Hydrogel based attachment to orthopedic implants

Abstract

Methods, hydrogel compositions, and apparatuses (e.g., implants) that address the need to attach hydrogels to implants that mimic human anatomy without the need for a cement or clamp, by forming the hydrogel in such a way as that it is securely attached to an underlying titanium or other material implant surface via coating the implant with one or more layers of compressed bacterial cellulose impregnated with a hydrogel and further molding and annealing the implant under desired temperature and duration ranges.

Description

HYDROGEL BASED ATTACHMENT TO ORTHOPEDIC IMPLANTSCLAIM OF PRIORITY

[0001] This patent application claims priority to U.S. provisional patent application no. 63 / 587,072, titled “HYDROGEL BASED ATTACHMENT TO ORTHOPEDIC IMPLANTS,” and filed on September 30, 2023, and herein incorporated by reference in its entirety.INCORPORATION BY REFERENCE

[0002] All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.BACKGROUND

[0003] Human cartilage has very unique properties. It is one of the few avascular tissues in the body. Cartilage is semipermeable and receives its nutrients from the synovial fluid which surrounds cartilaginous tissue in articulating joints, and which diffuses into the cartilage during motion of the joint. Cartilage itself also possesses viscoelastic and lubricating properties. Materials which are proposed for use in the repair or replacement of natural cartilage must possess physical and mechanical properties which are as close as possible to those of natural cartilage.

[0004] Historically the only choices available to patients with cartilage damage, especially the cartilage of an articulating joint, such as a knee or elbow, were to initially do nothing if the extent of the damage was only relatively minor in scope, which sooner or later usually led to a worsening of the condition and further damage to the cartilage and to the joint itself, with the patient feeling discomfort and pain when using the joint, thus ultimately requiring a complete joint replacement to restore mobility; or, if the extent of the damage was significant to start with, to immediately perform a complete joint replacement. In the case of very young patients, however, complete replacement of a joint is problematic in that the patient's overall skeletal bone structure is not yet fully developed and is still growing, so that the replaced joint may actually be outgrown and no longer be of appropriate size for the patient when their fully matured adult size, stature, and skeletal structure is attained. Moreover, in the past, many replacement knee, elbow joints and shoulder joints have typically had a maximum active useful life of only about ten years, due to wear and tear anderosion of the articulating surfaces of the joint with repetitive use over time, thereby necessitating periodic invasive surgery to replace the entire joint. For a very young patient this meant that they would have to face the prospect for several more such surgeries over their lifetime, notwithstanding progress and improvements in the wearability of materials used for joint surfaces that have been made and continue to be made as new materials are developed.

[0005] In recent years artificial cartilage materials have been proposed, and in particular, artificial cartilage made from hydrogels. Hydrogels are polymer networks typically swollen with water and are a promising synthetic material for replacement of cartilage because hydrogels can be made to have similar mechanical and tribological properties as natural cartilage. Such hydrogels may exhibit superior wear characteristics because their surfaces principally consist of water, which serves to lubricate the surface and lower the coefficient of friction. Such superior wear characteristics may result in a longer-lasting joint replacement. However, hydrogels may be difficult to use, and in particular may be difficult to integrate with bone on their own, since they lack the appropriate porosity and surface chemistry. Hydrogels may also be difficult to attach to materials, such as titanium, that integrate with bone. Previous work has disclosed methods of attaching hydrogels to a relatively simple titanium geometry through the use of cements or through a clamp. However, cements represent an extra cost and may introduce additional toxic compounds that may be deleterious to their use in an implant that is meant to reside in the body for decades. Clamps are also limited in that they may be able to attach hydrogels to an implant with a limited set of geometries, such as circular or cylindrical geometries, that enable an even pressure to be applied around the clamp radius. Clamps are also limited in that they can only be applied to relatively stiff materials that resist the clamp force. If a clamp is applied to a soft material, it will simply deform, and the material will not be tightly attached to the surface. Thus, it would be ideal if there were a method that enables the attachment of hydrogels to titanium or other appropriate material implants without the use of a clamp or cement, especially to complex geometries that mimic the human joint anatomy.SUMMARY OF THE DISCLOSURE

[0006] This disclosure relates generally to variations of artificial cartilage materials in implants suitable for repair of cartilage, including hydrogel composites and methods and for attaching a hydrogel composite including a compressed sheet of bacterial cellulose (BC) impregnated with a hydrogel to a surface of an implant.

[0007] Described herein are methods, hydrogel compositions, and apparatuses (e.g., implants) that address the need to attach hydrogels to implants that mimic human anatomy without the need for a cement or clamp, and instead focus on the forming of the hydrogel in such a way as that it is securely attached to a porous or non-porous surface of an underlying titanium or other appropriate material implant.

[0008] When used for partial knee resurfacing, the implant may be configured to wear an opposing cartilage surface to an extent not significantly greater than the extent to which cartilage wears cartilage. A top bearing surface of the implant may have a coefficient of friction (COF) that is not statistically different from that of cartilage.

[0009] The implants described herein may be configured as a medical implant, and may include a tissue engaging portion (e.g., a bone engaging portion such as a rod, screen, nail, etc.).

[0010] The nanofiber network may be secured to the implant (e.g., to a porous surface of the implant) by any appropriate method.

[0011] The implant may be formed of any appropriate biocompatible material. For example, the surface of the implant body may be titanium. The surface of the implant body may be one or more of: a stainless steel alloy, a titanium alloy, a Co-Cr alloy, tantalum, gold, niobium, bone, Al oxide, Zr oxide, hydroxyapatite, Tricalcium phosphate, calcium sodium phosphosilicate, poly(methyl methacrylate), polyether ether ketone, polyethylene, polyamide, polyurethane, or polytetrafluoroethylene.

