OA18472A - Keratoprosthesis and uses thereof - Google Patents

Abstract

The present invention provides a keratoprosthesis assembly comprising a central optical core; and a peripheral skirt comprising at least one porous biocompatible layer and methods of using it in keratoprosthesis procedures.

Description

The présent invention relates to keratoprosthesis assemblies (artificial comea) and methods of using them.

BACKGROUND

Diseases affecting the comea are a major cause of blindness worldwide, second only to cataract in overall importance. According to the World Health Organization, approximately 2 10 million new cases are reported each year. Over 50 million people in the worldare blind in one or both eyes from comeal injury or disease. Dégradation of visua) acuity impacts many more.

For various reasons, current solutions for comeal blindness and diseases only address 5%10% of cases. To date, most patients are treated with Keratoplasty - a procedure that relies on 15 transplanting comeal tissue harvested from the deceased. Ail artificial comea solutions that are based on implants hâve failed to address this potential for diversified reasons. Due to risks, complexity, and costs, these are selectively used as a last resort for patients that are not suited for comeal transplant or hâve failed one. Current solutions for comeal blindness are divided to Keratoplasty (Comeal transplantation) and Keratoprosthesis (Artificial comea).

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During keratoplasty surgery the graft is taken from a recently deceased donor with no known diseases or other factors that may affect the· chance of survival of the donated tissue or the health of the récipient. The disadvantage of keratoplasty is a lack of donor tissue, the complexity and costs of operating a comea bank, and the limited applicability to only some 25 cases. For example, comeal diseases and injuries that leads to vascularization (pénétration of blood vessels into the comeal tissue) are not suitable for keratoplasty. Multiple grafting also leads to elevated risk for rejection/failure.

When using an artificial comea the procedure is known as keratoprosthesis. Traditionally, 30 keratoprosthesis is recommended after a patient has had a failure of one or more donor comeal transplants. While different types of Keratoprosthesis hâve been approved for limited use by the FDA (see Salvador-Culla et al. Journal of Functional Biomaterial. 2016, 7, 13, with a review of recent advances in the field of keratoprosthesis), the only viable solution in '2 the marketplace today is the Boston KPro. Boston KPro is approved by the FDA only for cases that cannot be addressed by Keratoplasty. This is due to many complications and the need for close and lifelong monitoring by an ophthalmologist familiar with the Boston KPro. Lîfe-long topical steroids such as prednisolone acetate is necessary in ail KPro eyes to prevent ’ 5 inflammation.

There are multiple disadvantages and failures associated with the known keratoprosthesis options, including diversified postoperative complications which are mainly a resuit of the device intervention in the physiology of the anterior chamber. Most of the patients (60%10 75%) develop glaucoma, elevated intraocular pressure, which can lead to blindness, limited field of vision and cataract. Furthermore, there is poor biointegration of the known keratoprosthesis that nécessitâtes daily antibiotic drops, lifelong treatment with topical steroids, and intensive lifelong ophthalmologist follow up.

» 15 After the implantation of known keratoprosthesis the access to the internai parts of the eye for performing surgical procedures such as cataract and retinal surgery is very limited at best. Due to this, the primary keratoprosthesis surgery is often combined with other procedures including implantation of glaucoma filtration devices, and a cataract surgery (replacing the lens with synthetic Intra Ocular Lens) making the procedure longer, more dangerous and 20 costly.

GENERAL DESCRIPTION

The présent invention aims at improving the optical quality of the artificial graft, better biointegration and improved résistance to trauma.

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Thus, the présent invention provides a keratoprosthesis comprising: (a) a central optical core; and (b) a peripheral skirt (located around and substantially surrounding said optical core) comprising at least one porous biocompatible layer having pore size of at least about 2 pm.

