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Gina L Griffith, Barbara M Wirostko, Hee-Kyoung Lee, David O Zamora, Anthony James Johnson; Model development: Use of a biocompatible thiolated hyaluronic acid biomaterial for the treatment of corneal epithelial wounds. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3089.
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© ARVO (1962-2015); The Authors (2016-present)
Hyaluronic acid, a ubiquitously expressed polysaccharide, is of great interest in the biomedical engineering community for use as a biomaterial in wound healing and regenerative medicine. As a result, cross-linked carboxymethylated hyaluronic acid (CMHA)-based bioabsorbable strips (Jade Therapeutics) have been developed to provide sustained release of therapeutic drugs to facilitate the repair and regeneration of damaged ocular tissues. Our purpose was to test the hypothesis that CMHA strips with and without recombinant human growth hormone (rHGH) are biocompatible in vivo and can be safely and securely retained in the eye for the potential treatment of corneal epithelial wounds.
Dehydrated CMHA strips were obtained from Jade under a Cooperative Research and Development Agreement. The nictitating membranes of ten New Zealand (NZ) white rabbits (2.5-3.0 kg; Protocol A-13-038) were removed three weeks prior to placement of CMHA strips either with (n=5) or without (n=5) rHGH (150 µg/strip). Strips were re-hydrated in 0.1% rose bengal dye in sterile balanced buffered saline before placement in the left eye cul-de-sac. While animals were observed daily using the McDonald-Shadduck ophthalmic exam, all animals were also observed one week post strip placement via slit lamp and in vivo confocal microscopy. Corneal histology was performed using H&E and Masson’s Trichrome stains to investigate any potential ocular pathology due to the strip.
Upon re-hydration, the CMHA strips exhibited swelling to yield an oblong strip of approximately 4 mm width by 15 mm length. The strips maintained a clear, tinted appearance with enough tensile strength to be handled and placed into the lower eye cul-de-sac with surgical forceps. All strips were retained in the eye for 96 h with a maximum retention time of 11 days post placement. The strips appear to be highly biocompatible as determined by slit lamp examination, in vivo confocal microscopy, and McDonald-Shadduck exam scores. Corneal histology did not reveal any pathological effects as a result of treatments.
Our results demonstrate that CMHA strips with or without rHGH are biocompatible and retained in the eye when placed in the lower cul-de-sac. Future studies aim to determine the efficacy and release profile of rHGH-loaded strips as an approved pharmaceutical for the treatment of ocular surface wounds.
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