[0012] In general, the nanofiber network may be coupled to the top bearing surface of the implant. The cross-linked cellulose nanofiber network may be attached over the top load surface by clamping. For example, the nanofiber network may be bonded by cement to the top load surface; in some examples, the cement is not bonded to the hydrogel; the cement is only bonded to the nanofiber network. Alternatively, in some examples the nanofiber networks may be coupled to the implant, so that the nanofiber network, is secured over the top bearing surface without the use of a chemical adhesive, such as an epoxy. Instead, the nanofiber network may be secured over the top bearing surface by a clamp. For example, a clamp may secure the nanofiber network (e.g., one or more sheets of BC) over the top bearing surface around a periphery of the top bearing surface. Thus, in general, the use of an adhesive (such an epoxy) is optional.

[0013] Any appropriate implant may be used. The surface of the implant (e.g., top bearing surface, which may be equivalently referred to as simply the bearing surface) may be at least at the region to which the nanofiber network is attached over, may be titanium, stainless steel, etc. the bearing surface (e.g., top bearing surface) may be convex, flat,concave, or some mixture of these. For example, the surface of the implant body may comprise one or more of: a stainless steel alloy, a titanium alloy, a Co-Cr alloy, tantalum, gold, niobium, bone, Al oxide, Zr oxide, hydroxyapatite, Tricalcium phosphate, calcium sodium phosphosilicate, poly(methyl methacrylate), polyether ether ketone, polyethylene, polyamide, polyurethane, or polytetrafluoroethylene.

[0014] Also described herein are methods of making and / or using these implants. For example, described herein are implants, comprising: an outer surface; and a compressed bacterial cellulose (BC) layer impregnated with a hydrogel covering the outer surface, wherein the compressed BC impregnated with hydrogel has a thickness of between about 0.5- 8 mm, and wherein a cellulose fiber density of the compressed BC is between about 0.001 g / mm3to 0.00001 g / mm3.

[0015] In some examples, the compressed BC layer impregnated with the hydrogel of the implants comprises a plurality of layers of compressed BC layers impregnated with the hydrogel.

[0016] In some examples, the outer surface of the implants comprises a spherical or partially spherical shape.

[0017] In some examples, the implant surface is concave or convex.

[0018] In some examples, the outer surface comprises one or more slots.

[0019] In some examples, the compressed BC layer impregnated with a hydrogel is configured to have a water content of between 30%-70% when hydrated.

[0020] In some examples, the hydrogel comprises a polyvinyl alcohol (PVA) hydrogel.

[0021] In some examples, the implant is a titanium implant.

[0022] In general, the methods and apparatuses described herein may be used with any of the methods, apparatuses and compositions described in International Patent Application No. PCT / US2021 / 040031, titled “NANOFIBER REINFORCEMENT OF ATTACHED HYDROGELS,” filed on July 1, 2021, which is herein incorporated by reference in its entirety.

[0023] All of the methods and apparatuses described herein, in any combination, are herein contemplated and can be used to achieve the benefits as described herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0024] A better understanding of the features and advantages of the methods and apparatuses described herein will be obtained by reference to the following detailed description that sets forth illustrative embodiments, and the accompanying drawings.

[0025] FIG. 1 shows an exemplary process flow for orthopedic implants to form a femoral head component of a hip joint without the use of a clamp or cement.

[0026] FIG. 2 shows an example of concave cavity implants having keys or slots for adhering hydrogel and polyvinyl alcohol (PVA) implant coatings to the surface of the metal implant surface when the implant is compressed or vacuumed.

[0027] FIGS. 3 A and 3B illustrate examples of a vacuum drying method for bacterial cellulose (BC) hydrogel sheets.

[0028] FIGS. 4 A and 4B are images showing drying results of wet BC sheets of different thicknesses.

[0029] FIG. 5 is an image showing a vacuum drying BC setup.

[0030] FIGS. 6A-6B show dimensions of two laser cut floral shaped BC hydrogel layers.

[0031] FIG. 6C illustrates examples of offset laser cut floral shaped bacterial cellulose (BC) hydrogel layers.

[0032] FIG. 7 shows an exemplary implant surface for a femoral head component of a joint implant before and after layering with BC layers.

[0033] FIGS. 8A-8C show images of sequential BC layer wrapping around the implant surface (metal core) of a femoral head component of a hip joint implant.

[0034] FIGS. 9A-9C show images of a vacuumed femoral head component of a joint implant before and after surface smoothing.

[0035] FIG. 10 shows an example of an infiltration chamber containing a PVA solution and femoral head component of a hip joint.

[0036] FIGS. 11 A-l 1C show an example molding process progression 1100 after infiltration, in the mold, and after molding and cooling.

[0037] FIGS. 12A-12B show images of a two-part mold for a femoral head component of a hip joint.

[0038] FIG. 13 shows an image of a pneumatic press.

[0039] FIG. 14 shows various views of images of a hip ball joint after demolding and trimming.

[0040] FIG. 15 shows side and bottom views of images of a hip ball joint after excess PVA trimming.

[0041] FIG. 16 shows an image of a femoral head component of a hip joint after rehydration in a 37°C saline solution.

[0042] FIGS. 17A-17B show charts illustrating methods of forming an implant as described herein.DETAILED DESCRIPTION

[0043] Described herein are methods, hydrogel compositions, and apparatuses (e.g., devices and system, including implants) that address the need to attach hydrogels to titanium implants that mimic human anatomy without the need for a cement or clamp, by forming the hydrogel in such a way as that it is securely attached to an underlying titanium implant via coating the implant with radial layers of self-sealing bacterial cellulose hydrogel formed via vacuum drying, laser cutting, infiltration with a PVA solution, molding, cooling, annealing, and trimming.

