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Hirokazu Kaji, Toshinori Fujie, Nobuhiro Nagai, Toshiaki Abe; Local Delivery of an Engineered Epithelial Monolayer by Micropatterned Polymeric Nanosheets. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1449.
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Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly population, whose main complication is the development of subretinal choroidal neovascularization and degeneration of retinal pigment epithelial (RPE) cells. In this regard, subretinal transplantation of RPE cells to the degenerated site has attracted a great deal of attention as an innovative therapeutics for the treatment of AMD. However, poor viability, distribution and integration of the transplanted cells in suspension to the narrow subretinal space have limited this approach. Therefore, development of cell delivery devices would bring significant benefits for the AMD treatment. Here, we developed micropatterned nanosheets consisting of biodegradable poly(lactic-co-glycolic acid) (PLGA), which can deliver RPE monolayer to the subretinal space in a minimally invasive way.
Micropatterned nanosheets of PLGA were prepared by combination of spincoating and microcontact printing technique. RPE cells were cultured on the nanosheets and the cell activity on the nanosheets was evaluated using LIVE/DEAD staining assay. Moreover, syringe injection of the micropatterned nanosheet was examined using swine ocular globes ex vivo.
Despite the mechanical share stress during aspiration and injection by the syringe needle, the RPE monolayer on the nanosheet retained the original shape without any fracture, and kept the viability over 80% regardless of the sheet diameter. On the other hand, the micropatterned sheet with micrometric thickness hardly retained the cells (less than 30%). Finally, a micropatterned nanosheet of 1 mm in diameter was injected into the subretinal space of a swine ocular globe by a 24G intravenous catheter. The nanosheet was successfully released into the subretinal place, and fixed on the macula after removing the prefilled saline without structural distortion.
We developed micropatterned nanosheets consisting of biodegradable polymers, on which stable monolayer of the RPE cells were engineered. Owing to the high flexibility of the nanosheets, RPE cells were injected through the syringe needle without significant loss of the cellular viability. The flexible micropatterned nanosheets injectable by the syringe needle hold great promise to transplant organized RPE cells in a minimum invasive way.
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