Hydrogel reinforcement using expandable articles and hydrogel expandable article composites

Abstract

A reinforced hydrogel composite comprising a porous synthetic or naturally derived shrinkable membrane material having void volume and a hydrogel that at least partially fills the void volume, wherein the composite has a low strain (<50%) modulus of elasticity of about 0.01 to about 10 MPa and about 10 4 ~about 10 7 J·m 3 It has toughness. A method for manufacturing the reinforced hydrogel composite material and an article containing the reinforced hydrogel composite material are also provided.

Description

Technical Field

[0001] Cross - References to Related Applications This application claims the benefit of Provisional Application No. 63 / 526,774, filed on July 14, 2023, and is hereby incorporated by reference in its entirety for all purposes.

[0002] Field The present disclosure generally relates to hydrogels and methods of strengthening hydrogels. More particularly , the present disclosure relates to hydrogel - inflated article composites and methods of manufacturing and applying them.

Background Art

[0003] Background Hydrogels have unique properties that make them desirable for a wide range of applications in the biomedical, agricultural, cosmetic, electronic, consumer goods, energy, and 3D printing industries. However, their low mechanical properties can limit their adoption.Conventional efforts to improve the mechanical properties of hydrogels have mainly consisted of modifying the underlying polymer structure. These efforts have brought about a radical improvement in mechanical performance, but have often sacrificed the design of the polymer network in consideration of adjacent properties of interest such as cell response, cell seeding, transport properties, shape memory, or wear performance.

[0004] Recent research has focused on the fabrication of hydrogel composites. These strategies have brought about a radical improvement in strength, toughness, extensibility, and fracture resistance, but the elastic modulus of these composites often becomes several orders of magnitude higher than that of neat hydrogels. In many of the applications where hydrogels are being considered, particularly in the biomedical field, it is important to maintain the low elastic modulus of neat hydrogels.

Summary of the Invention

[0005] Summary The present disclosure provides a method for fabricating a hydrogel composite with a polymer fiber reinforcement, which advantageously produces a composite with high toughness and strength and achieves a low elastic modulus at physiologically relevant strains.

[0006] According to one embodiment, the present disclosure provides a reinforced hydrogel composite comprising a porous synthetic or naturally-derived shrinkable membrane material having a void volume and a hydrogel that at least partially fills the void volume, wherein the composite has a low strain (<50%) elastic modulus of from about 0.01 to about 10 MPa and a toughness of from about 10 4 ~ about 10 7 J·m 3 .

[0007] According to a second embodiment, the present disclosure provides a method for preparing a reinforced hydrogel composite, the method comprising: i) providing a synthetic or naturally-derived polymer membrane compressed in at least one direction, the polymer membrane having a node and fibril microstructure and a void volume; ii) optionally pretreating the polymer membrane; iii) at least partially filling the void volume with a hydrogel precursor; and iv) polymerizing the hydrogel precursor to produce a reinforced hydrogel composite comprising a hydrogel embedded in the polymer membrane, wherein the composite has a low strain (<50%) elastic modulus of from about 0.01 to about 10 MPa and a toughness of from about 10 4 ~ about 10 7 J·m 3 .

[0008] According to one embodiment ("Embodiment 1"), the present disclosure relates to a reinforced hydrogel composite comprising a porous synthetic or naturally-derived shrinkable membrane material having a void volume and a hydrogel that at least partially fills the void volume, wherein the composite material has a low strain (<50%) elastic modulus of from about 0.01 to about 10 MPa and a toughness of from about 10 4 ~ about 10 7 J·m 3 .

[0009] Embodiment 2 is the reinforced hydrogel composite material according to Embodiment 1, wherein the film has a microstructure and optionally includes serpentine fibrils or a node-fibril structure.

[0010] Embodiment 3 is a reinforced hydrogel composite material according to Embodiment 2, wherein the average diameter of the fibrils in the node and fibril microstructure is approximately 0.1 μm to 250 μm.

[0011] Embodiment 4 is a reinforced hydrogel composite material according to Embodiment 2, wherein the average separation distance of the nodes in the node and fibril microstructure is approximately 5 to 5000 μm.

[0012] Embodiment 5 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 4, wherein the membrane comprises macrostructure folds or microstructure folded fibrils.

[0013] Embodiment 6 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 5, wherein the membrane material is selected from the group consisting of stretched polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), fluorinated ethylene propylene (FEP), perfluoroalkoxyalkane (PFA), polyester sulfone (PES), expanded polyparaxylylene (ePPX), expanded ultra-high molecular weight polyethylene (eUHMWPE), expanded ethylene tetrafluoroethylene (eETFE), porous poly(tetramethyl-p-sylphenylenesiloxane), expanded porous polylactic acid (ePLLA), polycaprolactone (PCL), polyurethane (PU), copolymer of polyglycolic acid (PGA) and trimethylene carbonate (TMC), silk fibroin, silk spidoin, cellulose, nanocellulose, polyhydroxyalkanoate, and any combination thereof.

[0014] Embodiment 7 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 6, wherein the hydrogel is a polymeric amphoteric electrolyte hydrogel or an amphoteric ionic hydrogel.

[0015] Embodiment 8 is a reinforced hydrogel composite material according to Embodiment 7, wherein the polymeric amphoteric electrolyte hydrogel comprises at least one cationic group and at least one anionic group.

[0016] Embodiment 9 is a reinforced hydrogel composite material according to Embodiment 8, wherein the cationic and anionic groups are randomly dispersed.

[0017] Embodiment 10 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 9, wherein the hydrogel comprises polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly(2-hydroxyethyl methacrylate) (pHEMA), alginate, hyaluronic acid, or chitosan.

[0018] Embodiment 11 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 10, wherein the hydrogel is crosslinked.

[0019] Embodiment 12 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 11, wherein the hydrogel is crosslinked in situ.

[0020] Embodiment 13 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 12, wherein the hydrogel completely fills the void volume.

[0021] Embodiment 14 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 13, wherein the hydrogel further comprises one or more neutral groups.

[0022] Embodiment 15 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 14, wherein the reinforced hydrogel composite material contains 0.01 wt% to 99 wt% hydrogel based on the total mass of the reinforced hydrogel composite material.

[0023] Embodiment 16 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 15, further comprising at least one bioactive agent.

[0024] Embodiment 17 is a reinforced hydrogel composite material according to Embodiment 16, wherein the bioactive agent is selected from the group consisting of thrombotic resistance agents, antibiotic preparations, antitumor agents, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-inflammatory agents, cell cycle regulators and chemically modified equivalents thereof, and combinations thereof.

[0025] Embodiment 18 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 17, wherein the polymer film is in the form of a tape, sheet, tube, fiber, filament, or monolith.

[0026] Embodiment 19 is a reinforced hydrogel composite material according to Embodiment 18, wherein the thickness of the tape, sheet, or tube is approximately 1 μm to 5000 μm.

[0027] Embodiment 20 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 19, wherein the hydrogel is covalently bonded to the polymer film.

[0028] Embodiment 21 is a reinforced hydrogel composite material according to any one of Embodiments 1 to 20, wherein the reinforced hydrogel composite material contains 10 to 95 volume percent of hydrogel within the void volume of the polymer film.

[0029] Embodiment 22 is a laminate comprising the reinforced hydrogel composite material described in any one of Embodiments 1 to 21.

[0030] Embodiment 23 is an article comprising any one of the reinforced hydrogel composites of Embodiments 1 to 21 or the laminate described in Embodiment 22.

[0031] Embodiment 24 is an article that is an implantable medical device, stent, sensor, fuel cell, clothing, footwear, cosmetic, or filter.

[0032] Embodiment 25 is the article according to Embodiment 24, wherein the implantable medical device is selected from the group consisting of conduits, vascular grafts, intravascular grafts, stents, graft stents, catheters, guidewires, trocars, tissue scaffolds, and introducer sheaths.

[0033] Embodiment 26 is a method for producing a reinforced hydrogel composite, i) To provide a synthetic or naturally derived polymer film compressed in at least one direction, having a node-fibril microstructure and void volume, ii) Depending on the circumstances, the polymer film may be pretreated. iii) Filling the void volume at least partially with a hydrogel precursor, and iv) Polymerizing the hydrogel precursor to produce a reinforced hydrogel composite material containing a hydrogel embedded in the polymer film, Includes, Here, the composite material has a low strain (<50%) elastic modulus of approximately 0.01 to approximately 10 MPa and approximately 10 4 ~about 10 7 J·m 3 It possesses toughness.

