Dry Hydrogel Implants

Abstract

The dry cellulose-reinforced hydrogel can comprise a cellulose nanofiber network and interstitial hydrogel portions within the interstitial regions of the cellulose nanofiber network, the interstitial hydrogel portions comprising dry hydrogel. The dry hydrogel implant can be inserted into the body and allowed to rehydrate in situ.

Description

[Technical Field]

[0001] Priority claims

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 408,087, entitled "DRY HYDROGEL IMPLANTS," filed September 19, 2022, the entire contents of which are incorporated herein by reference.

[0002] 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 technology]

[0003]

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

[0004] Historically, the only option available to patients with cartilage damage, particularly in arthroplasty such as the knee or elbow, was to initially do nothing if the damage was only relatively limited, typically resulting in a deterioration of the condition and further damage to the cartilage and the joint itself, causing discomfort and pain when using the joint and ultimately requiring a total joint replacement to restore mobility; or, if the damage was severe from the start, a total joint replacement was performed immediately. However, for very young patients, the patient's general skeletal structure is not yet fully developed and they are still growing, so total joint replacement can be problematic in that, once they reach fully mature adult size, height, and skeletal structure, the replaced joint may not actually be sized appropriately for them. Moreover, in the past, many knee, elbow, and shoulder replacements typically had a maximum useful lifespan of only about 10 years due to wear and tear and erosion of the joint's articulating surfaces with repeated use over time, thereby necessitating periodic invasive surgery to replace the entire joint. Despite the advances and improvements that have been made and continue to be made in the durability of materials used on articular surfaces as new materials are developed, this has meant that for very young patients, they will likely undergo several more such surgeries over the course of their lifetime.

[0005]

[0005] Recently, artificial cartilage materials have been proposed, specifically artificial cartilage made from hydrogels. Hydrogels are typically water-swollen polymeric networks and are promising synthetic materials for cartilage replacement because they can be made to have mechanical and tribological properties similar to those of natural cartilage. However, hydrogels can be difficult to use, specifically, difficult to implant without causing damage. Described herein are methods, hydrogel compositions, and devices (e.g., implants) that can address these needs. Summary of the Invention [Means for solving the problem]

[0006]

[0006] The present disclosure generally relates to artificial cartilage material modifications in implants suitable for cartilage repair, including hydrogel composites, and methods for attaching the hydrogel composite to the surface of the implant, where the hydrogel is implanted in a dry state and allowed to rehydrate within the joint after implantation. Surprisingly, inserting the hydrogel material prior to hydration can prevent damage and allow sealing of the implant site as the implant with the attached material connects to tissue.

[0007]

[0007] Described herein are methods for fabricating hydrogel materials for use as artificial cartilage in implants, as well as methods for implanting them. Specifically, described herein are implants composed of dry (e.g., non-hydrated) hydrogels. These hydrogels can be impregnated or injected into nanofiber materials (e.g., nanofiber networks), bonded to the surface of the implant, such as a porous base, and then dried, such that the "dry" hydrogel material can be packaged, implanted into a patient, and allowed to hydrate and swell after implantation.

[0008]

[0008] Dry implants may have surface properties that prevent damage during implantation (e.g., making them hard and difficult to deform and / or scratch), while once implanted, the resulting hydrated hydrogel has physical properties such as strength, modulus, wear resistance, and coefficient of friction (COF) that approximate or exceed those of healthy cartilage bonded to bone.

[0009]

[0009] The initial formation of an implant using a hydrogel can involve a toughening process that increases the hydrogel's crystallinity and reduces its water content, thereby improving its mechanical properties for implementation as a cartilage substitute. As used and described herein, toughening a hydrogel can include one or more steps of drying and annealing the hydrogel while in contact with a fiber support. The resulting dried hydrogel can be rehydrated in vivo (e.g., by synovial fluid in the joint after surgery is completed). Thus, rehydration can be performed after surgery is completed (e.g., over hours and days), allowing the implant to swell and seal around the implantation site, which can also secure the implant in place and prevent or reduce complications such as cysts caused by synovial fluid.

[0010]

[0010] A technique for producing synthetic cartilage by infiltrating a hydrogel into a nanofiber network to mimic cartilage is described in International Patent Application No. PCT / US2021 / 040031, the entire contents of which are incorporated herein by reference. The methods described herein can be used to form hydrogels that have similar elastic moduli, coefficients of friction, and wear resistance to cartilage, while meeting or exceeding the higher end of the cartilage strength range.

[0011]

[0011] Described herein are methods of making and using implants having dry hydrogels to mimic or replace cartilage. Any of the hydrogels described herein can be interlocked with a nanofiber network, such as a cellulose nanofiber network. The incorporated hydrogel, when hydrated, can have a crystalline structure that imparts high tensile and / or compressive strength to the hydrogel. In some examples, a reinforcing hydrogel for use in the implants described herein can include a crosslinked cellulose nanofiber network; and a hydrogel injected into the interstitial regions of the crosslinked cellulose nanofiber network, wherein the hydrogel has a crystallinity of 20% or greater. In some examples, the hydrogel includes polyvinyl alcohol (PVA). In any of these examples, the hydrogel may exclude (or substantially exclude) PAMPS. The hydrogel can be greater than 90% PVA (e.g., greater than 92%, greater than 93%, greater than 94%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 99%, etc.) PVA that has been annealed as described herein.

[0012]

[0012] Described herein is an implant comprising an implant body, a cross-linked cellulose nanofiber network bonded to a porous surface of the implant body by cement, and a dried cellulose-reinforced hydrogel material comprising a dried hydrogel impregnated into the cross-linked cellulose nanofiber network. The implant body can include a porous surface. For example, the implant body can be a titanium body having a porous surface facing the bone and a non-porous surface facing the hydrogel.

