WO2010099256A1

WO2010099256A1 - Swellable articulating prosthesis

Info

Publication number: WO2010099256A1
Application number: PCT/US2010/025307
Authority: WO
Inventors: Mark Dingledine; Stephen Nitti; Mark Melton
Original assignee: Replication Medical, Inc.
Priority date: 2009-02-25
Filing date: 2010-02-25
Publication date: 2010-09-02

Abstract

A swellable, resilient joint prosthesis is provided that includes a swellable polymeric medium, said polymeric medium being dispersed throughout the prosthesis, the prosthesis being dimensioned and configured to fit between two bones of a hand or foot. In embodiments, the prosthesis has a first configuration of reduced size such that it can be inserted into a patient in a minimally invasive manner. Once inserted to an application point within the patient, the prosthesis expands in size to at least partially fill the implant cavity and dynamically mimic the movement of normal physiological joints.

Description

SWELLABLE ARTICULATING PROSTHESIS

CROSS-REFERENCE TO RELATED APPLICATION

The present application claims the benefit of and priority to U.S. Provisional Application Serial Number 61/155,377, filed on February 25, 2009, the entire contents of which are herein incorporated by reference.

BACKGROUND

1. Field of the Invention

The present disclosure is directed to prosthetic implants for joint replacement or augmentation.

2. Description of Related Art

The joints between elongated bones of the hand and feet can be damaged by accident or by diseases such as rheumatoid arthritis and osteoarthritis and may need to be surgically replaced. Procedures for replacing damaged or diseased joints often have involved surgical removal of substantial portions of the bone adjacent a joint's articulating surfaces and implantation of an articulating prosthesis.

SUMMARY

A swellable, resilient joint prosthesis is provided which includes a fluid absorbing polymer dimensioned and configured to fit and be retained between a first phalanx and an adjacent second phalanx of a hand or foot. The joint prosthesis expands from a compact first configuration to an expanded second configuration upon absorption of fluid. The second expanded configuration has a first end portion and an oppositely disposed second end portion which are connected by a centrally disposed pivotally flexible region of increased cross section relative to said first and second end portions. The first end portion may be dimensioned and configured to frictionally engage a contacting end of the first phalanx and the second end portion is dimensioned and configured to frictionally engage a contacting end of the second phalanx. A swellable, resilient joint prosthesis is provided that includes a swellable polymeric medium, said polymeric medium being dispersed throughout the prosthesis, the prosthesis being dimensioned and configured to fit between two bones of a hand or foot. In embodiments, the prosthesis has a first configuration of reduced size such that it can be inserted into the patient in a minimally invasive manner. Once inserted to an application point within the patient, the prosthesis expands in size to at least partially fill the implant cavity and dynamically mimic the movement of normal physiological joints.

A method of manufacturing a swellable, resilient joint prosthesis is provided which includes providing a mold having a cavity dimensioned and configured to approximate at least a portion of the space between two adjacent phalanges. The cavity defines first and second end portions and a center portion connecting the first and second end portions. A liquid fluid absorbing polymer is filled into the mold and then solidified to form a swellable, resilient joint prosthesis dimensioned and configured to fit and be retained between a first phalanx and an adjacent second phalanx. The prosthesis may be dehydrated under compression to form a compacted prosthesis of reduced dimension having a shape memory.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top view of an embodiment of a joint prosthesis in an unexpanded state according to the present disclosure.

FIG. 2 is a dimensional view of an embodiment of a joint prosthesis in an expanded state according to the present disclosure.

FIG. 3 A is a dimensional view of an embodiment of a swellable articulating prosthesis according to the present disclosure.

FIG. 3B is a dimensional view of an embodiment of a swellable articulating prosthesis according to the present disclosure.

FIG. 4 is a top view of an embodiment of a joint prosthesis including a support member in an unexpanded state according to the present disclosure.

FIG. 5 is a dimensional view of an embodiment of a joint prosthesis including a support member in an expanded state according to the present disclosure. FIG. 6 is a top view of an embodiment of a joint prosthesis including a support member in an unexpanded state according to the present disclosure.

FIG. 7 is a dimensional view of an embodiment of a joint prosthesis including a support member in an expanded state according to the present disclosure.

FIG. 8 is a top view of a skeleton of a hand having a joint prosthesis implanted therein.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

A swellable, resilient joint prosthesis according to the present disclosure may be implanted into hands or feet using minimally invasive surgery as a result of the ability of the prosthesis to achieve an optimum implantable substantially reduced configuration and further ability to expand anisotropically or isotropically to an expanded configuration which is adapted and configured to at least partially fill the desired implant space and securely attach the prosthesis to adjacent bone. The techniques described herein provide a joint prosthesis which, in the reduced configuration, has a relatively narrow cross-section and is elongate in the longitudinal direction so that an overall substantially rod-shaped configuration is manifest. The reduced configuration fits through a minimally invasive incision as a result of its small cross-section and stable structure. See, e.g., FIG. 1. The joint prosthesis 10 is shown in the reduced configuration. The ability to swell to an expanded configuration in situ allows the prosthesis to partially or substantially fill the required anatomical space and mimic the shape and function of the original physiological architecture. For example, an expanded prosthesis 20 is dimensioned and configured to provide proper joint spacing and excellent intermedullary bone fixation. Examples of expanded configurations are shown in FIGs. 2, 3A and 3B.

