WO2006040128A1 - Pva hydrogel - Google Patents
Pva hydrogel Download PDFInfo
- Publication number
- WO2006040128A1 WO2006040128A1 PCT/EP2005/010931 EP2005010931W WO2006040128A1 WO 2006040128 A1 WO2006040128 A1 WO 2006040128A1 EP 2005010931 W EP2005010931 W EP 2005010931W WO 2006040128 A1 WO2006040128 A1 WO 2006040128A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vinyl polymer
- pva
- hydrogel
- vinyl
- solution
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/28—Treatment by wave energy or particle radiation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2329/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal, or ketal radical; Hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Derivatives of such polymer
- C08J2329/02—Homopolymers or copolymers of unsaturated alcohols
- C08J2329/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S524/00—Synthetic resins or natural rubbers -- part of the class 520 series
- Y10S524/916—Hydrogel compositions
Definitions
- Vinyl polymers are used in a variety of industrial applications.
- poly vinyl alcohol (PVA) is a highly hydrophilic polymer that is used as sizing in the textile industry, as a base gel component for the cosmetics industry, as an adherent for the paper industry and as a general adhesive.
- the chemical formula of PVA is (C 2 H 4 O) n and the structural formula is (-CH 2 CH(OH)-) n .
- PVA elicits little or no host biological response when implanted in animals. For this reason PVA is also used in a variety of biomedical applications including drug delivery, cell encapsulation, artificial tears, contact lenses, and more recently as nerve cuffs. PVA has generally not been considered for use as a load bearing biomaterial, primarily because of its low modulus and poor wear characteristics. It has been reported in the literature that hydrogel modulus and wear characteristics can often be enhanced by the formation of either chemical or physical associations.
- Cross-linking PVA by the addition of chemical agents such as polyaldehydes, through irradiation, or by freeze-thaw cycling, has been shown to improve the durability of PVA, wherein the last one forms physical associations and the other ones form chemical crosslinkings.
- cross-linking and degradation can be understood by considering the case of irradiated solid PVA.
- the irradiation of solid PVA leads to main chain degradation as a result of ketone structure formation which is not due to an oxidation step via oxygen, but through keto-enol tautomerization.
- keto-enol tautomerism a simultaneous shift of electrons and a hydrogen atom occurs.
- Main chain scission can then occur in the backbone bearing the keto tautomer.
- Keto-enol degradation is thought to dominate when the concentration of the polymer limits chain movement and free radical mobility. Thus, as the concentration passes 300 g/dm 3 , scission becomes more prevalent.
- reactive intermediates can be formed either by direct ionization, or indirectly by interaction with reactive intermediates (hydroxyl radicals) in the aqueous solution.
- reactive intermediates hydroxyl radicals
- the indirect route dominates because of the electron fraction of the solution.
- the indirect route will be the primary mechanism responsible for the formation of reactive intermediates and subsequently, for the generation of crosslinks or scission.
- simple gel forming hydrophilic polymers do not have functional groups capable of efficient scavenging of free electrons, they do not participate in the formation of crosslinks extensively.
- the real workhorse is the hydroxyl radical in the aqueous solution.
- Nitrous oxide which converts the free electrons to hydroxyl radicals, is sometimes added to polymer solutions undergoing radiation induced crosslinking to improve yield.
- Rosiak & Ulanski showed that the dependence of gelation dose (determined by rheology) on concentration was found to have a local minimum in the neighborhood of about 20 g/dm 3 ( Figure 2, from Rosiak, J. M. & Ulanski, P., Synthesis of hydrogels by irradiation of polymers in aqueous solution, Radiation Physics and Chemistry 1999 55: 139-151).
- the method of crosslinking can by optimized by determining the local minimum in a corresponding gelation dose versus concentration curve for a given vinyl polymer and performing crosslinking in that range of irradiation doses.
- chain scission reactions are very slow because re-combination of radicals prevails.
- chain scission yield is near zero if the concentration of polymer is low enough.
- Additives can be used during the irradiation process to scavenge unwanted transient products (for example, tertbutanol scavenges OH- and nitrous oxide scavenges aqueous electrons). Other additives can help identify transient reaction products (tetranitromethane helps identify polymer radicals). Spin traps (2-methyl-2- nitrosopropane) allow EPR (or ESR) studies on short-lived species. Thiols are good H + donors and are frequently used as polymer radical scavengers. Metal ions such as Fe(H) are also known to significantly affect the kinetics and yields of radiation- induced transformations of polyacrylic acid (PAA) (for example).
- PAA polyacrylic acid
- Irradiated PVA films 60 Co gamma ray source, nitrogen atmosphere, dose-rate 0.0989 kGy/min, 86 kGy total dose; 10-15 wt% 78 kDa PVA in deionized water
- Compressive modulus obtained by dynamic mechanical analysis (DMA) on 10% solutions of PVA directly irradiated by electron beam in air (100 kGy total dose) yielded a 0.5 MPa storage modulus at 1 Hz.
- DMA dynamic mechanical analysis
- cryogels are solid elastomers containing over 80% water which are produced when solutions of higher molecular weight polyvinyl alcohol) (PVA) of high degree of hydrolysis are subjected to one or more freeze-thaw cycles.
- PVA polyvinyl alcohol
- Such cryogels are tough, slippery, elastomeric, resilient, insoluble in water below 50 degrees Celsius, and nontoxic.
- PVA cryogels are also highly biocompatible (as are PVA "thetagels,” discussed below). They exhibit very low toxicity (at least partially due to their low surface energy), contain few impurities and their water content can be made commensurate to that of tissue at 80 to 90 wt%.
- cryogels the physical characteristics depend on the molecular weight of the uncrosslinked polymer, the concentration of the aqueous solution, temperature and time of freezing and the number of freeze-thaw cycles. Thus the properties of a cryogel can be modulated. However, since the material's properties change dramatically at every freeze-thaw step, control over the properties of the finished gel is somewhat limited. The thetagels described broaden the range of functionality currently provided by PVA cryogels. hi general, the modulus of the PVA cryogel increases with the number of freeze-thaw cycles.
- thermally cycled PVA cryogels had compressive moduli in the range of 1 - 18 MPa and shear moduli in the range of 0.1 - 0.4 MPa (see Stammen, J. A., et al., Mechanical properties of a novel PVA hydrogel in shear and unconfmed compression Biomaterials, 2001 22: p. 799-806).
- cryogel was only freeze-thaw cycled once, although others have shown PVA dissolution following multiple freeze-thaw cycles, hi general, there is very little information about the stability of PVA cryogel modulus under repeated load cycling (fatigue).
- the swelling of PVA cryogels at any time point decreases with increasing number of freeze-thaw cycles, indicating a densification of the PVA gel, most likely due to a higher crosslink density.
- the ultimate swelling ratio decreases while the modulus increases with time, hi freeze-thaw processing, temperature is used to force a phase separation of the PVA solution, thus enhancing the gelation mechanism in the PVA (it should be noted that even at room temperature a solution of PVA begins to gel weakly over time).
- Pores can increase in size with the number of freezing-thawing cycles. It is thought that the polyvinyl polymer is rejected from the ice crystals as an impurity and is progressively "volume excluded" into increasingly polyvinyl polymer rich areas. As might be expected, the pore size increases with decreasing concentration of polyvinyl polymer.
- the melting point for freeze-thaw cycled cryogels in pure aqueous solutions is about 70 - 8O 0 C.
- the melting point of a PVA cryogel in water/dimethyl sulfoxide (DMSO) solutions increases with the number of freeze thaw cycles.
- DMSO dimethyl sulfoxide
- the concentration of DMSO 5 the concentration of the PVA and the number of freeze-thaw cycles is difficult, hi general, the melting point increased with PVA concentration and with the number of freeze thaw cycles.
- FIG 3 the melting point variation as a function of PVA concentration and the number of freeze thaw cycles is shown for PVA in a 1% DMSO/water solution.
- Figure 3 is a graphic illustration of the dependence of melting temperature on polymer concentration, with a family of curves for different numbers of freeze-thaw cycles for cryogels in 1 vol% DMSO at -40 0 C, where open circles represent data from gels treated with one cycle, closed circles represent data from gels treated with three cycles, open triangles represent data from gels treated with four cycles, closed triangles represent data from gels treated with eight cycles and open squares represent data from gels treated with fourteen cycles.
- the melting point of the PVA is extremely low (near or below 1O 0 C). hi general, the melting point increases with the number of freeze/thaw cycles and increasing PVA concentration. At very high concentrations of DMSO (90%), the cryogels have a very low melting point and were transparent. After the first freeze/thaw cycle, the melting point does not change appreciably.
- the melting temperature of PVA cryogels in low concentration DMSO (1-5%) is independent of freezing time. However, the melting temperature of PVA in 30% DMSO is strongly dependent on freezing time. This dependence is probably due to retarded freezing in higher concentrations of DMSO.
- Figure 4 is a graphic illustration of the dependence of the shear modulus on the log of the thawing rate for PVA hydrogels formed by a single freeze-thaw cycle of 7 g/dl solution of PVA in water (data from Yamaura, K., et al., Properties of gels obtained by freezing/thawing of poly(vinyl alcohol)/water/dimethyl sulfoxide solutions.
- Modulus hi general, the modulus of the PVA cryogel increases with the number of freeze -thaw cycles.
- the freeze-thaw effect has been exploited to generate PVA cryogels with fairly high moduli, hi an experimental series aimed at determining whether PVA cryogels could be used in load bearing applications (i.e. cartilage), thermally cycled PVA cryogels had compressive moduli in the range of 1-18 MPa (at very high strain) and shear moduli in the range of 0.1 -0.4 MPa.
- the material used in this series of experiments is SalubriaTM (available from SaluMedica, Atlanta, GA).
- PVA gels may also be produced through thermal cycling (not necessarily with freezing) with dehydration. Such gels are potentially suitable for use in load bearing applications, specifically, for use as an artificial articular cartilage, hi such applications, an artificial cartilage can be made from PVA with a high degree of polymerization (7000), which translates to an average molecular weight of 308,000 g/mol.
- 7000 degree of polymerization
- the polymer powder is dissolved in a mixture of water and DMSO. The solution is cooled to below room temperature to obtain a transparent gel. The gel is then dried using a vacuum dehydrator for 24 hours at room temperature and then heat treated in a silicone oil bath for 1 hour at 14O 0 C. The PVA is placed in water until maximum hydration was achieved.
- the water content can be controlled by varying the annealing, or heat- treating, process.
- the resulting PVA hydrogel can have a water content of approximately 20%, which is low.
- Examination of the material properties of this thermally cycled PVA found that the material distributes stress more homogeneously than stiff biomaterials (UHMWPE) and preserves the lubrication film gap readily in simulated articular cartilage loading.
- the material sustained and distributed pressure in the thin film of between 1 and 1.5 MPa. In transient load tests, the PVA withstood and distributed loads of nearly 5 MPa (Figure 5).
- the present invention provides methods of making covalently crosslinked vinyl polymer hydrogels having advantageous physical properties.
- the present invention provides covalently crosslinked vinyl polymer hydrogel compositions made by a method of the present invention.
- the present invention provides articles of manufacture comprising covalently crosslinked vinyl polymer hydrogel compositions made by a method of the present invention.
- the covalently crosslinked vinyl polymer hydrogels according to the present invention can be made translucent, preferably transparent, or opaque depending on the processing conditions. As far as transparency of the resulting polymer is concerned, the transparency is dependent from the remaining physical associations in the product, i.e. the more physical associations of the chemical crosslinked vinyl polymer hydrogel are removed, the more transparency could be achieved.
- the stability of the physical properties of the produced vinyl polymer hydrogel can be enhanced by controlling the amount of covalent crosslinks. Moreover, it was found that according to the methods of the present invention it is possible to maintain the shape/mold of the precursor gel during the whole process, wherein also vinyl polymer hydrogels may be produced which exhibit a memory of shape (see e.g. Figure 12, the coiled PVA hydrogel). Following the optional removal of the physical associations, the resulting vinyl polymer hydrogel exhibits chemical crosslinks having a very similar, but "inversed" pattern in comparison to the former physical associations, i.e. the physical associations are lost and at their former places there are no crosslinks anymore.
- a covalently cross-linked vinyl polymer hydrogel is produced by a.) providing a physically associated vinyl polymer hydrogel having a crystalline phase; b.) exposing said physically associated vinyl polymer hydrogel to ionizing radiation providing a radiation dose effective to form covalent crosslinks, and c.) optionally removing at least a part, preferably about 1% to 100%, of the physical associations by the feed of an amount of energy sufficient to break the physical associations to be removed.
- the invention is based on the surprisingly simple idea of forming covalent crosslinks through irradiation of a previously produced "crystalline" hydrogel and then - optionally - removing the physical associations responsible for the crystalline phase so that - preferably - only or predominantly the covalent crosslinks remain.
- the step of providing a physically associated vinyl polymer hydrogel having a crystalline phase includes the steps of al .) providing a vinyl polymer solution comprising a vinyl polymer dissolved in a solvent; a2.) heating the vinyl polymer solution to a temperature elevated above the melting point of the physical associations of the vinyl polymer; a3.) inducing gelation of the vinyl polymer solution; and a4.) optionally controlling the gelation rate to form crystalline physical associations in the vinyl polymer hydrogel.
- the gelation of steps a3.) and a4.) may be performed by subjecting the vinyl polymer solution to at least one freeze-thaw cycle and/or mixing the vinyl polymer solution with a gellant, wherein the resulting mixture has a higher Flory interaction parameter than the vinyl polymer solution and/or dehydrating the vinyl polymer solution.
- the ionizing radiation of step b.) maybe performed using gamma radiation and/or beta particles, wherein the radiation dose is typically in the range of about 1 - 1 ,000 kGy, preferably about 50 -1 ,000 kGy and more preferably about 10-200 kGy.
- the radiation dose rate is preferably in the range of about 0.1-1000 kGy/min, more preferably about 0.1-25 kGy/min and most preferably about 1-10 kGy/min.
- gamma radiation or beta particles can be used, hi another preferred embodiment, the radiation dose is within 20% of the optimum radiation dose, preferably within 10% of the optimum radiation dose and most preferably within 7% of the optimum radiation dose.
- the optimum radiation dose is a function of the actual polymer, solvent and concentration configuration and thus specific for a certain gel. This will also be discussed further below.
- a radiation mask can be used to manipulate the degree of radiation dose in order to produce vinyl polymer hydrogels exhibiting a gradient in the crosslinkage.
- Said radiation mask may be a step mask and/or a gradient mask.
- the energy of step c.) can be fed by exposing the irradiated vinyl polymer hydrogel to a temperature above the melting point of the physically associated crystalline phase and/or the energy can be fed by electromagnetic radiation, in particular microwave radiation, and/or ultrasonic.
- the quantity of the energy required for breaking a certain part of the existing physical associations may be determined by the heat of linkage of a single bonding, i.e. physical association multiplied with the number of associations to be broken. Therefore, other energy sources delivering energy to the vinyl polymer hydrogel to break the physical associations are suitable as well.
- microwave radiation has the advantage that the energy is effective within the complete hydrogel and not only at its surface. Thus, the required amount of energy can be controlled very accurately.
- a preferred vinyl polymer of the invention is selected from the group consisting of poly(vinyl alcohol), poly(vinyl acetate), poly(vinyl butyral), poly(vinyl pyrrolidone) and any mixture thereof.
- a polar solvent is preferred.
- the vinyl polymer of step c.) is immersed in a polar solvent during the feed of energy.
- Said polar solvent may be a polar solvent known to a person skilled in the art, preferably the polar solvent is selected from the group consisting of water, preferably deionized water, methanol, ethanol, dimethyl sulfoxide and any mixture thereof.
- the vinyl polymer in particular the vinyl polymer of step al mentioned above (i.e. so to speak the "starting material"), has the following properties:
- the vinyl polymer is highly hydrolyzed and/or has a molecular weight of about 15 kg/mol to about 15,000 kg/mol.
- the vinyl monomer is vinyl alcohol, vinyl acetate, vinyl butyral, vinyl pyrrolidone and/or any mixture thereof.
- the vinyl polymer is a, preferably highly hydrolyzed, poly(vmyl alcohol) of about 50 kg/mol to about 300 kg/mol molecular weight, preferably of about 100 kg/mol molecular weight.
- the vinyl polymer can be a, preferably highly hydrolyzed, poly(vinyl pyrrolidone) of about 1,000 kg/mol to about 1,500 kg/mol molecular weight.