[0013]

[0013] Hydrogels can be composed of one or more polymers. In some cases, the hydrogel may include polyvinyl alcohol (PVA). In some cases, the hydrogel may include only one type of polymer. In some variations, the hydrogel is selected from the group consisting of polyvinyl alcohol (PVA), poly(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt (PAMPS), poly(N,N'-dimethylacrylamide) (PDMAAm), copolymers of 1-vinylimidazole and methacrylic acid, amphiphilic triblock copolymers, polyampholyte hydrogels, PVA-tannic acid hydrogels, poly(N-acryloyl)glycinamide hydrogels, polyacrylic acid-acrylamide-C18 hydrogels, guanine-boric acid reinforced PDMAAm, polyelectrolyte hydrogels, poly(acrylonitrile-co-l-vinylimidazole) hydrogels (e.g., mineralized poly(acrylonitrile-co-l-vinylimidazole) hydrogels), polyacrylic acid-Fe3+-chitosan hydrogels, poly(methacrylic acid) gels, graphene oxide / xonotolite reinforced polyacrylamide (PAAm) gels, poly The hydrogels may be composed of one or more of the following: (stearyl methacrylate)-polyacrylic acid gel, annealed PVA-polyacrylic acid hydrogel, supramolecular hydrogel from multi-urea-linked segmented copolymer, polyacrylonitrile-PAAm hydrogel, microsilica-reinforced DMA gel, agar-polyhydroxyethyl methacrylate gel, polyfacryloyloethyl trimethylammonium chloride hydrogel, poly(3-(methylacryloylamino)propyl) trimethylammonium chloride hydrogel, poly(sodium p-styrenesulfonate) hydrogel, polyethylene glycol diacrylate hydrogel, and polyethylene glycol hydrogel. In some cases, it may be beneficial to exclude PAMPS (e.g., no PAMPS, less than 0.1%, less than 0.5%, less than 1%, etc.).

[0014] The nanofiber network may comprise a cellulose nanofiber network. The nanofiber network may comprise a crosslinked cellulose nanofiber network. In some examples, the nanofiber network comprises bacterial cellulose (BC). Additionally or alternatively, the nanofiber network may comprise at least one of electrospun polymer nanofibers, polyvinyl alcohol (PVA) nanofibers, aramid nanofibers, aramid-PVA nanofibers, wet-spun silk protein nanofibers, chemically crosslinked cellulose nanofibers, and polycaprolactone (PCL) fibers.

[0015] The cellulose-reinforced hydrogel may comprise: a cellulose nanofiber network; and a hydrogel impregnated into the cellulose nanofiber network, which may be dried after impregnation into the cellulose nanofiber network. The cellulose-reinforced hydrogel may comprise a hydrogel comprising bacterial cellulose and / or polyvinyl alcohol (PVA).

[0016] The cellulose-reinforced hydrogels described herein can be formed by: infiltrating a cellulose nanofiber network with a hydrogel to form a cellulose-reinforced hydrogel; and annealing and drying the hydrogel (e.g., to reduce the water content) and increase the crystalline content of the hydrogel. Annealing the hydrogel can include heating the cellulose-reinforced hydrogel. Annealing the hydrogel can include heating the cellulose-reinforced hydrogel to reduce the water content of the hydrogel. In some examples, the cellulose-reinforced hydrogel can be heated to a temperature ranging from 90 to 140°C. The hydrogel implant can remain in a dried form and be protected from contact with liquids (e.g., water) until implantation. For example, the implant can be sealed in an airtight and / or watertight container (e.g., bag, package, etc.).

[0017] Also described herein are methods for implanting an implant containing a dried hydrogel. For example, any of the methods may include implanting the hydrogel in a dry state into the body and rehydrating the hydrogel in vivo after implantation. In some instances, a liquid (e.g., saline, etc.) may be added to rehydrate the implant. Alternatively or additionally, the dried hydrogel may allow rehydration following absorption of synovial fluid from the joint after implantation. Rehydrating the hydrogel may include increasing the water content of the hydrogel to at least 20 wt% (from 5% or less in a dehydrated or unhydrated form). Rehydrating the cellulose-reinforced hydrogel may include rehydrating to 30% or more water, 35% or more water, 40% or more water, 45% or more water, 50% or more water, 55% or more water, 60% or more water, 65% or more water, 70% or more water, 75% or more water, 80% or more water, etc. (wt%).

[0018] When used in partial knee resurfacing procedures, the implant can be configured to abrade the opposing cartilage surface to a degree that is not significantly greater than the degree to which cartilage abrades the cartilage. The upper bearing surface of the implant can have a coefficient of friction (COF) that is not statistically different from the coefficient of friction of cartilage.

[0019]

[0019] The implants described herein may be configured as medical implants and may include a tissue-engaging portion (eg, a bone-engaging portion such as a rod, screen, nail, etc.).

[0020] The nanofiber network can be secured to the implant (e.g., to the porous surface of the implant) by any suitable method. For example, the nanofiber network can be secured to the implant by cement. In some cases, the nanofiber network is not secured to the implant by cement; for example, the nanofiber network can be secured as a sheet or other layer on a surface and held down by clamps or otherwise.

[0020]

[0021] The implant may be formed from any suitable 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 stainless steel alloy, titanium alloy, Co—Cr alloy, tantalum, gold, niobium, bone, Al oxide, Zr oxide, hydroxyapatite, tricalcium phosphate, sodium calcium phosphosilicate, poly(methyl methacrylate), polyether ether ketone, polyethylene, polyamide, polyurethane, or polytetrafluoroethylene.

[0021]

[0022] Generally, the nanofiber network can be connected to the upper support surface of the implant. The cross-linked cellulose nanofiber network can be attached to the upper support surface by clamps and / or adhesives. For example, the nanofiber network can be bonded to the upper support surface by cement; in some cases, the cement does not bond to the hydrogel; the cement only bonds to the nanofiber network. Alternatively, in some cases, the nanofiber network can be connected to the implant, such that the nanofiber network is fixed to the upper support surface without the use of a chemical adhesive such as epoxy. Instead, the nanofiber network can be fixed to the upper support surface by clamps. For example, the clamps can secure the nanofiber network (e.g., one or more sheets of BC) to the upper support surface around the periphery of the upper support surface. Therefore, generally, the use of adhesives (such as epoxy) is optional.

[0022]

[0023] Any suitable implant may be used. The surface of the implant (e.g., the upper support surface, which may equally simply be referred to as the support surface), at least the region on which the nanofiber network is deposited, may be titanium, stainless steel, or the like, and the support surface (e.g., the upper support surface) may be convex, flat, concave, or a mixture thereof. 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, sodium calcium phosphosilicate, poly(methyl methacrylate), polyether ether ketone, polyethylene, polyamide, polyurethane, or polytetrafluoroethylene.

[0023]

[0024] Also described herein are methods of making and / or using these implants. For example, described herein are methods of attaching a hydrogel to a surface. Any of these methods can include infiltrating a cellulose nanofiber network with a hydrogel to form a cellulose-reinforced hydrogel and annealing the hydrogel to increase the crystalline content of the hydrogel. For example, annealing the hydrogel can include heating the cellulose-reinforced hydrogel. In some examples, annealing the hydrogel can include heating the cellulose-reinforced hydrogel to reduce the water content of the hydrogel. For example, the cellulose-reinforced hydrogel can be heated to a temperature ranging from 90 to 140°C.