The expanded joint prosthesis 20 has a first stem 22, and oppositely disposed second stem 24 and an interconnecting central portion 26. In the expanded state, the central portion 26 can have a larger cross-section than either of the ends of the stems 22, 24. See, e.g., FIGs. 2, 3A and 3B. The prosthesis 20 is dimensioned and configured such that central portion 26 is disposed in the space between the opposing bone architecture defining the area previously occupied by the native joint upon implantation and expansion. The oppositely disposed first and second stems 22, 24 are dimensioned and configured to engage the ends of opposing bones by contact with the ends or insertion into the bones to which they become affixed. In embodiments, at least a portion of the stems 22, 24 are dimensioned and configured to fit into a canal such as an intramedullary canal of the bone. In embodiments, the stems 22, 24 are tapered at their ends. In embodiments, one stem 24 is smaller than the other stem 22 to account for the different sizes of the phalanges, i.e., a distal phalanx at the end of a small toe would be smaller than the proximal phalanx near the tarsal bones and would require a smaller stem than the proximal phalanx. FIG. 3A illustrates a smaller joint prosthesis 30 in the expanded state for e.g., insertion between a middle phalanx and a distal phalanx. The joint prosthesis 30 has a first stem 32, and oppositely disposed second stem 34 and an interconnecting central portion 36. FIG. 3B illustrates a joint prosthesis 30' which is larger than the one shown in FIG. 3A in the expanded state for e.g., insertion between a middle phalanx and a proximal phalanx. The joint prosthesis 30' has a first stem 32', and oppositely disposed second stem 34' and an interconnecting central portion 36'.

An implantable swellable joint prosthesis herein restores a joint between a distal bone and a proximal bone (for example a finger joint or toe joint) and is made of a material which is flexible and elastic (resilient) and has projections which optionally taper, extending in opposite directions from a central portion and adapted to fit into the respective bones. The central portion is formed at an intermediate location and is dimensioned and configured to create a zone of flexibility which can withstand repeated pivoting or articulating motion without substantial degradation. In embodiments, mimicking the movement of normal physiological joints, a joint prosthesis herein is capable of permitting limited lateral pivoting of one bone with respect to the other when the bones are substantially aligned (that is, when fingers or toes are extended) but restrain such lateral movement when the bones are flexed. In embodiments, the chemical makeup of the swellable polymer can be altered to make the portions of, or the entire prosthesis, softer or stiffer, i.e., more or less elastic.

Fluid absorbing polymers are well-suited for manufacturing a swellable, resilient joint prosthesis in accordance with the present disclosure. Suitable fluid absorbing polymers include synthetic polymers such as poly(ethylene glycol), poly( ethylene oxide), partially or fully hydrolyzed polyvinyl alcohol), poly(vinylpyrrolidone), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers (poloxamers and meroxapols), poloxamines, carboxymethyl cellulose, and hydroxyalkylated celluloses such as hydroxyethyl cellulose and methylhydroxypropyl cellulose, and natural polymers such as polypeptides, polysaccharides or carbohydrates such as Ficoll™, polysucrose, hyaluronic acid, dextran, heparan sulfate, chondroitin sulfate, heparin, or alginate, and proteins such as gelatin, collagen, albumin, or ovalbumin or copolymers or blends thereof. As used herein, "celluloses" includes cellulose and derivatives of the types described above; "dextran" includes dextran and similar derivatives thereof. Examples of materials that can be used to form a hydrogel include modified alginates. Alginate is a carbohydrate polymer isolated from seaweed, which can be crosslinked to form a hydrogel by exposure to a divalent cation such as calcium. Alginate is ionically crosslinked in the presence of divalent cations, in water, at room temperature, to form a hydrogel matrix. Modified alginate derivatives may be synthesized which have an improved ability to form hydrogels.

Additionally, polysaccharides which gel by exposure to monovalent cations, including bacterial polysaccharides, such as gellan gum, and plant polysaccharides, such as carrageenans, may be crosslinked to form a hydrogel using methods analogous to those available for the crosslinking of alginates described above. Polysaccharides which gel in the presence of monovalent cations form hydrogels upon exposure, for example, to a solution comprising physiological levels of sodium. Hydrogel precursor solutions also may be osmotically adjusted with a nonion, such as mannitol, and then injected to form a gel.

Other polymeric hydrogel precursors include polyethylene oxide-polypropylene glycol block copolymers such as Pluronics™ or Tetronics™, which may be crosslinked by hydrogen bonding and/or by a temperature change. Other materials which may be utilized include proteins such as fibrin, collagen and gelatin. Polymer mixtures also may be utilized. For example, a mixture of polyethylene oxide and polyacrylic acid which gels by hydrogen bonding upon mixing may be utilized. In one embodiment, a mixture of a 5% w/w solution of polyacrylic acid with a 5% w/w polyethylene oxide (polyethylene glycol, polyoxyethylene) 100,000 can be combined to form a gel over the course of time, e.g., as quickly as within a few seconds. Water soluble polymers with charged side groups may be crosslinked by reacting the polymer with an aqueous solution containing ions of the opposite charge, either cations if the polymer has acidic side groups or anions if the polymer has basic side groups. Examples of cations for cross-linking of the polymers with acidic side groups to form a hydrogel are monovalent cations such as sodium, divalent cations such as calcium, and multivalent cations such as copper, calcium, aluminum, magnesium, strontium, barium, and tin, and di-, tri- or tetra-functional organic cations such as alkylammonium salts. Aqueous solutions of the salts of these cations are added to the polymers to form soft, highly swollen hydrogels and membranes. The higher the concentration of cation, or the higher the valence, the greater the degree of cross-linking of the polymer. Additionally, the polymers may be crosslinked enzymatically, e.g., fibrin with thrombin. The polymers can be covalently crosslinked as well through the addition of ethylene diamine, NBS or a host of crosslinking agents routinely to react with amino, nitrile, urethane and carboxylic functional groups found on the polymer chain.

Suitable ionically crosslinkable groups include phenols, amines, imines, amides, carboxylic acids, sulfonic acids and phosphate groups. Negatively charged groups, such as carboxylate, sulfonate and phosphate ions, can be crosslinked with cations such as calcium ions. The crosslinking of alginate with calcium ions is an example of this type of ionic crosslinking. Positively charged groups, such as ammonium ions, can be crosslinked with negatively charged ions such as carboxylate, sulfonate and phosphate ions. Preferably, the negatively charged ions contain more than one carboxylate, sulfonate or phosphate group.