The term keratoprosthesis should be understood to encompass an artificial comea used in the keratoprothesis procedure when replacing a diseased comea of a subject in need thereof. The terms keratoprosthesis assembly, artificial comea and artificial cornea assembly are used herein interchangeably. Thus, the artificial comea of the invention comprises a •3 central optical core which is used to cover the anterior chamber of the eye, located at the center of the artificial comea of the invention and a peripheral skirt located around said optical core traversing the anterior sciera beneath the conjunctiva-tenon complex.

The term central optical core of an artificial comea of the invention (keratoprosthesis of the invention) provides the center part of the assembly which functions as the optical part of the keratoprosthesis covering the anterior chamber of the eye (after trephination of the diseases comea). -The optical core can be flexible in some embodiments, and can be rigid in others. The optical core is made from an acrylic, clear polymer, with varying dioptrie power in accordance with the need of the subject.

In some embodiments, said central optical core comprises acrylic, silicate or other clear, durable polymer and any combinations thereof.

The optical core optionally further comprises an extemal layer repelling optical dépositions. This extemal layer might be made of a silicone hydrogel similar to contact lenses.

In some embodiments, said optical core further comprises an extrusion centrally and posteriorly allowing for placement into a trephined comea so to traverse the width of the récipient comea.

In some embodiments, said central core extends towards the anterior chamber of the eye. Under these embodiments, the central core comprises edges extending below the surface formed by the central core and skirt of the assembly of the invention that allow it to extend into the anterior chamber of the eye. Thus, said central core further comprises an extended part (that is made of the same or other material) which extends on the concaved side of the assembly (towards the conjunctiva of the eye, when placed on the eye of a subject upon keratoprosthesis procedure). The extended part can hâve the same or different (in some embodiments smaller and in other embodiments larger) circumvent as that of the central transparent core. In other embodiments, said peripheral skirt is extended towards the conjunctiva of the eye.

The extended portion of the central core forms at least one groove extending from the posterior surface of the core that enables it to snap into the trephinted eut of the comea. In some embodiments, the central optical core further comprises at least one extended groove having a width of at least about 0.25mm (in other embodiments about 0.25mm to about 5 1mm).

In some embodiments, said central optical core has a diameter ranging from about 3 to about 15 mm. In other embodiments, said central optical core has a diameter of at least 3 mm. In other embodiments, said central optical core has a diameter in the range of about 3 to about 6 10 mm. In further embodiments, said central optical core has a diameter in the range of between to 14 mm. '

In further embodiments, said central optical core has a thickness ranging from about 500 micrometers to 3000 mierometers. In other embodiments said central optical core has a 15 thickness ranging from about 500 micrometers to 2500 mierometers. In further embodiments said central optical core has a thickness ranging from about 500 micrometers to 1500 micrometers.

In other embodiments, said central optical core has a diopter ranging from about 10 to about 20 70 diopters.

In other embodiments, said central optical core further comprises at its rim (i.e. the margin that is in contact with the skirt) at least one hole or open arc.

The term peripheral skirf should be understood to encompass the part of the keratoprosthesis of the invention that surrounds substantially ail the perimeter of the central optical core of the assembly. Said skirt comprises at least one porous biocompatible layer as defined herein above and below.

In some embodiments, said peripheral skirt is extended towards the conjunctiva of the eye. In further embodiments, said peripheral skirt is formed in a manner that enables placing it under the conjunctiva of the eye. Placing of the skirt beneath the conjunctiva is performed after dissecting the conjunctiva from its limbai ançhorage (this procedure is termed peritomy) and elevating it so to create a space to accommodate the said skirt.

tn some embodiments, said peripherai skirt has a width of at least 3 mm. In other 5 embodiments, said peripheral skirt has a width of between 3 to 9 mm. In further embodiments, said peripheral skirt has a width ranging from about 4 to about 6 mm.

In some embodiments, said peripheral skirt has a thickness ranging from about 100 to about 2000 micron.

In some embodiments, said peripheral skirt further comprises a biomolecule or an antibiotic agent. In other embodiments, said biomolecule is selected from a protein, type 1 collagen, fibronectin, or TGF- beta 2, heparin, growth factors, antibodies, antimetabolites, chemotherapeutic agents, and any combinations thereof. In further embodiments, said 15 biomolecule or antibiotic is covalently attached to saîd at least one porous biocompatible layer.