[0024]

[0025] In its dry (unhydrated) form, the exterior surface of the hydrogel can be smooth (e.g., have a roughness of less than 30 microns). The dry exterior surface can be mechanically polished to a roughness of less than 30 microns. In some cases, the exterior surface can be formed smooth by molding, which involves molding a heated polymer using a smooth mold. For example, infiltrating the hydrogel into the nanofiber network can include molding the hydrogel so that the exterior surface of the hydrogel has a roughness of less than 30 microns. Shaping the exterior surface can also allow a manufacturer to form the exterior surface into any desired shape. For example, the shape can be concave, convex, saddle-shaped, etc. Any desired shape (and smoothness) can be formed, for example, by molding and / or polishing.

[0025]

[0026] In any of these methods, fixing the (e.g., dried) nanofiber network can include fixing the freeze-dried nanofiber network with clamps and / or cementation, etc. As noted above, any of these devices and methods can use a dried nanofiber network that includes a cellulose nanofiber network. The dried nanofiber network can include at least one of electrospun polymer nanofibers, polyvinyl alcohol (PVA) nanofibers, aramid nanofibers, aramid-PVA nanofibers, wet-spun silk protein nanofibers, chemically crosslinked cellulose nanofibers, or polycaprolactone (PCL) fibers.

[0026]

[0027] For example, described herein is an implant comprising: an implant body having an upper support surface; an anchor base (which may extend from the back surface of the upper support surface); a dry cellulose-reinforced hydrogel; a crosslinked cellulose nanofiber network secured on the upper support surface of the implant body; and an interstitial hydrogel portion within the interstitial region of the crosslinked cellulose nanofiber network, the interstitial hydrogel portion having a crystallinity of 20% or greater. The interstitial hydrogel portion may be polyvinyl alcohol (PVA). The cellulose-reinforced hydrogel may contain less than 20% water by weight. The crosslinked cellulose nanofiber network may comprise bacterial cellulose (BC). The crosslinked cellulose nanofiber network may be secured on the upper support surface by a clamp. In some examples, the crosslinked cellulose nanofiber network comprises one or more sheets of bacterial cellulose (BC) held on the upper support surface by a clamp secured to a lip or rim of the upper support surface. The clamp may be used to secure the crosslinked cellulose nanofiber network without the need for epoxy. Alternatively, any of these implants may include an adhesive.

[0027]

[0028] For example, described herein is an implant (e.g., in some instances, an articular surface reconstruction implant) comprising: an implant body having a bearing surface; an anchor base connected to the implant body; a cellulose-reinforced dry hydrogel; a crosslinked cellulose nanofiber network fixed on the bearing surface of the implant body; and an interstitial hydrogel portion within the interstitial region of the crosslinked cellulose nanofiber network, the interstitial hydrogel portion having a water content of 20% or less. The water content of the cellulose-reinforced dry hydrogel including the interstitial hydrogel portion can be less than 20% (e.g., less than 19%, less than 18%, less than 17%, less than 16%, less than 15%, less than 14%, less than 13%, less than 12%, less than 11%, less than 10%, less than 9%, less than 8%, etc.). In some instances, the water content of the cellulose-reinforced dry hydrogel including the interstitial hydrogel portion is less than 5%.

[0028]

[0029] The interstitial hydrogel portion may specifically comprise polyvinyl alcohol (PVA). The crosslinked cellulose nanofiber network may comprise bacterial cellulose. For example, the crosslinked cellulose nanofiber network may comprise one or more sheets of bacterial cellulose (BC) held on the upper support surface by clamps secured to the lip or rim of the upper support surface. The crosslinked cellulose nanofiber network may be secured to the upper support surface by clamps. In any of these examples, the crosslinked cellulose nanofiber network is not cemented to the support surface.

[0029]

[0030] The interstitial hydrogel portion (e.g., in some cases, PVA) can have a crystallinity of 20% or more (e.g., 22% or more, 24% or more, 25% or more, 26% or more, 28% or more, 30% or more, 32% or more, 34% or more, 35% or more, 36% or more, 38% or more, 40% or more, 42% or more, 44% or more, 45% or more, 46% or more, 48% or more, 50% or more, etc.).

[0030]

[0031] For example, the implant may include an implant body having a support surface, an anchor base connected to the implant body, and a cellulose-reinforced dry hydrogel, the cellulose-reinforced dry hydrogel comprising a crosslinked cellulose nanofiber network fixed on the support surface of the implant body and an interstitial polyvinyl alcohol (PVA) hydrogel material within the interstitial regions of the crosslinked cellulose nanofiber network, wherein the water content of the cellulose-reinforced dry hydrogel including the interstitial hydrogel portion is 20% or less.

[0031]

[0032] Any of the methods described herein may be methods of forming an implant having a cellulose-reinforced hydrogel, which may include attaching a crosslinked cellulose nanofiber network to an upper support surface of the implant, infiltrating a hydrogel material into the interstitial regions of the crosslinked cellulose nanofiber network to form a cellulose-reinforced hydrogel, and heating the cellulose-reinforced hydrogel so that the water content of the cellulose-reinforced hydrogel is 20% or less. The heating step may include heating the cellulose-reinforced hydrogel so that the water content of the cellulose-reinforced hydrogel is 11% or less. In some examples, the heating step includes heating the cellulose-reinforced hydrogel so that the water content of the cellulose-reinforced hydrogel is 5% or less. The hydrogel material may include polyvinyl alcohol (PVA). The cellulose-reinforced hydrogel may be heated to a temperature ranging from 90 to 140°C.

[0032]

[0033] Any of the implants described herein can be used for knee joint surface reconstruction. For example, the knee joint surface reconstruction implant can include an upper support surface comprising a cellulose-reinforced hydrogel, the cellulose-reinforced hydrogel comprising a cellulose nanofiber network and a polyvinyl alcohol (PVA) hydrogel material impregnated into the cellulose nanofiber network to form a cellulose-reinforced hydrogel, and the cellulose-reinforced hydrogel has a water content of less than 20%. The cellulose-reinforced hydrogel can have a water content of less than 10%, less than 5%, etc. As mentioned, the PVA material can have a crystallinity of 20% or more.

[0033]

[0034] Also described herein are methods for implanting an articular surface reconstruction implant, which may include forming an opening in the bone (e.g., by drilling, tamping, etc.); inserting the articular surface reconstruction implant into the opening in the bone with the support surface of the implant facing away from the bone, the support surface comprising a cellulose-reinforced hydrogel having a water content of 20% or less, the cellulose-reinforced hydrogel comprising a crosslinked cellulose nanofiber network impregnated with polyvinyl alcohol (PVA) hydrogel; and rehydrating the cellulose-reinforced hydrogel in situ to a water content of greater than 30%. The support surface may be raised or flush with the bone surface. Rehydrating the cellulose-reinforced hydrogel may include swelling the articular surface reconstruction implant and sealing the ends of the articular surface reconstruction implant adjacent to the bone. Any of these methods may include dehydrating the articular surface reconstruction implant prior to insertion. The cellulose-reinforced hydrogel may have a crystallinity of 20% or greater.

