title: Ocular biocompatibility of carbodiimide cross-linked hyaluronic acid hydrogels for cell sheet delivery carriers.
abstract: Due to its innocuous nature, hyaluronic acid (HA) is one of the most commonly used biopolymers for ophthalmic applications. We recently developed a cell sheet delivery system using carbodiimide cross-linked HA carriers. Chemical cross-linking provides an improvement in stability of polymer gels, but probably causes toxic side-effects. The aim of this study was to investigate the ocular biocompatibility of HA hydrogels cross-linked by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC). HA discs without cross-linking and glutaraldehyde (GTA) cross-linked HA samples were used for comparison. The disc implants were inserted in the anterior chamber of rabbit eyes for 24 weeks and characterized by slit-lamp biomicroscopy, histology and scanning electron microscopy. The ophthalmic parameters obtained from biomicroscopic examinations were also scored to provide a quantitative grading system. Results of this study showed that the HA discs cross-linked with EDC had better ocular biocompatibility than those with GTA. The continued residence of GTA cross-linked HA implants in the intraocular cavity elicited severe tissue responses and significant foreign body reactions, whereas no adverse inflammatory reaction was observed after contact with non-cross-linked HA or EDC cross-linked HA samples. It is concluded that the cross-linking agent type gives influence on ocular biocompatibility of cell carriers and the EDC-HA hydrogel is an ideal candidate for use as an implantable material in cell sheet delivery applications.
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan 33302, Republic of China. jylai@mail.cgu.edu.tw
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Lai
authors.forename: David Hui-Kang
authors.initials: DH
authors.lastname: Ma
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Cheng
authors.forename: Chi-Chin
authors.initials: CC
authors.lastname: Sun
authors.forename: Shu-Jung
authors.initials: SJ
authors.lastname: Huang
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Li
authors.forename: Ging-Ho
authors.initials: GH
authors.lastname: Hsiue
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002234:Carbodiimides / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D005123:Eye / Q000648:ultrastructure; D005137:Eye, Artificial; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D011817:Rabbits
chemical_list: D001672:Biocompatible Materials; D002234:Carbodiimides; D003432:Cross-Linking Reagents; D020100:Hydrogels; D006820:Hyaluronic Acid