The term *'porous biocompatible layer should be understood to encompass any type of layer (or film) formed from material that has the ability to perform its desired function with respect 20 to a medical therapy (i.e. keratoprosthesis), without eliciting any undesirabïe local or systemic effects in the récipient or beneficiary of that therapy, but generating the most appropriate bénéficiai cellular or tissue response in that spécifie situation, and optimizing the clïnîcally relevant performance of that therapy. The biocompatible layer of the skirt of the assembly of the invention allows the implanted artificial comea to exist in harmony with tissue it is in 25 contact with without causing deleterious changes. The layer is porous, having pore size of at least at least about 2 pm (when referring to pore size it should be understood to relate to the average pore sizes).

In some embodiments, said porous biocompatible layer is a fibrous porous biocompatible 30 layer (i.e. the layer or film is formed of fibers), having pore size of at least about 2 pm.

In some embodiments, at least one porous bîocompatible layer has pores of between about 2 pm to about 100 pm in width.

In other embodiments, said at least one porous biocompatible layer is a polymeric layer. Thus, under this embodiment, the layer or film of the skirt is made of at least one polymer material.

In other embodiments, said at least one porous biocompatible layer is a nonwoven fabric. Thus, under this embodiment, said layer or film of the skirt is a fabric-like material made from long fibers, bonded together by chemical, mechanical, heat or solvent treatment.

In further embodiments, said porous biocompatible layer comprises nanofibers. Thus, under this embodiment, the skirt is formed of fibers with diameters of less than 2000 nanometres. In some embodiments, nanofibers are produced by any type of process including, but not limited to melt processing, interfacial polymerization, electrospinning, antisolvent-induced polymer précipitation, electrostatic spinning, catalytic synthesis and any combinations thereof.

In further embodiments, said at least one porous biocompatible layer comprises poly(DTE carbonate) polycaprolactone (PCL), polylactic acid (PLA), poly-L-lactic acid (PLLA), Poly(DL-lactide-co-caprolactone, Poly(ethylene-co-viny) acetate) vinyl acetate, Poly(methyl méthacrylate), Poly(propylene carbonate), Poly(vinylidene fluoride), Polyacrylonitrile, Polycaprolactone, Polycarbomethylsilane, Polylactic acid, Polystyrène, Polyvinylpyrrolidone, poly vinyl alcohol (PVA), polyethylene oxide (PEO), polyuréthane, polyvinyl chloride (PVC), hyaluronic acid (HA), chitosan, alginate, polyhydroxybuyrate and its copolymers, Nylon 11, Cellulose acetate, hydroxyappetite, poly(3-hydroxybutyric acid-co-3hydroxyvaleric acid), po)y(DL-lactide), polycaprolactone, and poly(L-lactide) or any combination thereof.

In some further embodiments, said porous biocompatible layer comprises electrospun nanofibers. In another embodiment, said at least one porous biocompatible layer is formed by electrospinning process.

The term electrospinning or electrospun or any of its lingual déviations should be understood to encompass a process using an electrical charge to draw very fine (typically on the micro or nano scale) fibers from a liquid. Electrospinning from molten precursors is also practiced; this method ensures that no solvent can bc carried over into the final product. The

Ί fibers produced using electrospinning processes hâve increased surface area to volume ratio. Various factors are known to affect electrospun fibers include, but are not limited to: solution viscosity, surface tension, electric field intensity and distance.