[0034]

[0035] In general, the methods and devices described herein may use any of the methods, devices, and compositions described in International Patent Application No. PCT / US2021 / 040031, entitled "NANOFIBER REINFORCEMENT OF ATTACHED HYDROGELS," filed July 1, 2021, the entire contents of which are incorporated herein by reference.

[0035]

[0036] All of the methods and devices described herein can be used in any combination to achieve the benefits contemplated and described herein.

[0037] A better understanding of the features and advantages of the methods and apparatus described herein will be obtained by reference to the following detailed description setting forth illustrative embodiments and the accompanying drawings. [Brief explanation of the drawings]

[0036] [Figure 1A]

[0038] Illustrates an exemplary process for attaching a hydrogel to a porous substrate via the Nanofiber-Enhanced Sticking (NEST) method. In this example, a nanofiber sheet (e.g., bacterial cellulose) is attached to a surface (e.g., a porous substrate such as porous titanium) with an adhesive (e.g., α-TCP cement), and then the hydrogel components are infiltrated into the nanofiber sheet. [Figure 1B]

[0039] FIG. 1 shows an example of a hydrogel bonded to a titanium plug. [Figure 1C]

[0040] FIG. 1 shows an SEM image of the surface of an exemplary freeze-dried bacterial cellulose sheet. [Figure 2A]

[0041] FIG. 2A is a schematic diagram of an example implant that includes a hydrogel attached (eg, forming a surface) as described herein. [Figure 2B] FIG. 2B is a schematic diagram of an example implant that includes a hydrogel attached (eg, forming a surface) as described herein. [Figure 3A]

[0042] FIG. 3A is an image showing one example of a method for attaching a hydrogel to a metallic plug, including using a clamp (eg, a shape memory alloy clamp). [Figure 3B]

[0043] 3A and 3B show examples of fixtures that can be used to align and form the materials described herein as described herein (e.g., to align BCs including rods, cut BCs, and ring clamps). [Figure 3C] 3A-3C show examples of fixtures that can be used to align and form the materials described herein as described herein (e.g., to align BCs including rods, cut BCs, and ring clamps). FIG. 3C shows a cross-sectional view through the fixture. [Figure 3D]

[0044] FIG. 10 shows an image showing an exemplary sheet of bacterial cellulose (BC) cut (e.g., with legs or crenellations) for overwrapping the end of a support surface (e.g., metal rod, head, etc.). [Figure 4]

[0045] FIG. 1 shows an example of the process of attaching BC-PVA-PAMPS hydrogel to titanium implants for the treatment of osteochondral defects. [Figure 5A]

[0046] FIG. 1 shows an example of an implant comprising a hydrated hydrogel injected into a fiber (bacterial cellulose) network. [Figure 5B]

[0047] FIG. 5B shows the implant of FIG. 5A after tamping with the edge of a tamp, illustrating potential sources of damage to the hydrogel. [Figure 6A]

[0048] FIG. 1 shows an example of an implant containing a dry hydrogel injected into a fiber (bacterial cellulose) network. [Figure 6B]

[0049] FIG. 6B shows the implant of FIG. 6A after tamping with the end of the tamp in the same manner (force and position), showing no visible damage to the hydrogel. [Figure 7A]

[0050] Figure 7A illustrates the implantation of a dry hydrogel implant into a knee joint and shows swelling. Figure 7A shows the inserted implant at day 0. [Figure 7B] Figure 7A illustrates the implantation of a dry hydrogel implant into a knee joint, showing swelling. Figure 7B shows the same implant after 1 day in the joint. [Figure 8A]

[0051] Figure 8A shows another example of a dry hydrogel implant in a knee joint, illustrating swelling. Figure 8A shows the inserted implant at day 0. [Figure 8B] Figure 8B shows another example of a dry hydrogel implant in a knee joint, illustrating swelling. Figure 8B shows the same implant after one day in the joint. [Figure 9]

[0052] FIG. 1 illustrates one method of implanting the dry hydrogel implant described herein. DETAILED DESCRIPTION OF THE INVENTION

[0037]

[0053] Described herein are dry hydrogel ("dry hydrogel," "non-hydrated hydrogel," or "dehydrated hydrogel") compositions for long-term cartilage repair. Specifically, described herein are methods and devices for implanting dry hydrogels that rehydrate in vivo and form crystalline structures that impart tensile and compressive strengths to the hydrogel equal to or exceed those of cartilage. The dry hydrogels can be incorporated into nanofiber networks (e.g., cellulose, such as bacterial cellulose) to facilitate implantation and attachment within a patient's body. These devices can be firmly implanted and can seal the implantation site, making them suitable for implementation in knee implants.

[0038]

[0054] The implants described herein include a hydrogel that is injected, impregnated, or interlocked into a fiber network that is attached to the implant surface (e.g., by chemical and / or mechanical attachment, such as by clamping). The hydrogel is dehydrated (e.g., annealed) to have less than 20% water in the dry state (e.g., less than 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, etc.). The resulting dried hydrogel surface (and fiber network) is much stronger than the hydrated state and can be applied to a target location in the body and associated with tamping or insertion into bone without risk of damaging the hydrogel / fiber network. Specifically, these dry hydrogel networks are dry and strong when implanted, so that they can be tamped to achieve a firm fit, but can hydrate in vivo within approximately 24 hours to become a smooth hydrogel with a coefficient of friction similar to that of cartilage.

[0039]

[0055] For example, the implants described herein may be formed from a hydrogel (e.g., including but not limited to, PVA), a fiber network (e.g., cellulose, such as bacterial cellulose), and attached to the surface of the implant (having a stem for insertion into bone and a large outward-facing surface to which the fiber network and hydrogel can be attached). In some cases, a dry hydrogel implant may be assembled by attaching a fiber network (e.g., a sheet of bacterial cellulose) to the outward-facing surface. After assembling the cellulose onto the implant, the implant is heated in a mixture of PVA and water for 24 hours to infuse the molten PVA into the cellulose. The molten PVA is then cast to a thickness of 1.2 mm. It is then dried in a 90°C oven for 24 hours, whereupon the hydrogel shrinks to a thickness of 0.85 mm. This is the "dry" state.

