyl sulfone; Hyaluronic acid; Molecular structure; Retinal pigment epithelium