In a typical electrospinning process a sufficiently high voltage is applied to a liquid droplet of a polymeric material (a polymer solution, a monomeric precursor thereof, sol-gel precursor, particulate suspension or melt), the body of the liquid becomes charged, and electrostatic repulsion counteracts the surface tension and droplet is stretched, at a critical point a stream of liquid erupts from the surface. If the molecular cohésion of the liquid is sufficiently high, stream breakup does not occur (if it does, droplets are electrosprayed) and a charged liquid jet îs formed. As the jet dries in flight, the mode of current flow changes from ohmic to convective as the charge migrâtes to the surface of the fiber. The jet is then elongated by a whipping process caused by electrostatic repulsion initiated at small bends in the fiber, until it is finally deposited on the grounded collecter. The élongation and thinning of the fiber that results from this bending instability leads to the formation of uniform fibers with nanometerscale diameters.

Biocompatible polymers which may be applied in an electrospinning process include but are not limited to poly(DTE carbonate) polycaprolactone (PCL), polylactic acid (PLA), po!y-Llactic acid (PLLA), Poly(DL-lactide-co-caprolactone, Poly(ethylene-co-vinyl acetate) vinyl acetate, Tolyirnethyl méthacrylate), Polyfpropylene carbonate), Poly(vinylidene fluoride), Polyacrylonitrile, Polycaprolactone, Polycarbomethylsilane, Polylactic acid, Polystyrène, Polyvinylpyrrolidone, poly vinyl alcohol (PVA), polyethylene oxide (PEO), polyvinyl chloride (PVC), hyaluronic acid (HA), chitosan, alginate, polyhydroxybuyrate and its copolymers, Nylon 11, Cellulose acetate, hydroxyappetîte, or any combination thereof. Biodégradable and biocompatible polymers include but are not limited to poly(3hydroxybutyric acid-co-3-hydroxyvaIeric acid), poIy(DL-lactide), poly urethane, polycaprolactone, and poIy(L-Iactide) or any combination thereof.

Electrospun fibers are typically several orders in magnitude smaller than those produced using conventional spinning techniques. By optimizing parameters such as: i) the intrinsic properties of the solution including the polarity and surface tension of the solvent, the molecular weight and conformation of the polymer chain, and the viscosity, elasticity, and electrical conductivity of the solution; and ii) the operational conditions such as the strength of electric field, the distance between spinneret and collector, and the feeding rate of the solution, electrospinning is capable of generating fibers as thin as tens of nanometers in diameter. Additional parameters that affect the properties of electrospun fiber include the 5 molecular weight, molecular-weight distribution and structure (branched, linear etc.) of the polymer, solution properties (viscosity, conductivity and surface tension), electric potential, flow rate and concentration, distance between the capillary and collection screen, ambient parameters (température, humidity and air velocity in the chamber), motion of target screen (collector) and so forth. Fabrication of highly porous fibers may be achieved by 10 electrospinning the jet directly into a cryogénie liquid. Well-defmed pores developed on the surface of each fiber as a resuit of temperature-induced phase séparation between the polymer and the solvent and the évaporation of solvent under a freeze-drying condition.

Severai approaches hâve been developed to organize electrospun fibers into aligned arrays.

For example, electrospun fibers can be aligned into a uniaxial array by replacing the singlepiece collector with a pair of conductive substrates separated by a void gap. In this case, the nanofibers tend to be stretched across the gap oriented perpendicular to the edges of the électrodes. It was also shown that the paired électrodes could be pattemed on an insulating substrate such as quartz or polystyrène so the uniaxially aligned fibers could be stacked layer20 by-layer into a 3D lattice. By controlling the electrode pattem and/or the sequence for applying high voltage, it is also possible to generate more complex architectures consisting of well-aligned nanofibers.

Electrospun nanofibers could also be directly deposîted on various objects to obtain 25 nanofiber-based constructs with well-defined and controllable shapes. In addition, one can manually process membranes of aligned or randomly oriented nanofibers into various types of constructs after electrospinning: for example, fabrication of a tube by rolling up a fibrous membrane or the préparation of dises with controllable diameters by punching a fibrous membrane.