[0044] Although the methods and apparatuses described herein are primary described in the context of bacterial cellulose (BC) and polyvinyl alcohol (PVA), other hydrogels may be used. Previously methods of forming implants with hydrogels comprising a bacterial cellulose (BC) network infused with both polyvinyl alcohol (PVA) and poly(2-acrylamido-2- methyl-1 -propanesulfonic acid sodium salt (PAMPS), referred to as BC-PVA-PAMPS hydrogels, are described in International Patent Application No. PCT / US2021 / 040031, which is incorporated herein by reference in its entirety.

[0045] The methods and apparatuses described herein include may generally allow secure attachment of the hydrogel (e.g., a BC-PVA hydrogel) to conform to surface of virtually any shape, including concave, convex, saddle, conical, etc., and including abutments of surfaces, including curved surfaces, such as the surface geometries in human joints. Thus, the methods and apparatuses described herein may include a total or partial joint implant with a hydrogel that covers the bearing surface, i.e., the surface that is in contact with the opposing joint surface. The hydrogel may be a BC-PVA hydrogel, or any other BC-based hydrogel, and does not require a clamp for fixation.

[0046] As described in greater detail here, in some cases the bacterial cellulose (BC) material forming part of the hydrogel may be formed by fusing multiple pieces of BC together, with a range of tensile strengths as described herein. Fusion of difference regions of BC as described herein may allow the creation of curved BC surfaces that are smooth and / or that lack cracks that may otherwise cause that surface to tear. The resulting BC surface may be infused with hydrogel (e.g., PVA).

[0047] The methods and apparatuses described herein may avoid the use of a clamp or other securement feature when securing the hydrogel (e.g., the BC-PVA) to the surface. In some cases, these methods and apparatuses may include molding the hydrogel around an object with undercuts or other locking features such that the geometry of the BC material (hydrogel) and the implant itself may ensure that the hydrogel remains fixed to the surface of the implant with the strength of the hydrogel.

[0048] In general, these methods and apparatuses may provide a consistent thickness of the hydrogel material. For example, the methods described herein may include the use of a vacuum to enable the formation of a hydrogel with a consistent thickness across the surface of the implant, thereby ensuring that the hydrogel thickness remains consistent (e.g., approximately the same) across a curved surface. For example, these methods may provide a consistency of thickness over even irregularly-shaped, and / or curved, surfaces that is, e.g., within + / - 10% of the thickness of the surface (e.g., within + / - 7%, within + / - 5%, within + / - 3%, within + / - l%e.g., within about + / - 0.2 mm, for example).

[0049] As mentioned above, the methods described herein allow attachment of a hydrogel, including a BC-PVA hydrogel, to an arbitrarily-shaped surface. For example, FIG.1 shows an exemplary process flow 100 for orthopedic implants to form a femoral head component of a hip joint without the use of a clamp or cement including compression step 101, laser cutting step 102, layering BC on sphere surface step 103, compression sealing the implant step 104, infiltrate step 105, molding and cooling step 106, and annealing and trimming step 107. FIG. 1 illustrates an example of a process for attaching a hydrogel to a geometry that mimics human anatomy, in this case, represented by a sphere that mimics the geometry of the femoral head.

[0050] As shown in FIG. 1, the process 100 for forming the femoral head of the hip joint utilizes a sphere-shaped implant surface such as a metal core and two layers of floral-shaped BC. This process, however, can be adapted to a variety of different joints dependent on the implant surface design and appropriate geometric cutting of BC. Within the human body, the shoulder joint is similar to the ball-and-socket hip joint, indicating that a similar process can be configured to form an implant that mimics the human humeral head. These implant surfaces can also be designed as concave cavities to mimic the acetabulum and glenoid fossa, the socket regions of the hip and shoulder joints. The implant surfaces may also be designed to mimic the triangular shape of the knee joint and elbow joints. The concave cavities may have small keys or slots 201 on their surface to allow for the BC and PVA to sit and adhere to the surface when vacuumed. According to other examples, a flat or other shaped surface such as a convex surface may be used instead of a metal core. The implant surfaces may contain both convex and concave surfaces depending on a desired joint, or according to yet other examples, the implant surface may be completely or partially flat.

[0051] To form an orthopedic implant, one sheet (20 cm x 10 cm x 1.5 cm) of hydrated bacterial cellulose (BC) is vacuum dried down to a thickness of 2 mm in 7 minutes or after removing approximately 350 mL of solution. According to certain examples, the compressed sheet of BC has a cellulose fiber density of between le-3 g / mm3to le-5 g / mm3. Using a lasercutter, the BC is cut into geometric-shaped layers that allow for full surface area coverage around the specific metal implant surface (such as a core). According to certain examples, the implant surface may be any appropriate material including, but not limited to, titanium, cobalt, stainless steel, and alloys of such metals. According to certain examples, the surface may or may not be porous. According to certain other examples, the geometric shapes may be radial or flower-like shapes or a string / ribbon shape.

[0052] After forming the layers of BC around the implant surface, the implant is placed in batting and vacuum sealed until the BC petals or legs adhere to one another and the metal implant surface. While the implant sits in the vacuum sealed bag, a 75 g 40% polyvinyl alcohol (PVA) solution (30 g of PVA to 45 g of H2O) is made in the Teflon infiltration chamber. The implant is then removed from the vacuum sealed bag and smoothed to remove any wrinkling from the vacuuming process. The implant is immersed into the PVA solution within an infiltration chamber stem up, for an appropriate time and temperature range, such as >12 hours and >100°C. The infiltration chamber may be formed of a non-reactive material, such as PTFE or an appropriate polymeric material (e.g., Teflon). The implant may be annealed at an appropriate time and temperature range (e.g., >80°C for >12 hours). After removing the implant from the infiltration chamber, excess PVA is removed from the implant by hand and the implant is compressed into its mold, for example via vacuum, pneumatic, or mechanical compression. Using a wrench and screwdriver, the mold is tightly shut. The mold is placed into the pressure chamber, pressurized, and left to cool in the freezer for 1 hour. Once the implant is pulled out of the mold, excess PVA is trimmed off the implant using a scalpel. The implant is then set into a laboratory oven at 90°C for 24 hours to anneal. Post annealing, the excess PVA ridge left on the implant as well as any additional PVA or BC near the stem of the implant is trimmed off, e.g., with a lathe or other trimming mechanism.EXAMPLE PROCEDURE

