Material-bonding compositions and related methods

Abstract

Generally, articles and / or integrated articles are provided that include a body portion (e.g., a catheter) and a component (e.g., a cuff) physically integrated with the body portion. For example, materials, methods, and uses are described herein for forming a body portion comprising a first material physically integrated with a component comprising a second material, the second material being the same or different from the first material. The disclosed compositions and devices can be useful for administration to a subject (e.g., a patient). Advantageously, the compositions and / or devices described herein can be substantially non-thrombogenic, lubricious, and / or biocompatible. In some embodiments, the devices described herein can be useful for delivering a biologically active agent (e.g., a therapeutic agent such as a drug) to a subject. Methods for forming such compositions and / or devices are also provided.

Description

[Technical Field]

[0001] Technical Field The technical field relates generally to porous biomaterials, including, for example, high strength hydrophilic nanoporous biomaterials, including catheters and / or polymeric materials. [Background technology]

[0002] background Biomaterials with high strength, low thrombogenicity, and smooth surface properties are useful in the medical field. Their porous nature allows them to function not only as high-strength bulk materials for medical devices but also as channels that allow for physical bonding with other materials. These properties may prevent or reduce biofilms, microbial colonization, infection, fibrin sheath formation, inflammation, pain, and / or tumor growth, and / or potentially treat physiological conditions such as tumor shrinkage, fungal and bacterial infections, inflammation, and pain. Complications associated with such devices can increase hospital stays and patient morbidity and mortality. Summary of the Invention [Problem to be solved by the invention]

[0003] Therefore, improved devices and methods are needed. [Means for solving the problem]

[0004] overview Generally, articles comprising and / or integral with a body portion (e.g., a catheter) are provided. In some embodiments, material bonding compositions and related methods are provided. In some embodiments, methods of forming catheter tips are provided. In some embodiments, intravenous catheters and related methods are provided.

[0005] For example, in some embodiments, described herein are materials, methods, and uses for forming a body portion comprising a first material physically integrated with a component comprising a second material, the second material being the same or different from the first material. The disclosed compositions and devices may be useful for administration to a subject (e.g., a patient). Advantageously, the compositions and / or devices described herein may be substantially non-thrombogenic, lubricious, and / or biocompatible. In some embodiments, the devices described herein may be useful for delivery of a biologically active agent (e.g., a therapeutic agent such as a drug) to a subject. Methods of forming such compositions and / or devices are also provided.

[0006] Some aspects of the present disclosure relate to an article comprising a body portion including a first material that includes a water-soluble polymer and a component physically integrated with the body portion. In some embodiments, the component comprises a second material different from the first material. In some embodiments, one or more of the following are true: (i) the first material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium water content state; (ii) the first material is configured to swell from a dehydrated state to an equilibrium water content state by an amount of 5% to 50% w / w within 60 minutes at 25°C; (iii) the first material does not have covalent crosslinks between the water-soluble polymers that form the first material; and / or (iv) the first material contains pores each having a diameter of 1 μm or less.

[0007] Some aspects of the present disclosure relate to articles comprising a hydrophilic porous polymeric material (or hydrophilic porous polymeric material) comprising a water-soluble polymer. In some embodiments, the hydrophilic porous polymeric material comprises a plurality of pores. In some embodiments, the hydrophilic porous polymeric material does not have covalent crosslinks between the water-soluble polymers. In some embodiments, a component is physically integrated with the hydrophilic porous polymeric material. In some embodiments, the component comprises a second material different from the first material. In some embodiments, the component comprises a plurality of fibers. In some embodiments, at least a portion of the plurality of fibers are embedded within the hydrophilic porous polymeric material.

[0008] Some aspects of the present disclosure relate to articles comprising a body portion, the body portion comprising a first material including a water-soluble polymer. In some embodiments, the first material has a plurality of pores, and a component is physically integrated with the body portion such that at least a portion of the component is embedded within the body portion. In some embodiments, the component comprises a second material different from the first material.

[0009] Some aspects of the present disclosure relate to methods of forming integrated articles. In some embodiments, these methods comprise carrying out the following steps with a polymer mixture comprising at least one water-soluble polymer and a solvent, the polymer mixture having a concentration of at least 10% w / w of the at least one water-soluble polymer: (i) heating the polymer mixture to achieve a temperature above the melting point of the polymer mixture; and (ii) removing the solvent from the extruded body portion at a temperature above the freezing point of the solvent until the body portion is porous. In some embodiments, the body portion is a porous body portion comprising at least one water-soluble polymer, and the porous body portion is made without the use of a covalent crosslinking agent to form covalent crosslinks between the extruded polymers to create the porous body. In some embodiments, during the step of extruding the polymer mixture, a component comprising a second material different from the first material is physically integrated with the body portion, thereby forming an integrated article.

[0010] A further aspect of the present disclosure relates to a method of forming a unitized article, the method comprising exposing the body portion to a solvent and, optionally, heating the body portion to a temperature of 100° C. or less. In some embodiments, the body portion comprises a first material comprising a water-soluble polymer, such that the water-soluble polymer softens in the presence of the solvent. In some embodiments, the method comprises contacting the body portion with a component in the presence of a solvent, such that the component physically integrates with the body portion to form the unitized article. In some embodiments, the method comprises cooling the unitized article.

[0011] In some embodiments, the method comprises exposing the body portion to a solvent and contacting the body portion with the component in the presence of the solvent, such that the component physically integrates with the body portion to form an integrated article. In some embodiments, the body portion comprises a first material comprising a first water-soluble polymer (or a first water-soluble polymer). In some embodiments, the solvent comprises water and a second water-soluble polymer (or a second water-soluble polymer). In some embodiments, the method comprises at least partially drying the integrated article.

[0012] Another aspect of the present disclosure relates to an article comprising a body portion, a solution coating disposed on a portion of a surface of the body portion, and a component in physical contact with the solution coating such that the component is adhered to the body portion via the solution coating. In some embodiments, the body portion comprises a first material comprising a water-soluble polymer. In some embodiments, the solution coating comprises water and polyvinyl alcohol (PVA). In some embodiments, the PVA is present in an amount of 0.1% by weight or more and 25% by weight or less in a solvent.

[0013] Another aspect of the present disclosure relates to a method for reforming a hydrophilic porous material. In some embodiments, the method comprises bending a hydrophilic porous material into a desired shape, the hydrophilic porous material comprising a lumen. In some embodiments, the method comprises heating the hydrophilic porous material in a bent configuration to 90° C. or greater, and (a) bending the hydrophilic porous material comprises forcing the hydrophilic porous material into a mold having the desired shape, and / or (b) bending the hydrophilic porous material comprises inserting a material into the lumen of the hydrophilic porous material to provide the desired shape, and / or (c) bending the hydrophilic porous material comprises physically deforming the hydrophilic porous material, and for any of (a)-(c), , satisfying one or more of the following: (i) the hydrophilic porous material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium water content state; (ii) the hydrophilic porous material is configured to swell from a dehydrated state to an equilibrium water content state by an amount of 5 w / w% or more and 50 w / w% or less within 60 minutes at 25°C; (iii) the hydrophilic porous material does not have covalent crosslinks between the water-soluble polymers that form the hydrophilic porous material; (iv) the hydrophilic porous material comprises pores each having a diameter of 1 μm or less.

[0014] An embodiment of the present disclosure relates to an article including an elongated tube, the elongated tube comprising a first material including a water-soluble polymer, the elongated tube having a first portion (or first section or first portion) and a second portion (or second section or second portion), wherein in a relaxed state of the elongated tube, the first portion comprises a radius of curvature that is different from the radius of curvature of the second portion, and wherein one or more of the following are satisfied: (i) the first material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium water content state; (ii) the first material is configured to swell from the dehydrated state to the equilibrium water content state by an amount of 5 wt% or more and 50 wt% or less within 60 minutes at 25°C; (iii) the first material does not have covalent crosslinks between the water-soluble polymers forming the first material; and (iv) the first material comprises pores each having a diameter of 1 μm or less.

[0015] Aspects of the present disclosure relate to a dual-lumen article. In some embodiments, the dual-lumen article comprises a first body portion (or first body portion) comprising a first material including a water-soluble polymer, the first body portion comprising a first lumen (or first lumen) having a first inner diameter (or first inner diameter), and a second body portion (or second body portion) comprising a second material different from the first material, the second body portion comprising a second lumen (or second lumen), wherein the first portion of the second body has an outer diameter smaller than the first inner diameter of the first lumen, and the second portion of the second body has a second inner diameter (or second inner diameter) approximately equal to the first inner diameter, and The first material is at least partially disposed within the first body portion and satisfies one or more of the following: (i) the first material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium hydrated state; (ii) the first material is configured to swell from a dehydrated state to an equilibrium hydrated state by an amount of 5 w / w% or more and 50 w / w% or less within 60 minutes at 25°C; (iii) the first material does not have covalent crosslinks between the water-soluble polymers forming the first material; and (iv) the first material comprises pores each having a diameter of 1 μm or less.

[0016] Some aspects of the present disclosure also relate to methods of forming a dual lumen article. In some embodiments, the methods include swelling a first body portion in a solvent, the first body portion comprising a first material including a water-soluble polymer, the first body portion comprising a first lumen having a first inner diameter; heating and / or mechanically deforming a second body portion comprising a second material different from the first material such that the second body portion has an outer diameter smaller than the first inner diameter of the first lumen; inserting the second body portion into the lumen of the first body portion, thereby forming the dual lumen article; and drying the dual lumen article such that the first body portion shrinks.

[0017] A further aspect of the present disclosure relates to an intravenous catheter. In some embodiments, the intravenous catheter comprises a polymeric material including a first water-soluble polymer having a plurality of pores, a lumen, and a distal end having a tip shape suitable for intravenous insertion into a subject, the polymeric material having a water content of less than 5 wt. % and greater than or equal to 0.1 wt. % in a dehydrated state and configured to swell from the dehydrated state to an equilibrium water content state by an amount of greater than or equal to 50 wt. % within 60 minutes at 25° C.

[0018] Another aspect of the present disclosure relates to a system that includes an intravenous catheter and components configured to administer therapeutic agents and / or fluids to a subject and / or withdraw bodily fluids from a subject.

[0019] Aspects of the present disclosure further relate to methods of inserting an intravenous catheter into a subject in need thereof. In some embodiments, the method includes inserting an intravenous catheter into a vein, the intravenous catheter comprising a polymeric material including a first water-soluble polymer having a plurality of pores, a lumen, and a distal end having a tip geometry suitable for intravenous insertion into a subject, wherein during the inserting step, the catheter has a water content of 5 wt% or less; and swelling the intravenous catheter to a water content of 5 wt% or more and 50 wt% or less.

[0020] In some embodiments, the method comprises inserting an intravenous catheter into a vein, the intravenous catheter comprising a polymeric material comprising a first water-soluble polymer having a plurality of pores, the polymeric material having a water content of 5% w / w or more and 50% w / w or less, a lumen, and a distal end comprising a tip shape suitable for intravenous insertion into a subject, wherein one or more of the following are satisfied: (i) the polymeric material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium water content state; (ii) the polymeric material does not have covalent crosslinks between the water-soluble polymers forming the polymeric material; and (iii) the polymeric material comprises pores each having a diameter of 1 μm or less.