The présent invention relates to any eletrospinning technique known in the art, which includes Electrospinning, J. Stanger, N. Tucker, and M. Staiger, I-Smithers Rapra publishing (UK), An Introduction to Electrospinning and Nanofibers, S. Ramakrishna , K. Fujihara , W-E Teo,

World Scientific Publishing Co. Pte Ltd (Jun 2005), Electrospinning of micro- and nanofibers: fondante niais and applications in séparation and filtration processes, Y. Fillatov, A. Budyka, and V. Kirichenko (Trans. D. Letterman), Begell House Inc., New York, USA, 2007, which are ali incorporated herein by reference in their entirety.

Suîtable electrospinning techniques are disclosed, e.g., in International Patent Application, Publication Nos. WO 2002/049535, WO 2002/049536, WO 2002/049536, WO 2002/049678, WO 2002/074189, WO 2002/074190, WO 2002/074191, WO 2005/032400 and WO 2005/065578, the contents of which are hereby incorporated by reference. It is to be understood that although the according to the presently preferred embodiment of the invention is described with a particular emphasis to the electrospinning technique, it is not intended to limit the scope of the invention to the electrospinning technique. Représentative examples of other spinning techniques suîtable for the présent embodiments include, without limitation, a wet spinning technique, a dry spinning technique, a gel spinning technique, a dispersion spinning technique, a reaction spinning technique or a tack spinning technique. Such and other spinning techniques are known in the art and disclosed, e.g., in U.S. Patent Nos., 3,737,508, 3,950,478, 3,996,321, 4,189,336, 4,402,900, 4,421,707, 4,431,602, 4,557,732, 4,643,657, 4,804,511, 5,002,474, 5,122,329, 5,387,387, 5,667,743, 6,248,273 and 6,252,031 the contents of which are hereby incorporated by reference.

In some embodiments, said optical core and peripheral skirt are mechanically attached to each other (using for example mechanical means for attaching the core to the skirt, such as for example a strip of layer connecting them or a suture). In other embodiments, said optical core and peripheral skirt are chemically attached to each other (using for example any gluing or connecting component, fusing them together using heat or pressure and so forth).

In a further aspect the invention provides a procedure for implanting a keratoprosthcsis in a subject in need thtereof comprising the steps of:

- Providing a keratoprosthesîs according to the invention;

- Performing a 360 degree peritomy in the eye of said subject;

- Elevating and dissecting both tenon capsule and conjunctiva from sciera of the eye of said subject;

- Performing trephination of central comea of said subject;

- Placing the transparent central core of said keratoprosthesis into the trephined space of said subject comea;

- Placing the peripheral skirt of said keratoprosthesis under the dissected tenon capsule and conjunctiva of said subject;

- Optionally suturing skirt to sciera, or placing the skirt on bare sciera without anchoring it to the tissue;

- Replacîng tenon capsule and conjunctiva onto the skirt of the keratoprosthesis; and

- Optionally suturing and repositionîng conjunctiva to original configuration.

The procedure of implanting the keratoprosthesis assembly of the invention is thus a single staged procedure. The eye is filled with viscoelastic material. A peritomy of 360 degrees is made elevating both conjunctiva and tenon. Trephination of the central comea is carried out. The optical zone is inserted into the trephined space. The bio-integrating skirt is laid on the bare sciera and optionally sutured to it. The tenon and conjunctiva are put back in place over the porous skirt and sutured tight. Viscoelastic is replaced with BSS (balanced saline solution).

BRIEF DESCRIPTION OF THE DRAWINGS

In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

Fig. I provides a schematic view of an exemplary keratoprosthesis of the invention and an eye to be implanted.

Fig. 2 provides a schematic view of an exemplary keratoprosthesis of the invention.

Fig. 3 is a cross section view of an exemplary keratoprosthesis of the invention implanted into the eye.

Figs. 4A-4B is a cross section view of an exemplary keratoprosthesis of the invention. Fig. 4A shows an exemplary central optical core part of the keratoprosthesis and Fig. 4B shows an exemplary central optical core with the peripheral skirt.

Fig. 5 is a cross section view of an exemplary keratoprosthesis of the invention.