- the vinyl polymer has a degree of hydrolysis of about 70 to about 100 percent, preferably about 95 to about 99.8 percent.
- the vinyl polymer is a poly(vinyl alcohol) having a degree of hydrolysis of about 80 to about 100 percent, preferably about 95 to about 99.8 percent.
- the vinyl polymer has a degree of polymerization of about 50 to about 200,000, preferably about 1,000 to about 20,000.
- the vinyl polymer is a poly(vinyl alcohol) having a degree of polymerization of about 100 to about 50,000, preferably about 1 ,000 to about 20,000.
- the vinyl polymer solution can be about 0.5 to about 80 weight percent, preferably about 1 to about 15 weight percent, more preferably about 10 to about 20 weight percent solution of the vinyl polymer based on the weight of the solution.
- the vinyl polymer solution is about 0.5 to about 50 weight percent, preferably about 1 to about 15 weight percent, more preferably about 10 to about 20 weight percent solution of poly(vinyl alcohol) based on the weight of the solution.
- the present invention provides a covalently crosslinked vinyl polymer hydrogel produced by the methods according to the present invention as well as an article of manufacture comprising the covalently crosslinked vinyl polymer hydrogel of the present invention, hi a further preferred embodiment the article of manufacture is selected from a device for delivery of active agents, a load bearing orthopedic implant, a bandage, a trans-epithelial drug delivery device, a sponge, an anti-adhesion material, an artificial vitreous humor, a contact lens, a breast implant, a stent and non-load-bearing artificial cartilage.
- the covalently crosslinked vinyl polymer hydrogel produced by the methods according to the present invention is used as coating material, especially in the medical and cosmetic area, preferably medical devices and implants.
- thermoreversible means a characteristic of the vinyl polymer. Whether a hydrogel is formed by the freeze-thaw technique or the solvent manipulation approach, in both cases if the formed hydrogel, lacking any additional covalent bond formation from irradiation, is raised above the melting point of the respective physical associations (around 30 to 150 ° C, preferably 50 to 100 0 C , more preferably around 80° C), the hydrogel returns into solution and does not reform, even when cooled to room temperature.
- Crvosel means a vinyl polymer gel formed by one or more cycles of cooling a vinyl polymer solution down, followed by returning to a temperature below the melting point of the gel, e.g. a vinyl polymer gel formed following freeze-thaw cycling.
- Thetagel means a vinyl polymer gel made by a process that includes a step of mixing the vinyl polymer solution with a gellant, wherein the resulting mixture has a higher Flory interaction parameter than the vinyl polymer solution.
- Radio ⁇ el refers to a vinyl polymer gel in which irradiation has been used to form covalent bonds between adjacent vinyl polymer chains having physical associations, followed by an optional step of heating the vinyl polymer gel above the melting point of the physical associations within the crystalline phase of the vinyl polymer gel.
- Precursor ⁇ el means the gel before the radiation step, which is defined by specific parameters, like a certain concentration, degree of polymerization of the vinyl polymer as well as a certain amount of physical associations.
- Gelling means the formation of a 3 -dimensional macroscale network from a solution of the vinyl polymer.
- Swelling is the increase in volume produced when a formed gel is placed in a good solvent for the gel.
- the gel swells to a degree depending on the quality of the solvent and the degree of network formation (crosslink density) of the hydrogel.
- Crystalline phase refers to the formation of physical associations and/or crystalline structures in vinyl polymers. It is believed that the crystalline regions are formed by forcing the vinyl polymer chains into close proximity, thereby allowing the chains to form physical associations. These physical associations form the network of the vinyl polymer hydrogel and hold it together.
- three models have been proposed to explain formation of said physical associations: 1) direct hydrogen bonding; 2) direct crystalline formation; and 3) liquid-liquid phase separation followed by a gelation mechanism.
- crystalline phase is defined as physical association within the vinyl polymer accomplished by at least one of said three possible interactions, preferably the direct crystalline formation.
- the physical properties of the produced hydrogel can be adjusted by varying controlled parameters such as the proportion of physical associations, the concentration of polymer and the amount of radiation applied.
- Such covalently crosslinked vinyl polymer hydrogels can be made translucent, preferably transparent, or opaque depending on the processing conditions.
- the stability of the physical properties of the produced vinyl polymer hydrogel can be enhanced by controlling the amount of covalent crosslinks.
- a part of the physical associations are removed.
- the fraction of physical associations removed ranges from about one tenth to substantially all of the physical associations. In other preferred embodiments, about 1-100%, preferably 10-90%, most preferably 20-80 % of the physical associations are removed.
- the method of manufacturing a covalently crosslinked vinyl polymer hydrogel includes the steps of providing a vinyl polymer solution comprising a vinyl polymer dissolved in a solvent; heating the vinyl polymer solution to a temperature elevated above the melting point of the physical associations of the vinyl polymer, inducing gelation of the vinyl polymer solution; controlling the gelation rate to form crystalline physical associations in the vinyl polymer hydrogel, exposing the physically associated vinyl polymer hydrogel to a dose of ionizing radiation of about 1-1,000 kGy effective to produce covalent crosslinks and melting the vinyl polymer hydrogel in a solvent to remove substantially all or a fraction of the physical associations.
- the produced covalently crosslinked vinyl polymer hydrogel substantially lacks physical associations.
- the desired physical property typically includes at least one of light transmission, gravimetric swell ratio, shear modulus, load modulus, loss modulus, storage modulus, dynamic modulus, compressive modulus, crosslinking and pore size.
- light transmission is increased sufficiently to make the resulting hydrogel translucent, hi more preferred embodiments, light transmission is increased sufficiently to make the resulting hydrogel transparent, hi PVA hydrogels, as with most polymers, crystallmity is always accompanied by opacity, due to the size of the crystalline structure (10-100 nm) and its difference in refractive index from amorphous PVA. Once the crystalline junctions are melted following irradiation, the local ordering is lost as the crystals melt, resulting in a loss in opacity.
- the vinyl polymer is selected from the group consisting of poly(vinyl alcohol), poly(vinyl acetate), poly(vinyl butyral), polyvinyl pyrrolidone) and a mixture thereof.
- the vinyl polymer is highly hydrolyzed poly(vinyl alcohol) of about 50 kg/mol to about 300 kg/mol molecular weight.
- the vinyl polymer is highly hydrolyzed poly(vinyl alcohol) of about 100 kg/mol molecular weight.
- the vinyl polymer solution is about 0.5 - 50 weight percent solution of poly(vinyl alcohol) based on the weight of the solution, hi certain preferred embodiments, the vinyl polymer solution is about 1 - 15 weight percent, hi other preferred embodiments, the vinyl polymer solution about 10 - 20 weight percent polyvinyl alcohol.
- the vinyl polymer preferably poly(vinyl alcohol), can be isotactic, syndiotactic or atactic.
- the solvent of the vinyl polymer solution is selected from the group consisting of polar solvents, preferably e.g. water, preferably deionized water (DI), methanol, ethanol, dimethyl sulfoxide and a mixture thereof.
- the solvent used in melting the vinyl polymer hydrogel to remove the physical associations is selected from the group consisting of polar solvents, preferably e.g. water, preferably deionized water, methanol, ethanol, dimethyl sulfoxide and a mixture thereof.
- the same solvent is used for the vinyl polymer solution and for melting the vinyl polymer hydrogel to remove the physical associations.
- the ionizing radiation is gamma radiation or beta particles (electron beam).
- the total radiation dose is suitably 1- 1 ,000 kGy, preferably 50- 1 ,000 kGy, more preferably 10-200 kGy.
- the radiation dose rate is suitably about 0.1 -25 kGy/min, preferably about 1-10 kGy/min.
- the irradiation dose used is within 20% of the optimum irradiation dose, preferably within 10%, more preferably within 7% of the optimum irradiation dose.
- the optimum irradiation dose is specific to each polymer.
- the suitable polymer concentration of the hydrogel product to be irradiated can be optimized within the polymer concentration range flanking the maximum of a plot of intermolecular crosslinking yield v. polymer concentration or the minimum of a plot of irradiation dose v. polymer concentration, i.e. the point at which the slope of the plot is zero.
- the polymer concentration falls in a range in which the intermolecular crosslinking yield or the irradiation dose is within 20% of the maximum or minimum value, respectively, preferably within 10%, more preferably within 7% of the value.
- the hydrogel comprises polyvinyl alcohol
- the hydrogel is suitably about 2 to about 35 weight percent poly(vinyl alcohol), preferably about 3.5 to about 30 weight percent poly(vinyl alcohol), more preferably about 5 to about 25 weight percent poly(vinyl alcohol), based on the weight of the composition.
- the physical associations are removed by raising the temperature of the hydrogel above the melting point of the thermo-reversible physical associations.
- the required temperature depends on the melting point of the cross ⁇ links and is suitably about 0-100 degrees Celsius, preferably about 40-80 degrees Celsius.
- the irradiated gels are heated to high temperatures while they are immersed in solvent to allow dissolution and elution of the PVA chains "melted out" of the physical associations.
- the duration of the exposure to the elevated temperature can be adjusted to melt out all of the physical associations, or just a fraction of the physical associations.
- the covalently crosslinked vinyl polymer hydrogels of the present invention have an advantageous inherent material stability that is exhibited when the crosslinking is covalent chemical rather than physical.
- covalent crosslinks by radiation rather than by chemical reagents avoids the potential problem of residual contaminants.
- both the irradiation and the sterilization steps can be performed simultaneously, simplifying manufacturing and reducing costs.
- the ability to control pore size by varying the degree of precursor gel physical crosslinking will be an advantage over other means of forming covalent vinyl polymer hydrogels.
- pore size can be tailored to facilitate the population of the hydrogel by a desired class of cells, such as chondrocytes or fibroblasts.
- the methods are applicable to the creation of materials for use in medical, biological and industrial areas including the controlled delivery of agents (which may include proteins, peptides, polysaccharides, genes, DNA, antisense to DNA, ribozymes, hormones, growth factors, a wide range of drugs, imaging agents for CAT, SPECT, x-ray, fluoroscopy, PET, MPJ and ultrasound), generation of load bearing implants for hip, spine, knee, elbow, shoulder, wrist, hand, ankle, foot and jaw, generation of a variety of other medical implants and devices (which may include active bandages, trans-epithelial drug delivery devices, sponges, anti-adhesion materials, artificial vitreous humor, contact lens, breast implants, stents and artificial cartilage that is not load bearing (i.e., ear and nose)), any application where gradients (single or multiple) in mechanical properties or structure are required.
- agents which may include proteins, peptides, polysaccharides, genes, DNA, antisense to DNA, ribozymes
- Figure IA is a graphic illustration of the efficiency of a dose of gamma irradiation measured as the intermolecular crosslinking yield Gx (10 "7 IiIoI-J "1 ) as a function of PVA concentration, as reported in Wang, S., et al.
- Figure IB is a graphic illustration of the efficiency of a dose of gamma irradiation measured as the intermolecular crosslinking yield Gx (10 "7 HiOl-J "1 ) as a function of the polymer concentration in the lower concentration range of 0- 100 g dm "3 .
- Figure 2 is a graphic illustration of the gelation dose of gamma irradiation as a function of poly(vinyl pyrrolidone) concentration, as reported in Rosiak, J. M. & Ulanski, P., Synthesis of hydrogels by irradiation of polymers in aqueous solution, Radiation Physics and Chemistry 1999 55: 139-151.
- the local minimum in the range 10-40 g dm "3 indicates an ideal polymer concentration.
- the roll-off at higher concentrations is due to overlapping polymer domains which restrict movement of the chains and limit the diffusion of radicals, causing chain scission instead of crosslinking.
- the gelling dosage increases rapidly with decreasing concentration; intramolecular cross-linking dominates because the distance between molecules is too large to facilitate intermolecular crosslinking at low polymer concentrations.
- Figure 3 is a graphic illustration of the dependence of melting temperature on polymer concentration, with a family of curves for different numbers of freeze-thaw cycles for cryogels in 1 vol% DMSO at -40 0 C, where open circles represent data from gels treated with one cycle, closed circles represent data from gels treated with three cycles, open triangles represent data from gels treated with four cycles, closed triangles represent data from gels treated with eight cycles and open squares represent data from gels treated with fourteen cycles.
- Figure 4 is a graphic illustration of the dependence of the shear modulus on the log of the thawing rate for PVA hydrogels formed by a single freeze-thaw cycle of 7 g/dl solution of PVA in water, data from Yamaura, K., et al., Properties of gels obtained by freezing/thawing of poly(vinyl alcohol)/water/dimethyl sulfoxide solutions. Journal of Applied Polymer Science 1989 37:2709-2718.
- Figure 6 is a flow chart 100 of a preferred embodiment of the method of the present invention, showing the steps of providing a physically associated hydrogel 110, exposing the physically associated hydrogel to ionizing radiation to form covalent crosslinks 112 and removing physical associations 114.
- Figure 7 is a flow chart 150 of another preferred embodiment of the method of the present invention, showing the steps of providing a vinyl polymer solution 152, heating the vinylpolymer solution above the melting point of physical associations 156, inducing gelation 160, controlling the gelation rate to form crystalline physical associations 166, exposing the physically associated hydrogel to ionizing radiation to form covalent crosslinks 170 and removing physical associations 180.
- Figure 8 is a graphic illustration of the results of dynamic mechanical analysis of 10-20 weight percent aqueous PVA hydrogels (10 "5 g/mole, 93%+ hydrolyzed) cast as thin (4 mm) sheets and subjected to one freeze-thaw cycle by immersion in a NaCl/ice bath at -21 degrees Celsius for eight hours and then allowing them to thaw at room temperature for four hours in accordance with a preferred embodiment of the present invention.
- the samples were then irradiated in a hydrated state to 0, 25, or 100 kGy with an electron beam. Some of the resultant gels were then raised to 8O 0 C to melt the crystals generated by the freeze-thaw cycle.
- Dynamic mechanical analysis was conducted at 37 0 C at IHz in distilled water.
- Figure 9 is a graphic illustration of the results of dynamic mechanical analysis of 10-20 weight percent aqueous PVA hydrogels (10 "5 g/mole, 93%+ hydrolyzed) cast as thin (4 mm) sheets and subjected to four freeze-thaw cycles by immersion in a NaCl/ice bath at -21 degrees Celsius for eight hours and then allowing them to thaw at room temperature for four hours in accordance with a preferred embodiment of the present invention.
- the samples were then irradiated in a hydrated state to O 5 25, or 100 kGy with an electron beam. Some of the resultant gels were then raised to 8O 0 C to melt the crystals generated by the freeze-thaw cycle.
- Figure 10 shows an array 200 of four cylindrical PVA hydrogels 210, 220, 230 and 240 comprising 10% PVA formed by a single freeze-thaw cycle.
- Solutions of poly(vinyl alcohol) 105 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of 10%.
- the solutions were cast in thin sheets (4 mm) and subjected to one freeze-thaw cycle by immersion in a NaCl/ice bath at —21 0 C for 8 hours and then allowed to thaw at room temperature. Cylindrical disk samples were cut from the sheets.
- Figure 11 shows an array 250 of two cylindrical PVA hydrogels 260 and 270 comprising 10% PVA formed by a single freeze-thaw cycle followed by irradiation, in accordance with a preferred embodiment of the present invention.
- Ten percent aqueous solutions of poly(vinyl alcohol) (10 5 g/mole; 93%+ hydrolyzed) were prepared. The solutions were cast in thin sheets (4 mm) and subjected to one freeze- thaw cycle by immersion in a NaCl/ice bath at -21 0 C for 8 hours and then allowed to thaw at room temperature. Cylindrical disk samples were cut from the sheets. The samples were then irradiated in a hydrated state to 100 kGy by an electron beam.
- Irradiated hydrogels of the present invention can show a "memory" of their original form, returning to the original form when released from constraint.
- Figure 12 shows a coil 300 formed of a PVA hydrogel 310 comprising 10% PVA showing retention of the coiled form after the melting-out of physical associations.
- Solutions of poly(vinyl alcohol) (10 5 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of 10 wt.%. The solutions were poured into flexible tubing with interior diameters of 0.25".
- each piece of tubing was sealed, the tubes were coiled into a spiral, and the spirals were subjected to one freeze-thaw cycle by immersing in an NaCl/ice bath at -21 0 C for 8 hours and then allowing them to thaw at room temperature for four hours.