[0021] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention, taken in conjunction with the accompanying drawings. In the event of conflicting and / or inconsistent disclosure between this specification and a document incorporated by reference, the present specification shall control. [Brief explanation of the drawings]

[0022] BRIEF DESCRIPTION OF THE DRAWINGS Non-limiting embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, which are schematic and not drawn to scale. In the drawings, identical or nearly identical components shown in the drawings are typically represented by a single numeral. For purposes of clarity, not every component is labeled in every drawing, nor are every component of every embodiment of the present invention shown where illustration is not necessary for those skilled in the art to understand the invention. In the drawings: [Figure 1] FIG. 1 is a schematic diagram of an exemplary article comprising a body portion including a plurality of pores and a component physically integrated with the body portion, according to one set of embodiments. [Figure 2]FIG. 2 is a schematic diagram of an exemplary article according to one set of embodiments, comprising a body portion including a plurality of pores and a component portion including a plurality of fibers, the fibers of the component portion being entangled within the pores of the body portion. [Figure 3] FIG. 3 is a schematic diagram of two materials physically integrated together according to one set of embodiments. [Figure 4] FIG. 4 is a schematic illustration of two materials physically integrated together using solution coating, according to one set of embodiments. [Figure 5A] FIG. 5A is a schematic illustration of a shaping catheter comprising an elongated tube, according to a series of embodiments. [Figure 5B] FIG. 5B is a schematic illustration of a cross section of the shaping catheter shown in FIG. 5A, according to one set of embodiments. [Figure 6A] FIG. 6A is a schematic diagram of a horizontal cross section of an exemplary dual-lumen article, according to one set of embodiments. [Figure 6B] FIG. 6B is a schematic illustration of a vertical cross section of the dual lumen article shown in FIG. 6A, according to one set of embodiments. [Figure 7] FIG. 7 is a schematic diagram of an exemplary intravenous catheter with a distal end having a tip shape suitable for intravenous insertion, according to one set of embodiments. [Figure 8] Figure 8A is a schematic diagram of an exemplary catheter with an inflatable cuff, according to one set of embodiments, and Figure 8B is a schematic diagram of a cross section of the catheter shown in Figure 8A in a collapsed and inflated state, according to one set of embodiments. [Figure 9A] FIG. 9A is a schematic diagram of an extrusion apparatus for forming a continuous foam, according to one set of embodiments, with a cross-sectional side view of a vessel. [Figure 9B] FIG. 9B is an enlarged view of a portion of the apparatus of FIG. 9A showing a perspective view of the die head from outside the vat, according to one set of embodiments. [Figure 9C] FIG. 9C is an enlarged view of a portion of the apparatus of FIG. 9A showing the die head positioned within the vat, according to one set of embodiments. [Figure 10] FIG. 10 is a longitudinal cross-sectional view of a portion of a continuous porous solid formed using the apparatus of FIGS. 9A-9C according to one set of embodiments. [Figure 11A] FIG. 11A is a schematic diagram of the process for bulk incorporation of polymers into porous solids. [Figure 11B] FIG. 11B is a cross-sectional view of a portion of a tube taken along line 3B-3B of FIG. 11A, according to one set of embodiments. [Figure 12] FIG. 12 is a process flow diagram for one set of embodiments for bulk incorporation of a surface polymer into a porous solid, including an extrusion process for producing the porous solid. [Figure 13] FIG. 13 is a graph illustrating stress-strain curves for polymeric materials, according to one set of embodiments. [Figure 14A] 14A-14C are photographs of exemplary shaped catheters according to some embodiments: Figure 14A is a photograph of a partially hydrated straight catheter. [Figure 14B] FIG. 14B is a photograph of a partially hydrated straight catheter (in 2.2% sodium chloride solution) mounted on a molded mandrel. [Figure 14C] Figure 14C (top) shows the molded mandrel, and Figure 14C (bottom) is a photograph of an exemplary catheter with the mandrel removed that was dried at 95°C for 90 minutes, annealed at 150°C for 90 minutes, and then rehydrated in 1x phosphate buffered saline (37°C). [Figure 15A] Figures 15A-15C are photographs of an example of a lumen reformed from a circular to a D-shape according to a set of embodiments: Figure 15A shows room temperature / 20°C (no change); [Figure 15B] FIG. 15B shows the mandrel at 70° C. with an aspect ratio of 65%. [Figure 15C] FIG. 15C shows the mandrel aspect ratio at 95° C., 87%. DETAILED DESCRIPTION OF THE INVENTION

[0023] Detailed Description Generally, articles and / or integrated articles are provided that include a body portion (e.g., a catheter) and a component (e.g., a cuff) physically integrated with the body portion. For example, disclosed herein are materials, methods, and uses for forming a body portion comprising a first material physically integrated with a component comprising a second material, the second material being the same or different from the first material. The disclosed compositions and devices can be useful for administration to a subject (e.g., a patient). Advantageously, the compositions and / or devices described herein can be substantially non-thrombogenic, lubricious, and / or biocompatible. In some embodiments, the devices described herein can be useful for delivering a biologically active agent (e.g., a therapeutic agent such as a drug) to a subject. Methods of forming such compositions and / or devices are also provided.

[0024] The articles described herein may be useful in a wide range of applications, including, for example, the manufacture of blood-contacting devices or devices that contact bodily fluids, including extracorporeal and / or intracorporeal devices such as blood-contacting implants. Examples of drug delivery devices that may embody or incorporate the articles described herein include, but are not limited to, medical tubing, wound dressings, contraceptive devices, feminine hygiene products, endoscopes, implants (including those small in diameter, e.g., 6 mm or less), pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, leads for cardiovascular devices, ventricular assist devices, catheters (including, for example, cochlear implants, endotracheal tubes, tracheostomy tubes, ports, shunts), implantable sensors (e.g., intravascular, percutaneous, intracranial), ventilator pumps, and ophthalmic devices, including drug delivery systems.

[0025] In one set of embodiments, physically integrated articles are provided. In some embodiments, the articles include a body portion and a component physically integrated with the body portion. Methods of forming the physically integrated articles are also provided. For example, in some embodiments, the integrated articles are formed using extrusion, thermal bonding, and / or solvent bonding.

[0026] In another set of embodiments, a shaped article is provided. In some embodiments, the shaped article comprises an elongated tube, at least a portion of the elongated tube having a particular radius of curvature. Methods of forming the shaped article are also provided. For example, in some embodiments, the article can be formed using thermoforming, e.g., by placing a wire (Nitinol, steel, etc.) within the lumen and heating the article to form it into the desired shape. The shaped article can have any suitable shape, including, but not limited to, straight, curved, bent, zigzag, spiral, loop, helical, wavy, irregular, twisted, etc.

[0027] In yet another embodiment, a dual lumen article is provided. In some embodiments, the dual lumen article comprises a first body portion and a second body portion, the second body portion being at least partially disposed within the first body portion. Methods of forming the dual lumen article are also provided. For example, in some embodiments, the dual lumen article can be formed by swelling the first body portion in a solvent until it is deformable and inserting the second body portion into the lumen of the first body portion. In some cases, the second body portion can also be deformed using heat and / or mechanical force.

[0028] In a further set of embodiments, an intravenous catheter is provided. In some embodiments, the intravenous catheter comprises a body (e.g., a polymeric material) comprising a first water-soluble polymer. In some embodiments, the polymeric material has a plurality of pores. In certain embodiments, the intravenous catheter comprises a lumen and a distal end with a tip shape (e.g., a bevel-tip needle stylet) suitable for intravenous insertion into a subject. Also provided is a method of inserting an intravenous catheter into a subject in need thereof. For example, in some embodiments, the intravenous catheter is inserted in a dehydrated state (e.g., percutaneously) and hydrated after insertion. In certain embodiments, the catheter is inserted in a hydrated state. In some embodiments, the hydrated intravenous catheter is softer and does not cause the discomfort associated with conventional polymeric catheters.

[0029] Some of the above-described embodiments utilize a solvent. For example, in some embodiments, a solvent is used to solubilize at least a portion of the polymer in the first material and / or the second material. In certain embodiments, the solvent is used to swell the material and make it deformable (e.g., to bend the catheter into a particular shape or expand the inner diameter of the lumen). In other embodiments, the solvent is used to indirectly bond the first material to the second material (e.g., to bond the first material to the solvent and the solvent to the second material).

[0030] In some embodiments, the solvent comprises a water-soluble polymer (e.g., polyvinyl alcohol) dissolved in an aqueous solution. In some embodiments, the solvent comprises an aqueous solution (e.g., without a water-soluble polymer). In certain embodiments, the solvent comprises a water-miscible organic compound (e.g., DMSO).

[0031] FIG. 1 illustrates an exemplary embodiment of an integrated article comprising a body portion and a component. For example, integrated article 100 comprises body portion 110 and component 130 physically integrated with the body portion. In some embodiments, body portion 120 is formed of a first material and comprises a polymeric material. The polymeric material may comprise a first water-soluble polymer. In some embodiments, component 130 is formed of a second material that is different from the first material. In some embodiments, body portion comprises a plurality of pores 120 (e.g., a plurality of pores having an average pore size of 1 micron or less).

[0032] 1 is depicted as a rectangle, those skilled in the art will understand, based on the teachings herein, that the body and other sections in the embodiments disclosed herein need not be rectangular, and that other cross-sectional shapes are possible (e.g., flat, circular, square, oval, rectangular, S-shaped, etc.). For example, in some embodiments, the body is S-shaped, which in some cases may facilitate implantation into a subject, reduce the rate of infiltration, and reduce the likelihood of dislodgement within the subject.

[0033] FIG. 2 illustrates an integrated article 200, comprising a body 210 (e.g., a polymeric material) having one or more components 230 (e.g., a catheter cuff) physically integrated with the body 210. In some cases, the body 210 comprises a first material including a hydrophilic, water-soluble polymer. In some embodiments, the components 230 comprise a second material (e.g., a first hydrophilic porous material) including a plurality of fibers 235 at least partially embedded within the body 210. While the components 230 are shown as fibers 235 in FIG. 2, one skilled in the art will understand, based on the teachings herein, that the components and other portions in the embodiments disclosed herein need not be fibers, and that other fabrics (e.g., mesh, cellular foam cavities, netting, etc.) are also possible.

[0034] As described herein, in some embodiments, at least a portion of an article may be physically integrated. The term "physically integrated" has its typical meaning in the art and generally refers to two or more components (e.g., layers, articles, surfaces) being physically joined together so as to be adhered to one another. In some embodiments, two or more components that are physically integrated with one another generally cannot be separated (e.g., by fracture, mechanical failure, and / or dissolution of chemical bonds) without irreversibly damaging at least a portion of one or more of the two or more components. For example, two or more physically integrated components share at least one surface where the two or more components are adhered (e.g., fused) to one another. Those skilled in the art will understand that the phrases "physically integrated" and "fused" do not simply refer to components that are in contact with one or more surfaces, but rather refer to components where at least a portion of the original surface of the individual components is no longer distinguishable from the other components (e.g., an intermediate layer is formed that includes at least a portion of a first component and at least a portion of a second component). In some embodiments, two or more components are physically united by bonding, entanglement, pore filling, or the like.

[0035] In some embodiments, a first component is physically integrated with a second component (e.g., a body) by embedding at least a portion of the first component in the second component. In some embodiments, a first component is physically integrated with a second component (e.g., a body) by embedding at least a portion of the second component in the first component. In some embodiments, a first component is physically integrated with a second component through the formation of a bond, such as, for example, an ionic bond, a covalent bond, a hydrogen bond, a van der Waals interaction, or the like. A covalent bond may be, for example, a carbon-carbon, carbon-oxygen, oxygen-silicon, sulfur-sulfur, phosphorus-nitrogen, carbon-nitrogen, metal-oxygen, or other covalent bond. A hydrogen bond may be, for example, a bond between hydroxyl groups, amine groups, carboxyl groups, thiol groups, and / or similar functional groups. In some embodiments, a first component is physically integrated with a second component through chain entanglement (e.g., between polymer chains of the first component and polymer chains of the second component).

[0036] In one exemplary embodiment, being physically integrated includes the hydrophilic polymer chains of the first material being physically entangled within the pores of the second material. In another exemplary embodiment, the hydrophilic polymers of the first material may be entangled within the polymer chains of the second material. In yet another exemplary embodiment, being physically integrated includes the second material (e.g., multiple fibers, mesh, cellular foam cavities, netting, or other structure) being entangled within the pores and / or bulk of the first material (e.g., hydrogel).

[0037] 3 illustrates an example in which two components, component 310 and component 320, are physically integrated with one another (e.g., in the presence of one or more solvents disclosed herein) to form integrated article 300. Integrated article 300, in some embodiments, includes at least a portion of component 310, at least a portion of component 320, and physically integrated region 330 (e.g., including the material of component 310 and the material of component 320).

[0038] In some embodiments, a solution coating is used to physically integrate the body portion with the component. For example, as shown in FIG. 4 , a solution coating 440 is applied to a first surface of the body portion 410 and brought into physical contact with the component 420 to provide the integrated article 400. In some embodiments, the solution coating includes a water-soluble polymer configured to entangle with the pores and / or polymer chains of a first material of the body portion. Also, according to certain embodiments, the solution coating may be entangled or embedded in the pores and / or polymer chains of a second material of the component. In this manner, the component is adhered to the body portion via the solution coating (e.g., the body portion is physically integrated with the solution coating, which is physically integrated with the component).

[0039] In some embodiments, the first component is adjacent to the second component, and in some embodiments, there can be an intervening layer between the first and second components, where the intervening layer comprises a solution coating.

[0040] Other aspects of the present disclosure relate to articles such as, for example, shaped catheters. For example, as illustratively shown in FIG. 5A, a shaped catheter can include an elongated tube 510 including a first portion 520 and a second portion 530. In some embodiments, the first portion 520 has a different radius of curvature than the second portion 530 (e.g., the catheter has a "hook-like" shape). FIG. 5B shows a cross section of an exemplary catheter 500. In some embodiments, the elongated tube 510 includes a lumen 540 and an outer shell including a first material 550 that includes a water-soluble polymer. In some embodiments, the first material includes a plurality of pores having an average diameter of 1 micron or less.

[0041] In some embodiments, the article is a dual-lumen article. An exemplary embodiment is shown in Figure 6. Figure 6A shows a longitudinal cross-section of a dual-lumen article comprising a first body 610 including a first lumen 620 having a first inner diameter and a second body 630 including a second material that includes a second lumen 640. In some embodiments, the second body 630 comprises a first portion 650 having an outer diameter smaller than the first inner diameter 670 of the first lumen 620, and in some embodiments, a second portion 660 of the second body 630 has a second inner diameter 680 that is approximately equal to the first inner diameter of the first lumen 620.