[0034] Embodiment 27 is the method according to Embodiment 26, wherein the pretreatment of the polymer film includes wetting the polymer film with a solvent.

[0035] Embodiment 28 is the method described in Embodiment 27, wherein the solvent is isopropyl alcohol or acetone.

[0036] Embodiment 29 is the method according to Embodiment 26, wherein the pretreatment of the polymer film includes wetting the polymer film with a hydrogel precursor solution.

[0037] Embodiment 30 is the method described in Embodiment 29, wherein the hydrogel precursor solution is UV-curable, chemically crosslinked, or physically crosslinked.

[0038] Embodiment 31 is the method described in Embodiment 26, wherein the polymer film is a film that has been treated to be hydrophilic.

[0039] Embodiment 32 is a reinforced hydrogel composite material according to Embodiment 7, wherein the amphoteric hydrogel comprises poly(sulfobetaine methacrylate) (SBMA), poly(carboxybetaine methacrylate) (CBMA), poly(2-methacryloyloxyethyl phosphorylcholine) (MPC), or carboxybetaine acrylamide (CBAA).

[0040] The above examples are merely illustrative and should not be construed as limiting or narrowing the scope of the inventive concept provided otherwise by this disclosure. Although several embodiments are disclosed, further embodiments will become apparent to those skilled in the art from the following detailed description, which illustrates and describes exemplary embodiments. Therefore, the drawings and detailed description should be considered as illustrative and not limiting in nature. [Brief explanation of the drawing]

[0041] Brief explanation of the drawing The accompanying drawings are included to provide a further understanding of this disclosure, are incorporated herein, constitute part thereof, illustrate embodiments, and, together with the description, are useful in explaining the principles of this disclosure.

[0042] [Figure 1]Figure 1 shows the stress-strain curves of neat PEG gel (dashed line) and PTFE-reinforced PEG composite material (solid line). The graph on the right is an enlarged version of the graph on the left. The PTFE film was first subjected to in-plane compression at 0% (no compression), 17%, or 29%.

[0043] [Figure 2] Figure 2 shows a log-log plot of elastic modulus versus toughness for neat PEG gel (black circles) and PTFE-reinforced PEG composites (white outlines). All composites showed significantly higher toughness than neat PEG gel, except for the composites with in-plane compressed reinforcement (white outlines and squares), which maintained a low strain modulus comparable to that of neat gel.

[0044] [Figure 3] Figure 3 is a graph showing the stress-strain curves of neat PEG gel (dashed line) and PE-reinforced PEG composite material (solid line). The graph on the right is an enlarged version of the graph on the left. First, the PE film was subjected to in-plane compression at 0% (no compression) or 29%.

[0045] [Figure 4] Figure 4 is a log-log plot showing the modulus versus toughness of neat PEG gel (black circles) and PE-reinforced PEG composite material (white outline). All composite materials showed significantly higher toughness than neat PEG gel, but only the composite material with in-plane compressed reinforcement (white outline) maintained a low strain modulus comparable to that of neat gel.

[0046] [Figure 5] Figure 5 shows the stress-strain curves of neat PAAm gel (dashed line) and PTFE-reinforced PAAm composite material (solid line). The graph on the right is an enlarged version of the graph on the left. First, the PTFE film was subjected to in-plane compression at 0% (no compression) or 23%.

[0047] [Figure 6]Figure 6 shows a log-log plot of elastic modulus versus toughness for neat PAAm gel (black circles) and PTFE-reinforced PAAm composite material (white outline). All composite materials showed significantly higher toughness than neat PAAm gel, but only the composite material with in-plane compressed reinforcement (white outline) maintained a low strain modulus comparable to that of neat gel. [Modes for carrying out the invention]

[0048] Detailed explanation Definitions and Terms This disclosure is not intended to be confined to any particular purpose. For example, terms used in this application should be interpreted broadly in the context of the meanings that a person skilled in the art might assign to such terms.

[0049] With regard to terms relating to inaccuracy, the terms “about” and “approximately” may be used interchangeably to refer to measurements that include the stated measurement and measurements that are reasonably close to the stated measurement. A measurement that is reasonably close to the stated measurement deviates by a reasonably small amount from the stated measurement to the extent that it is understandable and readily verifiable by a person skilled in the art in the relevant technology. Such deviations may result, for example, from measurement errors, differences in the calibration of measuring instruments and / or manufacturing equipment, human error in reading and / or setting of measurements, fine-tuning made to optimize performance and / or structural parameters to account for differences in measurements related to other components, specific implementation scenarios, improper adjustment and / or handling of an object by a person or machine, and / or similar. If it is determined that a person skilled in the art in the relevant technology cannot readily grasp the value of such a reasonably small difference, the terms “about” and “approximately” may be understood to mean plus or minus 10% of the stated value.

[0050] As used herein, the terms “densified,” “shrinked,” or “structured” may be used interchangeably to refer to a polymer-reinforced film that has been densified in one or more transverse or mechanical directions before the application of the hydrogel material. It should be understood that densification is not limited to one direction. Densification can be carried out sequentially or simultaneously in transverse, mechanical, or both directions. In one exemplary embodiment, a polymer-reinforced film is densified transversely before the application of the hydrogel material. The densified polymer-reinforced film forms macrostructural folds and / or microstructural folded fibrils within the film, giving the polymer-reinforced film a low modulus and flexibility. The densified polymer-reinforced film may further, or otherwise, exhibit out-of-plane features such as wrinkles or folds in the film. It should also be noted that a polymer-reinforced film may be “densified” non-mechanically by thermal shrinkage, solvent shrinkage, or other suitable method.

[0051] As used herein, “hydrogel” is defined as a three-dimensional polymer (natural or synthetic) network structure capable of absorbing and retaining large amounts of water, in most cases exceeding 50%. Hydrogels are typically non-soluble due to chemical or physical crosslinking and / or chain entanglement, but can also be designed to dissolve over time. Crosslinking can occur via primary covalent bonds, ionic forces, hydrogen bonds, affinity or biorecognition interactions, hydrophobic interactions, polymer microcrystals, physical entanglement of individual polymer chains, or a combination of two or more of the above interactions. Hydrogels can consist of natural polymers (to name a few, such as collagen, hyaluronic acid, chitosan, heparin, alginate, fibrin, agarose, methylcellulose, hyaluronan, elastin-like polypeptides, etc.) or synthetic polymers (such as polyvinyl alcohol, polyethylene glycol, sodium polyacrylate, acrylate polymers and their copolymers, etc.).

[0052] Throughout this application, the term “PTFE” is used herein for convenience and is intended to include not only polytetrafluoroethylene but also stretched PTFE, stretched modified PTFE, and copolymers of stretched PTFE, as described in Branca’s U.S. Patent No. 5,708,044, Baillie’s U.S. Patent No. 6,541,589, Sabol et al.’s U.S. Patent No. 7,531,611, Ford’s U.S. Patent No. 8,637,144, and Xu et al.’s U.S. Patent No. 9,139,669.

[0053] Description of various embodiments I. Hydrogels

[0054] This disclosure provides a reinforced hydrogel composite material comprising a membrane material and a hydrogel filled within the membrane.

[0055] A hydrogel is a three-dimensional network of hydrophilic polymers with polymer chains capable of absorbing and retaining water or aqueous solutions. Hydrogels are typically formed by a crosslinking process in which polymer chains are chemically bonded to form a network structure. Crosslinking can be achieved by covalent bonding, physical entanglement, or a combination of both.

[0056] Hydrogels have a wide range of applications and are commonly used in biomedical applications such as implantable articles. Other applications of hydrogels include tissue engineering scaffolds (cartilage, connective tissue, cardiovascular, nerve regeneration, reconstructive surgery), agriculture (seaweed, almonds, film cultivation, water supply, root systems), drug delivery, filtration and separation (chromatography, water purification, carbon dioxide recovery, aqueous reaction separation, dye and heavy ion removal), soft robotics (artificial muscles, surgery), energy storage (supercapacitors, battery anodes, separators, lithium ion conductors), wound dressings, and synthetic tissue replacement.