- the samples were then irradiated in a hydrated state to 100 IcGy with an electron beam.
- Some of the resultant coiled gels were then raised to 8O 0 C to melt the fireeze-thaw generated associations.
- the coiled gels could be stretched into a straight rod, but resumed their coiled state upon release of the applied tension.
- Suitably sized coils can be inserted through a cannula or lumen of an equivalent delivery device into an enclosed space and then resume their preformed shape following expulsion into the enclosed space from the delivery device, hi one embodiment, a coiled gel of the present invention can be inserted into the center of an intervertebral body to replace a nucleus pulposus.
- preformed hydrogel coils can be used to fill voids in reconstructive surgery, hi other embodiments, preformed hydrogel coils can be used as wound dressings.
- the space- filling chacteristics of such hydrogel coils can be advantageously combined with the use of the hydrogel material of the present invention as a depot of a releasable active agent.
- Figure 13 shows an array 400 of packaged PVA disks about to undergo electron beam irradiation where disks 410, 420 received no shielding, disks 430, 440 received gradient shielding and disks 450, 460 received stepped shielding.
- Figures 14A and 14B are an illustration 500 showing the effects of irradiation using a continuous gradient mask.
- Figure 14A shows a continuous gradient PVA hydrogel 510 formed by a single freeze-thaw cycle and then irradiated in a hydrated state to 100 kGy with an electron beam prior to melt-out.
- the arrow 520 points in the direction of increasing covalent crosslinks (higher received dose).
- Figure 14B shows the same continuous gradient PVA hydrogel 510 shown in Figure 14A following melt-out having the arrow 520 pointing in the direction of increasing covalent crosslinks (higher received dose), where the boxes 530, 540 indicate the locations where the swelling ratio was assessed. Note the increase in transparency following melt-out of physical associations.
- Figures 15A and 15B are an illustration 600 showing the effects of irradiation using a stepped gradient mask.
- Figure 15A shows a stepped gradient PVA hydrogel 610 formed by a single freeze-thaw cycle and then irradiated in a hydrated state to 100 kGy with an electron beam prior to melt-out.
- the circle 620 indicates the position during irradiation of the mask (an aluminum disk).
- Figure 15B shows the same stepped gradient PVA hydrogel 610 shown in Figure 15A following melt-out, where the boxes 630, 640 indicate the locations where the swelling ratio was assessed.
- Figure 16 shows an array 700 of PVA hydrogels prior to irradiation and melt- out, where sample 710 is a 10% PVA hydrogel formed by a single freeze-thaw cycle, sample 720 is a 20% PVA hydrogel formed by a single freeze-thaw cycle, sample 730 is a 10% PVA hydrogel formed by four freeze-thaw cycles, sample 740 is a 20% PVA hydrogel formed by four freeze-thaw cycles, and a U.S. penny 750 is provided for scale.
- Figure 17 shows an array 800 of PVA hydrogels after irradiation and melt-out (immersion in deionized water at 8O 0 C), where sample 810 is a 10% PVA hydrogel formed by a single freeze-thaw cycle and irradiated to 25 kGy, sample 820 is a 20% PVA hydrogel formed by a single freeze-thaw cycle and irradiated to 25 kGy, sample 830 is a 10% PVA hydrogel formed by a single freeze-thaw cycle and irradiated to 100 kGy, sample 840 is a 20% PVA hydrogel formed by a single freeze-thaw cycle and irradiated to 100 kGy, sample 850 is a 10% PVA hydrogel formed by four freeze- thaw cycles and irradiated to 25 kGy, sample 860 is a 20% PVA hydrogel formed by four freeze-thaw cycles and irradiated to 25 kGy, sample 870 is a 10% P
- Covalently cross-linked poly(vinyl alcohol) (PVA) gels can be produced by making a physically associated PVA hydrogel that has a crystalline phase, forming covalent crosslinks by exposing the physically associated PVA hydrogel to an effective amount of ionizing radiation, and removing the physical associations by exposure to a temperature above the melting point of the physically associated crystalline phase to produce a covalently cross-linked vinyl polymer hydrogel.
- the physical properties of the produced hydrogel can be adjusted by varying controlled parameters such as the proportion of physical associations, the concentration of polymer and the amount of radiation applied.
- PVA covalently cross-linked vinyl polymer hydrogels can be made translucent, preferably transparent, or opaque depending on the processing conditions.
- the stability of the physical properties of the produced hydrogel can be enhanced by controlling the amount of covalent crosslinks.
- the formation of physical associations and crystalline structure in PVA is known in the art to be accomplished effectively by freeze-thaw cycling or changing the solvency of the water enclosed in the PVA by adding a material that draws water from the PVA. It is believed that the crystalline regions are formed by forcing the PVA chains into close proximity, thereby allowing the chains to form physical associations. These physical associations form the network of the PVA hydrogel and hold it together.
- three models have been proposed to explain formation of physical associations that are formed during the freeze-thaw cycle: 1) direct hydrogen bonding; 2) direct crystallite formation; and 3) liquid-liquid phase separation followed by a gelation mechanism.
- the first is to cool a PVA solution down to -1O 0 C, which causes the water to separate from the PVA and causes the PVA to crystallize. Upon warming to room temperature, a gel has formed. This process forms a gel termed a 'cryogel', with reference to the cooling step.
- a second technique is to change the solvency of the water in the PVA by adding a material that draws the water from the PVA, again forming crystalline junctions but at temperatures greater than 0° C.
- These gels are termed 'thetagels', referring to forming the gel by contacting a PVA solution into a solvent which has a Flory interaction parameter, ⁇ , that is higher than the theta point for the PVA solvent pair, and subsequently immersing the contained PVA in another solvent having a Flory interaction parameter lower than the theta point for the PVA solvent pair.
- Techniques useful for producing thetagels are disclosed in U.S. published patent application US20040092653.
- Polymers in solution are complex molecules in perpetual dynamic motion.
- the configuration of an ideal polymer chain is usually described as a "random walk", where the molecule is assumed for simplicity to be freely jointed and free to move where it will. This behavior results in the polymer assuming a spherical shape with a Gaussian distribution.
- the chain has a number of forces acting on it to define its shape and behavior.
- free solution the chain is subject to random motion from Brownian fluctuations arising out of the temperature of the system. At the same time there is a force arising out of how the chain interacts with itself (since it is a long, extended molecule) and its surroundings.
- the polymer is easily solvated by the solution (i.e., it is in a first solvent not having a ⁇ value sufficient for gelation) it swells as it tries to maximize the amount of polymer chain that is exposed to the solvent.
- the energy of interaction between a polymer element and a solvent molecule adjacent to it exceeds the mean of the energies of interaction between the polymer-polymer and solvent- solvent pairs as described by Flory, PJ. in, Principles of Polymer Chemistry, page 424, Cornell University Press, 1953.
- the chain is now in a perturbed state and resists contact with neighboring chains and equally resists mechanical compression and deformation. As the solvency changes, this swollen configuration collapses as the quality of the solvent falls.
- the solvent quality is such that the random Brownian motions are enough to keep the chain in an ideal, Gaussian distribution.
- the chain segments prefer to be next to each rather than to a solvent molecule, and the chain shrinks (i.e. a second solvent having a ⁇ value sufficient for gelation).
- the Flory interaction parameter, ⁇ is dimensionless, and depends on temperature, pressure, etc.
- Li a lattice model this is the case where the free energy comes entirely from the entropy associated with various chain patterns on the lattice.
- temperature has no effect on structure, and the solvent is said to be "athermal.”
- Athermal solvents are a particularly simple example of good solvents.
- the parameter ⁇ is positive as described by de Gennes, P. G. in, Scaling Concepts in Polymer Physics, First ed. p. 72: Cornell University Press (1979). If the solvent quality is poor enough, the chain will completely precipitate out of solution. This effect can also be obtained by manipulation of the temperature of the solution.
- the PVA hydrogel is formed by the freeze-thaw technique or the solvent manipulation approach, in both cases if the formed hydrogel, lacking any additional covalent bond formation from irradiation, is raised above the melting point of the physical associations (around 80° C), the hydrogel returns into solution and does not reform, even when cooled to room temperature.
- This characteristic is described in the PVA literature as 'thermoreversible", since the PVA gel can be easily reverted back to a PVA solution by heating alone.
- the physical associations of the crystalline regions must be re-established using one of the two techniques, e.g., the freeze-thaw technique, discussed above.
- the PVA hydrogels of the present invention can be made to have a wide range of mechanical properties, such as very low to moderately high compressive moduli.
- Critical to the final modulus is the number of physical associations present in the precursor gels. A large number of physical associations serve to reduce the total yield of the radiation induced crosslinks, reducing the final modulus of the material.
- precursor gels having relatively weak physical associations produce stronger covalently cross-linked vinyl polymer hydrogels. This phenomenon allows control of the final material properties by modulation of the physical associations in the precursor gel.
- the porosity and pore size in covalently cross-linked vinyl polymer hydrogels can be controlled in that the melt-out step removes physical associations, leaving voids of controllable volume. This is not possible by direct irradiation of PVA solutions. In addition, upon completion of the processing, they will be inherently sterile due to the irradiation processing.
- Polyvinyl alcohols can be manufactured from polyvinyl acetate by alcoholysis using a continuous process. Polyvinyl alcohols are commonly divided into “fully hydrolyzed” and “partly hydrolyzed” types, depending on how many mole-percent of residual acetate groups remain in the molecule. By varying the degree of polymerization of the polyvinyl acetate and its degree of hydrolysis (saponification) a number of different grades can be supplied. Typically, suitable polyvinyl alcohols for the practice of the present invention have a degree of hydrolysis (saponification) of about 80-100 percent, preferably about 95-99.8 percent.
- the degree of polymerization of suitable polyvinyl alcohols for the practice of the present invention is in the range of about 100 to about 50,000, preferably about 1,000 to about 20,000.
- Crosslinks in PVA gels may be either covalent (chemical) crosslinks or physical associations (physical). Covalent crosslinks are formed typically through chemical modification, or through irradiation.
- the formation of a thetagel includes a step of mixing the vinyl polymer solution with a gellant, wherein the resulting mixture has a higher Flory interaction parameter than the vinyl polymer solution.
- both covalent and physical associations can be employed, in that an initially physically associated precursor gel will be covalently crosslinked by irradiation.
- crosslinking is often performed by the addition of a reactive metallic salt or aldehyde and subjecting the system to thermal radiation.
- crosslinking may be performed by adding (di-) isocyanates, urea-/phenolic- /melamine-resins, epoxies, or (poly-)aldehydes.
- the use of such reagents for chemical crosslinking can leave residues that decrease the biocompatibility of the PVA hydrogel.
- Crosslink formation by irradiation of polymers in solution is a suitable method for the generation of hydrogels for biomedical use.
- Crosslinking via an ionization source provides adequate control of the reaction, a lower number of unwanted processes (e.g. homografting of monomer to the side of a polymer chain) and generates an end product suitable for use with little additional processing or purification.
- the irradiation and sterilization steps can often be combined.
- “cryogel” means a PVA gel formed by one or more cycles of cooling a PVA solution down to -10 0 C, followed by returning to a temperature below the melting point of the gel.
- “thetagel” means a hydrogel made by a process that includes a step of mixing the vinyl polymer solution with a gellant, wherein the resulting mixture has a higher Flory interaction parameter than the vinyl polymer solution.
- radiogel refers to a hydrogel in which irradiation has been used to form covalent bonds between adjacent PVA chains having physical associations, followed by a step of heating the hydrogel above the melting point of the physical associations within the crystalline phase of the hydrogel,
- gelling means the formation of a 3-dimensional macroscale network from a solution. 'Swelling' is the increase in volume produced when a formed gel is placed in a good solvent for the gel. The gel swells to a degree depending on the quality of the solvent and the degree of network formation (crosslink density).
- Figures 6 and 7 are flow charts of preferred embodiments of the method of the present invention, hi a preferred embodiment, the present invention provides a method of making a covalently cross-linked vinyl polymer hydrogel comprising the steps of providing a physically crosslinked vinyl polymer hydrogel having a crystalline phase; exposing the physically crosslinked vinyl polymer hydrogel to an amount of ionizing radiation providing a radiation dose in the range of about 1-1,000 kGy effective to form covalent crosslinks; and removing the physical associations by exposing the irradiated vinyl polymer hydrogel to a temperature above the melting point of the physically associated crystalline phase to produce a covalently cross- linked vinyl polymer hydrogel.
- the step of providing a physically associated vinyl polymer hydrogel having a crystalline phase includes the steps of providing a vinyl polymer solution comprising a vinyl polymer dissolved in a solvent; heating the vinyl polymer solution to a temperature elevated above the melting point of the physical associations of the vinyl polymer; inducing gelation of the vinyl polymer solution; and controlling the gelation rate to form physical associations in the vinyl polymer hydrogel.
- the vinyl polymer is selected from the group consisting of poly(vinyl alcohol), poly(vinyl acetate), poly(vinyl butyral), polyvinyl pyrrolidone) and a mixture thereof.
- the vinyl polymer is poly(vinyl alcohol).
- the solvent of the vinyl polymer solution is selected from the group consisting of deionized water, methanol, ethanol, dimethyl sulfoxide and a mixture thereof.
- the irradiated vinyl polymer hydrogel is immersed in a solvent is selected from the group consisting of deionized water, methanol, ethanol, dimethyl sulfoxide and a mixture thereof while is exposed to a temperature above the melting point.
- Solutions of poly(vinyl alcohol) (10 5 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of 10% to 20%.
- the solutions were cast in thin sheets (4 mm) and subject to one cycle by immersion in a NaCl/ice bath at -21 0 C for eight hours and then allowing them to thaw at room temperature for four hours.
- the samples were then irradiated in a hydrated state to 0, 25, or 100 kGy with electron beam. Some of the resultant gels were then raised to 8O 0 C to melt the freeze-thaw generated crystals.
- Dynamic mechanical analysis was conducted at 37 0 C at IHz in distilled water.
- Figure 8 is a graphic illustration of the results of dynamic mechanical analysis of 10-20 weight percent aqueous PVA hydrogels (10 's g/mole, 93%+ hydrolyzed) cast as thin (4 mm) sheets and subjected to one freeze-thaw cycle by immersion in a NaCl/ice bath at -21 degrees Celsius for eight hours and then allowing them to thaw at room temperature for four hours in accordance with a preferred embodiment of the present invention.
- the samples were then irradiated in a hydrated state to 0, 25, or 100 kGy with an electron beam. Some of the resultant gels were then raised to 8O 0 C to melt the crystals generated by the freeze-thaw cycle.
- Solutions of poly(vinyl alcohol) (10 5 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of between 10% and 20%.
- the solutions were cast in thin sheets (4 mm) and subject to four cycles of freeze-thaw by immersion in a NaCl/ice bath at -21 0 C for eight hours and then allowing them to thaw at room temperature for four hours prior to the next cycle.
- the samples were then irradiated in a hydrated state to 0, 25, or 100 kGy with electron beam. Some of the resultant gels were then raised to 80 0 C to melt the freeze-thaw generated crystals.
- Dynamic mechanical analysis was conducted at 37 0 C at IHz in distilled water.
- Figure 9 is a graphic illustration of the results of dynamic mechanical analysis of 10-20 weight percent aqueous PVA hydrogels (10 "5 g/mole, 93%+ hydrolyzed) cast as thin (4 mm) sheets and subjected to four freeze-thaw cycles by immersion in a NaCl/ice bath at -21 degrees Celsius for eight hours and then allowing them to thaw at room temperature for four hours in accordance with a preferred embodiment of the present invention.
- the samples were then irradiated in a hydrated state to 0, 25, or 100 kGy with an electron beam. Some of the resultant gels were then raised to 8O 0 C to melt the crystals generated by the freeze-thaw cycle.
- a 10% PVA gel subjected to one freeze thaw cycle and 100 kGy has a modulus of 200 kPa following melt-out ( Figure 8).
- Figure 8 The same process performed on a precursor 10% PVA gel subjected to four freeze thaw cycles yields a modulus of 90 kPa.
- the stronger the physically associations in the precursor gel the lower the yield of chemical cross ⁇ links induced by radiation.
- This result also suggests the possibility that gradient gels can be created by first generating a gradient in physical associations (e.g. by differential dehydration of PVA gels) and then subjecting the precursor gel to a uniform irradiation. The final gel will have gradient in cross-linking opposite in direction to that formed in the precursor gel.