[0042] Further, in certain embodiments, the article may comprise an intravascular catheter. For example, as shown in Figure 7, a venous catheter may comprise a polymeric material 710 including a first water-soluble polymer (e.g., a first body) having a plurality of pores, a lumen 720, and a distal end 730 having a tip shape suitable for intravenous insertion into a subject.

[0043] In one set of exemplary embodiments, the article includes, for example, a catheter having a cuff for securing the catheter within a body cavity (e.g., the urinary cavity) of a subject. For example, as illustratively shown in FIG. 8 , a catheter 800 may include a first material 810 including a first water-soluble polymer having a plurality of pores; a second material 820 (e.g., a balloon or cuff); a first lumen 830 connected to a first opening (first opening) 840; a second lumen 850 connected to a second opening (second opening) 860; and a distal end having a tip shape appropriate for the desired application (e.g., a blunt tip for urinary applications or a pointed tip for intravascular applications). In some embodiments, the second material is physically integrated with the first material along its periphery such that the center of the second material is positioned over the first opening. In some embodiments, the second material is configured to radially expand upon introduction of gas 870 (e.g., air) into the first lumen (e.g., via a syringe).

[0044] Some embodiments of the present application utilize a solvent (e.g., to bond a first material to a second material). In some embodiments, the solvent comprises water. In some embodiments, the solvent comprises a water-soluble polymer (e.g., a second water-soluble polymer). In some embodiments, the solvent comprises a water-soluble organic compound (e.g., DMSO).

[0045] Without being bound by any particular theory, it is believed that contacting the body portion with the component in the presence of a solvent (e.g., water) causes the first water-soluble polymer of the body portion to interdiffuse into the second material of the component, forming a unified article. In some embodiments, the method causes the second material to interdiffuse into the first material of the body portion (e.g., when the second material is the same as the first material). Combinations are also possible. For example, in some embodiments, the first material may diffuse into the second material, and the second material may also diffuse into the first material.

[0046] In some embodiments, a solvent containing water and a second water-soluble polymer can be used to physically integrate a component comprising a second material into a body comprising a first material. Again, without being bound by theory, it is believed that contacting the body with the component in the presence of the solvent causes the second water-soluble polymer to interdiffuse into the first material of the body and the second material of the component, forming an integrated article. In other words, the solvent can act as a polymer bridge that physically integrates both the body and the component, thereby physically integrating the body and the component. For example, in some embodiments, a second water-soluble polymer (e.g., polyvinyl alcohol) can be incorporated into the body and one or more components (e.g., Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (atactic, syndiotactic, isotactic), and polyethylene (LLDPE, LDPE, HDPE)).

[0047] As described above and herein, the solvent may, in some embodiments, interact with two or more elements of the body or component. For example, in some cases, the solvent may physically integrate the body to the component by becoming entangled with the surface, bulk, and / or pores of the body and the surface, bulk, and / or pores of the component.

[0048] In some embodiments, the solvent comprises a homogeneous solvent (e.g., water, DMSO, etc.) or a heterogeneous mixture (e.g., a co-solvent). Exemplary embodiments of the solvent include, but are not limited to, water and DMSO. For example, in some embodiments, the solvent is a heterogeneous mixture of water / DMSO having a ratio of about 0:1, 0.1:0.9, 0.2:0.8, 0.3:0.7, 0.4:0.6, 0.5:0.5, 0.6:0.4, 0.7:0.3, 0.8:0.2, 0.9:0.1, 1:0 (or a combination or range thereof).

[0049] In some embodiments, the solvent comprises a polymer. The polymer may be the same as or different from the first material (e.g., a second water-soluble polymer). For example, in some embodiments, the solvent comprises a water-soluble polymer (e.g., a second water-soluble polymer) selected from the group consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylsulfobetaine), poly(acrylsulfobetaine), poly(methacrylcarboxybetaine), poly(acrylcarboxybetaine), povidone-polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In a preferred set of embodiments, the solvent comprises poly(vinyl alcohol).

[0050] In some embodiments, the water-soluble polymer in the solvent is present at a concentration lower than the concentration of the water-soluble polymer used to form the first material, for example, in some embodiments, the water-soluble polymer is present in the solvent at equilibrium water content in an amount of 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, 45 w / w% or more, 50 w / w% or more, 55 w / w% or more, 60 w / w% or more, 65 w / w% or more, 70 w / w% or more, 75 w / w% or more, 80 w / w% or more, 85 w / w% or more, or 90 w / w% or more. In some embodiments, the water-soluble polymer is present in the solvent at equilibrium water content in an amount of 95 w / w% or less, 90 w / w% or less, 85 w / w% or less, 80 w / w% or less, 75 w / w% or less, 70 w / w% or less, 65 w / w% or less, 60 w / w% or less, 55 w / w% or less, 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, or 25 w / w% or less. Combinations of the above ranges are also possible (e.g., 20 w / w% or more to 95 w / w% or less). Other ranges are also possible.

[0051] In some embodiments, the solvent comprises water and polyvinyl alcohol present in the solvent in an amount of 0.1% to 25% by weight. For example, in some embodiments, the solvent comprises 0.1% or more, 0.5% or more, 1.0% or more, 2.0% or more, 4.0% or more, 8.0% or more, 10% or more, 12% or more, 14% or more, 16% or more, 18% or more, 20% or more, or 25% or more by weight of poly(vinyl alcohol) at equilibrium water content. In some embodiments, the solvent comprises 25% or less, 20% or less, 18% or less, 16% or less, 14% or less, 12% or less, 10% or less, 8.0% or less, 4.0% or less, 2.0% or less, 1.0% or less, 0.5% or less, or 0.1% or less by weight of polyvinyl alcohol at equilibrium water content. Combinations of the above ranges are possible (eg, greater than or equal to 0.1 w / w % and less than or equal to 25 w / w %). Other ranges are also possible.

[0052] In some embodiments, the solvent comprises a polymer, including poly(vinyl alcohol). Poly(vinyl alcohol) can be purchased from commercial sources (e.g., MilliporeSigma) and / or synthesized by one of ordinary skill in the art, for example, by hydrolysis of polyvinyl acetate (or other vinyl ester-derived polymers having formate or chloroacetate groups instead of acetate). In some embodiments, the hydrolysis reaction is less than 100%, resulting in a polymer with a mixture of hydroxyl and acetate groups. In certain embodiments, the hydrolysis level is 20% or greater and 99% or less. For example, in some embodiments, the hydrolysis level is 20% or greater, 30% or greater, 40% or greater, 50% or greater, 60% or greater, 70% or greater, 80% or greater, 90% or greater, 95% or greater, or 99% or greater. In some embodiments, the level of hydrolysis is 99% or less, 95% or less, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, 40% or less, 30% or less, or 20% or less. In certain embodiments, the solvent comprises an 80% hydrolyzed poly(vinyl alcohol) polymer, which corresponds to about 20% acetate groups and about 80% hydroxyl groups.

[0053] The solvent may be applied to the materials (e.g., body portions) using any technique known to those skilled in the art. Exemplary embodiments include, but are not limited to, (1) a brush application method in which the solvent is applied to the joining surfaces with a brush and pressure is applied until full bond strength is achieved after the solvent has completely evaporated, (2) a capillary action method in which the solvent penetrates into the gap formed at the joint between two parts to be joined using capillary action, (3) a dip-dab method in which the joining surfaces are immersed in a container of solvent for a certain period of time before being combined with the desired component, and (4) a solvent dispenser method in which the amount of solvent applied to each joining surface is precisely controlled using a dispenser.

[0054] Other uses for solvents are also contemplated. For example, in some embodiments, solvents can be used to swell and bend the article into any desired shape. Additionally or alternatively, solvents can be used to incorporate or trap insoluble compounds, such as therapeutic agents, bioactive compounds, fabrics, metal meshes, color indicators, radiopaque materials, and reactive indicators, on the outer surface of the integrated article. In some cases, solvents can be used to incorporate conductivity indicators to aid in the detection of electrocardiogram p-waves. For example, iron powder that is insoluble in physiological fluids and incorporated into a second water-soluble polymer (e.g., poly(vinyl alcohol)) can provide a self-contained electrocardiogram probe (e.g., when placed at the tip of a catheter).

[0055] In certain embodiments, a solvent can be used to adhere one or more materials to a first water-soluble polymer (e.g., poly(vinyl alcohol)). For example, in some cases, a solvent can be used to adhere a bandage, tissue, stent, shunt, braided tube, and / or wall stent to one or more materials that also include a water-soluble polymer (e.g., poly(vinyl alcohol)).

[0056] In some embodiments, solvents may be used in combination with other techniques, such as heating. For example, as described herein and above, bonding may be achieved by applying a solvent to the first and second materials to be joined (e.g., at the overlapping joint) and heating the first and / or second materials to cause the polymer chains of the first material to flow into the bulk of the second material, or vice versa. Upon cooling, the first material physically integrates with the second material to form a single cohesive material.

[0057] Some aspects of the present disclosure generally relate to methods of making the integrated articles described herein. In some embodiments, the methods include heating a polymer mixture including a water-soluble polymer and a solvent, extruding the mixture into a body, and simultaneously extruding the body into physical contact with a component, thereby physically uniting the body and the component.

[0058] In some embodiments, the method comprises exposing the body portion to a solvent, optionally heating the body portion to a temperature of 100° C. or less, contacting the body portion with a component in the presence of the solvent to form an integrated article, and cooling the integrated article.

[0059] In some embodiments, the method comprises exposing the body portion to a solvent to soften a first material of the body portion, contacting the body portion with a component in the presence of the solvent to physically integrate the component with the body portion, thereby forming an integrated article, and at least partially drying the article.

[0060] Other methods are directed to forming articles. For example, in some embodiments, the methods comprise bending a hydrophilic porous material (e.g., a body portion) containing a lumen into a desired shape and heating the material in the bent state to 90° C. or above.

[0061] In some embodiments, the method is directed to forming a dual-lumen article. In certain embodiments, the method comprises swelling a first body portion including a first lumen with a first inner diameter in a solvent to soften the first body portion. In some embodiments, the method further comprises heating and / or mechanically deforming the second body portion so that the second body portion has an outer diameter smaller than the first inner diameter of the first lumen. The method further comprises inserting the second body portion into the lumen of the first body portion, thereby forming the dual-lumen article.

[0062] Yet another method is directed to inserting an article (e.g., a catheter) into a subject in need thereof. In some embodiments, the article is an intravenous catheter comprising a porous polymeric material comprising a first water-soluble polymer, a lumen, and a distal end having a tip shape suitable for intravenous insertion into a subject. In some embodiments, the article is inserted in a dehydrated state (e.g., the catheter has a water content of 5% wt / wt or less) and becomes hydrated after placement in the subject (e.g., the catheter swells to a water content of 5% wt / wt or more and 50% wt / wt or less).

[0063] In some embodiments, the intravenous catheter is hydrated (eg, the catheter is swelled to a water content of not less than 5% wt / wt and not more than 50% wt / wt) before being inserted into the subject.

[0064] Other embodiments are also contemplated herein. Also disclosed is a system that includes a catheter and components configured to deliver a therapeutic agent and / or withdraw bodily fluids from a subject.

[0065] Some aspects of the present disclosure generally relate to compositions, articles, and devices that include a body portion and a component physically integrated with the body portion. The body portion can be formed from a first material, for example, including a first water-soluble polymer (e.g., polyvinyl alcohol). In some embodiments, the first material includes non-covalently crosslinked polymer chains. In certain cases, the first material includes pores. In some cases, the first material includes a combination of non-covalently crosslinked polymer chains and pores.

[0066] The body portion may further comprise a component comprising a second material, which may in some cases be physically integrated with the body portion. In some embodiments, the second material may be the same as or different from the first material. In some embodiments, the second material comprises a polymer (e.g., a second polymer). In some cases, the polymer comprises a second water-soluble polymer, such as, for example, polyvinyl alcohol (e.g., PVA). In some embodiments, the polymer comprises a partially water-soluble polymer, and in certain embodiments, the polymer may comprise a water-insoluble polymer.

[0067] In some embodiments, the article comprises a body portion including a first material comprising a water-soluble polymer (e.g., PVA). As described elsewhere herein, the body portion can comprise any water-soluble polymer known to those skilled in the art. Exemplary embodiments include, but are not limited to, poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylsulfobetaine), poly(acrylsulfobetaine), poly(methacrylcarboxybetaine), poly(acrylcarboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In one exemplary set of embodiments, the first material is poly(vinyl alcohol).