Anions for cross-linking of the polymers to form a hydrogel are monovalent, divalent or trivalent anions such as low molecular weight dicarboxylic acids, for example, terepthalic acid, sulfate ions and carbonate ions. Aqueous solutions of the salts of these anions are added to the polymers to form soft, highly swollen hydrogels, as described with respect to cations.

A variety of polycations can be used to complex and thereby stabilize the polymer hydrogel into a semi-permeable surface. Examples of materials that can be used include polymers having basic reactive groups such as amine or imine groups, having a preferred molecular weight between 3,000 and 100,000, such as polyethylenimine and polylysine. These are commercially available. One polycation is poly(L-lysine); examples of synthetic polyamines are: polyethyleneimine, poly(vinylamine), and poly(allyl amine). There are also natural polycations such as the polysaccharide, chitosan.

In embodiments, the joint prosthesis is made of a hydrogel. Prior to coagulation, the liquid form of a suitable hydrogel is used to form the expanded configuration as it would be in the hydrated state. The hydrogel is then coagulated to form the prosthesis in an expanded configuration. The prosthesis is then dehydrated to a xerogel state which reduces the volume of the prosthesis to the reduced configuration. Many hydrogel polymers behave in a similar manner, which is to say they can be deformed, frozen into a deformed shape and they can maintain that shape indefinitely or until, e.g., a temperature change causes the polymer to "relax" into the shape originally held prior to freezing. This property can be referred to as shape memory or frozen deformation by those skilled in the art.

The temperature at which frozen deformation occurs is referred to as the glass transition temperature or T_g. At T_g several polymer properties such as density, entropy and elasticity may sharply change. Many polymers can be mixed with agents that can have a drastic effect on a polymer T_g. Polymers which absorb fluid are of particular interest and water is the preferred T_g altering agent. Hydrogels which contain less than about five percent water may be considered dehydrated or xerogels. The T_g of a xerogel will change as it absorbs fluids containing water. Once the T_g becomes lower than ambient the now partially hydrated hydrogel becomes pliant and may be elastically deformed. If the polymer is held in a state of elastic deformation while the T_g is raised above ambient the polymer will maintain the deformed state indefinitely. This can be accomplished by either lowering the ambient temperature (freezing) or by returning the polymer to its xerogel state thus raising the T_g.

Using this method, hydrogel articles may be produced with vastly differing xerogel shapes compared to hydrated shapes. This is especially useful in cases such as medical implants where, in delivering a prosthesis into the human body, every care should be taken to reduce trauma to the patient. An implant which is shaped, e.g., as the prostheses shown in FIGs. 2, 3A, 3B, 5 and 7 are re-shaped into a tapered elongate rod in order to facilitate minimally invasive implantation. See, e.g., FIGs. 1, 4 and 6. Alternatively, a portion of the prosthesis can be compressed as compared to another portion of the prosthesis. Indeed, various frozen shapes may be utilized to facilitate implantation and situation of the prosthesis. Once the prosthesis is indwelling and has absorbed liquid it will substantially return to the expanded shape and maintain that shape indefinitely. It should be understood that, in embodiments, various shapes may be cast to adjust to a particular patient's anatomy. As used herein, "substantially" is intended to mean any of "approximately", "nearly" or "precisely."

A preferred polymer configuration includes two polymer phases of different hydrophilicity, the less hydrophilic phase having higher content of hydrophobic groups and more hydrophilic phase having higher content of hydrophilic groups. The less hydrophilic phase is preferably crystalline and more hydrophilic phase is preferably amorphous, as can be established from X-ray diffraction.

Advantageous hydrophobic groups are pendant nitrile substituents in 1 ,3 positions on a polymethylene backbone, such as poly(acrylonitrile) or poly(methacrylonitrile). The hydrophilic phase may preferably contain a high concentration of ionic groups. Preferred hydrophilic groups are derivatives of acrylic acid and/or methacrylic acid including salts, acrylamidine, N-substituted acrylamidine, acrylamide and N-substituted acryl amide, as well as various combinations thereof. A particularly preferred combination contains approximately two thirds acrylic acid and its salts (on molar basis), the rest being a combination of plain and N-substituted acrylamides and acrylamidines.

At least one polymeric component is preferably a multiblock copolymer with alternating sequences of hydrophilic and hydrophobic groups. Such sequences are usually capable of separating into two polymer phases and form strong physically crosslinked hydrogels. Such multiblock copolymers can be, for example, products of hydrolysis or aminolysis of polyacrylonitrile or polymethacrylonitrile and copolymers thereof. For convenience, polymers and copolymers having at least about 80 molar % of acrylonitrile and/or methacrylonitrile units in their composition may be referred to as "PAN". Hydrolysis and aminolysis of PAN and products thereof are described, for example, in U.S. Pat. Nos. 4,107,121 ; 4,331,783; 4,337,327; 4,369,294; 4,370,451; 4,379,874; 4,420,589; 4,943,618, and 5,252,692, each being incorporated herein by reference in their respective entireties. A preferred fluid absorbing polymer for the joint prosthesis is a synthetic composite of a cellular (or domain) type with continuous phase formed by a hydrophobic polymer or a hydrophilic polymer with low to medium water content forming a "closed cell" spongy structure that provides a composite with good strength and shape stability. Examples of suitable polymers are polyurethanes, polyureas, PAN, and highly crystalline multiblock acrylic and methacrylic copolymers. The polymer should be sufficiently permeable to water. More preferably, the continuous phase is formed by a strong hydrophilic polymer with sufficient permeability for water but impermeable to high- molecular solutes. Examples of such polymers are highly crystalline hydrogels based on segmented polyurethanes, polyvinylalcohol or multiblock acrylonitrile copolymers with derivatives of acrylic acid. Typically, suitable polymers for the continuous phase in cellular composites have a water content in fully hydrated state between about 60% by weight and about 90% by weight, preferably between about 70% and about 85% by weight.

