Abstract
Chitosan is a naturally occurring cationic polysaccharide and has attracted much attention in the past decade as an important ophthalmic biomaterial. We recently demonstrated that the genipin (GP) cross-linked chitosan is compatible with human retinal pigment epithelial cells. The present work aims to further investigate the in vivo biocompatibility of GP-treated chitosan (GP-chi group) by adopting the anterior chamber of a rabbit eye model. The glutaraldehyde (GTA) cross-linked samples (GTA-chi group) were used for comparison. The 7-mm-diameter membrane implants made from either non-cross-linked chitosan or chemically modified materials with a cross-linking degree of around 80% were inserted in the ocular anterior chamber for 24 weeks and characterized by slit-lamp and specular microscopic examinations, intraocular pressure measurements, and corneal thickness measurements. The interleukin-6 expressions at mRNA level were also detected by quantitative real-time reverse transcription polymerase chain reaction. Results of clinical observations showed that the overall ocular scores in the GTA-chi groups were relatively high. In contrast, the rabbits bearing GP-chi implants in the anterior chamber of the eye exhibited no signs of ocular inflammation. As compared to the non-cross-linked counterparts, the GP-chi samples improved the preservation of corneal endothelial cell density and possessed better anti-inflammatory activities, indicating the benefit action of the GP cross-linker. In summary, the intracameral tissue response to the chemically modified chitosan materials strongly depends on the selection of cross-linking agents.
Highlights
It is well known that biocompatibility is an important factor in determining the success of new medical implants and devices in the physiological environment
Over the past few years, the anterior chamber of a rabbit eye model was used in our laboratory to test the ocular biocompatibility of various kinds of materials such as amniotic membrane [2], hyaluronic acid [3], gelatin [4], poly(2-hydroxyethyl methacrylate)-co-poly(acrylic acid) [5], and gelatin-g-poly(N-isopropylacrylamide) [6]
The structural integrity of the implants was deteriorated since significant loss of non-cross-linked chitosan materials might have occurred during a 24-week in vivo degradation
Summary
It is well known that biocompatibility is an important factor in determining the success of new medical implants and devices in the physiological environment. The eye has been considered to be an immune privileged site, the in vivo safety of a biomaterial should be checked before its ophthalmic application. A methodology based on this animal model for biocompatibility assessment in an immune privileged site has several advantages, including convenient access to view, excellent tissue sensitivity, and reliable ophthalmic parameters [2]. A naturally occurring cationic polysaccharide, is obtained by the deacetylation of chitin. It is primarily composed of repeating D-glucosamine units and has wide biomedical applications, such as tissue engineering/regenerative medicine [7,8] and controlled drug/gene delivery [9,10]
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