RESUMO
Ocular trauma and disorders that lead to corneal blindness account for over 2 million new cases of monocular blindness every year. A popular ocular surface reconstruction therapy, amniotic membrane transplantation, has been shown to aid corneal wound repair. However, the success rates of the procedure are variable. Here, we proposed to bioengineer a novel synthetic material that would serve as a biomimetic corneal bandage. The PLGA-PEG-PLGA triblock copolymer was synthesised via ring-opening polymerisation. Thermoreversible gelation behaviour was investigated at different polymer concentrations (23%, 30%, 35%, 40%, 45%, w/v) at temperatures ranging between 5 and 60 degrees C. Viscoelastic properties were studied in dynamic mechanical analysis with 1 degrees C/min temperature ramp. Cryo-SEM revealed a porous hydrogel with interconnecting networks. No adverse cytotoxicity was observed with an in vitro scratch-wound assay and in in vivo biocompatibility tests. We have demonstrated that the PLGA-PEG-PLGA hydrogel possessed a suitable gelling profile and, for the first time, the biocompatibility properties for this application as a potential bandage for corneal wound repair.
Assuntos
Córnea/efeitos dos fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Temperatura , Cicatrização/efeitos dos fármacos , Animais , Células Cultivadas , Córnea/cirurgia , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Ácido Láctico/química , Ácido Láctico/metabolismo , Ácido Láctico/farmacologia , Microscopia Eletrônica de Varredura , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polietilenoglicóis/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/metabolismo , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Polímeros/metabolismo , Polímeros/farmacologia , Coelhos , Soluções , ViscosidadeRESUMO
We designed a new ophthalmic drug-delivery system for epidermal growth factor (EGF) from the biodegradable hydrogel of cationized gelatin. We placed a cationized gelatin hydrogel (CGH) with incorporated (125)I-labelled EGF in the conjunctival sac of mice and measured the residual radioactivity at different times to evaluate the in vivo profile of EGF release. Approximately 60-67% and 10-12% of EGF applied initially remained 1 and 7 days after application, respectively; whereas EGF delivered in topically applied solution or via EGF impregnation of soft contact lenses disappeared within the first day. We also placed CGH films with 5.0 mug of incorporated EGF on round corneal defects in rabbits to evaluate the healing process using image analysis software and to assess epithelial proliferation immunohistochemically by counting the number of Ki67-positive cells. The application of a CGH film with incorporated EGF resulted in a reduction in the epithelial defect in rabbit corneas accompanied by significantly enhanced epithelial proliferation compared with the reduction seen after the topical application of EGF solution or the placement of an EGF-free CGH film. The controlled release of EGF from a CGH placed over a corneal epithelial defect accelerated ocular surface wound healing.