The second component of the fluid absorbing polymer may be a highly hydrophilic polymer of high enough molecular weight to prevent permeation of the hydrophilic polymer through the continuous phase. This component is contained inside the matrix of the continuous phase. The entrapped hydrophilic polymers (the so-called "soft block") may be high-molecular weight water-soluble polymers, associative water- soluble polymers or highly swellable hydrogels containing, in a fully hydrated state, an amount of hydration which is preferably at least about 5% greater than the hydrophobic component. For example, the second component hydrated to at least about 65% when the first component is hydrated to about 60%. In embodiments, e.g., from the second component could be fully hydrated at from about 95% of water and up to about 99.8% of water. Such hydrogels are very weak mechanically. However, it may not matter in composites where such polymers' role is generation of osmotic pressure rather than load- bearing, with e.g., compression strength in full hydration in the range of about 0.01 MN/m² or lower.

A system with closed cells (or domains) containing highly swellable or water- soluble polymers can form composites with very high swelling pressure as needed for the prosthesis anchoring function. Examples of suitable hydrophilic polymers are high- molecular weight polyacrylamide, polyacrylic acid, polyvinylpyrrolidone, polyethyleneoxide, copolymers of ethyleneoxide and propyleneoxide or hyaluronic acid; covalently crosslinked hydrogels such as hydrophilic esters or amides of polyacrylic or polymethacrylic acids; and physically crosslinked hydrogels, such as hydrolyzates or aminolysates of PAN.

Particularly suitable are associative water-soluble polymers capable of forming very highly viscous solutions or even soft physical gels. Preferred are associative polymers containing negatively charged groups, such as carboxylates, sulpho-groups, phosphate groups or sulfate groups. Particularly preferred are associative polymers formed by hydrolysis and/or aminolysis of PAN to high but finite conversions that leave a certain number of nitrile groups (typically, between about 5 and 25 molar %) unreacted.

Preferred fluid absorbing polymer composites have both a continuous phase and a dispersed phase formed by different products of hydrolysis or aminolysis of PAN. In this case, both components are compatible and their hydrophobic blocks can participate in the same crystalline domains. This improves anchorage of the more hydrophilic component and prevents its extraction or disassociation. The size of more hydrophilic domains may vary widely, from nanometers to millimeters, preferably from tens of nanometers to microns.

The ratio between the continuous discrete phase (i.e., between more hydrophobic and more hydrophilic components may vary from about 1 :2 to about 1 : 100 on a dry weight basis, and a preferred ratio ranges from about 1 :5 to about 1 :20. Examples of compositions and implants are described in US Pat. Nos. 6,264,695 and 6,726,721 , both of which are incorporated herein by reference in their entireties. A preferred method of making the fluid absorbing polymer composite is described in US Pat. No. 6,232,406, herein incorporated by reference in its entirety.

Examples of particularly suitable hydrogel forming copolymers are prepared by a partial alkaline hydrolysis of polyacrylonitrile ("HPAN") in the presence of sodium thiocyanate (NaSCN). The resulting hydrolysis product is a multi-block acrylic copolymer, containing alternating hydrophilic and hydrophobic blocks. Hydrophilic blocks contain acrylic acid, acrylamidine, and acrylamide. In embodiments, for example, a PAN hydrolysate polymer (referred to herein HPAN I) (46±1% conversion of hydrolysis) having the following composition: acrylonitrile units -53-55%, acrylic acid units -22-24%, acrylamide units ~17-19%, acrylamidine units -4-6%, as determined by ¹³C NMR, is dissolved in a suitable solvent such as a -55% solution of sodium thiocyanate in water to form a viscous solution. The viscous solution is poured into a porous mold having, e.g., a cavity defining the dimensions of the joint prosthesis. See, e.g., Figs 2 and 3. The solution can then be solvent cast, e.g., by solvent exchange (e.g., water for NaSCN). The pores should be sufficiently small as to not permit the polymer to diffuse or leak out of the mold. In another form, the hydrogel used to make the prosthesis is obtained by reacting an aquagel of PAN, formed by dissolving the polymer in an aqueous solvating solution such as high concentration of sodium thiocyanate. The resulted solution of PAN is thereupon coagulated through addition of a suitable aqueous solvent or water miscible solvent. The coagulum is further reacted in a hydrolyzing basic or acidic medium. The PAN aquagel can then be processed as a thermoplastic and molded to obtain the desired shape. These methods are described in US Patent No. 4,943,618.

A more rigid fluid absorbing polymer may be another PAN hydrosylate polymer, referred to herein as HPAN II (28±1% conversion of hydrolysis), having the following composition: acrylonitrile units -71-73%, acrylic acid units -13-15%, acrylamide units -10-12%, acrylamidine units -2-4%, as determined by ¹³C NMR, disolved in -55% NaSCN which can be solvent cast, washed, dried and cut to a suitable shape.