[0057] In implant applications, hydrogels typically involve matching the mechanical properties of the implantable object to those of the surrounding tissue. Many hydrogels lack sufficient strength or toughness for their intended applications. Therefore, in many applications, it may be necessary to combine the hydrogel with a reinforcing matrix to achieve greater mechanical durability.

[0058] II. Polymer-reinforced films and movies

[0059] Polymer-reinforced matrices are used in the manufacture of composite hydrogel articles with improved mechanical properties. Polymer-reinforced films are microporous films that can be made from a variety of polymers. In one embodiment, the polymer-reinforced film comprises a nonwoven fibrous microstructure formed by conventional spinning techniques (melt spinning, solvent spinning (dry, wet, gel, electrospinning, etc.)), and these spinning techniques can be combined with subsequent processing steps such as calendering, stretching / orientation, and heat treatment. In another embodiment, the polymer-reinforced film is formed by expanding / stretching (e.g., uniaxial, biaxial, radial) a fibrillable polymer. The resulting nonwoven fabric typically has polymer fiber / fibril diameters ranging from nanometers to micrometers.

[0060] In exemplary embodiments, polymer-reinforced films can be formed from fibrillable polymers by expanding / stretching a preform to create a porous article having a fibrillated microstructure. The fibrillated microstructure may include nodes interconnected by fibrils. Alternatively, the film may include macrostructure folds or microstructure folded fibrils.

[0061] Specific examples of fibrillable polymers (e.g., those that can be processed into films having node and fibril microstructures) include, but are not limited to, ultra-high molecular weight polyethylene (UHMWPE), polylactic acid, copolymers of vinylidene fluoride with tetrafluoroethylene or trifluoroethylene (e.g., VDF-co-(TFE or TrFE) polymers), poly(ethylenetetrafluoroethylene) (ETFE), polyparaxylxylene (PPX), polytetrafluoroethylene (PTFE), and (tetramethyl-p-sylphenylenesiloxane).

[0062] In another embodiment, the polymer-reinforced film is a porous fluoropolymer film. In at least one exemplary embodiment, the polymer-reinforced film is a polytetrafluoroethylene (PTFE) film or a stretched polytetrafluoroethylene (ePTFE) film. In a preferred embodiment, the polymer-reinforced film is a stretched polytetrafluoroethylene film. Stretched polytetrafluoroethylene (ePTFE) films are manufactured according to several different methods, including compression molding, lamb extrusion, paste extrusion, gel spinning, suspension coagulation, solvent-induced phase separation, biaxial stretching, permeable film lamination, and sintering. Treatment of the polytetrafluoroethylene polymer at a temperature below the melting temperature of the polytetrafluoroethylene polymer is also a suitable method. Preferably, stretched polytetrafluoroethylene (ePTFE) films manufactured by the above methods have high strength, a microstructure consisting of nodes and fibrils, and high porosity.

[0063] Other suitable membrane materials include polyvinylidene fluoride (PVDF), fluorinated ethylene propylene (FEP), perfluoroalkoxyalkanes (PFA), polyester sulfones (PES), expanded polyparaxylylene (ePPX), expanded ultra-high molecular weight polyethylene (eUHMWPE), expanded ethylene tetrafluoroethylene (eETFE), porous poly(tetramethyl-p-sylphenylenesiloxane), expanded porous polylactic acid (ePLLA), polycaprolactone (PCL), polyurethane (PU), copolymers of polyglycolic acid (PGA) and trimethylene carbonate (TMC) (e.g., GORE® BIO-A® available from WL Gore & Associates), as well as naturally isolated or synthesized biopolymers such as polypeptides / proteins (e.g., silk fibroin / spidoin), polyhydroxyalkanoate (PHA) homopolymers and copolymers, cellulose, nanocellulose, and combinations thereof.

[0064] Porous fluoropolymer films may include polymer materials containing functional tetrafluoroethylene (TFE) copolymer materials, where the functional TFE copolymer material includes functional copolymers of TFE and PSVE (perfluorosulfonyl vinyl ether), or functional TFE copolymers of TFE and other suitable functional monomers (e.g., but not limited to vinylidene fluoride (VDF), vinyl acetate, or vinyl alcohol). Functional TFE copolymer materials can be manufactured, for example, according to the methods described in U.S. Patent No. 9,139,707 or U.S. Patent No. 8,658,707 by Xu et al.

[0065] In another embodiment, porous reinforced films having node and fibril microstructures are formed from ultra-high molecular weight polyethylene (UHMWPE). In a preferred embodiment, the porous reinforced film is an expanded UHMWPE ("ePE") having a fibrilized microstructure, preferably a microstructure in which nodes are interconnected by fibrils, which is produced by expanding / stretching a UHMWPE preform formed by a solvent-free process (solid-phase processing), a solvent-type process (gel-treated UHMWPE), or a paste-process of UHMWPE resin particles with a suitable hydrocarbon lubricant. In a preferred embodiment, the ePE porous reinforced film is formed by a paste-process as described in Sbriglia's U.S. Patent No. 10,577,468. The ePE film may be formed from an ethylene homopolymer or a copolymer of ethylene and at least one suitable comonomer (including, but not limited to, α-olefins or cyclic olefins having 3 to 20 carbon atoms). Non-limiting examples of suitable comonomers include 1-butene, 1-pentene, 1-hexene, 1-heptene, 1-octene, cyclohexene, and dienes having up to 20 carbon atoms (e.g., butadiene, 1,4-cyclohexene). Comonomers can be present in the UHMWPE copolymer in amounts of about 0.001 mol% to about 10 mol%, about 0.01 mol% to about 5 mol%, or about 0.001 mol% to about 1 mol%. The ePE membrane / film may include a blend of fibrillable UHMWPE with one or more low molecular weight polyethylenes (e.g., with an average molecular weight of less than 1,000,000, e.g., HDPE).

[0066] In one embodiment, the fibrils in the nodes and fibril microstructure have average diameters as low as 0.01 μm, 0.1 μm, 1 μm, 5 μm, 10 μm, 25 μm, 50 μm, 75 μm, 100 μm, 125 μm, 150 μm, 175 μm, 200 μm, 225 μm, and 250 μm, or within any range encompassing any two of the aforementioned values ​​as endpoints. For example, the fibrils in the nodes and fibril microstructure have average diameters of approximately 0.1 μm to 250 μm.

[0067] In one embodiment, the nodes and nodes in the fibril microstructure have an average separation distance of as low as 1 μm, 50 μm, 100 μm, 500 μm, 1000 μm, 1500 μm, 2000 μm, 2500 μm, 3000 μm, 3500 μm, 4000 μm, 4500 μm, 5000 μm, 5500 μm, and 6000 μm, or any range encompassing any two of the aforementioned values ​​as endpoints.

[0068] In one embodiment, the polymer-reinforced film has a surface density of 5 g / m². 2 Below, 4g / m 2 Below 3g / m 2 Below, 2g / m 2 The following, or 1 g / m² 2 The following is the case: In another embodiment, the polymer-reinforced film has a surface density of 5 g / m². 2 ~0.01g / m 2 4g / m 2 ~0.1g / m 2 , 3g / m 2 ~0.1g / m 2 , 2g / m 2 ~0.1g / m 2 4g / m 2 ~0.2g / m 2 , or 3g / m 2 ~0.2g / m 2 It is within the range.

[0069] In another embodiment, the polymer-reinforced film has a thickness of 1 cm or less, 0.5 cm or less, 0.1 cm or less, or 0.01 cm or less. In yet another embodiment, the polymer-reinforced film has a thickness of at least 0.05 μm, at least 0.1 μm, or at least 0.2 μm. In another embodiment, the polymer-reinforced film has a thickness in the range of 0.5 cm to 0.05 μm, 5 mm to 0.05 μm, 1 mm to 0.05 μm, 500 μm to 0.05 μm, 100 μm to 0.05 μm, 50 μm to 0.05 μm, 40 μm to 0.05 μm, 30 μm to 0.05 μm, 20 μm to 0.05 μm, 15 μm to 0.05 μm, 40 μm to 0.1 μm, 30 μm to 0.1 μm, 20 μm to 0.1 μm, 15 μm to 0.1 μm, 10 μm to 0.1 μm, 40 μm to 0.2 μm, 30 μm to 0.2 μm, 20 μm to 0.2 μm, or 10 μm to 0.2 μm.