[0053] An example process of pre-vacuuming BC sheets down to a thickness of 2 mm and using batting as a cushion to prevent wrinkles is described below. Although specific examples of how each of these steps may be performed are described, the method of performing each step may be varied.1. BC Drying

[0054] The sheet(s) of BC material to be used may be dried in any appropriate manner, prior to cutting and shaping. For example, a vacuum oven may be used to reduce the water content of the BC material (e.g., “slabs”). To successfully form BC around a mold, fully hydrated BC slabs may remain un-compressed, as greater thickness may result in uneven pressure towards the top portion of the mold. As such, the example process described hereinmay involve compressing (i.e. vacuum compressing) the BC sheets down to a thickness of 2 mm prior to forming the implant. As previously mentioned, compression may also include other means of compression such as pneumatic compression or mechanical compression. Additionally, the compression or vacuuming process in the example process described herein may involve the use of batting to provide additional cushion to prevent the suction forces from severely wrinkling the BC around the implant.

[0055] To create the BC layers used during the forming stage of the procedure layers, the hydrated sheets of BC (20 cm x 10 cm x 1.5 cm) may be vacuumed down to 2 mm in thickness / density from an original thickness / density of roughly 15mm. At the original thickness / density, the BC sheet may be unable to successfully mold around the entire metal surface; thus, it may flatten to a thinner thickness / density, ideally within the range of 1.5 mm to 2.5 mm, while remaining hydrated, to be formed around the implant surface. An appropriate thickness / density may be within the range of 0.5 - 8 mm, corresponding to a cellulose fiber density of IE-3 g / mm3 to IE-5 g / mm3. Vacuum sealing produces a consistent thickness of the BC reinforced hydrogel coating of the BC layers across the implant and a uniform surface.

[0056] FIG. 2 shows an example of concave cavity implants 200 having keys or slots 201 for adhering hydrogel and polyvinyl alcohol (PVA) implant coatings to the surface of the metal implant core when the implant is compressed or vacuumed.

[0057] FIGS. 3 A and 3B illustrate examples of a vacuum drying method 300 for BC hydrogel sheets 310. As shown in Figures 3A-3B, each sheet of vacuumed wet BC 304 is placed between Peel Ply 303, batting 302, and perforated sheets of metal 301. Note that “Peel Ply” may refer to a layer of material which may be used as a backing or support (temporary) for the BC sheet, to simplify handling during performance of the methods described herein. This material may be removed during or after cutting and / or applying. As mentioned, for convenience, this temporary backing layer may be referred to herein as “Peel Ply” and may be removed (e.g., peeled off). The BC backing may be a woven fabric, glass, nylon or other synthetic material.

[0058] FIGS. 4 A and 4B are images showing drying results of wet BC sheets of different thicknesses. Wet BC can be dried and molded around metal implant surfaces but may be unable to hold its shape when drying around a contoured surface such as a metal ball. Thus, it may be unable to completely cover the bottom hemisphere of such a surface. An uneven drying method can lead to variations in thickness / density and surface wrinkles on the BC layer(s). One or more BC layers may be formed around a surface with a uniform thickness / density, e.g., by drying down the thickness / density of the wet BC to nearly 2 mm400. The BC thickness / density of 2 mm 401 was determined to be a suitable thickness / density for the forming process as the entire BC sheet was of equal thickness / density and hydration.

[0059] The BC sheet(s) may then be dried. For example, one or more sheets of BC may be wrapped in batting and dried 410 (as shown in Figure 4B), using a vacuum pump until sufficient solution has been removed. In these examples the BC sheets 411 were within a thickness / density range of 1.25 mm to 2.5 mm. For this particular trial, if the BC is above 4 mm, the BC was not easily moldable into shape around the implant surface; if the BC was under 1.5 mm, the side edges began to dry out before the center, resulting in uneven hydration levels of the BC slabs as shown in BC sheets 411. Thus, in some examples the range of BC thickness / density falls between 1.5 mm and 2.5 mm, where it remains relatively hydrated and flexible. At this thickness / density, using similar conditions, it can be molded successfully and efficiently around various implant surfaces. Other ranges, particular where the shape, level of hydration, etc. are varied, may be used.

[0060] In some examples, the wet BC may be dried (e.g., between perforated sheets of metal or otherwise) to an even thickness (e.g., within + / - 10%, + / - 8%, + / - 5%, + / - 4%, + / - 3%, etc.) and uniform hydration.

[0061] FIG. 5 is an image showing a vacuum drying BC setup 500. Vacuum drying BC setup includes vacuum pump 501, Ziploc bag 505, tubing 502, beaker 503 to hold suctioned solution, and the batting covered BC 504. After wrapping all BC layers in batting and sealing it in a sealable plastic bag 505, the vacuum pump 501 is run to remove roughly 350 mL of solution per BC sheet 304. An individual sheet of BC after this reduction weights between 20g to 25g.2. Cutting BC

[0062] The BC material may then be cut into the desired shape. For example, after the BC has dried to 2 mm in thickness 401, it is removed from the vacuum bag 505 and unwrapped, with only the Peel Ply sheets 303 remaining on either side. The BC sheets may be cut (e.g., laser cut) according to the geometric shape of the BC layers that will cover all metal surfaces of the core. Since each BC layer wraps around the previous layer and the metal core, the dimensions of each layer may account for the change in radius of the implant.

