title: Ocular biocompatibility of gelatin microcarriers functionalized with oxidized hyaluronic acid.
abstract: Given that the presence of aldehyde groups on the oxidized sugar residues may pose toxicity concerns, it is necessary to examine the safety of gelatin microcarriers (GMC) functionalized with oxidized hyaluronic acid (oHA) for potential ophthalmic applications. In this study, the ocular biocompatibility of biopolymer microcarriers was investigated in vitro using primary rabbit corneal cell cultures and in vivo using the anterior chamber of the rabbit eye model. Our results showed that different types of corneal cells including epithelial, stromal, and endothelial cells remain viable and actively proliferate following 2 and 4days of exposure to test materials. In addition, similar interleukin-6 gene expression levels and comet tail lengths were seen in the presence and absence of biopolymer microcarriers, suggesting no cellular inflammation and genotoxicity. After 7 and 14days of intracameral injection in the rabbit eyes, both the GMC samples and their counterparts functionalized with oHA were well tolerated in the ocular anterior chamber as demonstrated by slit-lamp biomicroscopy. Clinical observations including specular microscopic examinations, corneal topography, and corneal thickness measurements also showed that the rabbits bearing biopolymer microcarriers exhibit no signs of corneal edema and astigmatism as well as endothelial damage, indicating the absence of tissue response. It is concluded that the GMC materials functionalized with oHA (oxidation level: 10.4±0.9%) are compatible toward corneal cells and ocular anterior segment tissues at a concentration of 10mg/ml. The information about the effect of coupling of aldehyde-functionalized HA to gelatin on in vitro and in vivo biocompatibility of biopolymer composites can be used as further development of corneal stromal cell microcarriers for tissue engineering applications.
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan, Republic of China; Biomedical Engineering Research Center, Chang Gung University, Taoyuan 33302, Taiwan, Republic of China; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, Republic of China; Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, Republic of China; Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan, Republic of China. Electronic address: jylai@mail.cgu.edu.tw.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, Republic of China; Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, Republic of China; Department of Chinese Medicine, Chang Gung University, Taoyuan 33302, Taiwan, Republic of China.
authors.forename: David Hui-Kang
authors.initials: DH
authors.lastname: Ma
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D005780:Gelatin / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D006820:Hyaluronic Acid / Q000737:chemistry*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011817:Rabbits
chemical_list: D001672:Biocompatible Materials; D015850:Interleukin-6; D005780:Gelatin; D006820:Hyaluronic Acid
keywords: Biopolymer microcarrier; Gelatin; Ocular biocompatibility; Oxidized hyaluronic acid