[0070] The polymer-reinforced film (before coating or absorption) has a porosity of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, or at least 80%. In one embodiment, the polymer-reinforced film has a porosity in the range of 10% to 98%, 20% to 98%, 30% to 98%, 40% to 98%, 50% to 98%, 10% to 90%, 10% to 85%, 10% to 80%, 10% to 70%, or 20% to 85%.

[0071] The polymer-reinforced film has a matrix tensile strength (MTS) of at least about 30 MPa, at least about 50 MPa, at least about 100 MPa, at least about 150 MPa, at least about 200 MPa, or at least 300 MPa in both the mechanical direction (MD) and the transverse direction (TD) (direction perpendicular to MD) before densification. With respect to matrix tensile strength, the polymer-reinforced film before densification can be unbalanced (strength in one direction is significantly different from strength in the orthogonal direction) or balanced (strength in MD and TD are equal). In another embodiment, the polymer-reinforced film has a matrix tensile strength ratio measured as MD:TD of about 0.1:1.0 to 1.0:0.1, or about 0.5:1.0 to 1.0:0.5, or about 0.7:1.0 to 1.0:0.7.

[0072] In another embodiment, the polymer film is in the form of a tape, sheet, membrane / film, tube, fiber, filament, or monolith.

[0073] In some embodiments, when the polymer film is in the form of a tape, sheet, or tube, the thickness of the tape, sheet, or tube can be as low as 1 μm, 50 μm, 100 μm, 500 μm, 1000 μm, 1500 μm, 2000 μm, 2500 μm, 3000 μm, 3500 μm, 4000 μm, 4500 μm, 5000 μm, 5500 μm, or 6000 μm, or any range including any two of the aforementioned values ​​as endpoints. For example, the thickness of the tape, sheet, or tube can be approximately 1 μm to 5000 μm.

[0074] III. Structured or densified reinforced membranes

[0075] This disclosure also includes hydrogels having a structured or densified reinforced membrane.

[0076] In some embodiments, the porous polymer-reinforced membranes of Section II are subjected to a structuring / densification treatment before the application of the hydrogel component. As used herein, the terms “structured,” “densified,” or “compressed” refer to a porous-reinforced film / membrane that has undergone densification, thereby increasing the surface density of the porous film / membrane (compared to the porous film before densification) and reducing the modulus by introducing finely folded fibers / fibrils and / or macroscopic structures (wrinkles / folds) into the porous film / membrane. The relative amount of densification / compression can be adjusted to selectively introduce only finely folded fibrils (to minimize out-of-plane wrinkles / folds / buckling in the Z-axis direction), or to include a level of densification that can introduce out-of-plane shapes (in addition to finely folded fibers / fibrils). The amount of densification introduced is the rate of increase in surface density relative to the starting porous-reinforced membrane and can be adjusted to obtain the desired change in modulus. The densified film / membrane maintains sufficient porosity to be coated / absorbed with a hydrogel (or to form a hydrogel in situ within the densified porous film). In-plane densification / structuring can be performed uniaxially (in one direction) or biaxially (in two orthogonal directions). In one embodiment, in-plane densification / compression is performed in one direction (uniaxial). In another embodiment, in-plane densification / compression is performed in at least two orthogonal directions (biaxial).

[0077] In one embodiment, a densified porous film / membrane is formed using a general method described in U.S. Patent No. 11,097,527 by Zaggl et al., such that little or no substantial macroscopic structure in the Z-axis direction is introduced (i.e., by fiber / fibril densification).

[0078] In another embodiment, the densified polymer-reinforced film may additionally or alternatively exhibit out-of-plane features such as wrinkles or folds ("buckles"), as described in Zaggl et al. EP3061598 A1 and Zaggl et al. U.S. Patent No. 9,849,629, without limit. It should be noted that thermal shrinkage, solvent shrinkage, or other suitable methods may also be used to "densify" the polymer-reinforced film non-mechanically.

[0079] The "buckles" or out-of-plane structures in the densified film / film can have a height of at least twice the thickness of the undensified film / film. Furthermore, the height of the out-of-plane (i.e., z-direction) structures can be in the range of about 2 μm to about 2000 μm, or about 20 μm to about 1000 μm. Furthermore, the structural density in at least one direction is at least 1 buckle per mm, at least 2 buckles per mm, at least 3 buckles per mm, at least 4 buckles per mm, at least 5 buckles per mm, at least 6 buckles per mm, at least 7 buckles per mm, at least 8 buckles per mm, at least 9 buckles per mm, or at least 10 buckles per mm. In some embodiments, the structural density is 1 to 10 buckles per mm, 1 to 7 buckles per mm, 1 to 5 buckles per mm, or 1 to 3 buckles per mm.

[0080] The relative amount of densification / compression introduced in-plane into a porous polymer-reinforced membrane can be adjusted to achieve desired mechanical properties. The percentage of densification / compression introduced into the porous reinforced membrane / film is in the range of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% (relative to the increase in surface density of the porous reinforced film / membrane before densification) in at least one direction. The maximum amount of densification / compression is 80%, 70%, 60%, 50%, 40%, or 30% or less in at least one direction. In a further embodiment, the densification / compression percentage is 1% to 80%, 3% to 70%, 3% to 60%, 3% to 50%, 3% to 40%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, or 10% to 40% in at least one direction.

[0081] In some embodiments, the shrinkable membrane material can be a layer of polymer composite material, which can be non-porous, microporous, or porous. Various non-porous materials that can be used for the shrinkable membrane material include polymer films (e.g., TPU, PET, silicone, polystyrene block copolymer, FEP, etc.) or polymer composite materials. Porous materials, including stretched polytetrafluoroethylene (ePTFE) materials and ePTFE composite materials, offer a good balance of acoustic properties and waterproofing. Various porous and non-porous materials, in addition to being very thin and lightweight, can have excellent acoustic conductivity and provide excellent waterproofing. In some cases, the membrane material can be treated. For example, the membrane material may include an oleophobic coating, for example, with an oleophobic polymer, before or after the membrane material is shrunk.

[0082] In various embodiments, shrinkable film materials have a microstructure containing meandering fibrils. As used herein, the term “meandering fibril” means a plurality of fibrils that bend or rotate in one direction and then bend or rotate in another direction. Meandering fibrils can generally have a width of about 1.0 micron or less. Meandering fibrils can be connected by nodes. Meandering fibrils can be formed by controlled shrinkage, for example, as described in U.S. Patent Publication No. 2013 / 0183515. Controlled shrinkage can be achieved by shortening the length of an article in at least one direction by heating, solvent wetting, or other suitable means or a combination thereof, thereby suppressing folds, folds, or wrinkles in the subsequent article that are visible to the naked eye. Shrinkable films can be made by shrinking a precursor film, thereby converting a substantial portion of the fibrils therein into meandering fibrils. In some cases, articles shrunk in accordance with the teachings of this disclosure may need to be stretched in the direction of shrinkage in order to identify meandering fibrils.

[0083] IV. Reinforced Hydrogel Composites

[0084] This disclosure provides a hydrogel composite material in which at least one hydrogel is partially or completely absorbed into a densified polymer-reinforced film.

[0085] In one embodiment, the reinforced hydrogel composite comprises a porous synthetic or naturally occurring shrinkable membrane material having void volume and a hydrogel that at least partially fills the void volume, wherein the composite has a low strain (<50%) modulus of elasticity of about 0.01 to about 10 MPa and about 10 4 ~about 10 7 J·m 3 It possesses toughness.

[0086] Reinforced hydrogel composites can have low strain (<50%) modulus values ​​such as 0.01 MPa, 0.1 MPa, 1 MPa, 2 MPa, 3 MPa, 4 MPa, 5 MPa, 6 MPa, 7 MPa, and 8 MPa, as well as high values ​​such as 9 MPa, 10 MPa, 11 MPa, 12 MPa, 13 MPa, 14 MPa, and 15 MPa, or any range including any two of these values ​​as endpoints. For example, reinforced hydrogel composites can have low strain (<50%) modulus values ​​from 0.01 MPa to 10 MPa.