[0040]

[0056] The implant can be stored in a dry form, for example, by sealing it in a package that prevents exposure to water; for example, the implant may be packaged in an airtight and / or moisture-tight sealed container. Prior to implantation, the implant can be removed from the package and applied directly to the patient without the need for first rehydration. In the dry state, the implant can be driven into the bone using a tamp with little risk of damaging the surface of the implant. Once implanted, the dry hydrogel can rehydrate in vivo. During and immediately after the procedure, fluids (such as saline, Ringer's solution, or blood) may be applied, although generally no additional fluids are necessary. The implant can rehydrate itself (e.g., from synovial fluid) and regain a hydrated thickness of, for example, about 0.35 mm within about 24 hours.

[0041]

[0057] When implanting an implant containing a dry hydrogel, it may be beneficial to recess the implant so that, in its hydrated form, the implant is flush with the implant site or slightly raised. Additionally, hydration of the dry hydrogel may help seal the implant's hydrogel around the edges of the implant site. This may prevent synovial fluid from entering the bone and causing cysts.

[0042]

[0058] Although the methods and devices described herein are primarily described in the context of PVA, other hydrogels may be used. A method for forming an implant having a hydrogel 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 hydrogel, was previously described in International Patent Application No. PCT / US2021 / 040031, the entire contents of which are incorporated herein by reference.

[0043]

[0059] 1A-1C show an example of a device in which a hydrogel is bonded to an implant surface, as described herein. The hydrogel can be connected to the implant surface by first attaching a layer of nanofiber material, such as cellulose (e.g., bacterial cellulose), to the implant base using an adhesive (e.g., cement). The nanofiber material can be dried (e.g., before being attached to the implant base). The attachment surface of the implant base can be porous, for example, to enhance adhesion. The nanofiber layer can then be infiltrated with hydrogel components (e.g., material). In this way, the nanofiber portions can penetrate the porous bacterial cellulose network and be secured to the surface with an adhesive (e.g., cement), creating an interlocking bond without water interference. Once the hydrogel material has infiltrated into the nanofiber network, the reinforced hydrogel can be processed (e.g., annealed) to dehydrate the hydrogels described herein.

[0044]

[0060] For example, in Figure 1A, the nanofiber portion is bacterial cellulose (BC) 101, which is applied to the surface of a prepared implant (shown in this example as a porous titanium base) 103. A cement (e.g., any suitable medical or dental-grade cement can be used) is applied to anchor the dried bacterial cellulose to the implant surface. Hydrogel material 105 can then infiltrate the nanofiber portion, resulting in an intact hydrogel 107 attached to the base 103 via the bacterial cellulose 101. The reinforced hydrogel 107 then undergoes a crystallization reorganization process, enhancing its mechanical properties.

[0045]

[0061] Figure 1B shows an example of a titanium implant (e.g., a plug) with a cellulose-reinforced hydrogel attached, as described herein. In this example, the nanofiber portion of the hydrogel (e.g., BC) is bonded to the porous surface of the implant via an adhesive, binding the hydrogel to the nanofiber portion. Any suitable adhesive (e.g., cement) can be used to adhere the nanofiber portion of the hydrogel to the surface of the implant. In some variations, the cement is α-tricalcium phosphate (α-TCP), a hydroxyapatite-forming cement that can be used to attach the hydrogel due to its biocompatibility, osteoconductivity, and shear strength, which may exceed that of cyanoacrylates. In some cases, α-TCP is combined with phosphoserine (PPS) to promote adhesion. In some cases, the hydroxyapatite is reinforced with stainless steel powder (SSP) (e.g., having an average particle size of 150 μm) to prevent crack propagation. As described in more detail below, in some cases, no adhesive is used, and the nanofiber portion is secured to the support surface by mechanical means (such as a clamp).

[0046]

[0062] As described herein, nanofiber portions (e.g., BC) can be dried (e.g., freeze-dried) to increase adhesion to the nanofibers. Figure 1C shows a scanning electron microscope (SEM) image of the surface of an exemplary freeze-dried piece of BC, which consists of many nanoscale fibers that provide a large surface area for attachment with adhesives. In some cases, multiple freeze-thaw cycles can be performed to increase the tensile strength (if a hydrogel is injected therein) and / or the shear strength of the adhesion of the reinforcing hydrogel to the implant base.

[0047]

[0063] Any suitable implant may contain a hydrogel. Figures 2A-2B show two examples of implants configured as nail- or tack-like structures that can be inserted into bone and replace or repair defects in cartilage, such as in partial knee resurfacing procedures. Implants for partial knee resurfacing procedures can be relatively large and curved to mimic the natural curvature of the femoral condyle. Figure 4 shows an image of an implant with a 20 mm diameter and a 20 mm radius of curvature. The 20 mm implant diameter is a typical size used for osteochondral allografts, and the 20 mm radius of curvature is within the range of typical curvatures for femoral condyles. To improve bone integration, a 0.25-mm-thick coating of commercially available pure titanium was applied to the underside of the stem and base of the implant using a plasma spray process. Such implants with the dried hydrogel described herein can be used for knee resurfacing. A surgical procedure involves drilling a hole complementary to the shape of the hydrogel-capped implant over the defect site. A hole can be drilled at the same depth as the dry hydrogel on top of the implant, or slightly deeper. The dry hydrogel-capped implant can then be pushed or tamped into the hole while in the dry state to replace the damaged cartilage. The outer surface of the dry hydrogel may be slightly concave upon implantation and may swell to fill (or extend slightly beyond) the hole.

[0048]

[0064] As used herein, an implant may have a structure suitable for implantation into the body. In some (non-limiting) examples, the implant may have a shape capable of being implanted into bone with a hydrogel attached to its outwardly facing surface. For example, FIGS. 2A and 2B show examples of implants with a hydrogel attached as described herein. In FIG. 2A, the implant includes a base 1001 (e.g., a titanium base) having an elongated pin shape, which may be, for example, 2 mm x 7 mm (tapering to about 1.5 mm at about 3 mm from the end). The base may include one or more channels, openings, passageways, etc. for bone ingrowth. The implant may also include an upper portion 1005, which may be curved (e.g., single-curved or double-curved). For example, the surface may be curved with a radius of curvature of about 17 mm (single-curved) or about 19 mm x 12 mm (double-curved). In FIG. 2A, the upper portion has a diameter 1007 of approximately 7 mm. The outer surface of the implant can be approximately 1 mm or thicker 1009 and can be about 70% or more porous. A hydrogel can be attached to the top surface. In this example, the hydrogel is a BC-PVA-PAMPS triple network hydrogel, with the BC cemented to the porous top, while the PVA-PAMPS is impregnated within the BC. Figure 2B shows an implant similar to that shown in Figure 2A, with the hydrogel attached (e.g., via cementing the nanofiber portion of the hydrogel to the porous surface of the implant, as shown). The implant in Figure 2B is titanium.