- Example 1 Cylindrical covalently cross-linked vinyl polymer hydrogels were irradiated using a uniform irradiation distribution. Solutions of poly(vinyl alcohol) (10 5 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of 10%. The solutions were cast in thin sheets (4mm) and subjected to one freeze-thaw cycle by immersion in an NaCl/ice bath at -21 0 C for 8 hours and then allowing them to thaw at room temperature. Disks were cut from the sheets to form cylindrical disks. The samples were then irradiated in a hydrated state to 100 kGy by electron beam.
- Figures 10 and 11 show cylindrical PVA disks, generated by one freeze thaw of 10% PVA solution, prior to and following irradiation.
- Figure 10 shows an array 200 of four cylindrical PVA hydrogels 210, 220, 230 and 240 comprising 10% PVA formed by a single freeze-thaw cycle. Solutions of poly(vinyl alcohol) (105 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of 10%.
- FIG. 11 shows an array 250 of two cylindrical PVA hydrogels 260 and 270 comprising 10% PVA formed by a single freeze-thaw cycle followed by irradiation, in accordance with a preferred embodiment of the present invention.
- Solutions of polyvinyl alcohol) (10 5 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of 10%.
- the solutions were cast in thin sheets (4mm) and subjected to one freeze-thaw cycle by immersion in an NaCl/ice bath at -21 0 C for 8 hours and then allowing them to thaw at room temperature. Disks were cut from the sheets to form cylindrical disks. The samples were then irradiated in a hydrated state to 100 kGy by an electron beam. Table 1 gives the gravimetric swell ratio for the gel prior to and following the radiation melt-out procedure. All swelling measurements were performed in distilled water at 23 0 C. The swelling is dependent on the solvent, the temperature and the crosslink density of the hydrogel. Similar gravimetric swelling ratios obtained at the same temperature with the same solvent indicate that a comparable crosslink density remains after irradiation, even though the physical associations have been removed by the melting-out step.
- the samples were then irradiated in a hydrated state to a radiation dose of 100 kGy using an electron beam. Some of the resultant coiled gels were then raised to 8O 0 C to melt the physical associations produced by the freeze-thaw treatment.
- Figure 12 shows a coil 300 formed of a PVA hydrogel 310 comprising 10% PVA showing retention of the coiled form after the melting-out of physical associations.
- Solutions of poly(vinyl alcohol) (10 5 g/mole; 93%+ hydrolyzed) were prepared in water to concentrations of 10 wt.%. The solutions were poured into flexible tubing with interior diameters of 0.25". The ends of each piece of tubing were sealed, the tubes were coiled into a spiral, and the spirals were subjected to one freeze-thaw cycle by immersing in an NaCl/ice bath at -21 °C for 8 hours and then allowing them to thaw at room temperature for four hours.
- the samples were then irradiated in a hydrated state to 100 kGy with an electron beam. Some of the resultant coiled gels were then raised to 8O 0 C to melt the freeze-thaw generated associations.
- the coiled gels could be stretched into a straight rod, but resumed their coiled state upon release of the applied tension.
- Suitably size coils can be inserted through a cannula or lumen into the intervertebral space to replace a nucleus pulposus.
- Figure 13 shows three sets of PVA disks with various types of shielding to induce spatial gradients in covalent crosslinking.
- Figure 13 shows an array 400 of packaged PVA disks about to undergo electron beam irradiation where disks 410, 420 received no shielding, disks 430, 440 received gradient shielding and disks 450, 460 received stepped shielding.
- Figure 14A shows a continuous gradient PVA hydrogel 510 formed by a single freeze-thaw cycle and then irradiated in a hydrated state to 100 kGy with an electron beam prior to melt-out.
- Figure 14B shows the same continuous gradient PVA hydrogel 510 shown in Figure 14A following melt-out having the arrow 520 pointing in the direction of increasing covalent crosslinks (higher received dose), where the boxes 530, 540 indicate the locations where the swelling ratio was assessed. Note the increase in transparency following melt-out of physical associations. Table 2. Swell Ratio of Continuous Gradient Covalently Cross-linked Vinyl Polymer Hydrogels
- a physically associated PVA hydrogel was irradiated while masked by a centrally placed aluminum disk to produce a step change in radiation dose between masked and exposed regions of the hydrogel.
- Shielding can be utilized to crosslink PVA disks with a stepped difference in radiation crosslinks.
- the shielding is made from a material with a uniform density and thickness.
- different locations of the shield can have different thickness or different density and shaped to determine the area and degree of reduced radiation effectiveness.
- the material will block radiation (e-beam or gamma) in proportion to the thickness of the shielding piece.
- the gel can be held at high temperature to melt-out the physical associations producing a PVA hydrogel having a gradient of covalent crosslinks.
- Figure 15A shows a stepped gradient PVA hydrogel 610 formed by a single freeze-thaw cycle and then irradiated in a hydrated state to 100 kGy with an electron beam prior to melt-out.
- the circle 620 indicates the position during irradiation of the mask (an aluminum disk).
- Figure 15B shows the same stepped gradient PVA hydrogel 610 shown in Figure 15A following melt-out, where the boxes 630, 640 indicate the locations where the swelling ratio was assessed.
- Table 3 Swell Ratios of Stepped Gradient Covalently Cross-linked Vinyl Polymer Hydrogels
- This example demonstrates the ability to create sharp changes in the material properties of the covalently cross-linked vinyl polymer hydrogels by shielding with discrete, uniform materials.
- the unshielded region swells half as much as the shielded region indicating a sharp increase in the number of covalent cross-links.
- PVA covalently cross-linked vinyl polymer hydrogels suitable for use as material for contact lenses were made. Ih general, freeze -thaw cryogels produced in aqueous solutions do not produce clear gels ( Figure 16). In addition, PVA gels are known to be poorly permeable (permeability is a general requirement of any contact lens material).
- Figure 16 shows an array 700 of PVA hydrogels prior to irradiation and melt-out, where sample 710 is a 10% PVA hydrogel formed by a single freeze- thaw cycle, sample 720 is a 20% PVA hydrogel formed by a single freeze-thaw cycle, sample 730 is a 10% PVA hydrogel formed by four freeze-thaw cycles, sample 740 is a 20% PVA hydrogel formed by four freeze-thaw cycles, and a U.S. penny 750 is provided for scale.
- cryogels are irradiated and the physical associations are melted out, some of them become very transparent ( Figure 17). Also, because the bulky freeze-thaw crystals have been removed, their permeability should be greatly enhanced as well. Such materials might be useful for contact lenses. Since several gels made by differing processing steps were transparent, it is likely that a lens with a range of porosities can be made.
- Figure 17 shows an array 800 of PVA hydrogels after irradiation and melt-out (immersion in deionized water at 8O 0 C), where sample 810 is a 10% PVA hydrogel formed by a single freeze-thaw cycle and irradiated to 25 kGy, sample 820 is a 20% PVA hydrogel formed by a single freeze-thaw cycle and irradiated to 25 kGy, sample 830 is a 10% PVA hydrogel formed by a single freeze- thaw cycle and irradiated to 100 kGy, sample 840 is a 20% PVA hydrogel formed by a single freeze-thaw cycle and irradiated to 100 kGy, sample 850 is a 10% PVA hydrogel formed by four freeze-thaw cycles and irradiated to 25 kGy, sample 860 is a 20% PVA hydrogel formed by four freeze-thaw cycles and irradiated to 25 kGy, sample 840 is a 10% P
- gradient PVA covalently cross-linked vinyl polymer hydrogels can be made by first freeze-thawing a cylinder containing PVA solution once, or a number of times.
- the resulting PVA cryogel cylinders can be dehydrated in a variety of different ways (placed in warm silicone oil, dried in a vacuum, dried in air at a controlled relative humidity) such that the dehydration of the cryogel penetrates partially into the cylinder causing a radial gradient in physical associations.
- the resulting material can then be sectioned perpendicular to its axis to make discs and irradiated before or after subsequent rehydration.
- the resulting material should be soft on the outside and stiff in the middle.
- a nucleus implant created in this manner will space-fill the inner disc and carry loads while transmitting a controlled amount of that load to the annulus.
- the depth of modulus change can be controlled by the length of exposure to dehydration.
- the depth and the ultimate modulus of the outer part of the gel can be controlled via exposure time and humidity.
- PVA hydrogels can be useful for drug delivery applications.
- a desirable characteristic of drug delivery materials is the ability to control the drug release rate, often by controlling the pore size in the material. Typically a zero-order drug release rate is desired to eliminate burst effects.
- the typical approach is to create a material that restricts diffusion only at the surface interfacing the tissue to be treated.
- the present invention can provide the ability to modulate not only pore size but gradients in pore size.
- Aqueous solutions of PVA are made as described above and cast into thin films.
- the cast gels are then be freeze-thaw cycled from one to any number of times to produce varying densities of physical associations, depending on the number of cycles.
- the cryogels are kept in the casts and then irradiated with 1-1000 kGy.
- the gels are then immersed in DI at 80 0 C to remove the physical associations.
- pores increase in size with the number of freezing-thawing cycles. It is thought that the polyvinyl polymer is rejected from the ice crystals as an impurity and is progressively "volume excluded" into increasingly polyvinyl polymer rich areas. As might be expected, the pore size increases with decreasing concentration of polyvinyl polymer.
- Gradients in pore size are produced as follows. Aqueous solutions of PVA are made as described above and poured into thin film casts. The casts are freeze-thaw cycled 1 to 8 times to produce physical associations. The thawed cryogels are kept in the casts and then partially dehydrated (by any means). They can then be irradiated in a gradient pattern at 1 to 1000 KGy. The gels are then immersed in DI at 8O 0 C to remove the physical associations. Regions that are shielded from irradiation will have low to no junction points once the material is raised above its melting point, and will therefore have a pore left behind in these regions. Depending on the size of the gradient pattern, nanometer to millimeter sized holes can be made.
- the present invention further relates to
- a method of making a covalently cross-linked vinyl polymer hydrogel comprising the steps of: providing a physically associated vinyl polymer hydrogel having a crystalline phase; exposing the physically associated vinyl polymer hydrogel to an amount of ionizing radiation providing a radiation dose in the range of about 1-1,000 kGy effective to form covalent crosslinks; and removing physical associations by exposing the irradiated vinyl polymer hydrogel to a temperature above the melting point of the physically associated crystalline phase to produce a covalently cross-linked vinyl polymer hydrogel.
- step of providing a physically associated vinyl polymer hydrogel having a crystalline phase includes the steps of providing a vinyl polymer solution comprising a vinyl polymer dissolved in a solvent; heating the vinyl polymer solution to a temperature elevated above the melting point of the physical associations of the vinyl polymer; inducing gelation of the vinyl polymer solution; and controlling the gelation rate to form physical associations in the vinyl polymer hydrogel.
- vinyl polymer is selected from the group consisting of poly(vinyl alcohol), poly(vinyl acetate), poly(vinyl butyral), poly(vinyl pyrrolidone) and a mixture thereof.
- the method of item 1 wherein the irradiated vinyl polymer hydrogel is immersed in a solvent is selected from the group consisting of deionized water, methanol, ethanol, dimethyl sulfoxide and a mixture thereof while is exposed to a temperature above the melting point.
- the method of item 2 further comprising the step of mixing the vinyl polymer solution with a gellant, wherein the resulting mixture has a higher Flory interaction parameter than the vinyl polymer solution.
- the method of item 2 further comprising the step of dehydrating the vinyl polymer hydrogel.
- a covalently crosslinked vinyl polymer hydrogel produced by the method of item 1.
- a method of making a covalently cross-linked vinyl polymer hydrogel comprising the steps of: providing a vinyl polymer solution comprising a vinyl polymer dissolved in a solvent; heating the vinyl polymer solution to a temperature elevated above the melting point of the physical associations of the vinyl polymer; inducing gelation of the vinyl polymer solution; controlling the gelation rate to form crystalline physical associations in the vinyl polymer hydrogel; exposing the physically associated vinyl polymer hydrogel to a dose of ionizing radiation of about 1-1,000 kGy effective to produce covalent crosslinks; and melting the vinyl polymer hydrogel in a solvent to remove physical associations, thereby making a covalently cross-linked vinyl polymer hydrogel.