[0087] The reinforced hydrogel composite has a toughness of 10 1 J·m 3 , 10 2 J·m 3 , 10 3 J·m 3 , 10 4 J·m 3 , 10 5 J·m 3 , 10 6 J·m 3 , 10 7 J·m 3 , 10 8 J·m 3 , 10 9 J·m 3 , 10 10 J·m 3 It can be a low value, or any range that includes any two of the aforementioned values ​​as endpoints. For example, reinforced hydrogel composites have a toughness of approximately 10 4 J·m 3 ~about 10 7 J·m 3 It can be.

[0088] In some embodiments, the reinforced hydrogel composite material contains 0.01 wt% to 99 wt% hydrogel (mass percentage based on the total mass of the reinforced hydrogel composite material). In some embodiments, the reinforced hydrogel composite comprises at least 0.01 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%, 80 wt%, 85 wt%, 90 wt%, 95 wt%, 96 wt%, 97 wt%, 98 wt%, or 99 wt% hydrogel (mass percentage based on the total mass of the reinforced hydrogel composite).

[0089] In some embodiments, the reinforced hydrogel composite includes hydrogel in a range of low values ​​such as 0.01 wt% (mass based on the total mass of the reinforced hydrogel composite), 0.1 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, or high values ​​such as 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%, 80 wt%, 85 wt%, 90 wt%, 95 wt%, 96 wt%, 97 wt%, 98 wt%, or 99 wt%, or any range encompassing any two of the aforementioned values ​​as endpoints. For example, a reinforced hydrogel composite may contain 0.01 wt% to 99 wt% hydrogel, depending on the mass of the reinforced hydrogel composite.

[0090] In another embodiment, the reinforced hydrogel composite material comprises 1 wt% to 99 wt% porous synthetic or naturally derived shrinkage membrane material (mass percentage based on the total mass of the reinforced hydrogel composite material). In one embodiment, the reinforced hydrogel composite comprises at least 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%, 80 wt%, 85 wt%, 90 wt%, 95 wt%, 96 wt%, 97 wt%, 98 wt%, or 99 wt% of porous synthetic or naturally derived shrinkable membrane material (mass percentage based on the total mass of the reinforced hydrogel composite).

[0091] The hydrogel component partially or completely fills the void volume of the porous synthetic or naturally occurring shrinkage membrane material. In one embodiment, the hydrogel comprises at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the void volume of the densified and strengthened membrane. In another embodiment, substantially 100% of the void volume in the membrane is filled with hydrogel. In yet another embodiment, the hydrogel completely fills the void volume.

[0092] Reinforced hydrogel composites can contain as little as 10 volume% hydrogel within the void volume of the polymer membrane, or as low as 20, 30, 40, 50, or 60 volume%, or as high as 70, 80, 90, or 95 volume%, or any range encompassing any two of the above values ​​as endpoints. For example, reinforced hydrogel composites can contain 10 to 95 volume% hydrogel within the void volume of the polymer membrane.

[0093] The hydrogel can be crosslinked and subsequently absorbed into a membrane / film, or the hydrogel can be formed in situ (formed from a hydrogel precursor absorbed into a densified reinforcing membrane). In a preferred embodiment, the hydrogel is formed by polymerizing or crosslinking a hydrogel precursor absorbed into a densified reinforcing membrane.

[0094] In some embodiments, the hydrogel is covalently bonded to the polymer film.

[0095] The reinforced hydrogel composite material has a thickness of 1 cm or less, 0.5 cm or less, 0.1 cm or less, or 0.01 cm or less. In another embodiment, the polymer-reinforced film has a thickness of at least 0.05 μm, at least 0.1 μm, or at least 0.2 μm. In another embodiment, the polymer-reinforced film has a thickness in the range of 0.5 cm to 0.05 μm, 5 mm to 0.05 μm, 1 mm to 0.05 μm, 500 μm to 0.05 μm, 100 μm to 0.05 μm, 50 μm to 0.05 μm, 40 μm to 0.05 μm, 30 μm to 0.05 μm, 20 μm to 0.05 μm, 15 μm to 0.05 μm, 40 μm to 0.1 μm, 30 μm to 0.1 μm, 20 μm to 0.1 μm, 15 μm to 0.1 μm, 10 μm to 0.1 μm, 40 μm to 0.2 μm, 30 μm to 0.2 μm, 20 μm to 0.2 μm, or 10 μm to 0.2 μm.

[0096] In another embodiment, at a 5% stress, a reinforced hydrogel composite (including a densified reinforcing film) exhibits reduced strain compared to a reinforced hydrogel composite having an undensified (i.e., 0% densification) reinforcing film. In one embodiment, at a 5% stress, a reinforced hydrogel composite has greater strain than an unreinforced hydrogel. In another embodiment, at a 5% stress, a reinforced hydrogel composite has greater strain than an unreinforced hydrogel (e.g., greater than 2.5 kPa in the case of unreinforced PEG) and has strains of less than 500 kPa, less than 250 kPa, less than 200 kPa, less than 100 kPa, less than 50 kPa, or less than 25 kPa.

[0097] The components may include viscous chemical compositions, such as, but are not limited to, hydrogel materials. Bioactive substances may be combined with the hydrogel material or any other additive chemical components as needed. For example, when a hydrogel material is used, the bioactive substance may be released directly from the hydrogel material or released when the hydrogel material and the underlying expansion material are absorbed into the implant recipient's body.

[0098] Suitable hydrogels can be made from a variety of natural or synthetic polymers. Hydrogels included in this disclosure include polyvinyl alcohol, polyethylene glycol, polypropylene glycol, dextran, agarose, alginate, carboxymethylcellulose, hyaluronic acid, polyacrylamide, polyglycidol, poly(vinyl alcohol-co-ethylene), poly(ethylene glycol-co-propylene glycol), poly(vinyl acetate-co-vinyl alcohol), poly(tetrafluoroethylene-co-vinyl alcohol), poly(acrylonitrile-co-acrylamide), poly(acrylonitrile-co-acrylic acid-acrylamidine), and poly(acrylonitrile). The polymer may contain, alone or in combination with, or be derived from, polynitrile-co-acrylic acid-co-acrylamidine, polyacrylic acid, polylysine, polyethyleneimine, polyvinylpyrrolidone, polyhydroxyethyl methacrylate, poly(2-hydroxyethyl methacrylate) alginate, hyaluronic acid or chitosan, polysulfone, mercaptosilane, aminosilane, hydroxylsilane, polyallylamine, polyaminoethyl methacrylate, polyomitin, polyaminoacrylamide, polyacrolein, acrylooxysuccinimide, or copolymers thereof. Suitable solvents for dissolving hydrophilic polymers include, but are not limited to, water, alcohol, dioxane, dimethylformamide, tetrahydrofuran, and acetonitrile.

[0099] The hydrogels of this disclosure may be polymeric amphoteric electrolyte hydrogels. These polymeric amphoteric electrolyte hydrogels contain at least one cationic group and at least one anionic group, which may be randomly dispersed throughout the hydrogel (see, for example, Ihsan et al., Macromolecules (2016) 49:4245-4252 and Sun et al., Nat. Mat. (2013) 12:932-937). In another embodiment, the hydrogel can be an amphoteric hydrogel such as poly(sulfobetaine methacrylate) (SBMA), poly(carboxybetaine methacrylate) (CBMA), poly(2-methacryloyloxyethyl phosphorylcholine) (MPC), and carboxybetaine acrylamide (CBAA) (Carr et al., Biomaterials (2011) 32: 6893e6899 and Zhang et al., Carbohydrate Polymers (2021) 257:117627). In another embodiment, the hydrogel may further contain one or more neutral groups.

[0100] In some cases, the composition may undergo chemical changes after being mixed with the expanded PLA polymer. These chemical changes may be chemically reactive groups that interact with the polymer components of the expanded PLA polymer, or chemically reactive groups that interact with the chemically reactive groups of the composition itself. These chemical changes to the composition may function as binding sites for chemical bonding, but may also function as other chemical compositions, such as bioactive substances. Examples of "bioactive substances" include enzymes, organocatalysts, ribozymes, organometallic compounds, proteins, glycoproteins, peptides, polyamino acids, antibodies, nucleic acids, steroid molecules, antibiotics, antifungal agents, cytokines, carbohydrates, oleophobic agents, lipids, extracellular matrix materials and / or their individual components, pharmaceuticals and therapeutic agents. One non-limiting example of a chemically based bioactive substance is dexamethasone. Cells, e.g., mammalian cells, reptile cells, amphibian cells, avian cells, insect cells, plankton cells, cells of non-mammalian marine vertebrates and invertebrates, plant cells, microbial cells, protists, genetically modified cells, and organelles such as mitochondria are also bioactive substances. Furthermore, non-cellular biological entities such as viruses, virenus, and prions are considered bioactive substances in this specification.