[0049]

[0065] As noted above, any of these implant surfaces can include a porous structure. The porosity of the implant surface can be, for example, between 10% and 90% porous, e.g., between 30% and 90% porous, between 55% and 95% porous, between 65% and 85% porous, etc. The depth of the pores can also vary. For example, the surface can be porous to a depth of between 0.1 mm and 5 mm, between 0.2 mm and 3 mm, between 0.5 mm and 2 mm (e.g., 0.2 mm or more, 0.3 mm or more, 0.5 mm or more, 0.75 mm or more, 1 mm or more, 1.5 mm or more, etc.).

[0050]

[0066] As mentioned, any suitable nanofiber network may be used, including, but not limited to, nanofiber bacterial cellulose. Other nanofiber networks may include electrospun polymer nanofibers such as polyvinyl alcohol (PVA) nanofibers, aramid nanofibers (e.g., aramid-PVA nanofibers), wet-spun silk protein nanofibers, chemically crosslinked cellulose nanofibers, or polycaprolactone fibers (e.g., 3D woven PCL fibers). Additionally, any suitable double-network hydrogel may be used, including, but not limited to, PVA and PAMPS. For example, other hydrogel-forming polymers include poly(N,N'-dimethylacrylamide) (PDMAAm), copolymers of l-vinylimidazole and methacrylic acid, double-network hydrogels based on amphiphilic triblock copolymers, polyampholyte hydrogels, PVA-tannic acid hydrogels, poly(N-acryloyl)glycinamide hydrogels, polyacrylic acid-acrylamide-C18 hydrogels, guanine-boric acid reinforced PDMAAm, polyelectrolyte hydrogels, poly(acrylonitrile-co-l-vinylimidazole) hydrogels (e.g., mineralized poly(acrylonitrile-co-l-vinylimidazole) hydrogels), polyacrylic acid-Fe3+-chitosan hydrogels, poly(methacrylic acid) gels, and graphene oxide / xenotriazole hydrogels. The hydrogels may include hydrogels composed of a mixture of polymers, such as agar-reinforced polyacrylamide (PAAm) gels, poly(stearyl methacrylate)-polyacrylic acid gels, annealed PVA-polyacrylic acid hydrogels, supramolecular hydrogels from multi-urea-linked segmented copolymers, polyacrylonitrile-PAAm hydrogels, microsilica-reinforced DMA gels, agar-polyhydroxyethyl methacrylate gels, poly(acryloylethyltrimethylammonium chloride hydrogels), poly(3-(methylacryloylamino)propyl)trimethylammonium chloride hydrogels, poly(sodium p-styrenesulfonate) hydrogels, polyethylene glycol diacrylate hydrogels, polyethylene glycol hydrogels, or combinations of these polymers.

[0051]

[0067] The implants described herein can be made of any suitable material, including, but not limited to, titanium and stainless steel. For example, the hydrogel can be attached to the implant surface (e.g., the base, including the porous base) made of stainless steel alloy, other titanium alloy, Co-Cr alloy, tantalum, gold, niobium, bone, Al oxide, Zr oxide, hydroxyapatite, tricalcium phosphate, sodium calcium phosphosilicate (bioglass), poly(methyl methacrylate), polyether ether ketone, polyethylene, polyamide, polyurethane, polytetrafluoroethylene, or other materials used to make the implant, as described herein.

[0052]

[0068] Any of the implants described herein may include a hydrogel having a surface that is substantially smooth and / or has a predetermined configuration, such as, but not limited to, concave, convex, or saddle-shaped. For example, any of these devices (e.g., implants) may have a surface roughness of less than 30 microns. In some cases, the surface may be smoothed by molding. In some cases, the surface may be smoothed by polishing or sanding. For example, once the additional hydrogel material forms a network (e.g., a nanofiber-reinforced network), the hydrogel coating may optionally be finished by sanding; specifically, the surface may be sanded to a roughness of less than 30 microns by sanding. Sanding may be performed by sanding (e.g., using a fine-grit sandpaper surface, such as 600, 400, or 320 grit).

[0053]

[0069] Figures 3A-3C outline an example of how a hydrogel can be attached to a metal base (e.g., upper support surface). In this example, a freeze-dried BC sheet was cut into an octagonal shape with eight protrusions (e.g., "legs") that could be folded over the ends of the implant, as shown in the example in Figure 3D. This cut can remove excess BC that would otherwise fold over the sides of the cylinder. The cut BC piece was then placed in a fixture that facilitates centering and alignment of the BC piece and metal rod with the ring clamp. The metal rod was pressed down through the fixture so that the ring pressed the BC piece onto the metal rod. This process of pressing the ring onto the BC and rod could also be done manually. As shown in Figures 3B-3C, the use of alignment features can help consistently center the pieces during assembly. The sample can then be clamped (starting at a temperature of 50°C), for example, by heating to 90°C in an oven and initiating the clamp on a pre-mounted shape memory alloy material as described herein. The parts were then heated with PVA in a hot water bomb at 120°C for 24 hours to infiltrate the polymer into the BC. The parts were then dried and stored dry as described herein. [Example]

[0054]

[0070] In general, bone density and bone stiffness vary widely. Bone density and stiffness can vary by more than tenfold (0.14 to 1.4 g / cm3). Inserting implants such as those illustrated above, while typically recommended, can be particularly challenging because it must be strong enough for soft bone but not too hard for hard bone. Preliminary data testing the force required to apply a thumb press into bone with elastic moduli that vary from 58 to 445 MPa indicated that for implants nominally 5.5 mm, the actual machined diameter range is 5.4 to 5.6 mm (with a 100 μm tolerance). The range of implant sizes and the hole sizes that can be inserted by press-fitting are very narrow. For example, for a 5.6 mm implant, the hole size must be 5.4 to 5.5 mm to achieve a sufficient, but not too large, press-fit in the nominal bone. For a 5.4 mm implant, the hole size must be 5.2 to 5.3 mm to achieve that "just right" press-fit. Furthermore, these areas do not overlap, and therefore a proper press-fit is not possible in a single drill step. Some adaptation to the surgery may be required, increasing the complexity, time, and expense of the procedure.