The joint prosthesis optionally includes an interiorly embedded support member. See, e.g., FIGs. 4-7. The support member occupies at least a portion of the interior of the prosthesis. The support member can be a rod of relatively rigid material which can extend the entire length of the prosthesis or it can consist of two or more members. FIG. 4 illustrates a joint prosthesis 40 in an unexpanded state having an interiorly disposed support member 42 shown in phantom lines. The support member 42 extends from one end portion to the other end portion. FIG. 5 illustrates a joint prosthesis 50 in an expanded state. The joint prosthesis 50 has a first stem 52, and oppositely disposed second stem 54 and an interconnecting central portion 56. A support member 58 shown in phantom lines extends from an end portion of the first stem 52 through the central portion 56 to an end portion of the second stem 54. In embodiments, a first member can be made to occupy one stem and end prior to or in the interconnecting central portion. A second member may occupy the second stem and also end prior to or in the interconnecting central portion. In this manner, the stems each contain a relatively rigid support and the interconnecting central portion is elastic, mimicking the pivotable joint function. FIG. 6 illustrates a joint prosthesis 60 in an unexpanded state having an interiorly disposed support member consisting of two separate legs 62 and 64 shown in phantom lines. The central portion 66 of the prosthesis 60 does not contain a portion of the support member. FIG. 7 illustrates a joint prosthesis 70 in an expanded state. The joint prosthesis 70 has a first stem 72, and oppositely disposed second stem 74 and an interconnecting central portion 76. A support member consisting of two separate legs 78 and 80 is shown in phantom lines. The central portion 76 of the prosthesis 70 does not contain a portion of the support member. In embodiments, two oppositely disposed members of a support member are connected at their ends by an elastic support adapted to overlap the central portion that is biased to pivot in only one direction, thus preventing extension of the joint beyond a normal or natural range. In embodiments, the support member may be made of a series of individual fibers or ribbons which are arranged in parallel or non-parallel fashion and extend throughout the prosthesis. In embodiments, the support member is a solid. A support member may be made of a polymeric material which is natural, e.g., cotton, or synthetic, e.g., polyester, polyamide, or other materials such as metal fiber, fiber glass, and carbon fiber. A carbon fiber or fiberglass reinforced resin material may be utilized. Methods of making shaped objects from these materials and others are well-known to those skilled in the art. Foils or ribbons herein may also be made of metal or polymeric material and are well-known. Thus, the support member may be constructed from relatively durable materials including, but not limited to, metal foil, plastic foil, metal fibers, polymeric fibers of materials such as polycarbonate, polyethylene, polypropylene, polystyrene, polyethylene terephthalate, polyamide, polyurethane, polyurea, polysulfone, polyvinyl chloride, acrylic and methacrylic polymers, expanded polytetrafluoroethylene (Goretex®), ethylene tetrafluoroethylene, graphite, etc. These materials can be used either alone, or in a composite form in combination with elastomers or hydrogels. Alternatively, the suppport member may be exteriorly disposed, e.g., a jacket which surrounds all or part of the joint prosthesis. A joint prosthesis herein may be manufactured by providing a support member of desired configuration and placing it in a mold, e.g., in an area corresponding to one of the stems. A fluid absorbing liquid polymer is added to the mold and surrounds the support member. In one embodiment, a gap, e.g., about l-3mm or more, is left between one or more sides of the support member and the walls of the mold. Fluid absorbing liquid polymer is allowed to fill the gap between the mold and the support member. When the fluid absorbing polymer is cured or fixed, e.g., by solvent casting, ionic gelation, photo- polymerization and the like, it solidifies and encapsulates the support member. In the case of solvent casting, the mold may be made of material which is impermeable to the fluid absorbing polymer but permeable to water. The mold is placed in a water bath to extract the solvent (e.g., sodium thiocyanate) which causes the polymer to coagulate. The mold may then be opened and any remaining solvent in the prosthesis is extracted. If it is desired to leave one or more sides of the prosthesis open to the support member, then the desired side(s) of the support member is placed up against the wall of the mold to prevent formation of a gap for the liquid fluid absorbing polymer to fill.

In one embodiment, the fluid absorbing polymer is made to achieve a strong physical bond to the support member by incorporating an initial treatment of the support member with a relatively hydrophobic fluid absorbing polymer to create an encapsulating layer of the relatively hydrophobic fluid absorbing polymer. For example, a hydrogel such as HPAN II is applied to the support member as a 10% solution by weight in a solvent (sodium thiocyanate 55% by weight in water) and then coagulated onto the support member by solvent exchange with an aqueous solution such as water. As the polymer coagulates, it shrinks volumetrically around the support member, causing a tight physical bond to the support member. If desired, the treated support member is placed in a mold and a relatively more hydrophilic fluid absorbing polymer in the liquid state is added to create a cohesive continuous polymer matrix which surrounds the support member. For example, a 10% by weight HPAN I in a 55% by weight sodium thiocyanate solution, is added to the mold. The solvent from the HPAN I solution causes the outermost surface of the coagulated HPAN II layer surrounding the braided fibers to dissolve and allow commingling of the HPAN I and HPAN II hydrogel polymers at the surface interface which forms a strong adhesive bond when the HPAN I and commingled hydrogels are coagulated by solvent exchange. It should be understood that the support member is optional and that a mold may be filled without such a support member.

It is contemplated that regions of more or less modulus of elasticity and durability may be incorporated into the joint prosthesis. For example, it may be desirable to fashion the stems from a relatively more rigid fluid absorbing polymer, e.g., the portions which contact the vertebral bone and are not necessarily designed to articulate. If a softer or more elastic zone of fluid absorbing polymer is desired in the central portion of the prosthesis, a hydrogel such as HPAN I can be added to the portion of the mold defining the central region. It should be understood that any number of zones of varying or the same elasticity may created in this fashion. In addition, different fluid absorbing polymers can be used to create zones with different properties. If desired, an adhesive can be added between adjacent zones to insure bonding or, e.g., in the case of the HPAN polymers, the layers can be made to naturally adhere to one another. Some co-mingling of liquid fluid absorbing polymers at zone interfaces can provide for an advantageous smooth transition between layers and reduce or eliminate the need for an adhesive between layers.

Upon completion of the solvent exchange extraction process the joint prosthesis may be hydrated to its fullest extent (-90% equilibrium water content (EWC)). In this fully hydrated state the prosthesis is readily deformed and can articulate under modest loads and the hydrogel, e.g., HPAN I OR HPAN II, glass transition temperature (T₈) is well below room temperature. This is the "relaxed" state of the prosthesis, the state to which it will return after loading below the critical level. The critical level is the point at which permanent deformation occurs and is further discussed below. In order to provide a reduced configuration (also referred to herein as the first configuration), the prosthesis may be allowed to dehydrate and enter the xerogel state. A considerable amount of the prosthesis' volume is lost when in the xerogel state as compared to the hydrated state. Advantageously, the fully hydrated joint prosthesis may be deformed into a desirable insertion shape and the temperature of the prosthesis is lowered below its T_g (near freezing point of water). Such a prosthesis is in a state of "frozen deformation" and it would retain that deformed shape indefinitely. Once the prosthesis is warmed above its T_g, however, the prosthesis would recover to its original memorized configuration. The Tg of the hydro gel increases with decreasing water content. This characteristic is exploited by simultaneously raising the T_g while deforming the prosthesis into a desired shape. In other words, as the prosthesis dehydrates it is freezing the position of the polymer chains. To regain the original shape of the prostheis, the T_g may be lowered by hydration.