[0068] In some embodiments, the first material of the body has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium moisture content state. In some cases, the first material is configured to swell from a dehydrated state to an equilibrium moisture content state by an amount of 5% to 50% w / w within 60 minutes at 25°C. In certain embodiments, the first material does not have covalent crosslinks between the water-soluble polymers forming the first material and / or has pores each having a diameter of 1 μm or less. Other diameters, Young's moduli, and swelling ratios are discussed elsewhere herein (see the section on the body).

[0069] According to some embodiments, the body may comprise a hydrophilic porous polymeric material comprising a water-soluble polymer. The hydrophilic porous polymeric material may, in some cases, have multiple pores. In some embodiments, the hydrophilic porous polymeric material does not have covalent crosslinks between the water-soluble polymer chains and / or has multiple pores (e.g., pores with diameters of 1 μm or less).

[0070] According to additional embodiments, the article may further include a component. In some embodiments, the component includes a second material that is different from or the same as the first material. In one exemplary set of embodiments, the second material is different from the first material. In another exemplary set of embodiments, the second material is the same as the first material. In some embodiments, the body includes a second material (e.g., a component) that includes the first water-soluble polymer at a concentration that is lower than the concentration of the first water-soluble polymer in the first material.

[0071] In certain embodiments, the component comprises a second material that is different from or the same as the first material. In some cases, the second material comprises a medical-grade polymer, metal, or ceramic. The second material may be processed into multiple structures, including, but not limited to, multiple pores, multiple fibers, cellular foam cavities, meshes, nets, and / or other structures (e.g., bulk materials), using any technique known to those skilled in the art. For example, in some embodiments, the component may be processed into yarns and fabrics using techniques known to those skilled in the art to create complex three-dimensional shapes (e.g., tubular shapes with tapered angles, etc.). In some embodiments, the second material may be a porous structure, and in certain embodiments, the second material may be a woven structure with two sets of polymer yarns intertwined at right angles. In other embodiments, the second material may be a knit structure with intertwined loops of polymer yarns, and in some cases, the second material may be braided with three or more polymer yarns crossing each other in a diagonal pattern, according to other embodiments.

[0072] In some embodiments, the article comprises a component physically integrated with the body portion. In certain embodiments, the article comprises a component physically integrated with a hydrophilic porous polymeric material. In some cases, the component is physically integrated with the body portion such that at least a portion of the component is embedded within the body portion.

[0073] In certain embodiments, the article includes a solution coating disposed on a portion of a surface of the body portion configured to physically integrate the body portion and the component to form a unitary article. In some embodiments, the solution coating includes water and poly(vinyl alcohol) (e.g., PVA) at a concentration of 0.1% to 25% by weight. In some embodiments, the PVA concentration is 0.1% or more, 0.5% or more, 1% or more, 5% or more, 10% or more, 15% or more, 20% or more, or 25% or more by weight. In certain embodiments, the PVA concentration is 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, 1% or less, 0.5% or less, or 0.1% or less by weight. Combinations of the above ranges are also possible (e.g., 0.1% to 25% by weight).

[0074] In some embodiments, the solution coating includes a UV-curable adhesive (e.g., a UV-curable adhesive capable of reacting with poly(vinyl alcohol)), such that the UV-curable adhesive reduces the equilibrium water content, e.g., to prevent hydrophobic delamination upon exposure to water, saline, blood, or other physiological fluids.

[0075] In some embodiments, the solution coating comprises a crosslinkable adhesive (e.g., one that produces hydrolysis-resistant covalent crosslinks) by using etherification, diurea, thiocyanate, and carbon-based cyanate, and / or hydroxyl groups of poly(vinyl alcohol). Non-limiting examples of suitable (e.g., hydrolysis-resistant) crosslinkers include cyanates (e.g., diisocyanates, triisocyanates, diisothiocyanates) and ureas (e.g., isobutylidenediurea, ethylenediurea, propylenediurea), and the like. Without being bound by theory, etherification may be achieved at a relatively low pH using, for example, a mixture of sulfuric acid and polyethylene glycol, poly(tetrahydrofuran), poly(phenyl ether), or the like.

[0076] In some embodiments, without being bound by theory, esterification of PVA-based solution coatings may occur when polycarboxylic acids react to crosslink two or more PVA molecules. Esterification is generally susceptible to hydrolysis (e.g., especially in basic (high pH) environments). Therefore, in some embodiments, esterification may provide benefits such as biodegradable release of adhesive mechanisms, e.g., separating two non-hydrolyzable devices from each other. In some embodiments, esterification may be advantageously used when a PVA-based device has a temporary feature (e.g., subsequent rapid or slow degradation within the vascular system), such as a sharp tip for inserting the device into a vein. Non-limiting examples of suitable crosslinkers include oxalic acid, maleic acid, malonic acid, fumaric acid, malic acid, ascorbic acid, succinic acid, adipic acid, glutaric acid, tartaric acid, citric acid, poly(acrylic acid), poly(methacrylic acid), poly(caprolactone), poly(lactic acid), and poly(glycolic acid). Without being bound by theory, two or more carboxylic acid groups can form strong covalently crosslinked structures linked by carbon-carbon bond segments. Such dicarboxylic acid groups can be useful in some embodiments, for example, as useful hydrolyzable crosslinks, and can be formed under low pH conditions.

[0077] In some embodiments, the body portion comprises a first material and the component comprises a second material, which may be the same or different from the first material. In a preferred set of embodiments, the first material and / or the second material comprise a polymer. While not wishing to be bound by any particular theory, it is generally understood that a bulk polymer material comprises surface polymer chains (herein referred to as surface polymers) (e.g., polymer chains within 1-100 microns of the air-surface interface) and bulk polymer chains (herein referred to as bulk polymers) (e.g., polymer chains 100 microns or more away from the air-surface interface). In some embodiments, the first material and / or the second material may comprise pores. Combinations of these are also possible. For example, the first material and / or the second material may comprise surface polymers, bulk polymers, and / or pores.

[0078] Thus, the surface polymers, bulk polymers, and / or pores of a first material (e.g., the body) may be integrated with the corresponding surface polymers, bulk polymers, and / or pores of a second material. As used herein, the term "integrated" refers to the physical entanglement of polymer chains of the first and / or second material with the corresponding polymer chains and / or pores of the second material (e.g., the surface polymers of the first material may be entangled with the bulk polymers of the second material). In some cases, this entanglement may further result in one or more non-covalent bonds between the polymer chains of the first and / or second material. Non-limiting examples include electrostatic interactions (e.g., ionic bonds, hydrogen bonds, halogen bonds), van der Waals forces (e.g., dipole-dipole interactions, dipole-induced dipole interactions, London dispersion forces), π effects (e.g., π-π interactions, cation-π and anion-π interactions, polar-π interactions), and hydrophobic effects. In certain cases, the presence of one or more non-covalent bonds improves the mechanical properties of the integrated article (eg, body with components).

[0079] In some embodiments, the surface polymer interacts with at least a portion of the bulk polymer and at least a portion of the pores within the polymer bulk, hi certain embodiments, the surface polymer does not interact with at least a portion of the bulk polymer and at least a portion of the pores within the polymer bulk.

[0080] In some embodiments, the component (e.g., the second water-soluble polymer) is disposed within the bulk of the first material (e.g., the first water-soluble polymer). In some embodiments, the component (e.g., the second water-soluble polymer) is substantially uniformly dispersed within the bulk of the first material (e.g., the first water-soluble polymer), and the first material is substantially uniformly dispersed within the bulk of the second material. In some embodiments, the component (e.g., the second water-soluble polymer) is substantially non-uniformly dispersed within the bulk of the first material (e.g., the first water-soluble polymer), or vice versa.

[0081] In some embodiments, the surface polymer of the first material physically integrates with the surface polymer, bulk material, and / or pores of the second material, hi some embodiments, the surface polymer of the second material physically integrates with the surface polymer, bulk material, and / or pores of the first material.

[0082] In some embodiments, the bulk material of the first material physically integrates with the surface polymer, bulk material, and / or pores of the second material, hi some embodiments, the bulk material of the second material physically integrates with the surface polymer, bulk material, and / or pores of the first material.

[0083] In some embodiments, the pores of the first material are physically integrated with the surface polymer and / or bulk material of the second material, hi some embodiments, the pores of the second material are physically integrated with the surface polymer and / or bulk material of the first material.

[0084] In some embodiments, an adhesive may be present, hi some embodiments, the adhesive may be physically integral with the first component and / or the second component.

[0085] In some embodiments, the article may comprise a main body portion comprising an elongated tube (e.g., a catheter shaft). In some cases, the elongated tube may comprise a first material comprising a water-soluble polymer (e.g., PVA). As described elsewhere herein, the first material is a hydrophilic porous polymeric material that can be processed in either a dehydrated state (e.g., a tensioned state) or a hydrated state (e.g., a relaxed state). According to certain embodiments, the elongated tube may further comprise a first portion (e.g., a proximal end) and a second portion (e.g., a distal end). In some embodiments, when the elongated tube is in a relaxed state (e.g., a hydrated swollen state), the first portion has a radius of curvature that is different from the radius of curvature of the second portion. In certain embodiments, when the elongated tube is in a relaxed state, the first portion has a radius of curvature that is greater than the radius of curvature of the second portion. Meanwhile, in other certain embodiments, when the elongated tube is in a relaxed state, the first portion has a radius of curvature that is smaller than the radius of curvature of the second portion.

[0086] In some embodiments, the radius of curvature of the second portion (e.g., the distal end) is 1 degree or more, 2 degrees or more, 4 degrees or more, 5 degrees or more, 10 degrees or more, 15 degrees or more, 20 degrees or more, 40 degrees or more, 80 degrees or more, 100 degrees or more, 120 degrees or more, 140 degrees or more, or 180 degrees or more, relative to the first portion (e.g., the proximal end). In certain embodiments, the radius of curvature of the second portion (e.g., the distal end) is 180 degrees or less, 140 degrees or less, 120 degrees or less, 100 degrees or less, 80 degrees or less, 40 degrees or less, 20 degrees or less, 15 degrees or less, 10 degrees or less, 5 degrees or less, 4 degrees or less, 2 degrees or less, or 1 degree or less, relative to the first portion.

[0087] In some embodiments, the present invention describes a dual lumen article comprising a first body portion comprising a first material including a water-soluble polymer (e.g., PVA). The first body portion can comprise a first lumen (e.g., an elongated tube) having a first inner diameter. In some cases, the first body portion comprises a first section and a second section. In some embodiments, the inner diameter of the first section is larger, smaller, or equal to the inner diameter of the second section. In preferred embodiments, the first body portion comprises a first lumen (e.g., an elongated tube) of fixed dimensions (e.g., the inner diameter of the first section is equal to the inner diameter of the second section).

[0088] In some embodiments, the dual lumen article further comprises a second body portion comprising a second lumen (e.g., a second elongated tube) comprising a second material different from the first material and having a second inner diameter. In some cases, the second body portion comprises a first portion and a second portion. In some embodiments, the inner diameter of the first portion is greater than, less than, or equal to the inner diameter of the second portion (e.g., the second body portion may be tapered toward one end).

[0089] In a preferred set of embodiments, the dual lumen article comprises a second body portion disposed inside a first body portion (e.g., a dual lumen configuration). For example, in some embodiments, the first portion of the second body has an outer diameter smaller than the first inner diameter of the first lumen, and the second portion of the second body has a second inner diameter approximately equal to the first inner diameter. In other words, the dual lumen article comprises a configuration in which a second tube having a proximal end of a first diameter and a distal end of a second diameter is disposed within a first tube of constant diameter (approximately the same dimensions as the proximal end of the second tube). Other configurations are possible.

[0090] In some embodiments, the dual-lumen article comprises one or more surface features (e.g., barbs, bulges, etc.) at the interface between the first body portion and the second body portion. Without being bound by theory, it is generally believed that such surface features may mechanically reinforce the interface between the first body portion and the second body portion. In certain embodiments, the one or more surface features may be disposed on the first body portion and / or the second body portion.

[0091] In some embodiments, the article comprises an intravenous catheter. In certain embodiments, the intravenous catheter comprises a polymeric material comprising a first water-soluble polymer having a plurality of pores. As described elsewhere herein, a preferred polymeric material comprises a first water-soluble polymer comprising polyvinyl alcohol, which can be processed into a porous material without a covalent crosslinker, having a water content in a dehydrated state of less than 5 wt. % and greater than or equal to 0.1 wt. % and configured to swell from the dehydrated state to an equilibrium water content state by an amount of greater than or equal to 50 wt. % within 60 minutes at 25°C.

[0092] In some embodiments, the polymeric material is processed to have a moisture content in a dehydrated state of 0.1 wt / w% or more, 0.5 wt / w% or more, 1 wt / w% or more, 2 wt / w% or more, 3 wt / w% or more, 4 wt / w% or more, or 5 wt / w% or more. In certain embodiments, the polymeric material is processed to have a moisture content of 5 wt / w% or less, 4 wt / w% or less, 3 wt / w% or less, 2 wt / w% or less, 1 wt / w% or less, 0.5 wt / w% or less, or 0.1 wt / w% or less.

