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C. Scholz, W. Vayaboury, D. B. Shire, J. F. Rizzo, III; Biocompatible Block Copolymers for Coating Sub-Retinal Prostheses. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3019. doi: https://doi.org/.
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This work is related to the efforts of the Boston Retinal Implant Project to develop a sub-retinal prosthesis to restore vision to the blind. The specific purpose of this work is to synthesize, characterize and perform preliminary biocompatibility studies on derivatized block copolymer coatings for the electrode arrays that comprise the intraocular component of our device. These persistent coatings may be further chemically modified to enable the formation of factor-releasing gels to elute anti-inflammatory or neurotrophic factors.
Biocompatible block copolymers were synthesized by ring-opening polymerization of N-carboxyanhydrides (NCA’s) of protected L-lysine, L-glutamate, L-aspartate, L-cystein and L-leucine using a-methoxy-w-amino poly(ethylene glycol), PEG as a macroinitiator. A novel and improved mechanism for covalent anchoring of the block copolymers was developed based on cysteine chemistry, in which the poly(amino acid block) is a random, cysteine-containing copolypeptide. Triblock copolymers were synthesized to yield gels that find potential application as drug-carrying coatings.
Block copolymers consisting of PEG and a random peptidic block consisting of glutamate or lysine and cysteine repeat units were synthesized. By incorporating cysteine repeat units into the poly(amino acid) block, the oxygen-sensitive post-polymerization derivatization of the block copolymers could be prevented and the synthesis of reactive, biocompatible surface coatings became highly efficient. Triblock copolymers were synthesized as potential drug-carrying coatings. It was shown that the molecular architecture strongly determines the gelation behavior of the copolymer: while triblock copolymers with a terminal hydrophobic block yield strong gels at concentrations smaller than 1 wt%, copolymers with the hydrophobic block in the middle yield viscous gums, and do not gel, due to the entropic penalty imposed by the flanking hydrophilic blocks.
We have developed new experimental conditions for NCA polymerisations allowing the preparation of metal-free monodisperse polypeptides and peptidic block copolymers with total control over both composition and molecular weight and established experimental conditions under which the polymerisation proceeded as living polymerization. Under those conditions, side reactions are avoided and the hydrogen bond associations are limited. These persistent coatings have been shown to be biocompatible and suitable for future use in retinal prosthesis applications.
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