In order to obtain a rod-shape having a cross-sectional ellipsoid shape for implantation, e.g., suppository, bullet, tapered cylinder, etc., from, e.g., the configurations shown in FIGs. 2 and 3, reduction in volume deformation is advantageously maintained radially, substantially parallel with the longitudinal axis. This is accomplished by placing the prosthesis within a radially collapsible member for exerting circumferential compression on an object, e.g., a joint prosthesis, contained within the member. Suitable radially collapsible members include, e.g., a flexible sleeve such as a braided sock or tube, a flexible coil, iris diaphragm, collapsible loop, etc. In a preferred embodiment, the radially collapsible member is porous or semipermeable so that water, either as liquid or as vapor, passes through the member. The collapsible member may be made of an elastic material such as rubber or neoprene fabric which has been made porous by any technique known to those skilled in the art, or a woven or non-woven mesh or braid. The collapsible member may also be made of a flexible metal having sufficient porosity to allow water to exit from the prosthesis. The collapsible member does, however, need to be stiff enough to be able to exert sufficient compressive force when tension is applied to compress the prosthesis, i.e., it should not be so elastic that it deforms without being able to exert sufficient compressive force.

In operation, the radially collapsible member exerts substantially equilateral circumferential compression on the joint prosthesis by substantially uniformly decreasing in diameter while contacting the prosthesis. The preferred porous nature of the collapsible member allows water from the prosthesis to escape into the surrounding environment so that the prosthesis can become dehydrated. In one embodiment, the sleeve radially collapsible member is stretched in length which causes the inner diameter to decrease, thus compressing the prosthesis, including, e.g., a reinforcement member, into a desired implantation configuration. A more complete description of a suitable radial compression process is described in US Application Ser. No. 11/303,767, herein incorporated by reference in its entirety.

The collapsible member is loaded in tension via any tensioning device known to one skilled in the art, e.g., a pneumatic cylinder, a hydraulic cylinder, springs, weights, pulleys, etc. The tension on the collapsible member can be precisely controlled by regulating the pressure within the tensioning device, translating into constant, controlled radial load on the joint prosthesis. In the case of a sleeve collapsible member, once the prosthesis is loaded into the collapsible member and the collapsible member is tensioned, three things occur: the prosthesis dehydrates, the prosthesis deforms, and the collapsible member extends. By varying the tension on the collapsible member, the length of the prosthesis can optionally be extended, thereby decreasing the minor axis and height. This can also be controlled, to some extent, by the speed of dehydration (temperature, pressure and humidity), with longer dehydration time producing longer prosthesis length and vise versa. In certain embodiments, one portion of the collapsible member is made to collapse further than other portions to define a prosthesis having one end which is relatively more compressed than the other end.

Two concerns with respect to drying time and collapsible member tension should be considered. The first is creep, which may set in if the dehydration time is extended unreasonably long (over several days). The second is permanent deformation which may occur if excessive stress is applied to the prosthesis. Both of these concerns only occur at critical point extremes which are to be avoided. Permanent deformation may occur in the hydrogel prosthesis if the soft-block domains of the polymer are displaced to a point where they cannot reorient themselves into the original lattice configuration, i.e., the memorized shape. This can happen, e.g., by either deforming the original shape so severely that many of the bonds which hold the soft-blocks in place are severed, or by heating the prosthesis sufficiently above the T_g to cause the soft-block domains to permanently or irrevocably assume a new configuration outside of the originally contemplated structure, which causes an undesirable change in shape. Thus, the melting point of the soft block should not be exceeded. The melting point of the soft block may vary based on the amount of water content. Such melting points may be determined by conventional techniques known to those skilled in the art. For example, at 18% hydration of HPAN I, permanent deformation is manifest at temperatures over 105⁰C.

In embodiments, the majority of the dehydration process can occur at room temperature over an extended period of time (e.g., 18 to 36 hours). The prosthesis can be monitored to determine the extent of dehydration and the time period adjusted accordingly. Relative humidity, air circulation, air pressure and room temperature should be controlled during this period. Especially preferred conditions are about 21⁰C at 50% relative humidity under moderate airflow. Once the prosthesis has reached <~30% water content it may be forced dry at elevated temperature , e.g., from about 25⁰C to about 105⁰C for typically less than about 24 hours to rapidly remove remaining water. As above, the state of dehydration may be monitored to determine if greater or lesser amounts of time are needed. When the prosthesis is substantially completely dehydrated, the prosthesis is fairly rigid in its state of frozen deformation. Alternatively, a slight degree of hydration provides some flexibility to the prosthesis. The less dehydrated, the more flexible. It is contemplated herein that "substantially dehydrated" preferably encompasses from about 12% or less, to about 30% water by weight of the prosthesis.

Upon completion of forced dehydration, the joint prosthesis is extremely stable in terms of shelf life, providing that it is kept dry. Even brief exposure to humidity during the sterilization process should not have significant effects. Temperatures above about 8O⁰C should be avoided for extended periods as this may bring the prosthesis above its T_g if it has absorbed some small amount of water vapor.