[0093] In some embodiments, the polymeric material is configured to swell in an amount of 5 w / w% or more, 10 w / w% or more, 15 w / w% or more, 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, 45 w / w% or more, or 50 w / w% or more. In certain embodiments, the polymeric material is configured to swell in an amount of 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, 25 w / w% or less, 20 w / w% or less, 15 w / w% or less, 10 w / w% or less, or 5 w / w% or less.

[0094] In some embodiments, the polymeric material is configured to swell from a dehydrated state to an equilibrium moisture content state in 60 minutes or less, 50 minutes or less, 40 minutes or less, 30 minutes or less, or 15 minutes or less.

[0095] In some embodiments, the intravenous catheter can be configured to be inserted into a dehydrated, partially hydrated, or hydrated subject. In certain embodiments, the catheter can be at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% hydrated prior to device insertion. In some embodiments, the catheter can be no more than 50%, no more than 40%, no more than 30%, no more than 20%, or no more than 10% hydrated prior to device insertion. Combinations of the above ranges are also possible.

[0096] In some cases, the intravenous catheter further comprises a lumen and a distal end having a tip shape suitable for intravenous insertion into a subject. The lumen of the intravenous catheter may have any dimension known to those skilled in the art. For example, in some cases, the lumen dimension may be selected to correspond to the dimensions of a standard peripheral intravenous catheter. Without being bound by any particular theory, those skilled in the art will know that catheters are generally sized by gauge (e.g., 14G, 16G, 18G, 20G, 22G, 24G, 26G, and 30G, etc.), and each gauge has a standardized outer diameter and length. For example, a standard 14G catheter typically has an outer diameter of 2.1 mm, while a 26G catheter has an outer diameter of 0.6 mm.

[0097] In some embodiments, the intravenous catheter may have a tip shape to, for example, improve insertion into a subject's vein. Any tip shape known to those skilled in the art may be used. Non-limiting examples include a bevel-tip needle stylet, a bevel-tip needle cannula, a lancet-point needle stylet, a back-bevel needle stylet, a back-bevel needle cannula, a trocar-tip needle stylet, a francis-tip needle cannula, or a conical-tip needle stylet. In some embodiments, the tip has a symmetrical shape, while in certain embodiments, the tip has an asymmetrical shape.

[0098] Some aspects of the present disclosure generally relate to catheter systems comprising a catheter as described herein and components configured to administer therapeutic agents and / or fluids (e.g., saline, Plasmalyte, etc.) to a subject and / or withdraw bodily fluids (e.g., blood) from a subject.

[0099] In some embodiments, the catheter system is configured to secure venous access, which may include, for example, peripheral devices such as peripheral intravenous lines (e.g., PIV, for short-term access, e.g., up to 96 hours) and / or midline catheters, or, for example, PICCs (e.g., for medium-term access, approximately 6 months, particularly for antibiotics, TPN, chemotherapy, transfusions, and frequent blood draws), non-tunneled central venous catheters (e.g., for short-term access where PIV is not suitable, particularly for resuscitation and central venous pressure monitoring), tunneled central venous catheters (e.g., for frequent long-term access, particularly for TPN, transfusions, and frequent blood draws, and can be used when a PICC line is contraindicated or not possible), or implantable ports (e.g., for long-term, infrequent access, or when lifestyle concerns make any of the other options unattractive).

[0100] In some embodiments, the catheter system is configured to provide access to the urinary tract. Those skilled in the art will appreciate that current urinary catheter systems include intermittent urinary catheters, indwelling urinary catheters, and suprapubic catheters. Intermittent urinary catheters are the most common and are inserted into the bladder several times a day to drain urine, after which they are removed from the body. Indwelling urinary catheters are held in the bladder by a water-filled balloon to prevent them from falling out (commonly referred to as a Foley catheter). Urine drains through a tube connected to a collection bag. In some cases, indwelling catheters may include a valve that can be opened to drain urine and closed to allow the bladder to fill with urine until drainage is appropriate. Suprapubic catheters are left in place for long-term use. Rather than being inserted through the urethra, the catheter is inserted through a hole in the abdomen and placed directly into the bladder. Suprapubic catheters are commonly used when the urethra is damaged or blocked (such as due to cancer). Like indwelling catheters, suprapubic catheters may include a valve that allows for intermittent drainage.

[0101] Thus, the systems described herein may include any number of components in addition to the catheter body, with exemplary embodiments including, but not limited to, a collection bag, drainage tubing, drainage ports, catheter cuffs and / or catheter balloons, hubs and wings, valves, injection port caps, needle grips, flashback chambers, luer lock plugs, and, optionally, needles.

[0102] Articles of the present invention, in some embodiments, include a first material (e.g., a water-soluble polymer, a hydrophilic porous material, etc.) The following is a non-limiting description of various contemplated embodiments of the first material described elsewhere herein.

[0103] Some aspects of the present disclosure generally relate to an article (e.g., a device) comprising a body including a first porous material. In some embodiments, the plurality of pores has a particular average pore size. In some embodiments, the average pore size of the plurality of pores is 500 nm or less, 450 nm or less, 400 nm or less, 350 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, 150 nm or less, 100 nm or less, 75 nm or less, 50 nm or less, 25 nm or less, 20 nm or less, or 15 nm or less. In some embodiments, the plurality of pores has an average pore size of 10 nm or more, 15 nm or more, 20 nm or more, 25 nm or more, 50 nm or more, 75 nm or more, 100 nm or more, 150 nm or more, 200 nm or more, 250 nm or more, 300 nm or more, 350 nm or more, 400 nm or more, or 450 nm or more. Combinations of the above ranges are also possible (e.g., less than or equal to 500 nm and greater than or equal to 10 nm). Other ranges are also possible. As described herein, the average pore size may be measured by mercury intrusion porosimetry of the material in a first configuration (e.g., a state with less water content than the equilibrium water content, such as a dehydrated state). In some embodiments, the pores are interconnected.

[0104] In some embodiments, at least some of the pores may be characterized as nanopores, e.g., pores having an average cross-sectional dimension of less than 1 micron. In some embodiments, at least some of the pores may be characterized as micropores, e.g., pores having an average cross-sectional dimension of less than 1 mm and equal to or greater than 1 micron. In some embodiments, at least 50% (e.g., at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, at least 99%, at least 99.9%) of the pores have a diameter of 1 micron or less, 800 nm or less, 600 nm or less, 500 nm or less, 450 nm or less, 400 nm or less, 350 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, 150 nm or less, 100 nm or less, 75 nm or less, 50 nm or less, 25 nm or less, 20 nm or less, or 15 nm or less. In some cases, at least 50% of the pores have a diameter of 10 nm or more, 15 nm or more, 20 nm or more, 25 nm or more, 50 nm or more, 75 nm or more, 100 nm or more, 150 nm or more, 200 nm or more, 250 nm or more, 300 nm or more, 350 nm or more, 400 nm or more, 450 nm or more, 500 nm or more, 600 nm or more, or 800 nm or more. Combinations of the above ranges are also possible (e.g., 1000 nm or less and 10 nm or more). Other ranges are also possible. In some embodiments, the pores are interconnected.

[0105] The first material described herein can have a particular porosity, for example, in a first configuration (e.g., a state with a lower water content than the equilibrium water content, such as a dehydrated state). In some embodiments, the device (first water-soluble polymer) has a porosity of 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, or 45% or more in the first configuration (e.g., a state with a lower water content than the equilibrium water content, such as a dehydrated state). In some embodiments, the device (first water-soluble polymer) has a porosity of 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, or 10% or less in the first configuration (e.g., a state with a lower water content than the equilibrium water content, such as a dehydrated state). Combinations of the above ranges are also possible (eg, 5% to 50% in the first configuration (eg, a state with a moisture content lower than the equilibrium moisture content, such as a dehydrated state)). Other ranges are also possible.

[0106] In some embodiments, the first material (e.g., the first water-soluble polymer) is hydrophilic. As used herein, the term "hydrophilic" has its ordinary meaning in the art and refers to a material surface having a water contact angle of less than 90 degrees as measured by goniometry. In some embodiments, the polymeric material (or its surface) (e.g., the surface of a device) has a water contact angle of 45 degrees or less, 40 degrees or less, 35 degrees or less, 30 degrees or less, 25 degrees or less, 20 degrees or less, 15 degrees or less, 10 degrees or less, 5 degrees or less, or 2 degrees or less at equilibrium water content. In some embodiments, the polymeric material (or its surface) has a water contact angle of 1 degree or more, 2 degrees or more, 5 degrees or more, 10 degrees or more, 15 degrees or more, 20 degrees or more, 25 degrees or more, 30 degrees or more, 35 degrees or more, or 40 degrees or more at equilibrium water content. Combinations of the above ranges (e.g., 1 degree or more and 45 degrees or less) are also possible. Other ranges are also possible.

[0107] As used herein, equilibrium water content refers to the steady state of a device (or material) in which the bulk water content does not increase (e.g., absorb) or decrease when immersed in water at 25° C. without the application of external mechanical stress. Those skilled in the art will understand that steady state (or equilibrium water content) need not perfectly conform to the strict thermodynamic definition of the term, but rather means conforming as closely as possible to the thermodynamic definition of the term as understood by those skilled in the art most closely related to the subject matter (e.g., taking into account factors such as passive diffusion and / or Brownian motion).

[0108] In some embodiments, the first water-soluble polymer has an equilibrium water content of 10% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, or 70% or more. In some embodiments, the first water-soluble polymer has an equilibrium water content of 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, or 20% or less. Combinations of these ranges are possible (eg, 10% w / w or greater and 80% w / w or less). Other ranges are also possible.

[0109] In some embodiments, the first material is substantially lubricious at equilibrium water content. For example, in some embodiments, the first material (e.g., the first water-soluble polymer) has a surface roughness (Ra) of 1000 nm or less at equilibrium water content. In some embodiments, the first material (e.g., the first water-soluble polymer) has a surface roughness (Ra) of 500 nm or less, 400 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, 150 nm or less, 100 nm or less, 50 nm or less, 25 nm or less, 10 nm or less, or 5 nm or less at equilibrium water content. In some embodiments, the first material (or the polymeric material of the device) has a surface roughness (Ra) of 5 nm or more, 10 nm or more, 25 nm or more, 50 nm or more, 100 nm or more, 150 nm or more, 200 nm or more, 250 nm or more, 300 nm or more, 400 nm or more, or 500 nm or more at equilibrium water content. Combinations of the above ranges are also possible (eg, greater than or equal to 5 nm and less than or equal to 1000 nm). Other ranges are also possible.

[0110] In some embodiments, the first material has a surface with a coefficient of friction of 0.10 or less at equilibrium moisture content. For example, the coefficient of friction of the surface of the device (or the polymeric material of the device) is 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.05 or less, 0.04 or less, 0.03 or less, or 0.02 or less. In some embodiments, the coefficient of friction of the surface of the body (or the polymeric material of the device) is 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more, 0.07 or more, 0.08 or more, or 0.09 or more. Combinations of the above ranges are also possible (e.g., 0.1 or less and 0.01 or more). Other ranges are also possible.

[0111] Advantageously, the first material (e.g., first water-soluble polymer) described herein can have low adsorption of a substance, such as, for example, a therapeutic agent (and / or, for example, a protein), in the presence of a dynamic fluid containing the substance. Such devices and compositions can be useful, for example, for use in subjects where the presence of the device should not substantially reduce the availability and / or concentration of a therapeutic agent delivered to the subject (e.g., via the device). In some embodiments, administering a therapeutic agent via a fluid flowing through a device described herein does not substantially reduce the concentration of the therapeutic agent in the fluid. In some cases, the device may not absorb and / or adsorb a therapeutic agent, for example, during flow or use.

[0112] In some embodiments, adsorption of the therapeutic agent onto the surface and / or bulk of the first material (e.g., the first water-soluble polymer) is 0.5 wt% or less, measured at equilibrium water content after exposing the polymer to the therapeutic agent and rinsing with 5 volumes of the device with an aqueous solution, e.g., water or saline. In some embodiments, adsorption of the therapeutic agent onto the surface and / or bulk of the first water-soluble polymer is 0.5 wt% or less, 0.4 wt% or less, 0.3 wt% or less, 0.2 wt% or less, or 0.1 wt% or less. In some embodiments, the therapeutic agent adsorbs onto the surface and / or bulk of the first water-soluble polymer at 0.05 wt% or more, 0.1 wt% or more, 0.2 wt% or more, 0.3 wt% or more, or 0.4 wt% or more. Combinations of the above ranges are also possible (e.g., 0.5 wt% or less and 0.05 wt% or more). Other ranges are also possible.

[0113] Advantageously, the first materials described herein can have desirable swelling properties (eg, in water, saline, in the fluid environment of a subject).