Figs. 6A-6G provides the steps for the keratoprosthesis procedure using an artificial comea on the invention showing a single stage, 30 minute procedure that is significantly simpler than any existing solution.

DETAILED DESCRIPTION OF EMBODIMENTS

Fig. 1 shows an embodiment of a keratoprosthesis of the invention 100, consisting of a transparent central optical core 101 and a peripheral skirt 103. The central optical core 101 is extended towards the anterior chamber of the eye with an extension 102 suitable for anchoring said central core in place into the trephined space 104 of the central comea 105.

Fig. 2 shows an embodiment of a keratoprosthesis of the invention 200, consisting of a transparent central optical core 201 and a peripheral skirt 202. The central optical corc 201 is 10 extended towards the anterior chamber of the eye with an extension 203 suitable for anchoring said central core in place into the trephined space of the central comea.

Fig. 3 shows an embodiment of a keratoprosthesis of the invention 300, placed on the eye of a subject wherein said keratoprosthesis consisting of a transparent central optical core 301 and a 15 peripheral skirt 303. The central optical core 301 is extended towards the anterior chamber of the eye with an extension 302 suitable for anchoring said central core in place into the trephined space 304 (not shown) of the central comea 305. It is noted that the peripheral skirt 303 when placed on the eye after trephination of the catral comea extends anteriorly towards the spiral of tillux 306. .

Figs. 4A-4B is a cross section view of an exemplary keratoprosthesis of the invention. Fig. 4A shows an exemplary central optical core part 400 of the keratoprosthesis. The central optical core 400 is formed of PMMA (approved material for eye implants, similar to the material using in contact lenses) providing a large diameter optical zone. The central core is 25 extended from the concave plane of the central core 401 to form at least one groove 402 shown in Fig. 4B (of multiple optional shapes supporting laser and manual trephination) which enables the implant of the invention to snap and fit into a hole eut in the existing comea for immédiate water-tightness. The at least one groove 402 holds the remainîng comea margins (see also in Fig. 5). The at least one groove 402 also enables thorough clinical exam 30 and inter-ocular access. The central optical core further optionally comprises at least one hole/hollow arches 403 and 405 ensuring optical core-to-skirt (PMMA-to-nanofiber) stability and rétention once implanted into human tissue.

Fig. 4B shows an exemplary central optical core (400) with the peripheral skirt (404). The skirt is positioned subconjunctively and intégrâtes with the conjunctiva, including through at least one hole and arcs 403 eut into the optical element. The skirt is made from electrospun polymer which is biocompatible and stimulâtes cell growth. The biocompatible porous fibrous 5 material of the Scaffold for cellular prolifération enabling biointegration

Fig. 5 is a cross section view of an exemplary keratoprosthesis of the invention 500 implanted into comea after removal of the diseased comea. The optical central core 501 is placed above anterial chamber (not shown) and is held tightly into position due to two structural éléments 10 including an extension of the optical core 502 and an extension of the exterior optical core

503 forming a groove 504 that holds the remaining margins of the lessered comea. This at least one groove provides stable positioning of the artificial comea snapped in and fitting into a hole eut in the existing comea for immédiate water-tightness. The central core also comprises at least one hole and/or hollow arches 505 and 506 ensuring core (501) to skirt 15 (507) (PMMA-to-nanofiber) strength and rétention once infiltrated with human tissue. 507 is a représentative position of the peripheral skirt of the keratoprosthesis of the invention which is formed of nanofiber electrospun layer enabling cell tissue to grow and assimilate device into the conjunctiva.