[0063] FIGS. 6A-6B show dimensions of two laser cut floral shaped BC hydrogel layers. The floral or flower-shaped design in this example allows for an efficient use of BC to cover a spherical object. According to other examples, the laser cut shaped could be strips, ribbons, strings, or other geometric shapes as necessary to best cover and seal an implant surface.

[0064] An exemplary implant surface may require, for example, two layers of BC, cut into layers (e.g., flower-shaped layers 600 and 610) that may abut or overlap to cover the surface. According to some examples, only one layer of BC may be used. According to certain other examples, the layer(s) of BC may be other geometric shapes. To account for the change in diameter of the ball joint after BC layer 1 (600) may cover the implant surface or metal core 703 (32 mm in diameter), layer 2 (610)’s petals are slightly longer and of a different shape. In the example shown, dimensions of both layers (603-606, 613-616) and the individual petals (601-602, 607 and 611-612, 617) are given. For example, to create the curvature of the BC petals in the hip joint shown, the latitudinal circumference of the BC and PVA layer was calculated at various points along the spherical section of the hip joint. Each petal represented l / 6th of the total circumference of the BC / PVA layer, with each of the 6 petals being spaced 60 degrees about the origin. The origin of the petals are offset 604, 614 respectively for layer 1 (600) and layer 2 (610) to allow for the petals to overlap at the center. BC layer 1 (600) was calculated based on a 36mm outer diameter BC / PVA layer, providing a maximum petal width 601 a distance 603 from individual petal origin 604. BC layer 2 (larger petals) 610 was calculated based on an outer diameter BC / PVA layer, providing a maximum petal width 611, located away from the BC flower origin 613 and offset 614. The tip width of each petal 607, 617 was calculated from l / 6th of the circumference of the hip joint core stem at a distance from the intersection of the bottom flat and the BC / PVA shell to the core stem. The top BC petal layer had the total length of each petal extended to provide additional BC along the length of the stem (seen as having a longer tip, for example 612). The dimensions shown in FIGS. 6A-6B are exemplary only; other dimensions may be used.

[0065] FIG. 6C illustrates examples of offset laser cut floral-shaped bacterial cellulose (BC) hydrogel layers 620. Depending on the design of the implant surface 703, the BC 304 may be cut into geometric shaped layers that entirely cover the implant surface to then undergo the remaining steps of the example procedure 100. Shown here is exemplary BC layer offset 620 with BC layer 1 (600) and larger BC layer 2 (610), specifically following the procedure to form the femoral head component of the hip joint. The BC layers 600 and 610 may be overlapped at an offset angle, at which the petal cuts of one layer fall on the center of the petal of the layer above or below. The implant will use two layers of geometric shaped BC such as layer 1 (600) and layer 2 (610).3. Forming

[0066] In the example process to form BC around the implant surface described above, hydrated BC sheets 304 are preferably undamaged and of an even thickness. The pattern for the BC layers (e.g., layer 2 610 in FIG. 6C) may provide additional thickness added to eachBC (e.g., layer 1 600). In any of these examples a vacuum seal may be used to the mold the BC while maintaining relatively equal pressure around all areas is used; in some examples it may be particularly beneficial to use a cushioning material. For example, a material such as “Peel Ply” 303 and / or batting 302 may be used during the vacuuming processes. The use of such cushioning materials (individually or in combination) during the vacuuming process may protect the implant from suction forces experienced due to the vacuum. This may reduce the wrinkling of the BC surface 304 while further preventing the BC 304 from being pulled and exposing the implant surface. As previously mentioned, compression may also include other means of compression such as pneumatic compression or mechanical compression.

[0067] FIG. 7 shows an exemplary implant surface for a femoral head component of a joint implant before and after layering with BC layers 720. To form the implant, the layers of BC are oriented to cover the entire implant surface (in this case, a metal core). Slight damage to a fully hydrated BC sheet may cause unevenness in the layer during the forming process.

[0068] The layers may be sequentially wrapped over each other. For example, layer 1 may wrap around the implant surface, layer 2 around layer 1 and the implant surface beneath layer 1, until the last layer wraps around the previous layers and the implant surface beneath them. Since the implant changes size with each layer of BC added to the implant surface, the subsequent layers may be adjusted to accommodate the new implant size. As mentioned, the implant may be wrapped in a cushioning material (e.g., batting) and vacuumed to seal the BC layer to each other for an appropriate amount of time (e.g., in some examples for 10 to 30 minutes), that may be limited to prevent the BC from being vacuumed dry. In the example shown in FIG. 7, BC layer 1 (700) and layer 2 (710) wrap around the implant surface (metal core) 703 for the femoral head component 707.

[0069] In FIG. 7, the femoral head component is formed using only two layers of BC. Layer 1 (700) wraps around the metal core, with a diameter of 32 mm, and layer 2 (710) wraps around the core and layer 1. The bottom sheet of backing layer / sheet (e.g., Peel Ply) is removed off of layer 1 (700) and gently placed around the hip ball and smoothed until all its petals / legs covered the implant surface 703. After removing the top backing sheet off layer 1 (700) and the bottom sheet off layer 2 (710), BC layer 2 (710) is assembled around the implant surface 703 and layer 1 (700). FIG. 7 illustrates non-limiting examples of possible dimensions for implant without the hydrogel-impregnated BC 706 and with the hydrogel- impregnated BC 707. Other dimensions may be used, including other thicknesses of the BC.

[0070] Under specific conditions (such as drying in an oven under weight), BC has the potential to reseal with itself. The vapor pressure surrounding the material may be adjusted (e.g., reduced) to enhance resealing. Alternatively or additionally, a combination of hydrationand applied force, such as compression forces including vacuuming, pneumatic compression, mechanical compression, etc. can promote a BC layer to seal with itself and to mesh BC layers into one BC sheet.