- the article of manufacture of item 37 selected from a device for delivery of active agents, a load bearing orthopedic implant, a bandage, a trans-epithelial drug delivery device, a sponge, an anti-adhesion material, an artificial vitreous humor, a contact lens, a breast implant, a stent and non-load-bearing artificial cartilage.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2005293727A AU2005293727B2 (en) | 2004-10-12 | 2005-10-11 | PVA hydrogel |
JP2007535118A JP5237639B2 (en) | 2004-10-12 | 2005-10-11 | PVA hydrogel |
CA2582779A CA2582779C (en) | 2004-10-12 | 2005-10-11 | Pva hydrogel |
EP05806343A EP1812499B1 (en) | 2004-10-12 | 2005-10-11 | Method of preparation of radiation crosslinked polyvinyl hydrogels and its use |
US12/170,303 US7985781B2 (en) | 2004-10-12 | 2008-07-09 | PVA hydrogel |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/962,975 | 2004-10-12 | ||
US10/962,975 US7235592B2 (en) | 2004-10-12 | 2004-10-12 | PVA hydrogel |
EP05001009A EP1647569A1 (en) | 2004-10-12 | 2005-01-19 | PVA hydrogel |
EP05001009.9 | 2005-01-19 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11577585 A-371-Of-International | 2005-10-11 | ||
US12/170,303 Continuation US7985781B2 (en) | 2004-10-12 | 2008-07-09 | PVA hydrogel |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2006040128A1 true WO2006040128A1 (en) | 2006-04-20 |
WO2006040128B1 WO2006040128B1 (en) | 2006-06-01 |
Family
ID=34933366
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2005/010931 WO2006040128A1 (en) | 2004-10-12 | 2005-10-11 | Pva hydrogel |
Country Status (7)
Country | Link |
---|---|
US (2) | US7235592B2 (en) |
EP (2) | EP1647569A1 (en) |
JP (1) | JP5237639B2 (en) |
CN (1) | CN101111542A (en) |
AU (1) | AU2005293727B2 (en) |
CA (1) | CA2582779C (en) |
WO (1) | WO2006040128A1 (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1951965B (en) * | 1996-08-30 | 2011-07-20 | 诺沃挪第克公司 | Glp-1 derivatives |
US9446107B2 (en) | 2005-12-13 | 2016-09-20 | President And Fellows Of Harvard College | Scaffolds for cell transplantation |
US9486512B2 (en) | 2011-06-03 | 2016-11-08 | President And Fellows Of Harvard College | In situ antigen-generating cancer vaccine |
US9675561B2 (en) | 2011-04-28 | 2017-06-13 | President And Fellows Of Harvard College | Injectable cryogel vaccine devices and methods of use thereof |
US9821045B2 (en) | 2008-02-13 | 2017-11-21 | President And Fellows Of Harvard College | Controlled delivery of TLR3 agonists in structural polymeric devices |
US10045947B2 (en) | 2011-04-28 | 2018-08-14 | President And Fellows Of Harvard College | Injectable preformed macroscopic 3-dimensional scaffolds for minimally invasive administration |
US10682400B2 (en) | 2014-04-30 | 2020-06-16 | President And Fellows Of Harvard College | Combination vaccine devices and methods of killing cancer cells |
US11150242B2 (en) | 2015-04-10 | 2021-10-19 | President And Fellows Of Harvard College | Immune cell trapping devices and methods for making and using the same |
US11202759B2 (en) | 2010-10-06 | 2021-12-21 | President And Fellows Of Harvard College | Injectable, pore-forming hydrogels for materials-based cell therapies |
US11278604B2 (en) | 2012-04-16 | 2022-03-22 | President And Fellows Of Harvard College | Mesoporous silica compositions comprising inflammatory cytokines comprising inflammatory cytokines for modulating immune responses |
US11555177B2 (en) | 2016-07-13 | 2023-01-17 | President And Fellows Of Harvard College | Antigen-presenting cell-mimetic scaffolds and methods for making and using the same |
US11752238B2 (en) | 2016-02-06 | 2023-09-12 | President And Fellows Of Harvard College | Recapitulating the hematopoietic niche to reconstitute immunity |
US11786457B2 (en) | 2015-01-30 | 2023-10-17 | President And Fellows Of Harvard College | Peritumoral and intratumoral materials for cancer therapy |
Families Citing this family (145)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6050943A (en) | 1997-10-14 | 2000-04-18 | Guided Therapy Systems, Inc. | Imaging, therapy, and temperature monitoring ultrasonic system |
US7914453B2 (en) | 2000-12-28 | 2011-03-29 | Ardent Sound, Inc. | Visual imaging system for ultrasonic probe |
US7745532B2 (en) * | 2002-08-02 | 2010-06-29 | Cambridge Polymer Group, Inc. | Systems and methods for controlling and forming polymer gels |
US8002830B2 (en) | 2004-02-06 | 2011-08-23 | Georgia Tech Research Corporation | Surface directed cellular attachment |
US7910124B2 (en) | 2004-02-06 | 2011-03-22 | Georgia Tech Research Corporation | Load bearing biocompatible device |
US8235909B2 (en) | 2004-05-12 | 2012-08-07 | Guided Therapy Systems, L.L.C. | Method and system for controlled scanning, imaging and/or therapy |
US7393325B2 (en) | 2004-09-16 | 2008-07-01 | Guided Therapy Systems, L.L.C. | Method and system for ultrasound treatment with a multi-directional transducer |
US9011336B2 (en) | 2004-09-16 | 2015-04-21 | Guided Therapy Systems, Llc | Method and system for combined energy therapy profile |
US7824348B2 (en) | 2004-09-16 | 2010-11-02 | Guided Therapy Systems, L.L.C. | System and method for variable depth ultrasound treatment |
US10864385B2 (en) | 2004-09-24 | 2020-12-15 | Guided Therapy Systems, Llc | Rejuvenating skin by heating tissue for cosmetic treatment of the face and body |
US8535228B2 (en) | 2004-10-06 | 2013-09-17 | Guided Therapy Systems, Llc | Method and system for noninvasive face lifts and deep tissue tightening |
US8444562B2 (en) | 2004-10-06 | 2013-05-21 | Guided Therapy Systems, Llc | System and method for treating muscle, tendon, ligament and cartilage tissue |
US20090088846A1 (en) | 2007-04-17 | 2009-04-02 | David Myung | Hydrogel arthroplasty device |
US9827449B2 (en) | 2004-10-06 | 2017-11-28 | Guided Therapy Systems, L.L.C. | Systems for treating skin laxity |
ES2643864T3 (en) | 2004-10-06 | 2017-11-24 | Guided Therapy Systems, L.L.C. | Procedure and system for the treatment of tissues by ultrasound |
US20060111744A1 (en) | 2004-10-13 | 2006-05-25 | Guided Therapy Systems, L.L.C. | Method and system for treatment of sweat glands |
US11883688B2 (en) | 2004-10-06 | 2024-01-30 | Guided Therapy Systems, Llc | Energy based fat reduction |
WO2006042163A2 (en) | 2004-10-06 | 2006-04-20 | Guided Therapy Systems, L.L.C. | Method and system for cosmetic enhancement |
US8690779B2 (en) | 2004-10-06 | 2014-04-08 | Guided Therapy Systems, Llc | Noninvasive aesthetic treatment for tightening tissue |
US8133180B2 (en) | 2004-10-06 | 2012-03-13 | Guided Therapy Systems, L.L.C. | Method and system for treating cellulite |
US7758524B2 (en) | 2004-10-06 | 2010-07-20 | Guided Therapy Systems, L.L.C. | Method and system for ultra-high frequency ultrasound treatment |
US11235179B2 (en) | 2004-10-06 | 2022-02-01 | Guided Therapy Systems, Llc | Energy based skin gland treatment |
US9694212B2 (en) | 2004-10-06 | 2017-07-04 | Guided Therapy Systems, Llc | Method and system for ultrasound treatment of skin |
US11724133B2 (en) | 2004-10-07 | 2023-08-15 | Guided Therapy Systems, Llc | Ultrasound probe for treatment of skin |
US11207548B2 (en) | 2004-10-07 | 2021-12-28 | Guided Therapy Systems, L.L.C. | Ultrasound probe for treating skin laxity |
US7235592B2 (en) * | 2004-10-12 | 2007-06-26 | Zimmer Gmbh | PVA hydrogel |
JP4746883B2 (en) * | 2005-01-28 | 2011-08-10 | リンテック株式会社 | Hydrogel base, poultice base, poultice and aqueous gel sheet |
US8017139B2 (en) | 2005-02-23 | 2011-09-13 | Zimmer Technology, Inc. | Blend hydrogels and methods of making |
EP1875327A2 (en) | 2005-04-25 | 2008-01-09 | Guided Therapy Systems, L.L.C. | Method and system for enhancing computer peripheral saftey |
EP2277561B1 (en) * | 2005-08-18 | 2012-09-19 | Zimmer GmbH | Ultra high molecular weight polyethylene articles and methods of forming ultra high molecular weight polyethylene articles |
US20070098799A1 (en) * | 2005-10-28 | 2007-05-03 | Zimmer, Inc. | Mineralized Hydrogels and Methods of Making and Using Hydrogels |
AU2006321809A1 (en) * | 2005-12-07 | 2007-06-14 | Zimmer, Inc. | Methods of bonding or modifying hydrogels using irradiation |
US9361568B2 (en) | 2005-12-09 | 2016-06-07 | Tego, Inc. | Radio frequency identification tag with hardened memory system |
US8947233B2 (en) | 2005-12-09 | 2015-02-03 | Tego Inc. | Methods and systems of a multiple radio frequency network node RFID tag |
US9430732B2 (en) | 2014-05-08 | 2016-08-30 | Tego, Inc. | Three-dimension RFID tag with opening through structure |
US9418263B2 (en) | 2005-12-09 | 2016-08-16 | Tego, Inc. | Operating systems for an RFID tag |
US8988223B2 (en) | 2005-12-09 | 2015-03-24 | Tego Inc. | RFID drive management facility |
US9542577B2 (en) | 2005-12-09 | 2017-01-10 | Tego, Inc. | Information RFID tagging facilities |
US9117128B2 (en) | 2005-12-09 | 2015-08-25 | Tego, Inc. | External access to memory on an RFID tag |
US20070141108A1 (en) * | 2005-12-20 | 2007-06-21 | Zimmer, Inc. | Fiber-reinforced water-swellable articles |
JP2007177244A (en) * | 2005-12-22 | 2007-07-12 | Zimmer Inc | Perfluorocyclobutane crosslinked hydrogel |
EP1962919A1 (en) * | 2005-12-23 | 2008-09-03 | Zimmer GmbH | Coated textiles |
US8110242B2 (en) * | 2006-03-24 | 2012-02-07 | Zimmer, Inc. | Methods of preparing hydrogel coatings |
US9566454B2 (en) | 2006-09-18 | 2017-02-14 | Guided Therapy Systems, Llc | Method and sysem for non-ablative acne treatment and prevention |
GB0619322D0 (en) * | 2006-09-30 | 2006-11-08 | Greater Glasgow Nhs Board | Apparatus for coupling an ultrasound probe to an object |
US20080220062A1 (en) * | 2006-10-23 | 2008-09-11 | Psivida, Inc. | Sustained release of agents for localized pain management |
ITNO20060012A1 (en) * | 2006-11-03 | 2008-05-04 | Consige Sas Di Merlini Silvia & C | PROCEDURE FOR THE PREPARATION OF HYDROGEL WITH ALCOHOLS |
US20080145658A1 (en) * | 2006-12-15 | 2008-06-19 | Boston Scientific Scimed, Inc. | Freeze Thaw Methods For Making Polymer Particles |
US20100190920A1 (en) * | 2007-02-14 | 2010-07-29 | Anuj Bellare | Crosslinked polymers and methods of making the same |
US8664290B2 (en) | 2007-04-10 | 2014-03-04 | Zimmer, Inc. | Antioxidant stabilized crosslinked ultra-high molecular weight polyethylene for medical device applications |
EP2578248B1 (en) | 2007-04-10 | 2021-05-19 | Zimmer, Inc. | An antioxidant stabilized crosslinked ultra-high molecular weight polyethylene for medical device applications |
WO2008131410A1 (en) * | 2007-04-23 | 2008-10-30 | The General Hospital Corporation Dba | Pva hydrogels having improved creep resistance, lubricity, and toughness |
EP2166991A4 (en) * | 2007-04-24 | 2013-12-18 | Gen Hospital Corp | Pva-paa hydrogels |
WO2008137942A1 (en) | 2007-05-07 | 2008-11-13 | Guided Therapy Systems, Llc. | Methods and systems for modulating medicants using acoustic energy |
US20150174388A1 (en) | 2007-05-07 | 2015-06-25 | Guided Therapy Systems, Llc | Methods and Systems for Ultrasound Assisted Delivery of a Medicant to Tissue |
US8764687B2 (en) | 2007-05-07 | 2014-07-01 | Guided Therapy Systems, Llc | Methods and systems for coupling and focusing acoustic energy using a coupler member |
US8480651B2 (en) * | 2007-08-02 | 2013-07-09 | Covidien Lp | Cannula system |
US7731988B2 (en) | 2007-08-03 | 2010-06-08 | Zimmer, Inc. | Multi-polymer hydrogels |
US20090043398A1 (en) * | 2007-08-09 | 2009-02-12 | Zimmer, Inc. | Method of producing gradient articles by centrifugation molding or casting |
US8062739B2 (en) * | 2007-08-31 | 2011-11-22 | Zimmer, Inc. | Hydrogels with gradient |
EP2193018A4 (en) * | 2007-09-05 | 2011-01-26 | Gen Hospital Corp | Creep resistant, highly lubricious, tough, and ionic hydrogels including pva-paamps hydrogels |
US7947784B2 (en) * | 2007-11-16 | 2011-05-24 | Zimmer, Inc. | Reactive compounding of hydrogels |
US20090130160A1 (en) * | 2007-11-21 | 2009-05-21 | Fiber Innovation Technology, Inc. | Fiber for wound dressing |
KR100918645B1 (en) | 2007-12-14 | 2009-09-25 | 포항공과대학교 산학협력단 | Method for remotely controlling a sol-gel transition of hydrogel and method for delivering a drug using the same |
US20090171264A1 (en) * | 2007-12-21 | 2009-07-02 | Depuy Products | Medical Devices Based On Poly(Vinyl Alcohol) |
US20090169641A1 (en) * | 2007-12-26 | 2009-07-02 | Boston Scientifice Scimed, Inc. | Compressible particles |
US8034362B2 (en) * | 2008-01-04 | 2011-10-11 | Zimmer, Inc. | Chemical composition of hydrogels for use as articulating surfaces |
CA2712559C (en) | 2008-01-30 | 2015-03-31 | Zimmer, Inc. | Orthopedic component of low stiffness |
AU2008351582A1 (en) * | 2008-02-27 | 2009-09-03 | Athlone Institute Of Technology | Composite gel-based materials |
US20110111033A1 (en) * | 2008-04-09 | 2011-05-12 | Harald Stover | Hydrogel with covalently crosslinked core |
CN104545998B (en) | 2008-06-06 | 2020-07-14 | 奥赛拉公司 | System and method for cosmetic treatment and imaging |
EP2299894B1 (en) | 2008-06-18 | 2020-09-02 | Sarcos LC | Transparent endoscope head defining a focal length |
US8883915B2 (en) | 2008-07-07 | 2014-11-11 | Biomimedica, Inc. | Hydrophobic and hydrophilic interpenetrating polymer networks derived from hydrophobic polymers and methods of preparing the same |
US20120209396A1 (en) | 2008-07-07 | 2012-08-16 | David Myung | Orthopedic implants having gradient polymer alloys |
US8172902B2 (en) * | 2008-07-17 | 2012-05-08 | Spinemedica, Llc | Spinal interbody spacers |
GB0813659D0 (en) | 2008-07-25 | 2008-09-03 | Smith & Nephew | Fracture putty |
US8486735B2 (en) | 2008-07-30 | 2013-07-16 | Raytheon Company | Method and device for incremental wavelength variation to analyze tissue |
EP2323670A4 (en) | 2008-08-05 | 2013-12-25 | Biomimedica Inc | Polyurethane-grafted hydrogels |
US9060704B2 (en) | 2008-11-04 | 2015-06-23 | Sarcos Lc | Method and device for wavelength shifted imaging |
CN102307945B (en) * | 2008-11-20 | 2015-07-01 | 捷迈有限责任公司 | Polyethylene materials |
US8637063B2 (en) | 2008-12-05 | 2014-01-28 | Cambridge Polymer Group, Inc. | Hydrolyzed hydrogels |
WO2010067378A2 (en) | 2008-12-08 | 2010-06-17 | Reliance Life Sciences Pvt. Ltd. | Hydrogel composition |
JP2012513837A (en) | 2008-12-24 | 2012-06-21 | ガイデッド セラピー システムズ, エルエルシー | Method and system for fat loss and / or cellulite treatment |
WO2010077234A1 (en) | 2008-12-29 | 2010-07-08 | Synthes (U.S.A.) | A method of forming and the resulting membrane composition for surgical site preservation |
US8470231B1 (en) | 2009-06-01 | 2013-06-25 | Stratasys Ltd. | Three-dimensional printing process for producing a self-destructible temporary structure |
WO2011041720A2 (en) | 2009-10-01 | 2011-04-07 | Jacobsen Stephen C | Method and apparatus for manipulating movement of a micro-catheter |
US8717428B2 (en) * | 2009-10-01 | 2014-05-06 | Raytheon Company | Light diffusion apparatus |