Surface irregularities may be present on a dehydrated compressed joint prosthesis which was compressed as described above by a radially collapsible member by virtue, e.g., of some extrusion of the hydrogel through pores or through interstitial spaces of the member. For example, a woven or non-woven collapsible sleeve may have interstitial spaces that allow hydrogel to extrude therein under compressive force. In addition, after radial compression, as described above, the dimensions of the prosthesis may be different than the ultimate dimensions desired by the practitioner. Both of these instances can be remedied by post-compression thermoforming of the prosthesis. In this aspect, a dehydrated, compressed prosthesis is placed within a mold which may be advantageously pre-heated to about 70-150⁰C, but more preferably, closer to the melting point of the polymer, e.g., about 105⁰C. Care must be taken to avoid subjecting the prosthesis to excess heat which causes the hydrogel to exceed its critical point, and thus causing permanent deformation of the prosthesis. If the temperature is high, the prosthesis must be quickly removed from the mold to avoid permanent deformation. The mold is machined to the exact desired final dimensions of the xerogel prosthesis and essentially irons out surface roughness to a substantially smooth surface, which is less abrasive to surrounding tissue when implanted. If desired, and if the xerogel prosthesis is compressed by a radially compressive member or by gas compression, but has not achieved, e.g., an ideal enough straight rod-like configuration, or if the ends are not sufficiently blunted or otherwise tapered, post-compression thermoforming may be utilized to fine tune the shape as well as remove any surface irregularities which may be present. Post- compression thermoforming may also be utilized to bend a prosthesis to a desired configuration, e.g., to a boomerang shape.

A joint prosthesis according to the disclosure herein may contain a medicinal agent. "Medicinal agent" is used in its broadest sense and it includes any substance or mixture of substances which may have any clinical use. It is to be understood that medicinal agent encompasses any drug, including hormones, antibodies, therapeutic peptides, etc., or a diagnostic agent such as a releasable dye which has no biological activity per se. Thus, in its broadest aspect, a method of delivery herein may be defined as the release of any substance for clinical use, which may or may not exhibit biological activity.

Examples of medicinal agents that can be used include anticancer agents, analgesics, anesthetics, anti-inflammatory agents, growth factors such as BMPs, antimicrobials, and radiopaque materials. Such medicinal agents are well-known to those skilled in the art. The medicinal agents may be in the form of dry substance in aqueous solution, in alcoholic solution or particles, microcrystals, microspheres or liposomes. An extensive recitation of various medicinal agents is disclosed in Goodman and Gilman, The Pharmacological Basis of Therapeutics, 10th ed. 2001, or Remington, The Science and Practice of Pharmacy, 21 ed. (2005). As used herein, the term "antimicrobial" is meant to encompass any pharmaceutically acceptable agent which is substantially toxic to a pathogen. Accordingly, "antimicrobial" includes antiseptics, antibacterials, antibiotics, antivirals, antifungals and the like. Radiopaque materials include releasable and non-releasable agents which render the prosthesis visible in any known imaging technique such as X-ray radiographs, magnetic resonance imaging, computer assisted tomography and the like. The radiopaque material may be any conventional radiopaque material known in the art for allowing radiographic visualization of a prosthesis, and may be, e.g., metal wire or flakes made from a biocompatible material, such as titanium, tantalum, stainless steel, or nitinol; or metallic salts (such as barium compounds).

Medicinal agents may be incorporated into the prosthesis at various points in the manufacturing process. For example, a suitable medicinal agent can be mixed with a fluid absorbing liquid polymer before it is cured or fixed. Alternatively, a suitable medicinal agent may be dissolved into a solvent cast solution and then diffused into the hydrogel in accordance with normal kinetic principles. If the prosthesis is then dehydrated, the medicinal agent collects in the interstices of the hydrogel.

A dehydrated prosthesis according to the disclosure herein may be sterilized by any suitable conventional means, e.g., ethylene oxide, irradiation, etc. and packaged for distribution. A kit containing the sterilized prosthesis and a package insert describing the joint prosthesis, along with instructions is useful for medical practitioners.

Techniques for implanting joint prostheses in hands and feet are well-known. In the present case, minimally invasive implantation techniques are improved and facilitated by the reduced dimension and overall configuration of the reduced configuration. In addition, the ability to provide custom implantation shapes allows an optimal insertion shape to be manufactured. For implantation of the joint prosthesis into a hand, access to the metacarpal/phalanx joint may, e.g., be performed dorsally. For implantation into a foot, access to the metatarsal/phalanx joint may, e.g., also be performed dorsally. Indeed, palmar, dorsal, medial, and lateral surgical approaches can all be performed. The prosthesis is designed to reduce tissue trauma due to surgery by allowing implantation of the prosthesis in a reduced configuration, thus allowing for minimally invasive surgical techniques. The ability to assume a state of reduced configuration advantageously minimizes undue disruption to soft tissue. FIG. 8 is atop view of a hand skeleton 100 showing the thumb 102, index finger 104, second finger 106, third finger 108 and fourth finger 110. The thumb 102 consists of a metacarpal 112, a proximal phalanx 1 14 and a distal phalanx 116. An expanded joint prosthesis 120 is shown between the metacarpal 112 and proximal phalanx 1 14. The prosthesis 120 is dimensioned and configured such that central portion 122 is situated in the space between the opposing bone architecture defining at least a portion of the area previously occupied by the native joint upon implantation and expansion. Oppositely disposed first and second stems 124, 126 are dimensioned and configured to engage the ends of opposing bones by insertion into the bones. Portions of the stem 124, 126 that are disposed within the bones are shown in phantom lines.

In practice, the bony joint segments are exposed, care being taken to preserve as much as possible soft tissue connections. The opposing bone ends can be surgically sculpted to receive the ends of the stems, respectively, care being taken again to avoid damage to soft tissue connections. In embodiments, the prosthesis, whether unexpanded or expanded, is sufficiently narrow, as to avoid interference with the collateral ligaments and the flexor extension tendon of the joint, thereby enabling these ligaments and tendons to be preserved. Surgical access may also be gained to the marrow cavities of the respective bones, and the stems are then implanted in the marrow cavities, optionally using bone cement or other attachment modalities. It may be appropriate to cause the stems of the prosthesis members to fit fairly tightly in the marrow cavities of the bones in which they are implanted. For example, as the prosthesis swells in an intramedullary canal, pressure and/or compression act to frictionally engage the walls of the canal and fix the prosthesis in place. In embodiments, the unconstricted volume of the stems of the prosthetic joint, when expanded (also referred to herein as the second configuration), is slightly greater than the space created in the intramedullary canal such that, in situ, the stems of the prosthesis are compressed when situated in their respective canals. In this manner, the swellable stems exert positive pressure against the walls of the canal, thus maintaining pressure within the canal and securing the stems in place by virtue of the friction created thereby. In embodiments, the surface of the stems are shaped to encourage frictional affixation and/or treated to encourage bone ongrowth or ingrowth, as by providing, e.g., the stems with barbs, spurs or spikes and/or porous surfaces, by applying to the stems a growth factor, cell adhesion promoter such as collagen or the like, etc. In embodiments, a support member is anchored in an interior portion of the prosthesis and includes a portion which extends out of the swellable polymer for use in anchoring the prosthesis to nearby bone or tissue. In this manner, e.g., a tether can extend out of the swellable polymer and can be use to secure the prosthesis to bone or other tissue.