[0055]

[0071] As a result, it is often necessary to prepare additional instruments (e.g., tamps, presses, etc.) to apply the implant to the body. However, when tamps or other instruments are used, for example, there is a high possibility that implantation may damage the hydrogel, particularly if the hydrogel covers most, if not all, of the hydrogel's exterior surface. For example, Figures 5A and 5B illustrate potential problems with the insertion of a hydrated hydrogel implant. In Figure 5A, a top view of a hydrated hydrogel implant (similar to that shown in Figures 2A-2B and 4) is shown prior to implantation. As shown in Figure 5B, which shows the same hydrogel as in Figure 5A, the hydrated hydrogel is easily damaged by the edge of a tamp. Damaged area 505 is visible; this damage can pose a problem after insertion because the damaged surface can result in a biological response, potentially leading to postoperative pain.

[0056]

[0072] In contrast, the use of dry hydrogel prevents and protects against such damage. For example, FIG. 6A illustrates a top view of a dry hydrogel implant. Dry hydrogel implants have a hardened outer surface (similar to plastic) that can hydrate in vivo but may resist damage until then. For example, FIG. 6B shows the same implant as shown in FIG. 6A after being struck with the edge of a tamp in a similar manner (same force and location) as in FIGS. 5A and 5B. As can be seen, no visible damage is present in FIG. 6B. Generally, implants can be hammered into bone with a tamp or other instrument with little risk of damage to the dry hydrogel. Once implanted, the hydrogel swells and hydrates. Therefore, instead of relying on pressure fit using only the surgeon's fingers (which can be difficult, if not impossible, to achieve accurately and consistently), a tamp or other force-applying instrument can be used with dry hydrogel. When implanted as a dry hydrogel, the implant may start out recessed instead of flush to ensure the correct implantation depth is achieved. However, the use of a dry implant can help ensure that a good press fit is used without damaging the implant.

[0057]

[0073] In fact, using dry hydrogel implants may be easier and more efficient than expected. As mentioned above, dry hydrogel implants rehydrate within approximately 24 hours due to synovial fluid. Because the hydrogel area swells, the hole drilled for the implant may be slightly larger than previously used. For example, Figures 7A and 7B show a first example of a dry implant 705 (left knee) inserted into a drilled hole in the bone immediately after implantation. After 24 hours of rest, the same knee is exposed, showing that the hydrogel has hydrated and expanded within 24 hours (Figure 7B). The space between the cartilage and the implant 707 has become smaller. The hydrogel may swell and become wider, completely sealing around the edges, preventing synovial fluid from entering the bone and causing a cyst.

[0058]

[0074] 8A and 8B show similar results: in Fig. 8A, a dry hydrogel implant 805 was inserted into a slightly larger opening, while in Fig. 8B (after 25 hours), the hydrogel on the implant 805 had hydrated and swelled, resulting in the hydrogel expanding again relative to the opening 807, as shown.

[0059]

[0075] For example, Figure 9 shows a method of implanting a hydrogel-containing implant. In this example, the implant may be received in dry form (e.g., a dried hydrogel implant) or may be dried as described herein 901 (e.g., heated at elevated temperature for >1 hour or until the water percentage is, e.g., less than 20%). The body area may be prepared 903, for example, by forming an opening in the bone (e.g., by drilling) for inserting the implant. The dried hydrogel implant may then be inserted 905. A tamp or other force-applying instrument may be used. The hydrogel may then be allowed to rehydrate in vivo (e.g., over a period of 24 hours or less) 907.

[0060]

[0076] 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 executable by a processor (e.g., a computer, tablet, smartphone, etc.) that, when executed by the processor, cause the processor to control the processor to perform any of the following steps, including, but not limited to, displaying, communicating with a user, analyzing, changing parameters (including timing, frequency, intensity, etc.), making decisions, alerting, etc.

[0061]

[0077] It should be understood that all combinations of the foregoing concepts and additional concepts discussed in detail below (provided that such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein and may be used to achieve the advantages described herein.

[0062]

[0078] As used herein, when a feature or element is described as being "on" another feature or element, it may be directly on the other feature or element, or intervening features or elements may also be present. In contrast, when a feature or element is described 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 described as being "coupled," "attached," or "connected" to another feature or element, it may be directly coupled, attached, or connected to the other feature or element, or there may be intervening features or elements present. In contrast, when a feature or element is described as being "directly coupled," "directly attached," or "directly connected" to another feature or element, there are no intervening features or elements present. Although described or illustrated with respect to one embodiment, a feature or element so described or illustrated may be applicable to other embodiments. Those skilled in the art will also understand that a reference to a structure or feature located "adjacent" another feature may have portions that overlap or underlie the adjacent feature.

[0063]

[0079] The terms used herein are for the purpose of describing particular embodiments only and are not intended to be limiting of the present 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 dictates otherwise. It will be further understood that the terms "comprises" and / or "comprising," as used herein, 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 associated listed items and may be abbreviated as " / ."

[0064]

[0080] Spatially relative terms such as "under," "below," "lower," "over," and "upper" may be used herein for ease of description to describe the relationship of one element or feature 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 during use or operation in addition to the orientation shown in the figures. For example, if the device in the figures were turned upside down, an element described as "under" or "beneath" the other element or feature would then be positioned "over" the other element or feature. Thus, the exemplary term "under" can encompass both an above and below orientation. The device may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptions used herein will be interpreted accordingly. Similarly, the terms "upward," "downward," "vertical," "horizontal," etc. are used herein for descriptive purposes only, unless otherwise specified.

[0065]

[0081] 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 dictates otherwise. These terms may be used to distinguish one feature / element from another. Thus, a first feature / element discussed below could be referred to as a second feature / element, and similarly, a second feature / element discussed below could be referred to as a first feature / element, without departing from the teachings of the present invention.

[0066]

[0082] Throughout this specification and the claims that follow, unless the context requires otherwise, the word "comprise," and variations thereof, such as "comprises" and "comprising," mean that various components may be utilized jointly in methods and aspects (e.g., compositions and apparatuses, including instruments 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.

[0067]

[0083] In general, any apparatus and methods described herein should be understood to be inclusive, although all or subcomponents and / or steps may alternatively be exclusive and may be expressed as "consisting of" or alternatively "consisting essentially of" various components, steps, subcomponents or substeps.