[0114] In some embodiments, a first material (e.g., a first water-soluble polymer) described herein has a first configuration (e.g., a lower moisture content than the equilibrium moisture content state, e.g., a dehydrated state) having a moisture content of 40 w / w% or less, 30 w / w% or less, 20 w / w% or less, 10 w / w% or less, 5 w / w% or less, 4 w / w% or less, 3 w / w% or less, 2 w / w% or less, 1 w / w% or less, 0.8 w / w% or less, 0.6 w / w% or less, 0.4 w / w% or less, or 0.2 w / w% or less. In some embodiments, the first material described herein has a first configuration (e.g., a lower moisture content than the equilibrium moisture content state, e.g., a dehydrated state) having a moisture content of 0.1 w / w% or more, 0.2 w / w% or more, 0.4 w / w% or more, 0.6 w / w% or more, 0.8 w / w% or more, 1 w / w% or more, 2 w / w% or more, 3 w / w% or more, 4 w / w% or more, 5 w / w% or more, 6 w / w% or more, 7 w / w% or more, 8 w / w% or more, 9 w / w% or more, 10 w / w% or more, 15 w / w% or more, 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, or 35 w / w% or more. Combinations of the above ranges are also possible (e.g., 0.1 w / w% or more but less than 5 w / w%, 2 w / w% or more but less than 10 w / w%, 2 w / w% or more but less than 40 w / w%, or 6 w / w% or more but less than 40 w / w%). Other ranges are also possible.

[0115] In some embodiments, a first material described herein has a first configuration (e.g., a water content lower than the equilibrium water content state, e.g., a dehydrated state). In some embodiments, a first material (or polymeric material) described herein swells from the first configuration (e.g., a water content lower than the equilibrium water content state, e.g., a dehydrated state) to a second configuration (e.g., an equilibrium water content state) in 60 minutes or less (e.g., 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less). In some embodiments, a first material (or polymeric material) described herein swells from the first configuration (e.g., a water content lower than the equilibrium water content state, e.g., a dehydrated state) to a second configuration (e.g., an equilibrium water content state) at 25°C.

[0116] In some embodiments, a first material described herein swells, for example, from a first configuration (e.g., a dehydrated state having a moisture content less than the equilibrium moisture content state) to a second configuration (e.g., an equilibrium moisture content state) by an amount of 2 w / w% or more, 3 w / w% or more, 4 w / w% or more, 5 w / w% or more, 10 w / w% or more, 15 w / w% or more, 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, or 45 w / w% or more. In some embodiments, a first material (or polymeric material) described herein swells, for example, from a first configuration (e.g., a dehydrated state having a water content lower than the equilibrium water content state) to a second configuration (e.g., the equilibrium water content state) by an amount of 50 wt / w% or less, 45 wt / w% or less, 40 wt / w% or less, 35 wt / w% or less, 30 wt / w% or less, 25 wt / w% or less, 20 wt / w% or less, 15 wt / w% or less, 10 wt / w% or less, 5 wt / w% or less, 4 wt / w% or less, or 3 wt / w% or less. Combinations of these ranges are also possible (e.g., 5 wt / w% to 40 wt / w%).

[0117] In some embodiments, a first material described herein is in a first configuration (e.g., a water content lower than the equilibrium water content, e.g., a dehydrated state). For example, in some embodiments, a first material described herein (e.g., a first water-soluble polymer) in a first configuration (e.g., a water content lower than the equilibrium water content, e.g., a dehydrated state) has a water content of 40 wt / w% or less, 30 wt / w% or less, 20 wt / w% or less, 10 wt / w% or less, 5 wt / w% or less, 4 wt / w% or less, 3 wt / w% or less, 2 wt / w% or less, 1 wt / w% or less, 0.8 wt / w% or less, 0.6 wt / w% or less, 0.4 wt / w% or less, or 0.2 wt / w% or less. In some embodiments, the first material (e.g., first water-soluble polymer) described herein has a water content of 0.1 w / w% or more, 0.2 w / w% or more, 0.4 w / w% or more, 0.6 w / w% or more, 0.8 w / w% or more, 1 w / w% or more, 2 w / w% or more, 3 w / w% or more, or 4 w / w% or more. Combinations of the above ranges are also possible (e.g., 0.1 w / w% or more but less than 5 w / w%, or 2 w / w% or more but less than 40 w / w%). Other ranges are also possible. As used herein, a dehydrated state generally refers to a steady state, measured under ambient conditions, in which the water content of the device (first water-soluble polymer) does not significantly decrease below 5 w / w% over a 24-hour period. In some embodiments, the devices described herein may include a coating, such as a humectant coating, or unbound porogen, as described in more detail below.

[0118] Advantageously, the first materials (e.g., first water-soluble polymers) and compositions described herein can be configured to swell rapidly in the presence of, for example, water and / or aqueous solutions such as saline. In some embodiments, the first material is configured to swell, for example, from a first configuration (e.g., a dehydrated state having a lower moisture content than the equilibrium moisture content state) to a second configuration (e.g., an equilibrium moisture content state) by, for example, 2 wt. % or more, 5 wt. % or more, 10 wt. % or more, 15 wt. % or more, 20 wt. % or more, 25 wt. % or more, 30 wt. % or more, 35 wt. % or more, 40 wt. % or more, or 45 wt. % or more, for example, within a certain time period (e.g., within 60 minutes, 10 minutes, 5 minutes, 1 minute, or 10 seconds) at 25°C, as described in more detail below. In some embodiments, the first material is configured to swell from a first configuration (e.g., a dehydrated state, e.g., having a moisture content less than an equilibrium moisture content state, such as a dehydrated state) to a second configuration (e.g., an equilibrium moisture content state), e.g., by an amount of 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, 25 w / w% or less, 20 w / w% or less, 15 w / w% or less, or 10 w / w% or less, e.g., at 25°C, e.g., within a certain time (e.g., within 60 minutes, 10 minutes, 5 minutes, 1 minute, or 10 seconds), as described in more detail below. The swell range can be adjusted within minutes, 1 minute, or 10 seconds (or less). Combinations of the above ranges are also possible (e.g., 5 w / w% to 50 w / w%). Other ranges are also possible.

[0119] In exemplary embodiments, the first material is configured to swell in water from a first configuration (e.g., a water content lower than the equilibrium water content state, e.g., a dehydrated state) (e.g., less than 5 w / w% or from 2 to 40 w / w% w / w) to an equilibrium water content state (e.g., from 5 to 20 w / w% w / w) within 60 minutes (e.g., within 10 minutes, within 5 minutes, within 1 minute, or within 10 seconds). In some embodiments, the first material is configured to swell in, for example, normal saline from a first configuration (e.g., a water content lower than the equilibrium water content state, e.g., a dehydrated state) (e.g., less than 5 w / w%) to an equilibrium water content state (e.g., from 5 to 20 w / w% w / w) within 60 minutes (e.g., within 10 minutes, within 5 minutes, within 1 minute, or within 10 seconds). In another exemplary embodiment, the first material (e.g., a first water-soluble polymer) is configured to swell in saline, e.g., from a first configuration (e.g., a state having a lower water content than the equilibrium water content, e.g., a dehydrated state) (e.g., less than 5 w / w%) to the equilibrium water content (e.g., 5 w / w% or more, or 20 w / w% or more and 80 w / w% or less) within 60 minutes (e.g., 10 minutes or less, 5 minutes or less, 1 minute or less, or 10 seconds or less).

[0120] In some embodiments, the first material has a particular length in the first configuration (e.g., a lower moisture content than the equilibrium moisture content, e.g., a dehydrated state), and in some embodiments, the device (first water-soluble polymer) has an increase in overall length at the equilibrium moisture content state of 0.1% or more, 0.5% or more, 1% or more, 2% or more, 4% or more, 6% or more, 8% or more, 10% or more, 12% or more, 14% or more, 16% or more, or 18% or more compared to the overall length in the first configuration (e.g., a lower moisture content than the equilibrium moisture content, e.g., a dehydrated state). In some cases, the first material (first water-soluble polymer) increases in overall length at equilibrium moisture content by no more than 20%, no more than 18%, no more than 16%, no more than 14%, no more than 12%, no more than 10%, no more than 8%, no more than 6%, no more than 4%, no more than 2%, no more than 1%, or no more than 0.5% compared to its overall length at equilibrium moisture content relative to its overall length at equilibrium moisture content (e.g., a dehydrated state, e.g., a state with a moisture content lower than equilibrium moisture content). Combinations of the above ranges are also possible (e.g., 0.1% to 20%). Other ranges are also possible.

[0121] In some embodiments, the first material has a particular outer maximum cross-sectional dimension, such as the outer diameter of a cylindrical, oval, rectangular, or square tube. In embodiments in which the device includes multiple lumens, the outer diameter refers to the outer maximum cross-sectional dimension of one or more lumens. For example, in some embodiments, only one lumen may have the outer diameter. In other embodiments, each or all lumens may independently have the outer diameter. In some embodiments, the first material (e.g., the first water-soluble polymer) exhibits a maximum outer cross-sectional dimension (e.g., outer diameter) at equilibrium water content compared to the maximum cross-sectional dimension (e.g., outer diameter) in the first configuration (e.g., a dehydrated state, e.g., a state with a lower water content than the equilibrium water content) that increases by 0.1% or more, 0.5% or more, 1% or more, 2% or more, 4% or more, 6% or more, 8% or more, 10% or more, 12% or more, 14% or more, 16% or more, or 18% or more. In some cases, the first material (e.g., the first water-soluble polymer) exhibits a maximum cross-sectional dimension (e.g., outer diameter) increase of 20% or less, 18% or less, 16% or less, 14% or less, 12% or less, 10% or less, 8% or less, 6% or less, 4% or less, 2% or less, 1% or less, or 0.5% or less in the equilibrium moisture content state compared to the maximum cross-sectional dimension (e.g., outer diameter) in the first configuration (e.g., a state with a lower moisture content than the equilibrium moisture content state, e.g., a dehydrated state). Combinations of the above ranges are also possible (e.g., 0.1% to 20%, 0.1% to 10%). Other ranges are also possible.

[0122] In some embodiments, the first material (e.g., the first water-soluble polymer) has a particular inner diameter (e.g., in embodiments where the device comprises a hollow core), which is the maximum inner cross-sectional dimension, such as the inner diameter of a cylindrical or rectangular tube (or other non-circular device or body). In embodiments where the first material (e.g., the first water-soluble polymer) comprises multiple lumens, the inner diameter refers to the maximum inner cross-sectional dimension (i.e., the maximum inner cross-sectional dimension of the largest lumen). In some embodiments, the first material (e.g., the first water-soluble polymer) exhibits an increase in inner diameter at equilibrium moisture content of 0.1% or more, 0.5% or more, 1% or more, 2% or more, 4% or more, 6% or more, 8% or more, 10% or more, 12% or more, 14% or more, 16% or more, or 18% or more compared to the inner diameter in the first configuration (e.g., a dehydrated state having a moisture content lower than the equilibrium moisture content). In some cases, the first material (e.g., the first water-soluble polymer) increases its internal diameter at equilibrium moisture content by no more than 20%, no more than 18%, no more than 16%, no more than 14%, no more than 12%, no more than 10%, no more than 8%, no more than 6%, no more than 4%, no more than 2%, no more than 1%, or no more than 0.5% compared to its internal diameter at equilibrium moisture content in the first configuration (e.g., a dehydrated state, e.g., a state with a moisture content lower than equilibrium moisture content). Combinations of the above ranges are also possible (e.g., 0.1% to 20%). Other ranges are also possible.

[0123] In some embodiments, when a first material (e.g., a first water-soluble polymer) swells from a first configuration (e.g., a dehydrated state having a lower water content than the equilibrium water content) to a second configuration (e.g., an equilibrium water content state), the first material (e.g., a first water-soluble polymer) experiences a greater increase in overall length than in inner and / or outer diameter. For example, in some embodiments, the overall length may increase by 1-20% (e.g., 5-15%), while the inner and / or outer diameter may increase by 0.1-19% (e.g., 1-10%).

[0124] In some embodiments, when a first material (e.g., a first water-soluble polymer) swells from a first configuration (e.g., a dehydrated state, e.g., a state with a lower water content than the equilibrium water content) to a second configuration (e.g., an equilibrium water content), the ratio of the rate of increase in inner and / or outer diameter to the rate of increase in overall length is 1.1 or greater, 1.5 or greater, 2 or greater, 5 or greater, 7 or greater, or 10 or greater. In some embodiments, when a first material (e.g., a first water-soluble polymer) swells from a first configuration (e.g., a dehydrated state, e.g., a state with a lower water content than the equilibrium water content) to a second configuration (e.g., an equilibrium water content), the ratio of the rate of increase in inner and / or outer diameter to the rate of increase in overall length is 20 or less, 15 or less, 10 or less, 5 or less, or 2 or less. Combinations of these ranges are also possible (e.g., 1.1 to 20).

