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Gina L Griffith, Barbara M Wirostko, Hee-Kyoung Lee, Anthony James Johnson, David O Zamora; Human growth hormone released from a biocompatible hyaluronic acid biomaterial modulates wound healing in an in vivo corneal chemical burn model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1265.
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© ARVO (1962-2015); The Authors (2016-present)
Hyaluronic acid, a ubiquitously expressed polysaccharide, is of great interest in the bioengineering and regenerative medicine communities for use as an off-the-shelf biomaterial. In this study, cross-linked carboxymethylated hyaluronic acid (CMHA-S)-based film strips were utilized to provide a sustained release of recombinant human growth hormone (rHGH) and facilitate the repair and regeneration of damaged ocular tissues. Our purpose was to test the hypothesis that CMHA-S strips, with and without loaded rHGH, are biocompatible in vivo and can be securely and safely retained in the eye for the treatment of corneal epithelial chemical burns.
The nictitating membranes of 30 New Zealand white rabbits (~3.0 kg) were removed 3 wks prior to wound creation and strip placement. Burns 5.5 mm in diameter were created by placing a circular filter paper soaked in 1N NaOH centrally onto the cornea for 30 seconds. Wounds were immediately rinsed with sterile buffered saline, and the eye evaluated using the McDonald-Shadduck ophthalmic exam and fluorescein staining. Animals were randomly grouped (n=5 per group) for treatment with control CMHA-S strips or with CMHA-S strips containing 50 or 150 µg/strip of rHGH. At one and two weeks post strip placement, eyes were evaluated by slit lamp and in vivo confocal microscopy. Corneal histology was performed using H&E and Masson’s Trichrome stain.
Upon re-hydration, CMHA-S strips exhibited swelling to yield a clear soft oblong strip of ~4 mm wide by ~15 mm long, able to be manipulated with forceps and placed into the lower eye cul-de-sac. All strips were retained in the eye for a minimum of 96 hrs, with a maximum retention time of 14 days post placement. Wounds treated with rHGH loaded films exhibited an increase in wound closure compared to those treated with unloaded strips. Loaded and unloaded strips were biocompatible and did not reveal any pathological effects to the eye or surrounding tissues clinically or on histopathology.
CMHA-S film strips are biocompatible and easily retained in the ocular cul-de-sac. Furthermore, when compared to unloaded strips, the rHGH-loaded strips are capable of modulating the re-epithelialization of acute corneal burns. These results advance the overall efforts to develop the first FDA-approved ocular pharmaceutical indicated for corneal wound healing.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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