[0101] V. Additional materials

[0102] The hydrogel composites of this disclosure may also include additional materials such as certain organic and / or inorganic fillers, additional polymers, and bioactive agents. In one embodiment, examples of additional materials include materials that improve frictional dynamics and enhance antifouling properties.

[0103] In one embodiment, bioactive agents include thrombotic resistance agents, antibiotic preparations, antitumor agents, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-inflammatory agents, cell cycle regulators, and chemically modified equivalents and combinations thereof.

[0104] The reinforced hydrogel composite may contain additional material in amounts of 90 wt% or less (based on the total mass of the reinforced hydrogel composite). In one embodiment, the reinforced hydrogel composite may contain additional material in amounts of 0.1 wt% to 90 wt%, 0.1 wt% to 80 wt%, 0.1 wt% to 70 wt%, 0.1 wt% to 60 wt%, 0.1 wt% to 50 wt%, 0.1 wt% to 40 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 25 wt%, 0.1 wt% to 20 wt%, 0.1 wt% to 15 wt%, or 0.1 wt% to 10 wt%.

[0105] VI. Lamination

[0106] This disclosure also provides laminates comprising the reinforced hydrogel composite described in Section IV above. The reinforced hydrogel composite may be laminated to one or more woven or nonwoven support materials.

[0107] VII. Articles containing reinforced hydrogel composites

[0108] This disclosure also provides articles comprising the reinforced hydrogel composites or laminates described in Sections IV and VI above.

[0109] The articles may be implantable medical devices, stents, sensors, fuel cells, clothing, footwear, cosmetics, or filters.

[0110] Appropriate medical devices include conduits, vascular grafts, intravascular grafts, stents, graft stents, catheters, guidewires, trocars, tissue scaffolds, and introducer sheaths.

[0111] VIII. Method for manufacturing reinforced hydrogel composites

[0112] This disclosure also provides a method for producing the reinforced hydrogel composite described herein. This method comprises the following steps: i) To provide a synthetic or naturally derived polymer film compressed in at least one direction, having a node-fibril microstructure and void volume; ii) Pre-treating the polymer film as appropriate; iii) Filling the void volume at least partially with a hydrogel precursor; and iv) Polymerizing the hydrogel precursor to produce a reinforced hydrogel composite material containing hydrogel embedded in the polymer film. Includes, The aforementioned composite material has a low strain (<50%) modulus of elasticity of approximately 0.01 to approximately 10 MPa, and approximately 10 4 ~about 10 7 J·m 3 It possesses toughness.

[0113] In some embodiments, the pretreatment of the polymer film may include wetting the polymer film with a solvent or solvent mixture that provides sufficient wettability of the polymer film and solubility of the hydrogel precursor. Examples of suitable solvents include isopropyl alcohol, acetone, or mixtures thereof.

[0114] In some embodiments, the pretreatment of the polymer film may include wetting the polymer film with a hydrogel precursor solution. Suitable hydrogel precursor solutions include UV-curable solutions, chemically crosslinkable solutions, or physically crosslinkable solutions.

[0115] In another embodiment, an optional pretreatment step is omitted, and the polymer film can be a pre-treated film, such as a hydrophilic film.

[0116] Those skilled in the art will readily understand that various aspects of this disclosure can be realized by any number of methods and apparatus configured to perform the intended functions. Furthermore, it should be noted that the accompanying drawings referenced herein are not necessarily drawn to scale and may be exaggerated to illustrate various aspects of this disclosure; in this respect, the drawings should not be construed as limiting.

[0117] Test method The following describes specific methods and apparatus, but please understand that other methods or apparatus deemed appropriate by those skilled in the art may be used instead.

[0118] Various test methods (e.g., measurement of porosity, thickness, and mechanical properties) can be used to characterize reinforced films and composite materials.

[0119] Mass per unit area (mass / area)

[0120] The mass per unit area of ​​the sample is measured using a Mettler-Toledo scale, Model 1060, according to ASTM D 3776 (Standard test method for mass (weight) per unit area of ​​fabric) test method (Option C). The scale is recalibrated before measuring the weight of the sample, and the result is expressed in grams per square meter (g / m²). 2 ) will be reported.

[0121] thickness

[0122] The film thickness is measured by placing the sample (e.g., a composite film) between two plates of a Kafer FZ1000 / 30 thickness snap gauge (Kafer Messuhrenfabrik GmbH, Villingen-Schwenningen, Germany). The average of three measurements is used.

[0123] Bulk density

[0124] The bulk density of a sample is the density of the solid including all open pores and internal void volumes. Bulk density is calculated by dividing the sample mass by the volume of low-pressure mercury intrusion. The sample mass is determined by weighing it on an analytical balance with a sensitivity of ±0.01 mg.

[0125] Bulk density=M / (V low pressure )

[0126] Mercury porosimetry test

[0127] Porosity measurements can be performed using a Micromeritics AutoPore V mercury porosimeter (Micromeritics, Norcross, Georgia, USA) with Micromeritics MicroActive software version 2.0. For the test, 99.9995% pure quadruple-distilled virgin mercury (Bethlehem Apparatus, Bethlehem, Pennsylvania) is used as received. A solid-state penetrometer (serial number: 07-0979) with a valve volume of 5cc and a stem volume of 0.392cc can be used for the test. Cut the composite sample into 1cm x 2cm pieces, and weigh a sufficient quantity of these pieces on an analytical balance so that the total mass is approximately 0.25g. After recording the mass, place the sample pieces in the penetrometer.

[0128] The test parameters may be as follows: (1) Place the penetrometer in the low-pressure port of the autopore, reduce the pressure to 50 μmHg, and then reduce the pressure without restriction for 5 minutes. (2) Next, fill the penetrometer with mercury at 0.5 psia (approximately 3.5 kPa) and equilibrate for 10 seconds. Subsequently, apply pressure to the capillary in stages using nitrogen up to 30 psia (approximately 0.21 MPa), equilibrate for 10 seconds at each stage, and then measure the penetration volume by standard capacitance measurement using the penetrometer capillary. (3) Next, return the penetrometer to atmospheric pressure, remove it from the low-pressure port, and then determine the amount of mercury added by weighing it. (4) Next, place the penetrometer in the high-pressure port of the autopore, and gradually increase the pressure to approximately 60,000 psia (approximately 413.7 MPa), maintain equilibrium for 10 seconds at each stage, and then measure the penetration volume.

[0129] The penetration volume V at any given pressure is determined by capacitance measurement using a pre-calibrated capillary (i.e., a cylindrical capacitor with a metallized coating on the outer surface of a glass capillary at the outer contact, liquid mercury at the inner contact, and a glass capillary as the dielectric). Dividing the total penetration volume by the sample mass yields the specific penetration volume (mL / g).

[0130] Next, the volume occupied by the sample is calculated at two extreme target pressures, namely 0.5 psia (approximately 3.5 kPa) and 60,000 psia (approximately 413.7 MPa). Since the penetrometer has a known calibrated volume, the difference between this volume and the mercury volume (determined from the mass increase after mercury addition at low pressure and the density of mercury) is the volume of the sample including all pores. Dividing the mass of the sample by this volume at low pressure gives the bulk density of the sample. At high pressure, where the amount of mercury pushed into the pores is given by the intrusion volume, the skeleton density can be estimated by dividing the mass of the sample by the adjusted sample volume (e.g., the low-pressure volume minus the total intrusion volume).

[0131] Skeletal density

[0132] Skeleton density is the density of the solid excluding all open pores and internal void volumes. Skeleton density is calculated by dividing the sample mass by the adjusted sample volume (low-pressure volume minus total penetration volume). The sample mass is measured by weighing with an analytical balance with a sensitivity of ±0.01 mg. The formula for calculating skeleton density is provided below. Skeletal density = M / ((V low pressure )-(V high pressure ))

[0133] In the above formula, V low pressure V is the sample volume at 0.5 psia (approximately 3.5 kPa). high pressure This is the total intrusion volume at 60,000 psia (approximately 413.7 MPa).