US9661996B2 (en) | 2009-10-01 | 2017-05-30 | Sarcos Lc | Needle delivered imaging device |
US8828028B2 (en) | 2009-11-03 | 2014-09-09 | Raytheon Company | Suture device and method for closing a planar opening |
US8715186B2 (en) | 2009-11-24 | 2014-05-06 | Guided Therapy Systems, Llc | Methods and systems for generating thermal bubbles for improved ultrasound imaging and therapy |
US8399535B2 (en) | 2010-06-10 | 2013-03-19 | Zimmer, Inc. | Polymer [[s]] compositions including an antioxidant |
US9504446B2 (en) | 2010-08-02 | 2016-11-29 | Guided Therapy Systems, Llc | Systems and methods for coupling an ultrasound source to tissue |
US9149658B2 (en) | 2010-08-02 | 2015-10-06 | Guided Therapy Systems, Llc | Systems and methods for ultrasound treatment |
US8857438B2 (en) | 2010-11-08 | 2014-10-14 | Ulthera, Inc. | Devices and methods for acoustic shielding |
KR20230160959A (en) | 2011-02-16 | 2023-11-24 | 더 제너럴 하스피탈 코포레이션 | Optical coupler for an endoscope |
US9155543B2 (en) | 2011-05-26 | 2015-10-13 | Cartiva, Inc. | Tapered joint implant and related tools |
US8617519B2 (en) | 2011-07-07 | 2013-12-31 | DePuy Synthes Products, LLC | Injectable cross-linked hydrogels for biomaterial applications |
KR102068724B1 (en) | 2011-07-10 | 2020-01-21 | 가이디드 테라피 시스템스, 엘.엘.씨. | Systems and methods for improving an outside appearance of skin using ultrasound as an energy source |
KR20140047709A (en) | 2011-07-11 | 2014-04-22 | 가이디드 테라피 시스템스, 엘.엘.씨. | Systems and methods for coupling an ultrasound source to tissue |
WO2013052105A2 (en) | 2011-10-03 | 2013-04-11 | Biomimedica, Inc. | Polymeric adhesive for anchoring compliant materials to another surface |
US9114024B2 (en) | 2011-11-21 | 2015-08-25 | Biomimedica, Inc. | Systems, devices, and methods for anchoring orthopaedic implants to bone |
US9263663B2 (en) | 2012-04-13 | 2016-02-16 | Ardent Sound, Inc. | Method of making thick film transducer arrays |
US10350072B2 (en) | 2012-05-24 | 2019-07-16 | Cartiva, Inc. | Tooling for creating tapered opening in tissue and related methods |
US9510802B2 (en) | 2012-09-21 | 2016-12-06 | Guided Therapy Systems, Llc | Reflective ultrasound technology for dermatological treatments |
CN204017181U (en) | 2013-03-08 | 2014-12-17 | 奥赛拉公司 | Aesthstic imaging and processing system, multifocal processing system and perform the system of aesthetic procedure |
US10561862B2 (en) | 2013-03-15 | 2020-02-18 | Guided Therapy Systems, Llc | Ultrasound treatment device and methods of use |
JP6432860B2 (en) * | 2013-08-30 | 2018-12-05 | 国立大学法人横浜国立大学 | Method for producing hybrid gel |
EP3052562B1 (en) | 2013-10-01 | 2017-11-08 | Zimmer, Inc. | Polymer compositions comprising one or more protected antioxidants |
WO2015138137A1 (en) | 2014-03-12 | 2015-09-17 | Zimmer, Inc. | Melt-stabilized ultra high molecular weight polyethylene and method of making the same |
EP3131630B1 (en) | 2014-04-18 | 2023-11-29 | Ulthera, Inc. | Band transducer ultrasound therapy |
US9561095B1 (en) | 2015-10-12 | 2017-02-07 | Phi Nguyen | Body augmentation device |
US9459442B2 (en) | 2014-09-23 | 2016-10-04 | Scott Miller | Optical coupler for optical imaging visualization device |
US9953193B2 (en) | 2014-09-30 | 2018-04-24 | Tego, Inc. | Operating systems for an RFID tag |
CA2967306A1 (en) * | 2014-11-10 | 2016-05-19 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Stem cell-based technologies for avian skeletal tissue engineering and regeneration |
AU2015358476B2 (en) | 2014-12-03 | 2019-08-15 | Zimmer, Inc. | Antioxidant-infused ultra high molecular weight polyethylene |
EP3636226A1 (en) | 2015-03-31 | 2020-04-15 | Cartiva, Inc. | Carpometacarpal (cmc) implants |
WO2016161025A1 (en) | 2015-03-31 | 2016-10-06 | Cartiva, Inc. | Hydrogel implants with porous materials and methods |
RU2693041C2 (en) * | 2015-05-06 | 2019-07-01 | ЗОИТИС СЕРВИСЕЗ ЭлЭлСи | Composition of hydrogel with moderate adhesion |
US10548467B2 (en) | 2015-06-02 | 2020-02-04 | GI Scientific, LLC | Conductive optical element |
CN107920920B (en) * | 2015-06-12 | 2021-05-25 | 综合医院公司 | Corneal filler for correcting ametropia |
JP6621824B2 (en) * | 2015-07-14 | 2019-12-18 | 富士フイルム株式会社 | Method for manufacturing biological tube model and method for manufacturing biological organ model |
CN108289595B (en) | 2015-07-21 | 2021-03-16 | 图像科学有限责任公司 | Endoscopic accessory with angularly adjustable exit port |
US11077228B2 (en) | 2015-08-10 | 2021-08-03 | Hyalex Orthopaedics, Inc. | Interpenetrating polymer networks |
WO2017083774A1 (en) | 2015-11-11 | 2017-05-18 | Onefocus Vision, Inc. | Accommodating lens with cavity |
PL3405294T3 (en) | 2016-01-18 | 2023-05-08 | Ulthera, Inc. | Compact ultrasound device having annular ultrasound array peripherally electrically connected to flexible printed circuit board |
US10510268B2 (en) * | 2016-04-05 | 2019-12-17 | Synaptive Medical (Barbados) Inc. | Multi-metric surgery simulator and methods |
JP2018027155A (en) * | 2016-08-16 | 2018-02-22 | 安彦 杉本 | Stent |
CN114631846A (en) | 2016-08-16 | 2022-06-17 | 奥赛拉公司 | System and method for cosmetic ultrasound treatment of skin |
US10782450B2 (en) * | 2016-10-26 | 2020-09-22 | Alcon Inc. | Soft contact lenses with a lubricious coating covalently-attached thereon |
CN106491517B (en) * | 2016-11-23 | 2019-12-06 | 佛山科学技术学院 | Preparation method of pirfenidone PVA hydrogel and pirfenidone PVA hydrogel |
CN106810704B (en) * | 2017-02-08 | 2019-08-02 | 郑州大学 | Polyvinyl alcohol hydrogel and its preparation method and application |
JP7048238B2 (en) * | 2017-09-28 | 2022-04-05 | 日東電工株式会社 | Coating liquid manufacturing method, polarizing element manufacturing method, and coating liquid manufacturing equipment |
WO2019067942A1 (en) * | 2017-09-29 | 2019-04-04 | Amit Prakash Govil | Bioactive implants and methods of making |
US11944849B2 (en) | 2018-02-20 | 2024-04-02 | Ulthera, Inc. | Systems and methods for combined cosmetic treatment of cellulite with ultrasound |
EP3810021A1 (en) | 2018-06-19 | 2021-04-28 | Tornier, Inc. | Automated instrument or component assistance using mixed reality in orthopedic surgical procedures |
US10869950B2 (en) | 2018-07-17 | 2020-12-22 | Hyalex Orthopaedics, Inc. | Ionic polymer compositions |
CN109679604B (en) * | 2019-01-28 | 2021-01-05 | 中国石油大学(华东) | Salt-resistant and high-temperature-resistant hydrogel and preparation method and application thereof |
WO2020155041A1 (en) * | 2019-01-31 | 2020-08-06 | 西北大学 | Polyvinyl alcohol hydrogel having asymmetric pore size |
JP2022520182A (en) * | 2019-02-08 | 2022-03-29 | オハイオ・ステイト・イノベーション・ファウンデーション | Vitreous substitutes that release antioxidants and their use |
JPWO2020226157A1 (en) * | 2019-05-09 | 2020-11-12 | ||
CN110591121A (en) * | 2019-10-22 | 2019-12-20 | 四川轻化工大学 | Preparation method of full-physical crosslinked triple interpenetrating network hydrogel |
US11882992B2 (en) * | 2019-11-27 | 2024-01-30 | View Point Medical, Inc. | Composite tissue markers detectable via multiple detection modalities including radiopaque element |
US11903767B2 (en) | 2019-11-27 | 2024-02-20 | View Point Medical, Inc. | Composite tissue markers detectable via multiple detection modalities |
KR102585893B1 (en) | 2020-02-21 | 2023-10-10 | 성균관대학교산학협력단 | Reconstructed hydrogel and preparing method of the same |
CN114015079B (en) * | 2021-12-14 | 2022-11-15 | 四川大学 | Polyvinyl alcohol-based piezoelectric active hydrogel and preparation and forming method thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3875302A (en) * | 1970-09-16 | 1975-04-01 | Kuraray Co | Gelled vinyl alcohol polymers and articles therefrom |
US4874562A (en) * | 1986-02-13 | 1989-10-17 | Biomaterials Universe, Inc. | Method of molding a polyvinyl alcohol contact lens |
JPH1036534A (en) * | 1996-07-30 | 1998-02-10 | Kyocera Corp | Method for enhancing abrasion resistance of polyvinyl alcohol hydrogel |
US20040092653A1 (en) * | 2002-08-02 | 2004-05-13 | Cambridge Polymer Group, Inc. | Systems and methods for controlling and forming polymer gels |
Family Cites Families (206)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB919390A (en) * | 1960-12-14 | 1963-02-27 | Kurashiki Rayon Kk | Polyvinyl alcohol fibres having excellent dyeability and whiteness |
US3862265A (en) * | 1971-04-09 | 1975-01-21 | Exxon Research Engineering Co | Polymers with improved properties and process therefor |
DE2364675C2 (en) | 1972-12-29 | 1983-06-23 | Kuraray Co., Ltd., Kurashiki, Okayama | Copolymer consisting of a polymer main chain and polymer side chains and its use for the manufacture of articles for biomedical purposes |
US4058491A (en) | 1975-02-11 | 1977-11-15 | Plastomedical Sciences, Inc. | Cationic hydrogels based on heterocyclic N-vinyl monomers |
US4071508A (en) | 1975-02-11 | 1978-01-31 | Plastomedical Sciences, Inc. | Anionic hydrogels based on hydroxyalkyl acrylates and methacrylates |
US4036788A (en) | 1975-02-11 | 1977-07-19 | Plastomedical Sciences, Inc. | Anionic hydrogels based on heterocyclic N-vinyl monomers |
US4060678A (en) | 1975-02-11 | 1977-11-29 | Plastomedical Sciences, Inc. | Cationic hydrogels based on hydroxyalkyl acrylates and methacrylates |
SU1243627A3 (en) | 1979-12-05 | 1986-07-07 | Дзе Кендалл Компани (Фирма) | Jelly-forming composition |
US4379874A (en) | 1980-07-07 | 1983-04-12 | Stoy Vladimir A | Polymer composition comprising polyacrylonitrile polymer and multi-block copolymer |
EP0058497B1 (en) | 1981-02-05 | 1985-08-28 | Nippon Oil Co. Ltd. | Process for preparing a hydrogel |
US4451599A (en) * | 1981-04-01 | 1984-05-29 | American Can Company | Plasticized EVOH and process and products utilizing same |
US4734097A (en) | 1981-09-25 | 1988-03-29 | Nippon Oil Company, Ltd. | Medical material of polyvinyl alcohol and process of making |
US4699146A (en) * | 1982-02-25 | 1987-10-13 | Valleylab, Inc. | Hydrophilic, elastomeric, pressure-sensitive adhesive |
US4956122A (en) * | 1982-03-10 | 1990-09-11 | Uniroyal Chemical Company, Inc. | Lubricating composition |
JPS5930881A (en) | 1982-08-13 | 1984-02-18 | Nippon Oil Co Ltd | Manufacture of low-temperature insulating gel |
JPS5956446A (en) | 1982-09-24 | 1984-03-31 | Nippon Oil Co Ltd | Method for lowering flexibility of frozen polyvinyl alcohol gel |
GB8311788D0 (en) | 1983-04-29 | 1983-06-02 | Coopervision Uk | Hydrogel contact lenses |
US4464438A (en) * | 1983-05-02 | 1984-08-07 | Mobil Oil Corporation | Blends of polyvinyl alcohol and ethylene-vinyl alcohol copolymer as grease resistant melt extrudable films |
US4771089A (en) | 1983-09-08 | 1988-09-13 | Minnesota Mining And Manufacturing Co. | Polymer blends with high water absorption |
US4859719A (en) | 1983-09-08 | 1989-08-22 | Minnesota Mining And Manufacturing Company | Polymer blends with high water absorption |
DE3410241A1 (en) * | 1984-03-21 | 1985-10-03 | Hoechst Ag, 6230 Frankfurt | THERMOPLASTICALLY PROCESSABLE POLYVINYL ALCOHOL COMPOSITIONS, METHOD FOR THEIR PRODUCTION AND FILMS AND MOLDED PARTS MADE THEREOF |
JPH0678460B2 (en) | 1985-05-01 | 1994-10-05 | 株式会社バイオマテリアル・ユニバース | Porous transparent polyvinyl alcohol gel |
US4956133A (en) | 1985-08-19 | 1990-09-11 | Le Roy Payne | Continuous molding apparatus and method |
US4640941A (en) | 1985-11-25 | 1987-02-03 | Alcon Laboratories | Hydrogels containing siloxane comonomers |
GB8611838D0 (en) | 1986-05-15 | 1986-06-25 | Yarsley Technical Centre Ltd | Hydrophilic copolymers |
JPS6317904A (en) | 1986-07-09 | 1988-01-25 | Mitsubishi Chem Ind Ltd | Production of crosslinked porous polyvinyl alcohol particle |
JPH0611290B2 (en) | 1986-11-05 | 1994-02-16 | 住友ベークライト株式会社 | Γ-ray sterilization method for polyvinyl alcohol gel |
PL151581B1 (en) | 1986-12-30 | 1990-09-28 | Method of manufacturing of hydrogel dressing | |
US5244799A (en) | 1987-05-20 | 1993-09-14 | Anderson David M | Preparation of a polymeric hydrogel containing micropores and macropores for use as a cell culture substrate |
US5306311A (en) | 1987-07-20 | 1994-04-26 | Regen Corporation | Prosthetic articular cartilage |
US4772287A (en) | 1987-08-20 | 1988-09-20 | Cedar Surgical, Inc. | Prosthetic disc and method of implanting |
JPH0286838A (en) * | 1988-09-22 | 1990-03-27 | Terumo Corp | Water insoluble hydrogel and production thereof |
JP2746387B2 (en) | 1988-09-22 | 1998-05-06 | 株式会社ビーエムジー | Method for producing polyvinyl alcohol hydrogel |
DE3835840A1 (en) * | 1988-10-21 | 1990-05-31 | Hoechst Ag | GRAY POLYMERISATES CONTAINING POLYVINYL ACETAL GROUPS ON POLYURETHANE GRAIN BASES, METHOD FOR THEIR PRODUCTION AND THEIR USE |
US4851168A (en) | 1988-12-28 | 1989-07-25 | Dow Corning Corporation | Novel polyvinyl alcohol compositions and products prepared therefrom |
US4915974A (en) * | 1989-02-17 | 1990-04-10 | Nabisco Brands, Inc. | Polyvinyl oleate as a fat replacement |
IT1233599B (en) * | 1989-05-30 | 1992-04-06 | Butterfly Srl | POLYMERIC COMPOSITIONS FOR THE PRODUCTION OF BIODEGRADABLE PLASTIC ITEMS AND PROCEDURES FOR THEIR PREPARATION |
US5364547A (en) * | 1989-06-09 | 1994-11-15 | The Dow Chemical Company | Lubricants containing perfluorocyclobutane rings |
WO1991000681A1 (en) | 1989-06-30 | 1991-01-10 | Poqet Computer Corporation | Memory card tray for portable computer |
US5288765A (en) * | 1989-08-03 | 1994-02-22 | Spherilene S.R.L. | Expanded articles of biodegradable plastics materials and a method for their production |
US5118779A (en) | 1989-10-10 | 1992-06-02 | Polymedica Industries, Inc. | Hydrophilic polyurethane elastomers |
US5157093A (en) | 1990-05-10 | 1992-10-20 | Ciba-Geigy Corporation | Hydroxyethyl cellulose derivatives containing pendant (meth)acryloyl units bound through urethane groups and hydrogel contact lenses made therefrom |
US5028648A (en) * | 1990-07-12 | 1991-07-02 | Air Products And Chemicals, Inc. | Extrudable polyvinyl alcohol compositions containing thermoplastic polyurethane |
US5122565A (en) * | 1990-10-26 | 1992-06-16 | Shell Oil Company | Stabilized polyketone polymers containing a mixture of a hydroxyapatite and an alumina hydrogel |
US5410016A (en) * | 1990-10-15 | 1995-04-25 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
TW203065B (en) * | 1990-10-24 | 1993-04-01 | Hoechst Ag | |
US5362803A (en) | 1990-12-07 | 1994-11-08 | Rohm And Haas Company | Polymeric blends of polyvinyl alcohol copolymers with copolymers of unsaturated monomers |
US5189097A (en) | 1990-12-07 | 1993-02-23 | Rohm And Haas Company | Polymeric blends |
US5047055A (en) * | 1990-12-21 | 1991-09-10 | Pfizer Hospital Products Group, Inc. | Hydrogel intervertebral disc nucleus |
US5192326A (en) | 1990-12-21 | 1993-03-09 | Pfizer Hospital Products Group, Inc. | Hydrogel bead intervertebral disc nucleus |
JP3007903B2 (en) | 1991-03-29 | 2000-02-14 | 京セラ株式会社 | Artificial disc |