[0071] In the example shown in FIG. 7, the entire implant surface was wrapped in batting and compressed (vacuumed) for 20 minutes to reseal the BC petals and layers to each other.

[0072] Sealing and resealing via sequential contouring of BC layers may be performed independent of fasteners and adhesives including clamps and cements, and may be based on one or more of a strength of the BC reinforced hydrogel coating of the BC layers and a geography of the implant core and / or subsequent BC layers.

[0073] FIGS. 8A-8C show examples of sequential BC layer wrapping around an implant surface (metal core) of a femoral head component of a hip joint implant. FIG. 8 A shows a flower-shaped BC layer 800 used to form the femoral head implant. FIG. 8B shows BC layer 1 (700) wrapped around the core at 801. FIG. 8C shows BC layer 2 (710) wrapped around the core and BC layer 1 at 802. In any of these examples, each BC layer may be sequentially contoured to at least a bearing surface of the implant that comes into contact with an opposing joint surface. Each BC layer may contour to arbitrary curved surfaces of human joints, as previously discussed.

[0074] Vacuuming or otherwise compressing BC slabs can effectively reduce the water content of the BC slabs so that they assume a paper-like thicknesses and help them seal together. In some examples, vacuuming BC slabs without any form of cushioning may lead to wrinkles in the BC layer or an uneven thickness or level of hydration. As mentioned above, adequate cushioning can prevent wrinkles and other deformities during the vacuuming / compression process.

[0075] FIGS. 9A-9C show images of a compressed / vacuumed femoral head component of a joint implant before and after surface smoothing 903. After vacuum sealing the implant, the BC layers around the implant may be slightly wrinkled 901 / 902. As such, the implant may be smoothed (e.g., by hand or mechanically) 903 to remove the wrinkling. After the BC surface is smooth 904, the implant may be placed into the mold to determine and confirm it will fit. If the implant is too large, it may be smoothed further to thin down the BC layers so that the entire implant can easily fit into the mold with limited BC being cut off.4. Infiltration

[0076] Prior to infiltration, the material, on the implant surface, may be placed in a holder or mold. The mold may be sized to allow the BC layers to fit without being cut during the molding process. The implant may be compressed into the mold and tightened shut (e.g., by hand). Extra space may be left in the molds to account for the size of the BC and PVA layersafter infiltration. The implant’s BC layer may be smoothed prior to infiltration and molding to remove wrinkling.

[0077] FIG. 10 shows an example of an infiltration chamber 1004 containing a PVA solution and femoral head component of a hip joint 1000.

[0078] As mentioned above, the BC may be hydrated prior to infiltration in an infiltration chamber 1004). Depending on the size and shape of the implant and infiltration chamber 1004, the total amount of PVA solution 1003 may be determined and made in the Teflon infiltration chamber 1004, for example a 40-60 wt% PVA solution. The implant 1001 may be placed stem up 1002 into the solution, and then the Teflon chamber 1004 may be placed into a metal pressure chamber and sealed shut with a wrench. The pressure chamber may be placed into the laboratory oven at >100°C for >12 hours, for example at 120°C for 24 hours to infiltrate the PVA 1003 into the BC layers.

[0079] For an exemplary implant such as a hip ball as shown in the example above, a 75 g 40% PVA solution (30 g of PVA to 45 g of H2O) may be used for infiltration. In this process, the 40% PVA solution was made with 31.3 g PVA and 47.2 g of H2O. In some examples, the implant may be further infiltrated or fused with material other than PVA having a desired tensile stability to form a contourable seal. According to yet other examples, the compressed BC impregnated with hydrogel has a thickness of between about 0.5-8 mm, and a cellulose fiber density between about 0.001 g / mm3to 0.00001 g / mm3.5. Molding

[0080] Once infiltrated with the hydrogel (e.g., PVA), the apparatus with infiltrated BC may be molded. For example, a hip ball implant with hydrogel -impregnated BC as described above may be molded into its spherical shape using a two-piece mold that is designed for the implant. FIGS. 11 A-l 1C show an example molding process progression 1100 after infiltration 1101, in the mold 1105, and after molding and cooling 1110. Each implant has a specific mold with various parts and features that allow for a smooth surface to form.Implants and implant molds may be for various joints such as hip joints, knee joints, shoulder joints, elbow joints, etc. For example, a hip mold may be of a specific size that allows for the BC layers to fit into the mold without being cut by the knife edge. The hip ball prior to infiltration may be configured to easily fit within the mold with no cuts to the BC being made to ensure that the molding process will result in a hip ball with no cuts to the BC layers. In the example of a process described above, molds for the implants may leave extra space, e.g., approximately 2 mm of extra space, for the BC and PVA layers. This extra space may be configured to accommodate the BC layers while minimizing the amount of excess PVA on the implant surface, as unreinforced PVA may be weaker and may have wear characteristicsthat are inferior to PVA that is reinforced by BC. After the forming process, the implant may be smoothed to ensure that it fits within the mold prior to infiltration and molding.

[0081] The implant may then be removed from the infiltration chamber, and excess hydrogel (e.g., PVA) may be removed from the implant (e.g., by hand or otherwise). The implant may be gently compressed into the mold to ensure that the BC is not cut during this process. After the implant is sitting in the mold, the mold may be compressed around the implant, for example via pneumatic press 1500, via vacuum compression, or via mechanical compression. In some examples, the mold may be tightly shut (e.g., using a bolt, a wrench, screwdriver, etc.). The mold may be placed back into the metal pressure chamber, pressurized, and cooled, e.g., by placing it in a freezer to cool (e.g., for one hour or more).

[0082] FIGS. 12A-12B show images of a two-part mold for a femoral head component of a hip joint 1200. Figure 12A shows an image of a mold 1201 having a bottom hemisphere mold portion 1202 with the hole for the stem 1203 and knife edge 1204. Figure 12B shows an image of a mold 1210 having a top hemisphere mold portion 1211.

