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Michael A Washington, Katherine Duncan, Susannah Waxman, Nils A Loewen, Jenny Y Yu, Morgan V Fedorchak; Incorporation of survey data from ophthalmologists and first responders in the development of a novel, point-of-injury treatment for ocular trauma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):111.
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Proper treatment and protection of traumatic ocular injuries at the point-of-injury are critical to preserving the form and function of the eye and its supporting adnexa. This study tested the hypothesis that thermoresponsive gels (TRGs) possessing in situ semi-interpenetrating network (s-IPN) formation abilities are viable candidates for immediate stabilization and treatment of open-globe injuries.
Poly(N-isopropylacrylamide-co-ethyl acrylate) (pNIPAAm-co-EA) copolymers were synthesized using a free radical polymerization method. Microstructural composition and physical properties of all copolymers were characterized via NMR, FT-IR, GPC, DSC, and DMA. s-IPN formation within the TRG was achieved via in situ crosslinking of sodium alginate or deacetylated chitosan. An ex vivo porcine eye model was used to test intraocular pressure stabilization efficacy of TRGs for full thickness globe lacerations. Ocular irritation was assessed using the hen’s egg test on chorioallantoic membrane and bovine corneal opacity and permeability test. The in vitro proliferation and migration of keratinocytes incubated with TRGs was assessed in a scratch wound assay. Traumatic ocular injury survey data was acquired from 33 clinicians in the fields of ophthalmology and emergency medicine.
pNIPAAm-co-EA copolymers were successfully synthesized and lower critical solution temperatures (LCST) decreased from 36 °C to 26 °C with increasing mol% of EA. Incorporation of in situ crosslinking agents within TRGs had little influence on the LCST. Ex vivo studies simulating corneoscleral lacerations demonstrated that pNIPAAm-co-EA TRGs conformed and covered the globe, while providing immediate and sustained IOP stabilization over 6 h. Expanded ex vivo open-globe studies incorporating in situ crosslinking agents within TRGs will be reported. Cytocompatibility assays provide further justification for advancing pNIPAAm-co-EA-based TRGs to in vivo studies. Survey responses suggest that our material addresses the most pressing perceived needs for point-of-injury ocular trauma care.
Poly(N-isopropylacrylamide-co-ethyl acrylate)-based TRGs were shown to have ideal phase transition temperatures and physical properties for ocular wound coverage and open-globe IOP stabilization. Future studies will evaluate these materials in large animal ocular trauma models.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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