It should be understood that the examples and embodiments provided herein are preferred embodiments. Various modifications may be made to these examples and embodiments without departing from the scope of the disclosure which is defined by the appended claims. For example, those skilled in the art may envision additional polymers and/or hydrogels which can be compacted and shaped according to the techniques described herein. Similarly, the shapes of the hydrated or expanded joint prosthesis described herein are exemplary and any suitable expanded prosthesis shape can be subjected to the techniques described herein to create an optimally shaped, substantially dehydrated prosthesis for minimally invasive insertion into the implantation space. Although especially well-suited for implantation in a dehydrated state, the prosthesis can be delivered in a hydrated state at the time of implantation. Moreover, those skilled in the art can envision additional radially collapsible members for exerting substantially uniform radial compression on the prosthesis which are not set forth herein. In addition, process parameters such as temperature, humidity, pressure, time and concentration may be varied according to conventional techniques by those skilled in the art to optimize results. These are merely examples of many modifications those skilled in the art may make.

Claims

What is claimed is:

1. A swellable, resilient joint prosthesis which comprises a fluid absorbing polymer dimensioned and configured to fit and be retained between a first phalanx and an adjacent second phalanx, wherein said joint prosthesis expands from a compact first configuration to an expanded second configuration upon absorption of fluid, the second expanded configuration having a first end portion and an oppositely disposed second end portion which are connected by a centrally disposed pivotally flexible region of increased cross section relative to said first and second end portions, the first end portion being dimensioned and configured to frictionally engage a contacting end of the first phalanx and the second end portion being dimensioned and configured to frictionally engage a contacting end of the second phalanx.

2. The swellable, resilient joint prosthesis according to claim 1, wherein the fluid absorbing polymer is a hydrogel.

3. The swellable, resilient joint prosthesis according to claim 1, wherein the compact first configuration is rod-shaped.

4. The swellable, resilient joint prosthesis according to claim 1, further comprising an interiorly disposed support member.

5. The swellable, resilient joint prosthesis according to claim 4, wherein the support member is a rod which is more rigid than the fluid absorbing polymer.

6. The swellable, resilient joint prosthesis according to claim 5, wherein the rod extends from the first end portion of the prosthesis to the second end portion of the prosthesis, the rod having two end portions and a central portion located between the end portions, the central portion being flexible relative to the end portions.

7. The swellable, resilient joint prosthesis according to claim 4, wherein the support member is made of a material selected from the group consisting of fabric, foil and three- dimensional braid.

8. The swellable, resilient joint prosthesis according to claim 1 , wherein the fluid absorbing polymer expands from the first configuration to the second configuration due to a shape memory property of the polymer.

9. The swellable, resilient joint prosthesis according to claim 1, wherein said first and second end portions are dimensioned and configured to be inserted into and frictionally engage an interior portion of a phalanx.

10. The swellable, resilient joint prosthesis according to claim 1 , wherein the centrally disposed pivotally flexible region has a different modulus of elasticity as compared to said first and second end portions.

1 1. The swellable, resilient joint prosthesis according to claim 2, wherein the hydrogel is a polyacrylonitrile.

12. The swellable, resilient joint prosthesis according to claim 1, further comprising a medicinal agent.

13. The swellable, resilient joint prosthesis according to claim 4, wherein the support member includes an exteriorly disposed portion extending out of the fluid absorbing polymer that is dimensioned and configured to be attached to surrounding tissue and/or bone.

14. The swellable, resilient joint prosthesis according to claim 4,wherein the support member comprises a first member and a second member, the first member being disposed in the first end portion and the second member being disposed in the second end portion.

15. A method of treating a damaged phalange comprising: creating an incision in a finger or a toe; exposing an end of a first phalanx; exposing an end of a second phalanx adjacent to the first phalanx; inserting, through the incision, between the first phalanx and the second phalanx, a swellable, resilient joint prosthesis according to claim 1; attaching said first end portion of the prosthesis to a contacting end of the first phalanx; attaching said second end portion of the prosthesis to a contacting end of the second phalanx; and closing the incision.

16. A method of manufacturing a swellable, resilient joint prosthesis comprising: providing a mold having a cavity dimensioned and configured to approximate at least a portion of the space between two adjacent phalanges, the cavity defining first and second end portions and a center portion connecting the first and second end portions; providing a liquid fluid absorbing polymer; filling the mold with the liquid polymer; solidifying the liquid polymer to form a swellable, resilient joint prosthesis dimensioned and configured to fit and be retained between a first phalanx and an adjacent second phalanx; and dehydrating the prosthesis under compression to form a compacted prosthesis of reduced dimension having a shape memory.

17. The method of manufacturing a swellable, resilient joint prosthesis according to claim 16, further comprising providing a support member which is placed in the mold prior to completely filling the mold with liquid polymer.

18. The method of manufacturing a swellable, resilient joint prosthesis according to claim 16, wherein the polymer is solidified by a technique selected from the group consisting of solvent casting, ionic gelation and photopolymerization.

19. The method of manufacturing a swellable, resilient joint prosthesis according to claim 16, wherein the compacted prosthesis has a rod shape.

20. The method of manufacturing a swellable, resilient joint prosthesis according to claim 16, further comprising removing surface irregularities by post-compression thermoforming.