US5276079A (en) * | 1991-11-15 | 1994-01-04 | Minnesota Mining And Manufacturing Company | Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using same |
US5552096A (en) * | 1991-12-13 | 1996-09-03 | Exxon Chemical Patents Inc. | Multiple reaction process in melt processing equipment |
US5681300A (en) | 1991-12-17 | 1997-10-28 | The Procter & Gamble Company | Absorbent article having blended absorbent core |
US5260066A (en) | 1992-01-16 | 1993-11-09 | Srchem Incorporated | Cryogel bandage containing therapeutic agent |
CA2096386A1 (en) * | 1992-05-18 | 1993-11-19 | Masahiro Kamauchi | Lithium secondary battery |
US6162456A (en) | 1992-09-24 | 2000-12-19 | Ortho-Mcneil Pharmaceutical, Inc. | Adhesive transdermal drug delivery matrix of a physical blend of hydrophilic and hydrophobic polymers |
US5407055A (en) * | 1992-11-19 | 1995-04-18 | Kao Corporation | Conveyor apparatus and method having flexible goods receptacle members |
US5336551A (en) * | 1992-12-14 | 1994-08-09 | Mizu Systems, Inc. | Reinforced polyvinyl alcohol hydrogels containing uniformly dispersed crystalline fibrils and method for preparing same |
US5358525A (en) | 1992-12-28 | 1994-10-25 | Fox John E | Bearing surface for prosthesis and replacement of meniscal cartilage |
US5256751A (en) | 1993-02-08 | 1993-10-26 | Vistakon, Inc. | Ophthalmic lens polymer incorporating acyclic monomer |
FR2704431B1 (en) | 1993-04-30 | 1995-07-21 | Sebbin Laboratoires | Use of hydrogels based on hyaluronic acid and / or polydeoxyribonucleotides as filling materials for prostheses and prostheses resulting therefrom. |
US5709854A (en) | 1993-04-30 | 1998-01-20 | Massachusetts Institute Of Technology | Tissue formation by injecting a cell-polymeric solution that gels in vivo |
EP0677297B1 (en) | 1993-09-24 | 2000-12-13 | Takiron Co. Ltd. | Implantation material |
US5540033A (en) * | 1994-01-10 | 1996-07-30 | Cambrex Hydrogels | Integrated Manufacturing process for hydrogels |
US5527271A (en) | 1994-03-30 | 1996-06-18 | Bristol-Myers Squibb Co. | Thermoplastic hydrogel impregnated composite material |
US5723331A (en) * | 1994-05-05 | 1998-03-03 | Genzyme Corporation | Methods and compositions for the repair of articular cartilage defects in mammals |
AU2621295A (en) | 1994-05-24 | 1995-12-18 | Smith & Nephew Plc | Intervertebral disc implant |
US5834029A (en) | 1994-07-20 | 1998-11-10 | Cytotherapeutics, Inc. | Nerve guidance channel containing bioartificial three-dimensional hydrogel extracellular matrix derivatized with cell adhesive peptide fragment |
EP0700671B1 (en) | 1994-09-08 | 2001-08-08 | Stryker Technologies Corporation | Hydrogel intervertebral disc nucleus |
US6180606B1 (en) * | 1994-09-28 | 2001-01-30 | Gensci Orthobiologics, Inc. | Compositions with enhanced osteogenic potential, methods for making the same and uses thereof |
AU700903B2 (en) * | 1994-10-12 | 1999-01-14 | Focal, Inc. | Targeted delivery via biodegradable polymers |
DE69532856T2 (en) | 1994-10-17 | 2005-04-21 | Raymedica Inc | Spinal disc-GRAFT |
US5716404A (en) | 1994-12-16 | 1998-02-10 | Massachusetts Institute Of Technology | Breast tissue engineering |
US5632774A (en) | 1995-01-17 | 1997-05-27 | Babian; Hamik | In-the-shell hydration to make implant filler material and prosthesis employing same |
US6017577A (en) | 1995-02-01 | 2000-01-25 | Schneider (Usa) Inc. | Slippery, tenaciously adhering hydrophilic polyurethane hydrogel coatings, coated polymer substrate materials, and coated medical devices |
US5576072A (en) * | 1995-02-01 | 1996-11-19 | Schneider (Usa), Inc. | Process for producing slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with at least one other, dissimilar polymer hydrogel |
US5919570A (en) * | 1995-02-01 | 1999-07-06 | Schneider Inc. | Slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with a poly(N-vinylpyrrolidone) polymer hydrogel, coated polymer and metal substrate materials, and coated medical devices |
US5941909A (en) | 1995-02-14 | 1999-08-24 | Mentor Corporation | Filling material for soft tissue implant prostheses and implants made therewith |
US6962979B1 (en) * | 1995-03-14 | 2005-11-08 | Cohesion Technologies, Inc. | Crosslinkable biomaterial compositions containing hydrophobic and hydrophilic crosslinking agents |
US5900245A (en) | 1996-03-22 | 1999-05-04 | Focal, Inc. | Compliant tissue sealants |
JP4209941B2 (en) * | 1995-03-23 | 2009-01-14 | ジェンザイム・コーポレーション | Undercoat redox and photoinitiator systems for improved adhesion of gels to substrates |
JPH08283570A (en) | 1995-04-17 | 1996-10-29 | Sumitomo Chem Co Ltd | Resin composition |
US6129761A (en) * | 1995-06-07 | 2000-10-10 | Reprogenesis, Inc. | Injectable hydrogel compositions |
US6509098B1 (en) | 1995-11-17 | 2003-01-21 | Massachusetts Institute Of Technology | Poly(ethylene oxide) coated surfaces |
ATE330644T1 (en) | 1995-12-18 | 2006-07-15 | Angiotech Biomaterials Corp | CROSS-LINKED POLYMER MATERIALS AND METHODS FOR USE THEREOF |
EP0784987B1 (en) | 1996-01-16 | 2003-10-01 | Mentor Corporation | Method of making in situ filler material for mammary, penile and testicular prosthesis and tissue expanders |
US6015576A (en) | 1997-08-29 | 2000-01-18 | Bio-Sphere Technology, Inc. | Method for inducing a systemic immune response to an antigen |
US6117449A (en) | 1996-03-22 | 2000-09-12 | Bio-Sphere Technology, Inc. | Method for inducing a systemic immune response to a hepatitis antigen |
US6207185B1 (en) * | 1996-03-22 | 2001-03-27 | Bio-Sphere Technology | Method for inducing a systemic immune response to an HIV antigen |
DE69716505T2 (en) * | 1996-05-10 | 2003-06-26 | Isotis Nv | Implant material and process for its manufacture |
DE69721265T2 (en) * | 1996-07-01 | 2004-05-06 | Universiteit Utrecht | HYDROLYZABLE HYDROGELS FOR CONTROLLED RELEASE |
JPH1036524A (en) | 1996-07-30 | 1998-02-10 | Polyplastics Co | Packaging material and its use |
US6706690B2 (en) | 1999-06-10 | 2004-03-16 | Baxter Healthcare Corporation | Hemoactive compositions and methods for their manufacture and use |
US6063061A (en) | 1996-08-27 | 2000-05-16 | Fusion Medical Technologies, Inc. | Fragmented polymeric compositions and methods for their use |
US6184197B1 (en) * | 1996-09-19 | 2001-02-06 | The Procter & Gamble Company | Polymeric compound comprising one or more active alcohols |
WO1998017215A1 (en) | 1996-10-24 | 1998-04-30 | Tyco Group S.A.R.L. | Hydrogel wound dressing and the method of making and using the same |
EP1230902A1 (en) | 1996-11-15 | 2002-08-14 | Advanced Bio Surfaces, Inc. | Biomaterial system for in situ tissue repair |
US6139963A (en) | 1996-11-28 | 2000-10-31 | Kuraray Co., Ltd. | Polyvinyl alcohol hydrogel and process for producing the same |
US6224893B1 (en) * | 1997-04-11 | 2001-05-01 | Massachusetts Institute Of Technology | Semi-interpenetrating or interpenetrating polymer networks for drug delivery and tissue engineering |
JP3570850B2 (en) * | 1997-04-15 | 2004-09-29 | 日本原子力研究所 | Method for producing cross-linked polycaprolactone |
US5981826A (en) | 1997-05-05 | 1999-11-09 | Georgia Tech Research Corporation | Poly(vinyl alcohol) cryogel |
US20030008396A1 (en) | 1999-03-17 | 2003-01-09 | Ku David N. | Poly(vinyl alcohol) hydrogel |
US6271278B1 (en) | 1997-05-13 | 2001-08-07 | Purdue Research Foundation | Hydrogel composites and superporous hydrogel composites having fast swelling, high mechanical strength, and superabsorbent properties |
GB9714580D0 (en) | 1997-07-10 | 1997-09-17 | Wardlaw Douglas | Prosthetic intervertebral disc nucleus |
US6180132B1 (en) | 1997-09-18 | 2001-01-30 | Sherwood Services, Ag | Hydrogel wound dressing and the method of making and using the same |
US6375634B1 (en) | 1997-11-19 | 2002-04-23 | Oncology Innovations, Inc. | Apparatus and method to encapsulate, kill and remove malignancies, including selectively increasing absorption of x-rays and increasing free-radical damage to residual tumors targeted by ionizing and non-ionizing radiation therapy |
US5891826A (en) | 1997-11-26 | 1999-04-06 | Eastman Kodak Company | Affixing thermal dye transfer image on magnet |
US6428811B1 (en) | 1998-03-11 | 2002-08-06 | Wm. Marsh Rice University | Temperature-sensitive polymer/nanoshell composites for photothermally modulated drug delivery |
US6007833A (en) | 1998-03-19 | 1999-12-28 | Surmodics, Inc. | Crosslinkable macromers bearing initiator groups |
US6040493A (en) | 1998-04-24 | 2000-03-21 | Replication Medical, Inc. | Bioreactor wound dressing |
GB2338958A (en) | 1998-06-26 | 2000-01-12 | Eastman Kodak Co | Hyperbranched-graft hybrid copolymers from vinyl branching monomers and vinyl macromonomers |
US6132468A (en) | 1998-09-10 | 2000-10-17 | Mansmann; Kevin A. | Arthroscopic replacement of cartilage using flexible inflatable envelopes |
US6861067B2 (en) | 1998-09-17 | 2005-03-01 | Sherwood Services Ag | Hydrogel wound dressing and the method of making and using the same |
US6630457B1 (en) | 1998-09-18 | 2003-10-07 | Orthogene Llc | Functionalized derivatives of hyaluronic acid, formation of hydrogels in situ using same, and methods for making and using same |
US6211296B1 (en) | 1998-11-05 | 2001-04-03 | The B. F. Goodrich Company | Hydrogels containing substances |
FR2786400B1 (en) | 1998-11-30 | 2002-05-10 | Imedex Biomateriaux | PROCESS FOR THE PREPARATION OF A COLLAGENIC MATERIAL HAVING IN VIVO CONTROLLED BIODEGRADATION SPEED AND MATERIALS OBTAINED |
US6451346B1 (en) * | 1998-12-23 | 2002-09-17 | Amgen Inc | Biodegradable pH/thermosensitive hydrogels for sustained delivery of biologically active agents |
WO2000049084A1 (en) | 1999-02-19 | 2000-08-24 | Denki Kagaku Kogyo Kabushiki Kaisha | Hyaluronic acid gel composition, process for producing the same, and medical material containing the same |
US6692738B2 (en) | 2000-01-27 | 2004-02-17 | The General Hospital Corporation | Delivery of therapeutic biologicals from implantable tissue matrices |
US6372283B1 (en) * | 1999-04-02 | 2002-04-16 | Medtronic, Inc. | Plasma process for surface modification of pyrolitic carbon |
CA2368617C (en) * | 1999-04-12 | 2010-03-16 | Cornell Research Foundation, Inc. | Hydrogel-forming system with hydrophobic and hydrophilic components |
US6268405B1 (en) | 1999-05-04 | 2001-07-31 | Porex Surgical, Inc. | Hydrogels and methods of making and using same |
US7491235B2 (en) * | 1999-05-10 | 2009-02-17 | Fell Barry M | Surgically implantable knee prosthesis |
WO2001000246A2 (en) * | 1999-06-11 | 2001-01-04 | Shearwater Corporation | Hydrogels derived from chitosan and poly(ethylene glycol) |
US6333029B1 (en) | 1999-06-30 | 2001-12-25 | Ethicon, Inc. | Porous tissue scaffoldings for the repair of regeneration of tissue |
US6306424B1 (en) | 1999-06-30 | 2001-10-23 | Ethicon, Inc. | Foam composite for the repair or regeneration of tissue |
EP1328221B1 (en) | 1999-08-18 | 2009-03-25 | Intrinsic Therapeutics, Inc. | Devices for nucleus pulposus augmentation and retention |
US6287870B1 (en) | 1999-08-20 | 2001-09-11 | Robert A. Levine | Method and assembly for separating formed constituents from a liquid constituent in a complex biologic fluid sample |
US6371984B1 (en) | 1999-09-13 | 2002-04-16 | Keraplast Technologies, Ltd. | Implantable prosthetic or tissue expanding device |
US6783546B2 (en) | 1999-09-13 | 2004-08-31 | Keraplast Technologies, Ltd. | Implantable prosthetic or tissue expanding device |
US6232406B1 (en) * | 1999-09-30 | 2001-05-15 | Replication Medical Inc. | Hydrogel and method of making |
US6387325B1 (en) | 1999-10-08 | 2002-05-14 | Becton Dickinson & Company | Assembly for separating formed constituents from a liquid constituent in a complex biologic fluid sample |
US6710126B1 (en) | 1999-11-15 | 2004-03-23 | Bio Cure, Inc. | Degradable poly(vinyl alcohol) hydrogels |
US6632246B1 (en) | 2000-03-14 | 2003-10-14 | Chondrosite, Llc | Cartilage repair plug |
US6626945B2 (en) | 2000-03-14 | 2003-09-30 | Chondrosite, Llc | Cartilage repair plug |
US6629997B2 (en) | 2000-03-27 | 2003-10-07 | Kevin A. Mansmann | Meniscus-type implant with hydrogel surface reinforced by three-dimensional mesh |
US6969480B2 (en) * | 2000-05-12 | 2005-11-29 | Matregen Corp. | Method of producing structures using centrifugal forces |
US6710104B2 (en) | 2000-05-29 | 2004-03-23 | Kawamura Institute Of Chemical Research | Organic/inorganic hybrid hydrogel and manufacturing method therefor |
US6533817B1 (en) | 2000-06-05 | 2003-03-18 | Raymedica, Inc. | Packaged, partially hydrated prosthetic disc nucleus |
JP2002003614A (en) * | 2000-06-19 | 2002-01-09 | Rika Morikawa | Polymer gel composite and method of manufacturing the same |
US7186419B2 (en) | 2000-08-25 | 2007-03-06 | Contura Sa | Polyacrylamide hydrogel for arthritis |
US6620196B1 (en) | 2000-08-30 | 2003-09-16 | Sdgi Holdings, Inc. | Intervertebral disc nucleus implants and methods |
US20020026244A1 (en) | 2000-08-30 | 2002-02-28 | Trieu Hai H. | Intervertebral disc nucleus implants and methods |
WO2002034111A2 (en) | 2000-10-24 | 2002-05-02 | Cryolife, Inc. | In situ bioprosthetic filler and methods, particularly for the in situ formation of vertebral disc bioprosthetics |
US9050192B2 (en) | 2001-02-05 | 2015-06-09 | Formae, Inc. | Cartilage repair implant with soft bearing surface and flexible anchoring device |
US6436883B1 (en) | 2001-04-06 | 2002-08-20 | Huntsman Petrochemical Corporation | Hydraulic and gear lubricants |
US8840918B2 (en) * | 2001-05-01 | 2014-09-23 | A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences | Hydrogel compositions for tooth whitening |
DE60239528D1 (en) | 2001-05-01 | 2011-05-05 | Corium International Redwood City | TWO-PHASE, WATER-ABSORBING BIOADHESIVE COMPOSITION |
ES2331302T3 (en) | 2001-05-01 | 2009-12-29 | A.V. Topchiev Institute Of Petrochemical Synthesis | HYDROGEL COMPOSITIONS. |
US6608117B1 (en) | 2001-05-11 | 2003-08-19 | Nanosystems Research Inc. | Methods for the preparation of cellular hydrogels |
AU2002345795B2 (en) * | 2001-06-20 | 2008-01-10 | Microvention, Inc. | Medical devices having full or partial polymer coatings and their methods of manufacture |
US6780840B1 (en) * | 2001-10-09 | 2004-08-24 | Tissue Adhesive Technologies, Inc. | Method for making a light energized tissue adhesive |
US6855743B1 (en) * | 2001-10-29 | 2005-02-15 | Nanosystems Research, Inc. | Reinforced, laminated, impregnated, and composite-like materials as crosslinked polyvinyl alcohol hydrogel structures |
US6783721B2 (en) | 2001-10-30 | 2004-08-31 | Howmedica Osteonics Corp. | Method of making an ion treated hydrogel |
WO2003059200A1 (en) * | 2002-01-04 | 2003-07-24 | Massachusetts General Hospital | A high modulus crosslinked polyethylene with reduced residual free radical concentration prepared below the melt |
US6949590B2 (en) | 2002-01-10 | 2005-09-27 | University Of Washington | Hydrogels formed by non-covalent linkages |
