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Bevacizumab (Avastin(®)) has been used by ophthalmologists in many countries as an off-label drug for the treatment of wet age-related macular degeneration (AMD). Due to its short half-life necessitating frequent intravitreal injection, a method for sustained delivery is in need. We demonstrated that bevacizumab could be released in a sustained fashion over 90 days from nano- and microspheres fabricated from poly(DL-lactide-co-glycolide) and poly(ethylene glycol)-b-poly(D,L-lactic acid), respectively. The drug release rate could be adjusted by alteration of the drug/polymer ratio. The use of such nano- and microspheres as bevacizumab delivery vehicles may improve the treatment of wet AMD.

Our objective was to develop collagen-based hydrogels as tissue substitutes for corneal transplantation The design of the full-thickness corneal grafts includes prevention of cell migration onto the posterior surface of the implants, using a plasma-assisted surface modification technique. Briefly, the hydrogel materials were Subjected to ammonia plasma functionalization followed by grafting of alginate macromolecules to the target surface. The treated materials Surfaces showed observable decreases in endothelial cell attachment. The decrease in cell attachment and adhesion was dependant upon the concentration of alginate and plasma radio frequency (RF) power. High concentrations of alginate 5%, (w/v) and high I F power of 100 W produced surfaces with minimal cell attachment. The plasma-alginate treatment did not adversely affect the optical or swelling properties of the constructs. Contact angle measurement analysis revealed that the posterior surface hydrophilicity significantly increased after the treatment. The grafting of alginate to the implants surfaces was confirmed by fourier transform infrared spectroscopy. Both of the untreated and alginate grafted corneal materials were found to be superior to human cornea in optical and swelling properties.

PURPOSE. To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. METHODS. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. RESULTS. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. CONCLUSIONS. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.

A transparent matrix composed of collagen and poly(N, N-dimethylacrylamide-coacryloxysuccimide), 8mm in diameter and 350 mu m thick was implanted into pigs corneas using the lamellar keratoplasty (LKP) technique. No adverse immune or inflammatory reaction was observed during 4 month implantation period. Regenerated nerve filaments were observed in the subepithelial region and stroma by confacal microscopy. The endothelium of the operated eye was not touched by LKP and remained similar to that of the contra lateral (not operated) eye. The implant remained transparent over the four-month post-operative period, and clinical topography showed reconstitution of a smooth cornea surface. These preliminary results indicated that a new, functional cornea was re-established from the implanted biosynthetic matrix. This bio-synthetic matrix may have applications in other tissue engineering areas,, especially where innervation is important.

Devices, methods, and compositions for improving vision or treating diseases, disorders or injury of the eye are described. Ophthalmic devices, such as corneal onlays, corneal inlays, and full-thickness corneal implants, are made of a material that is effective in facilitating nerve growth through or over the device. The material may include an amount of collagen greater than 1% (w/w), such as between about 10% (w/w) and about 30% (w/w). The material may include collagen polymers and/or a second biopolymer or water-soluble synthetic polymer cross-linked using EDC/NHS chemistry. The material may additionally comprise a synthetic polymer. The devices are placed into an eye to correct or improve the vision of an individual or to treat a disease, disorder or injury of an eye of an individual., L'invention concerne des dispositifs, des procédés et des compositions visant à améliorer la vision ou à traiter des maladies, des troubles ou une lésion de l'oeil; des dispositifs ophtalmiques tels qu'une greffe cornéenne du type onlay ou inlay, des implants cornéens d'épaisseur totale, faits d'une matière qui facilite la croissance des nerfs à travers ou par-dessus le dispositif. La matière comprend une quantité de collagène supérieure à environ 1 % (M/M), comprise par exemple entre environ 10 % (M/M) et environ 30 % (M/M). Cette matière comprend des polymères de collagène et/ou un second biopolymère ou un polymère synthétique soluble dans l'eau réticulé à l'aide de compositions chimiques d'EDC/NHS. Ladite matière comprend en outre un polymère synthétique. Les dispositifs sont mis en place dans un oeil afin de corriger ou d'améliorer la vision du sujet ou de traiter une maladie, un trouble ou une lésion de l'oeil.

Devices, methods, and compositions for improving vision or treating diseases, disorders or injury of the eye are described. Ophthalmic devices, such as corneal onlays, corneal inlays, and full-thickness corneal implants, are made of a material that is effective in facilitating nerve growth through or over the device. The material may include an amount of collagen greater than 1% (w/w), such as between about 10% (w/w) and about 30% (w/w). The material may include collagen polymers and/or a second biopolymer or water-soluble synthetic polymer cross-linked using EDC/NHS chemistry. The material may additionally comprise a synthetic polymer. The devices are placed into an eye to correct or improve the vision of an individual or to treat a disease, disorder or injury of an eye of an individual., L’invention porte sur des dispositifs, des procédés et des compositions pour améliorer la vision ou traiter les maladies, les troubles ou les blessures de l’oeil. Les dispositifs ophtalmiques, comme les implants externes de la cornée, les implants internes de la cornée et les implants de cornée sur toute l’épaisseur, sont réalisés dans un matériau facilitant la croissance nerveuse à travers ou sur le dispositif. Le matériau peut englober une quantité de collagène supérieure à 1% (en poids), par exemple entre environ 10% (en poids) et environ 30% (en poids). Le matériau peut inclure des polymères collagènes et/ou un second biopolymère ou polymère synthétique soluble dans l’eau réticulé à l’aide de la chimie EDC/NHS. Le matériau peut en outre comprendre un polymère synthétique. Les dispositifs sont placés dans l’œil pour corriger ou améliorer la vision d’un individu ou traiter une maladie, un trouble ou une blessure de l’œil d’un individu.

Purpose. To review the development of artificial corneas (prostheses and tissue equivalents) for transplantation, and to provide recent updates on our tissue-engineered replacement corneas. Methods. Modified natural polymers and synthetic polymers were screened for their potential to replace damaged portions of the human cornea or the entire corneal thickness. These polymers, combined with cells derived from each of the three main corneal layers or stem cells, were used to develop artificial corneas. Functional testing was performed in vitro. Trials of biocompatibility and immune and inflammatory reactions were performed by implanting the most promising polymers into rabbit corneas. Results. Collagen-based biopolymers, combined with synthetic crosslinkers or copolymers, formed effective scaffolds for developing prototype artificial corneas that could be used as tissue replacements in the future. We have previously developed an artificial cornea that mimicked key morphologic and functional properties of the human cornea. The addition of synthetic polymers increased its toughness as it retained transparency and low light scattering, making the matrix scaffold more suitable for transplantation. These new composites were implanted into rabbits without causing any acute inflammation or immune response. We have also fabricated full-thickness composites that can be fully sutured. However, the long-term effects of these artificial corneas need to be evaluated. Conclusions. Novel tissue-engineered corneas that comprise composites of natural and synthetic biopolymers together with corneal cell lines or stem cells will, in the future, replace portions of the cornea that are damaged. Our results provide a basis for the development of both implantable temporary and permanent corneal replacements.