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Ben Muirhead, Scott Fitzpatrick, Kevin Gregory-Evans, Mick Bhatia, Heather Sheardown; NIPAAm Based Cell Delivery Scaffolds for Posterior Segment Therapeutics. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4627.
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Age related macular degeneration (AMD) is a leading cause of blindness, and the fastest growing source of visual impairment afflicting the elderly. Dry-AMD is fundamentally characterized by loss of the retinal pigment epithelium (RPE) layer. Stem cells have enormous clinical utility, both through the direct replacement of damaged tissues, as well as through paracrine maintenance of the tissue microenvironment. While it is currently possible to differentiate both induced pluripotent (iPS) and embryonic (ES) stem cells into RPE, there is a lack of effective delivery mechanism to ensure clinical efficacy. To address this need, we have developed novel, in situ gelling artificial cell scaffolds based on poly-n-isopropylacrylamide (PNIPAAm). These materials exists as a liquid at room temperature allowing facile injection, then undergo a phase transition initiated by body temperature creating an effective delivery scaffold. We will evaluate the effectiveness of scaffold materials on dry-AMD model systems.
Several poly(NIPAAm-NAS- PEO-DBA) (pNNPD) copolymers with were prepared by free radical polymerization. Briefly, constituents were dissolved in dioxane and heated to 70C for 24 hours. Copolymers were collected by precipitation in anhydrous ethyl ether, and dialysed to remove impurities. Materials were sterilized with 4MRads of gamma radiation. Materials underwent a series of in vivo and in vitro assays to ensure biocompatibility. Retinal progenitor cells were used to treat disease models both in vitro, as well as in Lewis rats and New Zealand white rabbits.
Materials were found to be immunologically silent, and caused no adverse reactivity in any tissues into which it was implanted. Materials were successfully implanted into both the vitreous and sub-retinal space of model animals using a 33 gauge syringe, whereupon they formed robust gels as designed. RPE cells were successfully harvested from cadaver sources, and transformed into pluripotent stem cells. Model systems were created to establish the treatment potential of this approach.
NIPAAm based in situ gelling cell delivery scaffolds are promising materials facilitating cell therapy in the back of the eye. Cells have successfully been implanted into the subretinal space, and model systems have been devised to test the ability of these materials to treat dry-AMD.
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