[0125] In some embodiments, when the first material (e.g., the first water-soluble polymer) swells from a first configuration (e.g., a state having a water content lower than the equilibrium water content, e.g., a dehydrated state), the first material (e.g., the first water-soluble polymer) experiences a greater increase in inner and / or outer diameter than in overall length.

[0126] In some embodiments, when a first material (e.g., a first water-soluble polymer) swells from a first configuration (e.g., a state having a lower water content than the equilibrium water content, e.g., a dehydrated state) to a second configuration (e.g., an equilibrium water content state), the ratio of the rate of increase in inner and / or outer diameter to the rate of increase in overall length is 1.1 or greater, 1.5 or greater, 2 or greater, 5 or greater, 7 or greater, or 10 or greater. In some embodiments, when a first material (e.g., a first water-soluble polymer) swells from a first configuration (e.g., a state having a lower water content than the equilibrium water content, e.g., a dehydrated state) to a second configuration (e.g., an equilibrium water content state), the ratio of the rate of increase in inner and / or outer diameter to the rate of increase in overall length is 20 or less, 10 or less, 5 or less, or 2 or less. Combinations of these ranges are also possible (e.g., 1.1 to 20).

[0127] In some embodiments, the first material comprises one or more polymers having desirable mechanical properties. For example, in some embodiments, the first material has a Young's modulus in a first configuration (e.g., a water content less than equilibrium water content, e.g., a dehydrated state) (e.g., a water content less than 5% w / w) of 100 MPa or more, 250 MPa or more, 500 MPa or more, 600 MPa or more, 750 MPa or more, 800 MPa or more, 900 MPa or more, 1000 MPa or more, 1250 MPa or more, 1500 MPa or more, 1750 MPa or more, 2000 MPa or more, 2500 MPa or more, 3000 MPa or more, 3500 MPa or more, or 4000 MPa or more. In some embodiments, the first material and / or the second material have a Young's modulus in a first configuration (e.g., a water content less than equilibrium water content, e.g., a dehydrated state) (e.g., a water content less than 5 w / w%) of 5000 MPa or less, 4000 MPa or less, 3500 MPa or less, 3000 MPa or less, 2500 MPa or less, 2000 MPa or less, 1750 MPa or less, 1500 MPa or less, 1250 MPa or less, 1000 MPa or less, 900 MPa or less, 800 MPa or less, 750 MPa or less, 600 MPa, 500 MPa or less, or 250 MPa or less. Combinations of the above ranges are also possible (e.g., 100 MPa or more to 5000 MPa or less). Other ranges are also possible.

[0128] In some embodiments, the first material has a Young's modulus at equilibrium water content of 300 MPa or less, 250 MPa or less, 200 MPa or less, 150 MPa or less, 100 MPa or less, 75 MPa or less, 50 MPa or less, 25 MPa or less, 20 MPa or less, or 10 MPa or less. In some embodiments, the first material has a Young's modulus at equilibrium water content of 5 MPa or more, 10 MPa or more, 20 MPa or more, 25 MPa or more, 50 MPa or more, 75 MPa or more, 100 MPa or more, 150 MPa or more, 200 MPa or more, or 250 MPa or more. Combinations of the above ranges are also possible (e.g., 300 MPa or less and 5 MPa or more). Other ranges are also possible.

[0129] In a preferred set of embodiments, the first material has a Young's modulus in the dehydrated state of 500 MPa or more, 600 MPa or more, 700 MPa or more, 800 MPa or more, 900 MPa or more, or 1000 MPa or more. In certain embodiments, the first material has a Young's modulus in the dehydrated state of 1000 MPa or less, 900 MPa or less, 800 MPa or less, 700 MPa or less, 600 MPa or less, or 500 MPa or less.

[0130] In another preferred embodiment, the first material has a Young's modulus of elasticity of 300 MPa or less and 5 MPa or more at equilibrium moisture content. In some cases, the first material may have a Young's modulus of elasticity of 500 MPa or more at dehydrated state and a Young's modulus of elasticity of 300 MPa or less and 5 MPa or more at equilibrium moisture content.

[0131] In some embodiments, the polymeric material has a Young's modulus at equilibrium water content of 100 MPa or less and 5 MPa or more.

[0132] In a preferred set of embodiments, the devices / articles (e.g., intravascular catheters) described herein have mechanical properties (e.g., stiffness) that support insertion into a subject's vein via percutaneous injection (e.g., to prevent buckling or lumen occlusion (or collapse)) or their intended use (e.g., drawing blood from a subject). Additionally or alternatively, the devices / articles acquire appropriate flexibility after insertion to allow for longer indwell times.

[0133] In some embodiments, the composition (e.g., comprising or formed of) of the first material (e.g., first water-soluble polymeric material) does not include covalent crosslinks, as described in more detail below. However, in other embodiments, the composition (e.g., first material) includes physical crosslinks (e.g., interpenetrating networks, chain entanglements, and / or one or more bonds such as covalent, ionic, and / or hydrogen bonds). In certain embodiments, no covalent crosslinking agents are used to form the body (e.g., first material and / or second material).

[0134] The first material can be present in the device in any suitable amount. For example, in some embodiments, the first material (e.g., a first water-soluble polymer) is present in the device and / or body at equilibrium water content in an amount of 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, 45 w / w% or more, 50 w / w% or more, 55 w / w% or more, 60 w / w% or more, 65 w / w% or more, 70 w / w% or more, 75 w / w% or more, 80 w / w% or more, 85 w / w% or more, or 90 w / w% or more. In some embodiments, the first and / or second material (e.g., the first and / or second water-soluble polymer) is present in the device and / or body at equilibrium water content in an amount of 95 w / w% or less, 90 w / w% or less, 85 w / w% or less, 80 w / w% or less, 75 w / w% or less, 70 w / w% or less, 65 w / w% or less, 60 w / w% or less, 55 w / w% or less, 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, or 25 w / w% or less. Combinations of the above ranges are also possible (e.g., 20 w / w% or more and 95 w / w% or less). Other ranges are also possible.

[0135] In some embodiments, the first material (e.g., a water-soluble polymeric material) comprises or is selected from the group consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylic acid sulfobetaine), poly(acrylic acid sulfobetaine), poly(methacrylic acid carboxybetaine), poly(acrylic acid carboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In an exemplary set of embodiments, the first material is poly(vinyl alcohol).

[0136] In some embodiments, the first material (e.g., the first water-soluble polymer material) comprises a mixture of the first water-soluble polymer and another (e.g., a third) water-soluble polymer. In some embodiments, the third water-soluble polymer comprises or is selected from the group consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylsulfobetaine), poly(acrylsulfobetaine), poly(methacrylcarboxybetaine), poly(acrylcarboxybetaine), povidone, polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. The first water-soluble polymer and the other (e.g., the third) water-soluble polymer may have different chemical compositions.

[0137] In some embodiments, the total weight of the first material (e.g., the first and / or third polymer) in the device at equilibrium water content is 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, 45 w / w% or more, 50 w / w% or more, 55 w / w% or more, 60 w / w% or more, 65 w / w% or more, 70 w / w% or more, 75 w / w% or more, 80 w / w% or more, 85 w / w% or more, 90 w / w% or more, 95 w / w% or more, 98 w / w%, or 99 w / w% or more. In some embodiments, the total weight of the first water-soluble polymer and another (e.g., third) water-soluble polymer in the device at equilibrium water content is 100 w / w% or less, 90 w / w% or less, 98 w / w% or less, 95 w / w% or less, 90 w / w% or less, 85 w / w% or less, 80 w / w% or less, 75 w / w% or less, 70 w / w% or less, 65 w / w% or less, 60 w / w% or less, 55 w / w% or less, 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, or 25 w / w% or less. Combinations of the above ranges are also possible (e.g., 20 w / w% or more to 100 w / w% or less). Other ranges are also possible.

[0138] In some embodiments, the ratio of the first water-soluble polymer to the third water-soluble polymer present in the device is 100:0 or less, 99:1 or less, 95:5 or less, 90:10 or less, 80:20 or less, 70:30 or less, 60:40 or less, or 55:45 or less. In some embodiments, the ratio of the first water-soluble polymer to the third water-soluble polymer present in the device is 50:50 or more, 60:40 or more, 70:30 or more, 80:20 or more, 90:10 or more, 95:5 or more, or 99:1 or more. Combinations of the above ranges are also possible (e.g., 100:0 or less and 50:50 or more). Other ranges are also possible.

[0139] In some embodiments, the water-soluble polymers (eg, the first water-soluble polymer, the second water-soluble polymer, the third water-soluble polymer) have a particular molecular weight. In some embodiments, the molecular weight of a water-soluble polymer (e.g., each independently the first water-soluble polymer, the second water-soluble polymer, or the third water-soluble polymer) can be 40 kDa or more, 50 kDa or more, 75 kDa or more, 100 kDa or more, 125 kDa or more, 150 kDa or more, 175 kDa or more, 200 kDa or more, 250 kDa or more, 300 kDa or more, 350 kDa or more, 400 kDa or more, 450 kDa or more, 500 kDa or more, 600 kDa or more, 700 kDa or more, 800 kDa or more, 900 kDa or more, 1000 kDa or more, 1500 kDa or more, 2000 kDa or more, 3000 kDa or more, or 4000 kDa or more. In some embodiments, the molecular weight of a water-soluble polymer (e.g., each independently a first water-soluble polymer, a second water-soluble polymer, or a third water-soluble polymer) can be 5000 kDa or less, 4000 kDa or less, 3000 kDa or less, 2000 kDa or less, 1500 kDa or less, 1000 kDa or less, 900 kDa or less, 800 kDa or less, 700 kDa or less, 600 kDa or less, 500 kDa or less, 450 kDa or less, 400 kDa or less, 350 kDa or less, 300 kDa or less, 250 kDa or less, 200 kDa or less, 175 kDa or less, 150 kDa or less, 125 kDa or less, 100 kDa or less, 75 kDa or less, or 50 kDa or less. Combinations of the above ranges are also possible (e.g., molecular weights of 40 kDa to 5000 kDa). Other ranges are also possible.

[0140] In some embodiments, the body portion may comprise a first material, a second material, a third material, a fourth material, etc. The first material, the second material, the third material, the fourth material, etc. may be composed of the same material or different materials. For example, in some embodiments, a second body portion comprising a second material (e.g., poly(vinyl alcohol)) may be disposed within the lumen of a first body portion comprising a first material (e.g., polyvinyl alcohol). However, in certain cases, the first and second components may comprise different materials. In some embodiments, the first material, the second material, the third material, the fourth material, etc. may comprise a water-soluble polymer. The water-soluble polymer may, in some embodiments, be a first water-soluble polymer, a second water-soluble polymer, a third water-soluble polymer, a fourth water-soluble polymer, etc. Combinations of the above-referenced ranges are also possible (e.g., the first material comprises a fourth water-soluble polymer, or the second material comprises the first water-soluble polymer).

[0141] As described above and herein, in some embodiments, the body includes a component comprising a second material physically integrated with the first material of the body. In some embodiments, the second material comprises a water-soluble polymer (e.g., a third water-soluble polymer) that is the same as or different from the first water-soluble polymer. In some embodiments, the second material is selected from the group comprising or consisting of poly(vinyl alcohol), poly(acrylic acid), polyethylene glycol, poly(vinylpyrrolidone), poly(methacrylic acid sulfobetaine), poly(acrylic acid sulfobetaine), poly(methacrylic acid carboxybetaine), poly(acrylic acid carboxybetaine), povidone polyacrylamide, poly(N-(2-hydroxypropyl)methacrylamide), polyoxazoline, polyphosphate, polyphosphazene, polyvinyl acetate, polypropylene glycol, poly(N-isopropylacrylamide), poly(2-hydroxymethyl methacrylate), and combinations thereof. In some embodiments, the second material is polyacrylic acid, and in a preferred set of embodiments, the second material is polyvinyl alcohol. The second material can have a different chemical composition than the first water-soluble polymer.

[0142] In some embodiments, the second material comprises a water-soluble polymer disposed within at least a portion (e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, at least 99%, at least 99.99%) of the plurality of pores (e.g., of the first material). In some embodiments, the second material (e.g., a third water-soluble polymer) is disposed within no more than 100%, no more than 90%, no more than 80%, no more than 70%, no more than 60%, no more than 50%, no more than 40%, no more than 30%, no more than 20%, or no more than 10% of the plurality of pores of the first material (e.g., at least 10% and no more than 100% of the plurality of pores). Combinations of the above ranges are also possible.

[0143] In some embodiments, the component includes a second material comprising a porous, water-insoluble polymer. In some embodiments, the second material includes or is selected from the group consisting of cellulose, cellulosic materials, nylon, polyethylene terephthalate (e.g., Dacron), poly(1,4-butylene terephthalate), and polyurethane. In certain embodiments, the component is comprised of a fabric such as Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (atactic, syndiotactic, isotactic), polyethylene (LLDPE, LDPE, HDPE), cellulose, modified cellulose, hydroxyapatite, and combinations thereof.