[0083] FIG. 13 shows an image of a pneumatic press 1300. The hip ball mold 1200 is compressed using pneumatic press 1300, with the compression pushing out excess PVA and pressing the two part mold 1200 together. In some examples, other types of compression forces including vacuuming and mechanical compression may be used.6. Demolding and Trimming

[0084] Following molding the implant with hydrogel -impregnated BC may be removed from the mold and shaped (trimmed) as mentioned above. FIG. 14 shows various views of images of a hip ball joint after demolding and trimming 1400. After retrieving the pressure chamber from the freezer, the mold is removed from the chamber and unscrewed. Excess PVA around the implant may be trimmed off using a scalpel. Trimming at this stage may remove the excess PVA (smoothing the surface of the implant may be performed separately).

[0085] Thus, when demolding the hip ball, excess PVA along the equator of the ball joint may be trimmed off, e.g., using a scalpel. In some examples, after the molding process 106, only a small amount of the BC may need to be cut off by the mold. The majority of the hip ball may remain successfully intact with only excess PVA remaining at the equator. FIG. 14 shows a top view 1401, bottom view 1402, side view attached to base 1403, and free-standing side view 1404 of the hip ball joint after demolding and trimming.7. Annealing and Trimming

[0086] FIG. 15 shows side 1501 and bottom 1502 views of images of a hip ball joint after excess PVA trimming 1500. Implants including the compressed BC impregnated with hydrogel are placed in a laboratory oven for an appropriate time and temperature, forexample >80°C for >12 hours. According to one example, annealing is done for 24 hours at 90°C.

[0087] After annealing the hip ball, a lathe may be used to smooth the excess PVA ridge at the equator 1501A of the implant 1501. Additionally, in some examples, at the bottom hemisphere of the hip ball, near the stem, a lathe may be used to trim off the excess PVA build up as well as BC legs that covered the threads of the stem. A clamp may be screwed on and pressed into the base of the hydrogel, but such a clamp is not required for holding the hydrogel in place.

[0088] Compression and annealing of the compressed BC impregnated with hydrogel may be confirmed via microscope or other means of visualizations of thickness / density measurement.8. Rehydration

[0089] The shaped and trimmed implant with hydrogel -impregnated BC may then be rehydrated. FIG. 16 shows an image of a femoral head component 1601 of a hip joint after rehydration in a 37°C saline solution 1600. To rehydrate, the implant may be placed in saline at 37°C. This final rehydration step results in a hydrogel with a water content of 40-60 wt%, with the balance consisting of a composite of BC and PVA. In general, although a hip joint implant is shown, these methods and apparatus may be implants for any desired joint or body part.

[0090] FIG. 17A shows a chart illustrating one method 1700 of forming an implant as described herein. At block 1705, the surface of the implant is covered with a compressed sheet of bacterial cellulose (BC). At block 1710, the sheet of BC is compressed against the surface of the implant. At block 1715, the sheet of BC compressed on the surface is impregnated with a hydrogel. At block 1720, the impregnated BC is molded in a mold, under pressure. At block 1725, the implant including the impregnated BC is annealed. In some examples, method 1700 further includes compressing the thickness of the BC by more than half prior to covering the surface of the implant. In some examples the method 1700 further includes hydrating the BC prior to compressing it.

[0091] The method 1700 described herein may further include forming two or more layers of the compressed sheet of BC to cover the surface of the implant. In some examples, method 1700 further includes the compressed sheet of BC having a cellulose fiber density of between 2.55e-4 g / mm3to 1.59e-5 g / mm3. In some examples, method 1700 further includes compressing the sheet of BC onto the implant surface by applying a vacuum.

[0092] In some examples the method 1700 may include smoothing the sheet of BC on the surface after compressing the sheet of BC against the surface of the implant. As mentioned,the surface of the implant may have a spherical or partially spherical surface (concave) or a convex surface (or both).

[0093] Any of these methods 1700 may include cutting the sheet of BC prior to covering the surface of the implant with the compressed sheet of BC so that the sheet of BC fits over the surface with overlapping edges. Any of these methods 1700 may include impregnating the BC with a hydrogel such as a polyvinyl alcohol (PVA) hydrogel. Impregnating may be performed by impregnating the BC by immersing the BC into the hydrogel for >12 hours at >100 degrees C. In some examples the method may include removing excess hydrogel after impregnating the BC. Any of these examples may include molding the impregnated BC in the mold by cooling the impregnated BC to < 20 degrees C for >30 minutes. Any of these methods may include removing the implant from the mold and trimming the impregnated BC prior to annealing.

[0094] Any of these examples may include annealing the implant at >80 degrees C for >12 hours. Any of these examples may include packaging the implant following annealing. The methods described herein may include instructing a user to rehydrate the annealed implant in saline at 37 degrees C until the impregnated BC hydrogel is between 40-60% water prior to implantation.

[0095] FIG. 17B shows a chart illustrating another method 1701 of forming an implant as described herein. For example, at block 1750, the surface of the implant may be covered with a compressed sheet of bacterial cellulose (BC) to form two or more layers of the compressed sheet of BC. The sheet of BC may be compressed against the surface by applying a vacuum 1755. The sheet of BC may be smoothed on the surface after compressing 1760. The BC may be compressed on the surface is impregnated with a polyvinyl alcohol (PVA) hydrogel by immersing into the hydrogel for >12 hours at >100 degrees C 1765. The impregnated BC may be molded into a mold 1770. Finally, the implant with the hydrogel -impregnated BC may be annealed 1775 (e.g., at greater then 80 degrees C for more than 12 hours).