[0068]

[0084] As used in this specification and claims, including in the examples, unless otherwise specified, all numbers may be read as being prefaced by the word "about" or "approximately," even if such term is not specifically indicated. The phrase "about" or "approximately" may be used when describing a magnitude and / or location, and indicates that the stated value and / or location is within a reasonably expected range of value and / or location. For example, a numerical 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 value given herein should be understood to include approximately that value or approximately that value unless the context indicates otherwise. For example, if the value "10" is disclosed, "about 10" is also disclosed. Any numerical range recited herein is intended to include all subranges encompassed therein. When a value is disclosed, it is understood that "less than or equal to" that value, "greater than or equal to" that value, and possible ranges therebetween, are also disclosed, as appropriately understood by one of ordinary skill in the art. For example, if a value "X" is disclosed, "greater than or equal to X" is also disclosed, as is "less than or equal to X" (e.g., where X is a numerical value). It is also understood that throughout this 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 specific data point "10" and a specific data point "15" are disclosed, it is understood that values ​​greater than 10 and 15, greater than or equal to 10 and 15, less than 10 and 15, less than or equal to 10 and 15, and equal to 10 and 15 are also considered to be disclosed, as are values ​​between 10 and 15. It is also understood that each unit between two specified units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0069]

[0085] While various exemplary embodiments have been described above, many modifications may be made to the various embodiments without departing from the scope of the present invention, as set forth in the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments, one or more method steps may be omitted entirely. Optional features of the various apparatus and system embodiments may be included in some embodiments and not in other embodiments. Accordingly, the foregoing description has been provided primarily for illustrative purposes and should not be construed as limiting the scope of the present invention, as set forth in the claims.

[0070]

[0086] The examples and diagrams contained herein illustrate, by way of illustration only, and not by way of limitation, specific embodiments in which the subject matter may be practiced. As noted, other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of the present disclosure. Such embodiments of the inventive subject matter may be referred to herein, individually or collectively, by the term "invention" merely for convenience, and in fact, where more than one invention is disclosed, it is not intended to automatically limit the scope of the present application to any single invention or inventive concept. Thus, while specific embodiments have been illustrated and described herein, any proposed modifications calculated to achieve the same purpose may be substituted for the specific embodiments shown. The present disclosure is intended to cover any and all adaptations or variations of the various embodiments. Combinations of the above-described embodiments, as well as other embodiments not specifically described herein, will be apparent to those skilled in the art upon reference to the above description.

Claims

1. An implant, an implant body having a support surface; an anchor base connected to the implant body; A cellulose-reinforced dry hydrogel comprising: a crosslinked cellulose nanofiber network fixed on a support surface of the implant body; and Interstitial hydrogel portions within the interstitial regions of the crosslinked cellulose nanofiber network, the interstitial hydrogel portions having a water content of 20% or less. a cellulose-reinforced dry hydrogel comprising: Including implants.

2. 10. The implant of claim 1, wherein the water content of the cellulose-reinforced dry hydrogel, including the interstitial hydrogel portion, is less than 10%.

3. 10. The implant of claim 1, wherein the water content of the cellulose-reinforced dry hydrogel, including the interstitial hydrogel portion, is less than 5%.

4. The implant of claim 1 , wherein the interstitial hydrogel portion comprises polyvinyl alcohol (PVA).

5. The implant of claim 1 , wherein the crosslinked cellulose nanofiber network comprises bacterial cellulose.

6. The implant of claim 1 , wherein the crosslinked cellulose nanofiber network is secured onto the upper support surface by a clamp.

7. 7. The implant of claim 6, wherein the crosslinked cellulose nanofiber network comprises one or more sheets of bacterial cellulose (BC) held on the upper support surface by clamps secured to a lip or rim of the upper support surface.

8. 10. The implant of claim 1, wherein the crosslinked cellulose nanofiber network is not cemented to a support surface.

9. The implant of claim 1 , wherein the interstitial hydrogel portion has a crystallinity of 20% or greater.

10. An implant, an implant body having a support surface; an anchor base connected to the implant body; A cellulose-reinforced dry hydrogel comprising: a crosslinked cellulose nanofiber network fixed on a support surface of the implant body; and a cellulose-reinforced dry hydrogel comprising an interstitial polyvinyl alcohol (PVA) hydrogel material within the interstitial regions of the crosslinked cellulose nanofiber network, wherein the water content of the cellulose-reinforced dry hydrogel including the interstitial hydrogel portion is 20% or less; Including implants.

11. 1. A method of forming an implant having a cellulose-reinforced hydrogel, comprising: attaching a crosslinked cellulose nanofiber network to the upper support surface of the implant; infiltrating a hydrogel material into the interstitial regions of the crosslinked cellulose nanofiber network to form a cellulose-reinforced hydrogel; heating the cellulose-reinforced hydrogel so that the water content of the cellulose-reinforced hydrogel is 20% or less; A method comprising:

12. 12. The method of claim 11, wherein the heating step comprises heating the cellulose-reinforced hydrogel such that the water content of the cellulose-reinforced hydrogel is 11% or less.

13. 12. The method of claim 11, wherein the heating step comprises heating the cellulose-reinforced hydrogel so that the water content of the cellulose-reinforced hydrogel is 5% or less.

14. The method of claim 11 , wherein the hydrogel material comprises polyvinyl alcohol (PVA).

15. The method of claim 11, wherein the cellulose-reinforced hydrogel is heated to a temperature in the range of 90 to 140°C.

16. 1. An implant for knee joint resurfacing surgery, comprising: The implant comprises an upper bearing surface comprising a cellulose-reinforced hydrogel; The cellulose-reinforced hydrogel is a cellulose nanofiber network; and and a polyvinyl alcohol (PVA) hydrogel material impregnated into the cellulose nanofiber network to form a cellulose-reinforced hydrogel, the cellulose-reinforced hydrogel having a water content of less than 20%.

17. 17. The method of claim 16, wherein the cellulose-reinforced hydrogel has a water content of less than 10%.

18. 17. The method of claim 16, wherein the cellulose-reinforced hydrogel has a water content of less than 5%.

19. 17. The method of claim 16, wherein the PVA material has a crystallinity of 20% or greater.

20. 1. A method of implanting an articular surface reconstruction implant, comprising: forming an opening in the bone; inserting an articular surface reconstruction implant into the opening in the bone with a bearing surface of the implant facing away from the bone, the bearing surface comprising a cellulose-reinforced hydrogel having a water content of 20% or less, the cellulose-reinforced hydrogel comprising a crosslinked cellulose nanofiber network impregnated with polyvinyl alcohol (PVA) hydrogel; rehydrating the cellulose-reinforced hydrogel in situ to have a water content greater than 30%; A method comprising:

21. 21. The method of claim 20, wherein rehydrating the cellulose-reinforced hydrogel comprises swelling the articular surface reconstruction implant and sealing the ends of the articular surface reconstruction implant adjacent the bone.

22. 21. The method of claim 20, further comprising the step of dehydrating the articular surface reconstruction implant prior to insertion.

23. 21. The method of claim 20, wherein the cellulose-reinforced hydrogel has a crystallinity of 20% or greater.

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