[0134] Total porosity

[0135] The total porosity within the substrate is the value obtained by dividing the sample's void volume by the total volume of the sample. This can be calculated using the following formula: % porosity = 100 × (total penetration volume at 60,000 psia (approximately 413.7 MPa)) / (sample volume at 0.5 psia (approximately 3.5 kPa)).

[0136] Tensile properties

[0137] Tensile properties can be measured using an Instron tensile testing machine based on ASTM standard D412F. The tensile test specimen is 12.70 cm (5.0 inches) in length and 0.64 cm in width. 2 It is molded into a dogbone shape (0.25 inches). The gauge length is 5.89 cm (2.32 inches), and the crosshead speed is 47.12 cm / min (18.55 inches / min). Three measurements can be taken in both the MD and TD directions. The breaking load in each direction is calculated as the average of the three measurements. [Examples]

[0138] example Unless otherwise specified herein, all technical and scientific terms used herein have the meanings generally understood by those skilled in the art in which the present invention pertains. The present invention is described in further detail in the following examples. These examples illustrate preferred embodiments of the present invention, but should be understood to be provided for illustrative purposes only. From the above description and these examples, those skilled in the art can grasp the essential features of the present invention and can make various changes and modifications to adapt the present invention to various uses and conditions without departing from the spirit and scope of the present invention.

[0139] Unless otherwise specified, the materials and solvents used in the preparation of the hydrogels were obtained from Sigma-Aldrich, Inc. in St. Louis, Missouri. The polytetrafluoroethylene film was manufactured by WL Gore & Associates, Inc. in Newark, Delaware.

[0140] Example 1 This first example demonstrates the mechanical strengthening of a polyethylene glycol (PEG) hydrogel using an in-plane compressed polytetrafluoroethylene (PTFE) film without substantially altering the elastic modulus of the gel. Two levels of in-plane compression (17% and 29%) are shown compared to a comparative example with no film compression (0%).

[0141] Uniaxial in-plane compression of porous reinforced film

[0142] A stretched PTFE (ePTFE) porous film, prepared according to the method described in U.S. Patent No. 5,814,405 by Branca et al., was subjected to uniaxial in-plane compression with the assistance of a silicone carrier using the method described in U.S. Patent No. 11,097,527 by Zaggl et al. Briefly, a rectangular silicone sheet with a thickness of 0.4 mm and a jurometer Shore A hardness of 27 was fixed to a laboratory machine, with approximately six clamps attached to each of its four sides. Using software-controlled clamps, the silicone was uniformly stretched until one side of the rectangular sheet was stretched to a target elongation ratio λ. Next, the reinforced film was placed flat on the silicone sheet, with the desired compression axis parallel to the deformation axis of the silicone sheet. Residual air pockets between the film and silicone were removed with the assistance of a vacuum plate. Then, by returning the clamps to their original positions, an in-plane uniaxial compression of 1-1 / λ was applied to the film while effectively restoring the silicone to its undeformed state. [Table 1]

[0143] Removal of compressed film from silicone carrier

[0144] After in-plane compression, small areas of the film were individually peeled from the silicone using a flexible adhesive-backed plastic frame as an aid. Briefly, an adhesive-backed plastic sheet was cut into approximately 40mm squares, and the center of each sheet was punched out with a 25 x 19mm die. Next, the frame was attached to the compressed film, with its 25mm length aligned with the film compression axis. The film was cut around the frame using a cutting tool, and the frame was curled around the film compression axis, thereby peeling the frame (with the film attached) from the silicone, which relieved the stretching in that direction. The film attached to the frame was set aside for later immersion in a hydrogel precursor solution or for testing as a neat film.

[0145] Hydrogel precursor solution

[0146] A precursor solution of polyethylene glycol diacrylate (PEG-DA) (product number 455008, CAS number: 26570-48-9, Sigma-Aldrich, St. Louis, MO 63103) was prepared and cured as neat hydrogels or reinforced hydrogel composites. PEG-DA with an average Mn of 700 and 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (CAS 106797-53-9, MW 224.25, IRGACURE® 2959, PubChem substance ID: 24865712, product number: 410896, Sigma-Aldrich, St. Louis, Missouri 62103) were used as received. The precursor was prepared by dissolving PEG-DA (10 wt.%) and 0.075 wt.% IRGACURE® 2959 in a mixed solvent of deionized water (DI) (50 wt.%), isopropyl alcohol (IPA) (30 wt.%), and n-butanol (20 wt.%). This precursor was prepared in advance and stored at 4°C until the day of injection and curing.

[0147] Preparation of reinforced gel composites by absorption and curing of hydrogel precursors

[0148] A hollow, airtight well was formed between clean glass plates by sandwiching them with 1 mm thick silicone. A film with a pre-attached frame was placed in the well, and the precursor was injected from around the silicone using a subcutaneous injection needle. Next, the composite was cured for at least 5 minutes under a broadband-spectrum UV lamp (Loctite 7411-S UV flood system), and then immersed in DI water to replace the butanol and IPA.

[0149] Uniaxial tensile test

[0150] The uniaxial stress-strain behavior of neat gels and composites was characterized using a TA Instruments ELECTROFORCE® 3200 Dynamic Mechanical Analyzer (DMA) (TA Instruments-Waters LLC, New Castle, Delaware) with an extension stroke actuator and a 22N load cell. Samples were cut to a width of 10 mm and gripped with a gauge length of 25 mm. Composites were oriented so that the pre-plane compression axis of the reinforcing film coincided with the load direction. In the case of composites, the unreinforced gel layer (because the gel is thicker than the reinforcing layer) was removed from the gripping area to ensure a strong grip under relatively high loads. In the case of neat gels, two pieces of sandpaper were bonded to the front and back of both ends of the gel to facilitate gripping without crushing the gel. All samples were pulled to fracture at a speed of 10% / second. Time, displacement, and force signals were collected at 100 Hz, and a 30 Hz digital filter was applied to the force signal. Stress was calculated by dividing the force by the cross-sectional area of ​​the sample (width 10 mm, thickness approximately 1 mm). The modulus of elasticity was measured by fitting a straight line to the stress-strain curve over a strain range of 0-2%. Toughness was calculated as the area below the stress-strain curve until fracture. The values ​​in the table are shown as mean ± standard deviation.

[0151] result

[0152] Analysis of stress-strain curves (Figure 1) and their quantification (Figure 2) showed that all composite materials had significantly higher strength and toughness than unreinforced gels, except that composite materials containing in-plane compressed reinforcing materials exhibited a low strain modulus comparable to that of gels. The mean (± standard deviation) values ​​of the modulus and toughness shown graphically in Figure 2 are presented in Table 2. [Table 2]

[0153] Furthermore, Example 1 demonstrates that a relatively steep transition between the low modulus region and the high modulus region can be achieved. In some applications, it is desirable for strain-stiffening to occur before a predetermined strain is reached. This steep transition makes it possible to achieve a low initial modulus while maximizing the strain range.

[0154] Example 2 The method of Example 1 was used, except that the reinforcing film was made from ultra-high molecular weight polyethylene (UHMWPE) prepared according to the method described in Sbriglia's U.S. Patent No. 10,266,670. The properties of the ePE film are shown in Table 3. In this invention, the PEG hydrogel is re-reinforced, but without substantially changing the elastic modulus of the gel. The in-plane film compression level was set to one level (29%) and compared with no compression of the reinforcing film before the hydrogel was absorbed and cured (0%). [Table 3]

[0155] The compression and handling of the film, the absorption and curing of the gel, and the subsequent evaluation of its mechanical properties were all carried out and analyzed using the same methods outlined in Example 1.

[0156] Similar to Example 1, the stress-strain curves (Figure 3) and their quantification (Figure 4) showed that all composites exhibited improved strength and toughness compared to the unreinforced gel, but only the composites subjected to in-plane compression before absorption and curing maintained a low strain modulus comparable to the gel. The mean values ​​(± standard deviation) for Figure 4 are reported in Table 4. [Table 4]

[0157] Example 3 The method was followed in Example 1 (PTFE-reinforced PEG hydrogel), except that a PTFE film was used to reinforce the polyacrylamide (PAAm) hydrogel. It was demonstrated that this could be done without substantially changing the elastic modulus of the gel. The in-plane compressibility of the film was set to one step (23%) and compared with no compression of the reinforced film before the hydrogel was absorbed and cured (0%).

