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Igor Kozak, Zbynek Stranak, Stepan Popelka, Taras Ardan, David Rais, Jana Cizkova, Sonali Rohiwal, Jan Motlik; Safety and feasibility of new nanofiber subretinal delivery system with injector for RPE cell transplantation.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5670. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We developed a new delivery system for potential transplantation of retinal pigment epithelial (RPE) cells in the subretinal space. The purpose of this study was to test feasibility of surgical implantation and safety of the nanofiber membrane in subretinal space in minipig model.
Electrospun nanofiber membrane of poly(DL-lactide) with a stiffer frame made of a poly(4-dioxanone) monofilament suture fibre was previously manufactured by our group. The fiber width and pore diameter distribution were determined from scanning electron microscope photographs. Membrane stiffness was assessed by punch test and porosity was calculated using density of the porous structure (ds) and the density of structure material (d) as (1-ds/d). In vivo experiements using minipig model were performed at the Institute of Animal Physiology and Genetics in Libechov, Czech Republic. Pars plana vitrectomy surgery with subretinal implantation of RPE cells loaded nanofiber memebrane was performed in six adult minipigs under general anesthesia. Retinal photography, optical coherence tomography, histology and immunohistochemistry were perfomed 2 months after implantation.
The 3.7 µm nanofiber membrane had on average the stiffness of 0.25 Nmm-1 and 77% porosity - much higher in comparisoon to currently available membrane carriers. In animal experiments, the frame supported membranes were successfully implanted through 2.5 mm retinotomy. There were no post-operative ocular adverse events and imaging studies demonstrated stable subretinal placement of implants. Histopathology and immunohistochemistry confirmed subretinal location and cellular survival, respectively (Figure 1).
The design of the suggested nanofibrous carrier with a peripheral frame was optimized to provide a minimal diffusion barrier for the flow of nutrients in the subretinal space and at the same time to resist surgical handling. Novel cell carrier for RPE transplantation based on an ultrathin nanofibrous membrane with supporting structure facilitates surgical manipulation and enables the carrier to regain a flat shape in the subretinal space. At 2 months post implantation in pigs, it is biologically inert and surviving RPE cells can be identified using immunohistochemistry.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Figure 1. Enucleated porcine eye showing subretinal placement of implant.
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