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Marion Jamard, Scott D Fitzpatrick, Jafar Mazumder, Amanda Fawcett, Stefan Paterson, Heather Sheardown, Sheardown group; Minimally Invasive Copolymers For Ocular Therapeutics. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5180.
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Cellular transplantation therapy has become an increasingly investigated strategy for regeneration of ocular tissues. In the current work, the use of an in-situ gelling scaffold is considered as a means of cell delivery in order to overcome the poor survival and integration of those cells by providing enhanced cellular attachment. Thermo-responsive copolymers are attractive materials for the design of such minimally invasive scaffolds and were employed in the current work. These polymers can be synthesized to exhibit promising features including lower critical solution temperatures (LCST) below 37°C, mechanical strength and transparency.
N-isopropylacrylamide (NIPAM) based copolymers containing poly(ethylene glycol) (PEG), acryloyloxy dimethyl-g-butyrolactone (DBA) and acrylic acid (AA) or acrylic acid N-hydroxysuccinimide ether (NAS) have been developed. To improve the properties, various ratios and composition modifications have been investigated to create a broader range of those properties. Furthermore, cellulose including hydroxypropyl methylcellulose (HPMC), methyl cellulose and hydroxypropyl cellulose (HPC), thermo-responsive, degradable and FDA approved, have been considered as an alternative to NIPAM. Modification by graft polymerization has been employed to modify their properties (transparency and LCST) to tune them for their application as ocular therapeutics for cell delivery.
The NIPAM based materials study resulted in a selection of materials undergoing fast thermo-gellation at physiologic temperature. The gels synthesized with AA were found to exhibit a stickier texture compared to those with NAS. PEG ratio and molecular weight appeared as a determining parameter of the gels’ properties. The gels synthesized with low molecular weight PEG (500 g/mol) were found to be opaque but cohesive. Increasing the PEG ratio (from 4% to 12%) had a weakening effect on the mechanical properties of the gels. The materials synthesized with 4% of high molecular weight PEG (950 g/mol) for 12% DBA were found to result in strong and transparent gels (LCST at 36°C). The results on cellulose derivatives-based materials are pending.
Materials featuring encouraging properties in terms of LCST, mechanical properties and LCST have been developed for their application as ocular therapeutics for cell delivery. Further study will aim at functionalizing them for cell attachment and improved viability.
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