Figs. 6A-6G provides the steps for the keratoprosthesis procedure using an artificial comea on the invention showing a single stage, 30 minute procedure that is significantly simpler than any existing solution. The process is performed for example using the following steps:

- Fig. 6A the eye is filled with viscoelastic material

- Fig. 6B a peritomy of 360 degrees is made elevating both conjuctive and tenon

- Fig. 6C trephination of the central comea is carried out

- Fig. 6D the optical zone is inserted into the tephinated space

- Fig. 6E the biointegrating skirt is laid on the bare sciera and optionally sutured to it

- Fig. 6F the tenon and conjunctiva is put back in place over the prous skirt and optionally sutured tight

- Fig. 6G viscoelastic is replaced with BSS (balanced saline solution)

Claims (17)

1. CLAIMS:

   1. A keratoprosthesîs comprising: (a) a central optical core; and (b) a peripheral skirt comprising at least one porous biocompatible layer having pore size of at least
2. 2 pm; wherein 5 said transparent central core has a diameter of at least 3 mm and further comprises an extended portion extending below the surface formed by the central core and skirt; and wherein said peripheral skirt has a width of at least 3 mm so that it can be placed under the conjunctiva and above sciera of the eye.

   10 2. A keratoprostesis according to claim 1, wherein said at least one porous biocompatible layer having pore size of 2 pm to 100 pm.
3. 3. A keratoprostesis according to claims 1 or 2, wherein said at least one porous biocompatible layer is a polymerîc layer.
4. 4. A keratoprostesis according to claims 1 or 2, wherein said at least one porous biocompatible layer is a nonwoven fabric.
5. 5. A keratoprostesis according to claim 1 or 2, wherein said porous biocompatible layer 20 comprises nanofibers.
6. 6. A keratoprosthesîs according to any one of the preceding claims, wherein said at least one porous biocompatible layer is formed by êlectrospinning process.

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7. 7. A keratoprosthesîs according to claim l, wherein said at least one porous biocompatible layer comprises poly(DTE carbonate) polycaprolactone (PCL), polylactic acid (PLA), poly-L-lactic acid (PLLA), Poly(DL-lactide-i-o-caprolactone, Poly(ethylene-co-vinyl acetate) vinyl acetate, Poly(methyl méthacrylate), Poly(propylene carbonate), Polyfvinylidene fluoride), Polyacrylonitrile, Polycaprolactone, Polycarbomethylsilane, Polylactic acid, 30 Polystyrène, Polyvinylpyrrolidone, poly vinyl alcohol (PVA), polyethylene oxide (PEO), polyuréthane, polyvinyl chloride (PVC), hyaluronic acid (HA), chitosan, alginate, polyhydroxybuyrate and its copolymers, Nylon 11, Cellulose acetate, hydroxyappetite, poly(3-hydroxybutyric acid-co-3-hydroxyvaIeric acid), poIy(DL-lactide), polycaprolactone, and poIy(L-Iactide) or any combination thereof.
8. 8. The keratoprosthesis of claim 1, wherein the central optical core has a diameter ranging from about 3 to 15 mm.
9. 9. The keratoprosthesis of claim 1, wherein the central optical core has a thickness ranging from about 500 micrometers to 3000 micrometers.
10. 10. The keratoprosthesis of claim 1, wherein the central optical core has a diopter ranging from about 10 to about 70 diopters.
11. 11. The keratoprosthesis of daim 1, wherein the peripheral skirt further comprises a biomolecule or an antibiotic agent.
12. 12. The keratoprosthesis of claim 1, wherein the biomolecule is selected from a protein, type I collagen, fibronectin, or TGF- beta 2, heparin, growth factors, antibodies, antimetabolites, chemotherapeutic agents, and any combinations thereof.
13. 13. The keratoprosthesis of claim I, wherein the biomolecule or antibiotic is covalently attached .to said at least one porous biocompatible layer.
14. 14. The keratoprosthesis of claim 1, wherein the peripheral skirt has a width of between 3 to 9 mm.
15. 15. The keratoprosthesis of claim I, wherein the peripheral skirt has a thickness ranging from about 100 to about 2000 micron.
16. 16. The keratoprosthesis of claim 1, wherein said optical core and peripheral skirt are mechanically or chemically attached to each other.
17. 17. The keratoprosthesis of claim 1, wherein the peripheral skirt is formed in a manner that enables placing it under the conjunctiva of the eye.