[0158] The compression and handling of the film, as well as the evaluation and analysis of its mechanical properties, were carried out using the same methods as outlined in Example 1.

[0159] Hydrogel precursor solution

[0160] Hydrogel precursor solutions were prepared using acrylamide (CAS 79-06-1; Sigma-Aldrich, cited above), N'N'-methylenebis(acrylamide) (CAS 110-26-9; Sigma-Aldrich, cited above), and ammonium persulfate (CAS 7727-54-0; Sigma-Aldrich, cited above). A 25 mL solution containing 10 wt% acrylamide and 0.3 wt% N'N'-methylenebis(acrylamide) was prepared with deionized water and degassed with N2. Subsequently, 250 μL of 10 wt% ammonium persulfate was added and degassed. This solution was prepared immediately before absorption and curing. Hydrogels were prepared according to the method outlined in Sun et al., Nature, (2012), 489(7414): 133-136.

[0161] Preparation of reinforced gel composites by absorption and curing of hydrogel precursors

[0162] The absorption and curing process was identical to that described in Example 1, except that the frame was first wetted with isopropyl alcohol (IPA), then replaced with water, quickly sandwiched, the precursor was injected, and the composite material was cured at 50°C for at least 5 hours.

[0163] result

[0164] Similar to Example 1, the stress-strain curves (Figure 5) and their quantification (Figure 6) show that all composites exhibited improved strength and toughness compared to the unreinforced gel, but only the composites subjected to in-plane compression before absorption and curing maintained a low strain modulus comparable to the gel. The mean values ​​(± standard deviation) of Figure 6 are reported in Table 5. [Table 5]

[0165] The invention of this application has been described both in general terms and with respect to specific embodiments. It will be apparent to those skilled in the art that various modifications and variations can be made to the embodiments without departing from the scope of this disclosure. Accordingly, the embodiments are intended to cover modifications and variations of the invention, insofar as they fall within the scope of the appended claims and their equivalents.

Claims

1. A reinforced hydrogel composite comprising a porous synthetic or naturally derived shrinkable membrane material having void volume and a hydrogel that at least partially fills the void volume, The low strain (<50%) modulus of elasticity is approximately 0.01 to approximately 10 MPa, and the toughness is approximately 10 ４ ~about 10 ７ J.m. ３ This is a reinforced hydrogel composite material.

2. The reinforced hydrogel composite material according to claim 1, wherein the membrane has a microstructure and optionally includes a meandering fibril or node-fibril structure.

3. The reinforced hydrogel composite material according to claim 2, wherein the nodes and the fibrils in the fibril microstructure have an average diameter of about 0.1 μm to 250 μm.

4. The reinforced hydrogel composite material according to claim 2, wherein the nodes and the nodes in the fibril microstructure have an average separation distance of about 5 to 5000 μm.

5. The reinforced hydrogel composite material according to any one of claims 1 to 4, wherein the membrane has macrostructure folds or microstructure folded fibrils.

6. The membrane material is selected from the group consisting of stretched polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), fluorinated ethylene propylene (FEP), perfluoroalkoxyalkane (PFA), polyester sulfone (PES), expanded polyparaxylylene (ePPX), expanded ultra-high molecular weight polyethylene (eUHMWPE), expanded ethylene tetrafluoroethylene (eETFE), porous poly(tetramethyl-p-sylphenylenesiloxane), expanded porous polylactic acid (ePLLA), polycaprolactone (PCL), polyurethane (PU), copolymer of polyglycolic acid (PGA) and trimethylene carbonate (TMC), silk fibroin, silk spidoin, cellulose, nanocellulose, polyhydroxyalkanoate, and any combination thereof, as described in any one of claims 1 to 5.

7. The reinforced hydrogel composite material according to any one of claims 1 to 6, wherein the hydrogel is a polymeric amphoteric electrolyte hydrogel or an amphoteric ionic hydrogel.

8. The reinforced hydrogel composite material according to claim 7, wherein the polymeric amphoteric electrolyte hydrogel comprises at least one cationic group and at least one anionic group.

9. The reinforced hydrogel composite material according to claim 8, wherein the cationic groups and the anionic groups are randomly dispersed.

10. The hydrogel is a reinforced hydrogel composite material according to any one of claims 1 to 9, comprising polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly(2-hydroxyethyl methacrylate) (pHEMA), alginate, hyaluronic acid, or chitosan.

11. The reinforced hydrogel composite material according to any one of claims 1 to 10, wherein the hydrogel is crosslinked.

12. The reinforced hydrogel composite material according to any one of claims 1 to 11, wherein the hydrogel is crosslinked in situ.

13. The reinforced hydrogel composite material according to any one of claims 1 to 12, wherein the hydrogel completely fills the void volume.

14. The reinforced hydrogel composite material according to any one of claims 1 to 13, wherein the hydrogel further comprises one or more neutral groups.

15. The reinforced hydrogel composite material according to any one of claims 1 to 14, wherein the reinforced hydrogel composite material contains 0.01 wt% to 99 wt% hydrogel based on the total mass of the reinforced hydrogel composite material.

16. A reinforced hydrogel composite according to any one of claims 1 to 15, further comprising at least one bioactive agent.

17. The reinforced hydrogel composite material according to claim 16, wherein the bioactive agent is selected from the group consisting of thrombotic resistance agents, antibiotic preparations, antitumor agents, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-inflammatory agents, cell cycle regulators and chemically modified equivalents thereof, and combinations thereof.

18. The reinforced hydrogel composite material according to any one of claims 1 to 17, wherein the polymer film is in the form of a tape, sheet, tube, fiber, filament, or monolith.

19. The reinforced hydrogel composite material according to claim 18, wherein the tape, sheet, or tube has a thickness of approximately 1 μm to 5000 μm.

20. The reinforced hydrogel composite material according to any one of claims 1 to 19, wherein the hydrogel is covalently bonded to the polymer film.

21. The reinforced hydrogel composite material according to any one of claims 1 to 20, wherein the reinforced hydrogel composite material contains 10 to 95 volume percent of hydrogel within the void volume of the polymer film.

22. A laminate comprising a reinforced hydrogel composite material according to any one of claims 1 to 21.

23. An article comprising a reinforced hydrogel composite material according to any one of claims 1 to 21 or a laminate according to claim 22.

24. The article according to claim 23, wherein the article is an implantable medical device, stent, sensor, fuel cell, clothing, footwear, cosmetic, or filter.

25. The article according to claim 24, wherein the implantable medical device is selected from the group consisting of conduits, vascular grafts, intravascular grafts, stents, graft stents, catheters, guidewires, trocars, tissue scaffolds, and introducer sheaths.

26. i) To provide a synthetic or naturally derived polymer film compressed in at least one direction, having a node and fibril microstructure and void volume, ii) Depending on the circumstances, the polymer film may be pretreated. iii) Filling the void volume at least partially with a hydrogel precursor, and iv) Polymerizing the hydrogel precursor to produce a reinforced hydrogel composite material containing hydrogel embedded in the polymer film, A method for preparing a reinforced hydrogel composite, comprising: The aforementioned composite material has a low strain (<50%) elastic modulus of approximately 0.01 to approximately 10 MPa and approximately 10 ４ ~about 10 ７ J.m. ３ A method having toughness.

27. The method according to claim 26, wherein the pretreatment of the polymer film includes wetting the polymer film with a solvent.

28. The method according to claim 27, wherein the solvent is isopropyl alcohol or acetone.

29. The method according to claim 26, wherein the pretreatment of the polymer film includes wetting the polymer film with a hydrogel precursor solution.

30. The method according to claim 29, wherein the hydrogel precursor solution is UV-curable, chemically crosslinked, or physically crosslinked.

31. The method according to claim 26, wherein the polymer film is a hydrophilic treated film.

32. The reinforced hydrogel composite material according to claim 7, wherein the amphoteric hydrogel comprises poly(sulfobetaine methacrylate) (SBMA), poly(carboxybetaine methacrylate) (CBMA), poly(2-methacryloyloxyethyl phosphorylcholine) (MPC), or carboxybetaine acrylamide (CBAA).

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