US20040131582A1 (en) * | 2002-02-26 | 2004-07-08 | Grinstaff Mark W. | Novel dendritic polymers and their biomedical uses |
US6960617B2 (en) | 2002-04-22 | 2005-11-01 | Purdue Research Foundation | Hydrogels having enhanced elasticity and mechanical strength properties |
US7015262B2 (en) * | 2002-05-01 | 2006-03-21 | Lifescan, Inc. | Hydrophilic coatings for medical implements |
US7122602B2 (en) * | 2002-06-21 | 2006-10-17 | Isp Investments Inc. | Process of making polymeric hydrogels by reactive extrusion |
US7033393B2 (en) | 2002-06-27 | 2006-04-25 | Raymedica, Inc. | Self-transitioning spinal disc anulus occulsion device and method of use |
US7485670B2 (en) | 2002-08-02 | 2009-02-03 | Cambridge Polymer Group, Inc. | Systems and methods for controlling and forming polymer gels |
EP1546281A1 (en) | 2002-09-27 | 2005-06-29 | Basf Aktiengesellschaft | Polymerized hydrogel adhesives with high levels of monomer units in salt form |
ATE469179T1 (en) | 2002-10-02 | 2010-06-15 | Coloplast As | HYDROGEL |
US20050069572A1 (en) | 2002-10-09 | 2005-03-31 | Jennifer Elisseeff | Multi-layered polymerizing hydrogels for tissue regeneration |
US7091297B2 (en) | 2002-10-11 | 2006-08-15 | The University Of Connecticut | Shape memory polymers based on semicrystalline thermoplastic polyurethanes bearing nanostructured hard segments |
US8110222B2 (en) | 2002-11-15 | 2012-02-07 | Ut-Battelle, Llc. | Composite material |
US6733533B1 (en) * | 2002-11-19 | 2004-05-11 | Zimmer Technology, Inc. | Artificial spinal disc |
CN1713863A (en) | 2002-11-21 | 2005-12-28 | Sdgi控股股份有限公司 | Systems and techniques for interbody spinal stabilization with expandable devices |
WO2004047690A2 (en) | 2002-11-26 | 2004-06-10 | Raymedica, Inc. | Prosthetic spinal disc nucleus with elevated swelling rate |
EP1569607A4 (en) * | 2002-11-27 | 2006-08-23 | Isp Investments Inc | Tough polymers |
WO2004056321A2 (en) | 2002-12-18 | 2004-07-08 | The Regents Of The University Of California | Biocompatible hydrogel bone-like composites |
US20060127878A1 (en) | 2002-12-18 | 2006-06-15 | Salomon David H | Hydrogel preparation and process of manufacture thereof |
US7264859B2 (en) | 2002-12-19 | 2007-09-04 | Kimberly-Clark Worldwide, Inc. | Lubricious coating for medical devices |
US7004971B2 (en) | 2002-12-31 | 2006-02-28 | Depuy Acromed, Inc. | Annular nucleus pulposus replacement |
US6982298B2 (en) | 2003-01-10 | 2006-01-03 | The Cleveland Clinic Foundation | Hydroxyphenyl cross-linked macromolecular network and applications thereof |
KR100980170B1 (en) | 2003-01-16 | 2010-09-03 | 리플리케이션 메디칼, 인크 | Hydrogel-Based Prosthetic Device for Replacing at Least a Part of the Nucleus of a Spinal Disc |
EP1631375B1 (en) | 2003-01-17 | 2011-11-02 | Cornell Research Foundation, Inc. | Injectable hydrogel microspheres from aqueous two-phase system |
US20070003525A1 (en) | 2003-01-31 | 2007-01-04 | Moehlenbruck Jeffrey W | Hydrogel compositions comprising nucleus pulposus tissue |
US6994730B2 (en) | 2003-01-31 | 2006-02-07 | Howmedica Osteonics Corp. | Meniscal and tibial implants |
US20060148958A1 (en) | 2003-02-17 | 2006-07-06 | Kawamura Institute Of Chemical Research | Polymer gel containing biocompatible material, dry gel, and process for producing polymer gel |
US20040242770A1 (en) | 2003-04-16 | 2004-12-02 | Feldstein Mikhail M. | Covalent and non-covalent crosslinking of hydrophilic polymers and adhesive compositions prepared therewith |
CN1816357B (en) | 2003-04-30 | 2012-11-28 | 德崇大学 | Thermogelling polymer blends for biomaterial applications |
US20040244978A1 (en) * | 2003-06-04 | 2004-12-09 | Sun Drilling Products Corporation | Lost circulation material blend offering high fluid loss with minimum solids |
US7067169B2 (en) * | 2003-06-04 | 2006-06-27 | Chemat Technology Inc. | Coated implants and methods of coating |
NL1023924C2 (en) | 2003-07-15 | 2005-01-18 | Stichting Tech Wetenschapp | Tissue replacement material. |
US7736619B2 (en) * | 2003-11-05 | 2010-06-15 | Ust Inc. | Hydrogel compositions and manufacturing process for ultrasound couplants |
KR100553327B1 (en) * | 2003-11-18 | 2006-02-20 | 광주과학기술원 | Siloxane monomers containing trifluorovinylether group, sol-gel hybrid polymers prepared by using the siloxane monomers |
FR2865939B1 (en) | 2004-02-06 | 2007-08-31 | Biomatlante | USE OF SILANIZED ORGANIC POLYMERS FOR CREATING BIOACTIVE COATING, FOR IMPLANT OR PROSTHESIS |
FR2866571B1 (en) | 2004-02-20 | 2007-09-21 | Philippe Zanchetta | USE OF A MIXTURE OF SPECIFIC POLYSACCHARIDES AS INDICATED BY THE EZBONE INVENTOR COMPRISING HYALURONIC ACID, CHONDROID SULFATE, DERMATANE SULFATE AND HEPARIN IN BONE HEALING. |
CN100412097C (en) * | 2004-03-05 | 2008-08-20 | 日本合成化学工业株式会社 | Aqueous emulsion and uses thereof |
EP1593400A1 (en) | 2004-05-04 | 2005-11-09 | Depuy Products, Inc. | Hybrid biologic-synthetic bioabsorbable scaffolds |
WO2006013627A1 (en) * | 2004-08-04 | 2006-02-09 | Sekisui Chemical Co., Ltd. | Process for producing polyvinyl acetal resin, polyvinyl butyral resin, and process for producing esterified polyvinyl alcohol resin |
EP1796747B1 (en) | 2004-08-27 | 2017-07-05 | Antonio Lauto | Bioadhesve film for tissue repair |
US7235592B2 (en) * | 2004-10-12 | 2007-06-26 | Zimmer Gmbh | PVA hydrogel |
WO2006075392A1 (en) * | 2005-01-14 | 2006-07-20 | Mitsui Chemicals, Inc. | Polyvinyl acetal resin varnish, gelling agent, nonaqueous electrolyte and electrochemical element |
US8017139B2 (en) * | 2005-02-23 | 2011-09-13 | Zimmer Technology, Inc. | Blend hydrogels and methods of making |
US7291169B2 (en) * | 2005-04-15 | 2007-11-06 | Zimmer Technology, Inc. | Cartilage implant |
US20070004861A1 (en) * | 2005-07-01 | 2007-01-04 | Kevin Cai | High melt strength polypropylene resins and method for making same |
ITTO20050549A1 (en) | 2005-08-03 | 2007-02-04 | Consiglio Nazionale Ricerche | COMPOSITE MATERIAL INJECTABLE TO BE USED AS A BONUS SUBSTITUTE |
AU2006321809A1 (en) | 2005-12-07 | 2007-06-14 | Zimmer, Inc. | Methods of bonding or modifying hydrogels using irradiation |
US7601383B2 (en) * | 2006-02-28 | 2009-10-13 | Advanced Cardiovascular Systems, Inc. | Coating construct containing poly (vinyl alcohol) |
US7799352B2 (en) * | 2006-08-09 | 2010-09-21 | Korea Atomic Energy Research Institute | Therapeutic hydrogel for atopic dermatitis and preparation method thereof |
US7731988B2 (en) | 2007-08-03 | 2010-06-08 | Zimmer, Inc. | Multi-polymer hydrogels |
US20090053318A1 (en) * | 2007-08-21 | 2009-02-26 | Sharon Mi Lyn Tan | Forming Embolic Particles |
-
2004
- 2004-10-12 US US10/962,975 patent/US7235592B2/en not_active Expired - Fee Related
-
2005
- 2005-01-19 EP EP05001009A patent/EP1647569A1/en not_active Withdrawn
- 2005-10-11 EP EP05806343A patent/EP1812499B1/en not_active Not-in-force
- 2005-10-11 AU AU2005293727A patent/AU2005293727B2/en not_active Ceased
- 2005-10-11 CN CNA2005800349079A patent/CN101111542A/en active Pending
- 2005-10-11 CA CA2582779A patent/CA2582779C/en not_active Expired - Fee Related
- 2005-10-11 JP JP2007535118A patent/JP5237639B2/en active Active
- 2005-10-11 WO PCT/EP2005/010931 patent/WO2006040128A1/en active Application Filing
-
2008
- 2008-07-09 US US12/170,303 patent/US7985781B2/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3875302A (en) * | 1970-09-16 | 1975-04-01 | Kuraray Co | Gelled vinyl alcohol polymers and articles therefrom |
US4874562A (en) * | 1986-02-13 | 1989-10-17 | Biomaterials Universe, Inc. | Method of molding a polyvinyl alcohol contact lens |
JPH1036534A (en) * | 1996-07-30 | 1998-02-10 | Kyocera Corp | Method for enhancing abrasion resistance of polyvinyl alcohol hydrogel |
US20040092653A1 (en) * | 2002-08-02 | 2004-05-13 | Cambridge Polymer Group, Inc. | Systems and methods for controlling and forming polymer gels |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1951965B (en) * | 1996-08-30 | 2011-07-20 | 诺沃挪第克公司 | Glp-1 derivatives |
US9446107B2 (en) | 2005-12-13 | 2016-09-20 | President And Fellows Of Harvard College | Scaffolds for cell transplantation |
US11096997B2 (en) | 2005-12-13 | 2021-08-24 | President And Fellows Of Harvard College | Scaffolds for cell transplantation |
US10137184B2 (en) | 2005-12-13 | 2018-11-27 | President And Fellows Of Harvard College | Scaffolds for cell transplantation |
US10149897B2 (en) | 2005-12-13 | 2018-12-11 | President And Fellows Of Harvard College | Scaffolds for cell transplantation |
US10568949B2 (en) | 2008-02-13 | 2020-02-25 | President And Fellows Of Harvard College | Method of eliciting an anti-tumor immune response with controlled delivery of TLR agonists in porous polymerlc devices |
US9821045B2 (en) | 2008-02-13 | 2017-11-21 | President And Fellows Of Harvard College | Controlled delivery of TLR3 agonists in structural polymeric devices |
US10258677B2 (en) | 2008-02-13 | 2019-04-16 | President And Fellows Of Harvard College | Continuous cell programming devices |
US10328133B2 (en) | 2008-02-13 | 2019-06-25 | President And Fellows Of Harvard College | Continuous cell programming devices |
US11202759B2 (en) | 2010-10-06 | 2021-12-21 | President And Fellows Of Harvard College | Injectable, pore-forming hydrogels for materials-based cell therapies |
US10045947B2 (en) | 2011-04-28 | 2018-08-14 | President And Fellows Of Harvard College | Injectable preformed macroscopic 3-dimensional scaffolds for minimally invasive administration |
US9675561B2 (en) | 2011-04-28 | 2017-06-13 | President And Fellows Of Harvard College | Injectable cryogel vaccine devices and methods of use thereof |
US10406216B2 (en) | 2011-06-03 | 2019-09-10 | President And Fellows Of Harvard College | In situ antigen-generating cancer vaccine |
US9486512B2 (en) | 2011-06-03 | 2016-11-08 | President And Fellows Of Harvard College | In situ antigen-generating cancer vaccine |
US11278604B2 (en) | 2012-04-16 | 2022-03-22 | President And Fellows Of Harvard College | Mesoporous silica compositions comprising inflammatory cytokines comprising inflammatory cytokines for modulating immune responses |
US10682400B2 (en) | 2014-04-30 | 2020-06-16 | President And Fellows Of Harvard College | Combination vaccine devices and methods of killing cancer cells |
US11786457B2 (en) | 2015-01-30 | 2023-10-17 | President And Fellows Of Harvard College | Peritumoral and intratumoral materials for cancer therapy |
US11150242B2 (en) | 2015-04-10 | 2021-10-19 | President And Fellows Of Harvard College | Immune cell trapping devices and methods for making and using the same |
US11752238B2 (en) | 2016-02-06 | 2023-09-12 | President And Fellows Of Harvard College | Recapitulating the hematopoietic niche to reconstitute immunity |
US11555177B2 (en) | 2016-07-13 | 2023-01-17 | President And Fellows Of Harvard College | Antigen-presenting cell-mimetic scaffolds and methods for making and using the same |
Also Published As
Publication number | Publication date |
---|---|
JP2008515503A (en) | 2008-05-15 |
EP1812499A1 (en) | 2007-08-01 |
AU2005293727A1 (en) | 2006-04-20 |
US20090131548A1 (en) | 2009-05-21 |
US7985781B2 (en) | 2011-07-26 |
EP1647569A1 (en) | 2006-04-19 |
AU2005293727B2 (en) | 2010-12-16 |
CA2582779A1 (en) | 2006-04-20 |
CN101111542A (en) | 2008-01-23 |
JP5237639B2 (en) | 2013-07-17 |
US7235592B2 (en) | 2007-06-26 |
US20060079597A1 (en) | 2006-04-13 |
EP1812499B1 (en) | 2012-06-13 |
WO2006040128B1 (en) | 2006-06-01 |
CA2582779C (en) | 2013-07-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2005293727B2 (en) | PVA hydrogel | |
Li et al. | Controllable fabrication of hydroxybutyl chitosan/oxidized chondroitin sulfate hydrogels by 3D bioprinting technique for cartilage tissue engineering | |
US7745532B2 (en) | Systems and methods for controlling and forming polymer gels | |
Xu et al. | Poly (N-acryloyl glycinamide): a fascinating polymer that exhibits a range of properties from UCST to high-strength hydrogels | |
US7485670B2 (en) | Systems and methods for controlling and forming polymer gels | |
JP2008515503A5 (en) | ||
JP3069746B2 (en) | Method for producing water-swellable product using ultrafine powder of water-swellable polymer | |
JP2010525154A (en) | PVA-PAA hydrogel | |
WO2005017000A1 (en) | Systems and methods for controlling and forming polymer gels | |
Roy et al. | PVP-based hydrogels: Synthesis, properties and applications | |
WO2009032921A1 (en) | Creep resistant, highly lubricious, tough, and ionic hydrogels including pva-paamps hydrogels | |
Abd El-Mohdy et al. | Control release of some pesticides from starch/(ethylene glycol-co-methacrylic acid) copolymers prepared by γ-irradiation | |
EP1713851A2 (en) | Systems and methods for controlling and forming polymer gels | |
Dafader et al. | Effect of kappa-carrageenan on the properties of poly (vinyl alcohol) hydrogel prepared by the application of gamma radiation | |
Bardakova et al. | 3D printing biodegradable scaffolds with chitosan materials for tissue engineering | |
US20100063174A1 (en) | Systems and methods for controlling and forming polymer gels | |
JP2007500764A (en) | Apparatus and method for controlling and forming polymer gels | |
Bhunia | Different PVA-hydroxypropyl guar gum irradiated nanosilica composite membranes for model drug delivery device | |
US20070010481A1 (en) | Solid State Irradiation of Hyaluronan-Based Solid Preparations, Its Derivatives And Mixtures In An Unsaturated Gaseous Atmosphere And Their Use | |
Tsvetkova et al. | Polyvinyl alcohol cryogels as the matrix for biomaterials | |
Banat et al. | Study on the properties of crosslinking of poly (ethylene oxide) and hydroxyapatite–poly (ethylene oxide) composite | |
Guha | Articles Related to A Biomimetic Approach to Synthesized 3-Dimensional Poly (Vinyl Alcohol) Hydroxyapatite Scaffolds. Trends in Nanotechnology & Material Science 1: 1-4 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV LY MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
DPEN | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed from 20040101) | ||
B | Later publication of amended claims |
Effective date: 20060321 |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2005806343 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005293727 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2582779 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007535118 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200580034907.9 Country of ref document: CN |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2005293727 Country of ref document: AU Date of ref document: 20051011 Kind code of ref document: A |
|
WWP | Wipo information: published in national office |
Ref document number: 2005293727 Country of ref document: AU |
|
WWP | Wipo information: published in national office |
Ref document number: 2005806343 Country of ref document: EP |