[0096] Any of the methods (including user interfaces) described herein may be implemented as software, hardware or firmware, and may be described as a non-transitory computer-readable storage medium storing a set of instructions capable of being executed by a processor (e.g., computer, tablet, smartphone, etc.), that when executed by the processor causes the processor to control perform any of the steps, including but not limited to: displaying, communicating with the user, analyzing, modifying parameters (including timing, frequency, intensity, etc.), determining, alerting, or the like.

[0097] It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are notmutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein and may be used to achieve the benefits described herein.

[0098] When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and / or elements may also be present. In contrast, when a feature or element is referred to as being “directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being “connected”, “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly connected”, “directly attached” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one example, the features and elements so described or shown can apply to other examples. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.

[0099] Terminology used herein is for the purpose of describing particular examples only and is not intended to be limiting of the invention. For example, as used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and / or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “ / ”.

[0100] Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly”,“downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.

[0101] Although the terms “first” and “second” may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature / element from another feature / element. Thus, a first feature / element discussed below could be termed a second feature / element, and similarly, a second feature / element discussed below could be termed a first feature / element without departing from the teachings of the present invention.

[0102] Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising” means various components can be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps.

[0103] In general, any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and / or steps may alternatively be exclusive and may be expressed as “consisting of’ or alternatively “consisting essentially of’ the various components, steps, sub-components or sub-steps.

[0104] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and / or position to indicate that the value and / or position described is within a reasonable expected range of values and / or positions. For example, a numeric value may have a value that is + / - 0.1% of the stated value (or range of values), + / - 1% of the stated value (or range of values), + / - 2% of the stated value (or range of values), + / - 5% of the stated value (or range of values), + / - 10% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “X” is disclosed the “less than or equal to X” as well as “greater than or equal to X” (e.g., where X is a numerical value) is alsodisclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0105] Although various illustrative examples are described above, any of a number of changes may be made to various examples without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative examples, and in other alternative examples one or more method steps may be skipped altogether. Optional features of various device and system examples may be included in some examples and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.

[0106] The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.

Claims

CLAIMSWhat is claimed is:

1. A method of forming an implant, the method comprising: covering a surface of an implant with a compressed sheet of bacterial cellulose (BC); compressing the sheet of BC against the surface of the implant; impregnating the BC compressed on the surface with a hydrogel; molding the impregnated BC in a mold, under pressure; and annealing the implant including the impregnated BC.

2. The method of claim 1, further comprising compressing the thickness of the BC by more than half prior to covering the surface of the implant.

3. The method of claim 1, wherein covering the surface of the implant with the compressed sheet of bacterial cellulose (BC) comprises forming two or more layers of the compressed sheet of BC.

4. The method of claim 1, wherein the compressed sheet of BC has a cellulose fiber density of between 1.0-3 g / mm3to 1.0e-5 g / mm3.

5. The method of claim 1, wherein compressing the sheet of BC comprises compressing the sheet onto the implant surface by applying a vacuum.

6. The method of claim 1, further comprising smoothing the sheet of BC on the surface after compressing the sheet of BC against the surface of the implant.

7. The method of claim 1, wherein the surface of the implant comprises a spherical or partially spherical surface.

8. The method of claim 1, further comprising cutting the sheet of BC prior to covering the surface of the implant with the compressed sheet of BC so that the sheet of BC fits over the surface with overlapping edges.

9. The method of claim 1, wherein the implant surface is concave or convex.

10. The method of claim 1, wherein impregnating the BC compressed on the surface with a hydrogel comprises impregnating the BC with a polyvinyl alcohol (PVA) hydrogel.

11. The method of claim 1, wherein impregnating the BC compromises impregnating by immersing the BC into the hydrogel for >12 hours at >100°C.

12. The method of claim 1, further comprising removing excess hydrogel after impregnating the BC.

13. The method of claim 1, wherein molding the impregnated BC in the mold comprise cooling the impregnated BC to < 20°C for >30 min.

14. The method of claim 1, further comprising removing the implant from the mold and trimming the impregnated BC prior to annealing.

15. The method of claim 1, wherein annealing the implant comprises annealing at >80°C for >12 hours.

16. The method of claim 1, further comprising packaging the implant following annealing.

17. The method of claim 1, further comprising instructing a user to rehydrate the annealed implant in saline at 37°C until the impregnated BC hydrogel is between 40-60% water prior to implantation.

18. A method of forming an implant, the implant comprising: covering a surface of an implant with a compressed sheet of bacterial cellulose (BC) to form two or more layers of the compressed sheet of BC; compressing the sheet of BC against the surface by applying a vacuum; smoothing the sheet of BC on the surface after compressing; impregnating the BC compressed on the surface with a polyvinyl alcohol (PVA) hydrogel by immersing into the hydrogel for >12 hours at >100°C; molding the impregnated BC in a mold; and annealing the implant including the impregnated BC at >80°C for >12 hours.

19. An orthopedic implant, the implant comprising: an outer surface; and a compressed bacterial cellulose (BC) layer impregnated with a hydrogel covering the outer surface, wherein the compressed BC impregnated with hydrogel has a thickness of between about 0.5-8 mm, and wherein a cellulose fiber density of the compressed BC is between about 0.001 g / mm3to 0.00001 g / mm3.

20. The implant of claim 19, wherein the compressed BC layer impregnated with the hydrogel comprises a plurality of layers of compressed BC layers impregnated with the hydrogel.

21. The implant of claim 19, wherein the outer surface comprises a spherical or partially spherical shape.

22. The implant of claim 19, wherein the implant surface is concave or convex.

23. The implant of claim 19, wherein the outer surface comprises one or more slots.

24. The implant of claim 19, wherein the compressed BC layer impregnated with a hydrogel is configured to have a water content of between 30%-70% when hydrated.

25. The implant of claim 19, wherein the hydrogel comprises a polyvinyl alcohol (PVA) hydrogel.

26. The implant of claim 19, wherein the implant is a titanium implant.

Images