[0144] The water-insoluble polymer can be processed into any porous structure using any technique known to those skilled in the art. Exemplary embodiments include structures such as cellular foam cavities, fibers, meshes, and nets. For example, in some embodiments, the second polymer material can be processed into threads and fabrics to create complex three-dimensional shapes (e.g., tubular shapes with tapered angles). In some embodiments, the second material can be a woven structure in which two sets of polymer threads are intertwined at right angles, in other embodiments, the second material can be a knitted structure in which loops of polymer threads are intertwined, and in some cases, according to other embodiments, the second material can be a braided structure in which three or more polymer threads are crossed at an angle.

[0145] The second material (e.g., a third water-soluble polymer) can be present in the device in any suitable amount. For example, in some embodiments, the second material is present in the device in an amount of 0.05 w / w% or more, 0.1 w / w% or more, 0.2 w / w% or more, 0.5 w / w% or more, 1.0 w / w% or more, 2.0 w / w% or more, 3.0 w / w% or more, 4.0 w / w% or more, 5.0 w / w% or more, 10 w / w% or more, 20 w / w% or more, 30 w / w% or more, 40 w / w% or more, 50 w / w% or more, 60 w / w% or more, 70 w / w% or more, 80 w / w% or more, or 90 w / w% or more at equilibrium water content. In some embodiments, the second material is present in the device in an amount of 95 w / w% or less, 90 w / w% or less, 80 w / w% or less, 70 w / w% or less, 60 w / w% or less, 50 w / w% or less, 40 w / w% or less, 30 w / w% or less, 20 w / w% or less, 10 w / w% or less, 5.0 w / w% or less, 4.0 w / w% or less, 3.0 w / w% or less, 2.0 w / w% or less, 1.0 w / w% or less, less than 0.5 w / w%, less than 0.2 w / w%, or 0.1 w / w% at equilibrium moisture content. Combinations of the above ranges are also possible (e.g., 0.05 w / w% or more and 95 w / w% or less). Other ranges are also possible.

[0146] In some embodiments, the component is a preformed device, such as a preformed medical instrument, hi some embodiments, the component is a catheter cuff.

[0147] In some embodiments, the components may include materials that are gas impermeable, for example to air. For example, in some cases, the material may be impermeable to oxygen, nitrogen, carbon dioxide, air, or any combination thereof.

[0148] In some embodiments, a component may comprise a first material, a second material, a third material, a fourth material, etc. The first material, the second material, the third material, the fourth material, etc. may be composed of the same or different materials. For example, in some embodiments, a first component comprising a second material and a second component comprising a third material may be joined to a body comprising the first material. However, in some cases, the first component and the second component may be composed of the same material (e.g., the second material). In some embodiments, the first material, the second material, the third material, the fourth material, etc. may comprise a water-soluble polymer. The water-soluble polymer may, in some embodiments, be a first water-soluble polymer, a second water-soluble polymer, a third water-soluble polymer, a fourth water-soluble polymer, etc. Combinations of the above ranges are also possible (e.g., the first material comprises a fourth water-soluble polymer or the second material comprises the first water-soluble polymer).

[0149] Some aspects of the present disclosure generally relate to methods of integrating one or more components into a body. In some embodiments, a body comprising a polymer is softened and placed in contact with one or more components under pressure. Without being bound by theory, it is generally believed that softening the body softens the polymer, promoting interdiffusion of polymer chains at the joint under pressure to form an integrated article.

[0150] In some embodiments, the polymer-containing body is softened during extrusion of the article. Extrusion processes for producing the articles of the present invention are described in International Patent Application Publication Nos. WO 2018 / 237166 and WO 2017 / 112878, each of which is incorporated herein by reference in its entirety. A detailed description of the extrusion process is provided elsewhere herein. Briefly, in some embodiments, however, the method for forming the integrated article includes a polymer mixture comprising at least one water-soluble polymer and a solvent. According to some embodiments, the concentration of the polymer mixture is at least 10% w / w. For example, in some cases, the concentration of the polymer mixture is at least 10% w / w, at least 15% w / w, at least 20% w / w, at least 25% w / w, at least 30% w / w, at least 35% w / w, at least 40% w / w, at least 45% w / w, or at least 50% w / w.

[0151] In some embodiments, the solvent can be a homogeneous solvent, such as water, or a heterogeneous mixture, such as a water / DMSO mixture. In a preferred embodiment, the solvent is water. In certain embodiments, the solvent is a cosolvent (e.g., comprising two solvents). Those skilled in the art will understand that a cosolvent system must include solvents that are miscible or at least partially miscible with each other. For example, in some embodiments, the cosolvent system includes a first solvent (e.g., water) and a second solvent (e.g., DMSO). The relative ratio of the first solvent to the second solvent is about 0:1, 0.1:0.9, 0.2:0.8, 0.3:0.7, 0.4:0.6, 0.5:0.5, 0.6:0.4, 0.7:0.3, 0.8:0.2, 0.9:0.1, or 1:0.

[0152] In some embodiments, the method comprises heating the polymer mixture to a temperature above the melting point of the polymer mixture and extruding the polymer mixture as a body, hi some embodiments, the method comprises heating the polymer mixture to a temperature at least 10 degrees, at least 15 degrees, at least 20 degrees, at least 30 degrees, at least 40 degrees, at least 50 degrees, at least 60 degrees, at least 70 degrees, at least 80 degrees, at least 90 degrees, or at least 100 degrees above the melting point of the polymer mixture.

[0153] After extrusion, a component (e.g., a catheter cuff) comprising a second material different from the first material may be placed in contact with the softened body portion using an externally applied force to promote interdiffusion of polymer chains at the bonded joints to form a unified article.

[0154] In some embodiments, the solvent (or co-solvent) is removed from the extrudate portion at a temperature above or below the freezing point of the solvent. In some preferred embodiments, the solvent is removed from the extrudate portion at a temperature above the freezing point of the solvent. Solvent removal can, in some cases, produce multiple pores in the extrudate portion. This is particularly true when the co-solvent includes at least one non-solvent for the water-soluble polymer. Without being bound by theory, it is known in the art that removing solvent from a polymer mixture containing a solvent and a non-solvent (e.g., a water / DMF solution containing PVA) promotes phase separation into a non-solvent-rich phase and a solvent / polymer-rich phase. The evaporation rate can, in some embodiments, control the porous structure. For example, in some embodiments, a slow solvent extraction rate favors coalescence of the non-solvent phase within the solvent / polymer-rich phase, resulting in larger pores. On the other hand, a fast solvent extraction rate inhibits coalescence of the non-solvent phase, resulting in smaller pores.

[0155] In some embodiments, the solvent is evaporated using heat, for example, from furnaces and ovens. However, other methods of evaporating the solvent are contemplated. For example, in some embodiments, the extruded body is exposed to one or more solvent baths containing a non-solvent for the polymer. In other embodiments, the solvent may be removed by placing the extruded body in a stream of inert gas (e.g., argon, nitrogen, etc.). Combinations of these are also possible. For example, the extruded body may be heated, exposed to a solvent bath, and / or exposed to a stream of inert gas.

[0156] Solvent bonding techniques are believed to have advantages over other bonding methods (e.g., plastic welding, adhesive bonding, etc.) because bonding can occur below the glass transition temperature of the polymer, although this is not required. Any method and / or technique known to those skilled in the art may be used to heat the materials described herein. For example, in some embodiments, heating the materials to form a bond can be performed using a split die bonder, RF welder, or hot air station. Depending on the hydration level of the body portion (e.g., poly(vinyl alcohol)) and the thickness of the materials being joined, the temperature and process time (treatment time or processing time) required to reflow the body portion to form a bond can vary. For example, based on these factors, the process temperature (or treatment temperature or processing temperature) can range from 60°C to 95°C, and the process time can range from 15 seconds to 5 minutes. In some embodiments, the process temperature can be 60°C or higher, 65°C or higher, 70°C or higher, 75°C or higher, 80°C or higher, 85°C or higher, 90°C or higher, or 95°C or higher. In some embodiments, the process temperature can be 95°C or less, 90°C or less, 85°C or less, 80°C or less, 75°C or less, 70°C or less, 65°C or less, or 60°C or less.

[0157] In some embodiments, the process time can be 15 seconds or more, 30 seconds or more, 45 seconds or more, 60 seconds or more, 2 minutes or more, 3 minutes or more, 4 minutes or more, or 5 minutes or more. In some cases, the process time can be 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, 60 seconds or less, 45 seconds or less, 30 seconds or less, or 15 seconds or less.

[0158] For example, in some embodiments, the bonding method comprises exposing the body portion to a solvent to soften the polymer and heating the body portion to further soften the material. In some embodiments, the body portion is heated to a temperature of 100° C. or less, less than 90° C., 80° C. or less, 70° C. or less, 60° C. or less, or 50° C. or less. In one set of preferred embodiments, the method comprises heating the body portion to a temperature of 100° C. or less.

[0159] The body portions may be dehydrated, partially hydrated, or fully hydrated during the bonding process. In some embodiments, the moisture content of the body portions during bonding is 5% w / w or more, 10% w / w or more, 20% w / w or more, 30% w / w or more, 40% w / w or more, or 50% w / w or more. In certain embodiments, the moisture content of the body portions during bonding is 50% w / w or less, 40% w / w or less, 30% w / w or less, 20% w / w or less, 10% w / w or less, or 5% w / w or less.

[0160] In some embodiments, the body portion can be hydrated using any solvent known to those skilled in the art. Preferred embodiments include the use of an aqueous solvent, such as an aqueous buffer solution. Exemplary embodiments include, but are not limited to, phosphate-buffered saline, MEPS, TRIS, citric acid-sodium citrate buffer, citric acid-sodium phosphate buffer, sodium acetate-acetic acid buffer, imidazole buffer, and carbonate buffer. In some cases, the body portion and / or components can be hydrated for a period of time (e.g., overnight) to reach an equilibrium water content (e.g., a steady state where no further water is absorbed or released). Without being bound by theory, it is generally known in the art that varying the concentration of a buffer can be used to control the equilibrium water content of a material; the higher the salt concentration, the faster the hydration rate.

[0161] The hydration period may in some cases be 1 hour or more, 5 hours or more, 10 hours or more, 15 hours or more, 20 hours or more, or 24 hours or more, and in other cases the hydration period is 24 hours or less, 20 hours or less, 15 hours or less, 10 hours or less, 5 hours or less, or 1 hour or less.

[0162] Those skilled in the art will appreciate that bonding can result in undesirable flow / burrs of the materials being joined. Therefore, in some cases, tools designed to prevent undesirable flow / burrs of the materials may be used. Examples of tools include, but are not limited to, specially configured split die bonders / RF welders, and / or fluorinated ethylene propylene (FEP) (and / or PEEK, and / or nylon, and / or polyolefin) heat shrink tubing formed to a size and shape suitable for hot air processing. The latter is particularly useful because compressing the materials promotes a strong contact surface and chain interlocking of the materials being joined.

[0163] In some embodiments, the method comprises cooling the integrated article. The article may be cooled using any technique known to those skilled in the art. In certain embodiments, the method comprises cooling the article at ambient temperature without external control. However, in some cases, the method comprises cooling the article in a controlled manner, for example, using an indirect heat exchanger. Additionally or alternatively, cooling may be achieved by placing the integrated article in an oven, where the temperature is systematically reduced at regular intervals.

[0164] Some aspects of the present disclosure generally relate to methods for molding an article (e.g., a catheter) that includes a body portion. In some embodiments, the body portion comprises a hydrophilic porous material that includes a lumen (e.g., a tubular structure). In some embodiments, molding the article is achieved by first molding the hydrophilic porous material into a desired shape and then heating the hydrophilic porous material to set it in the desired structure. In certain embodiments, the hydrophilic porous material is heated before molding it into the desired structure. Without being bound by theory, it is generally believed that heating a hydrophilic porous material (e.g., poly(vinyl alcohol)) increases the chain mobility of polymer chains within the hydrophilic porous material, resulting in the material being flexible or moldable at certain elevated temperatures and solidifying and retaining the desired shape upon cooling.

[0165] In some embodiments, the hydrophilic porous material is heated to a temperature equal to or greater than its glass transition temperature and less than its melting point. For example, in some embodiments, the hydrophilic porous material is heated to a temperature of 70° C. or greater, 90° C. or greater, 100° C. or greater, 125° C. or greater, 150° C. or greater, 175° C. or greater, 200° C. or greater, or 225° C. or greater. In certain embodiments, the hydrophilic porous material is heated to a temperature of 225° C. or less, 200° C. or less, 175° C. or less, 150° C. or less, 125° C. or less, 100° C. or less, 90° C. or less, or 70° C. or less.

[0166] In some embodiments, shaping the hydrophilic porous material comprises bending it into a desired shape (e.g., a twist, a curve, a circle, etc.). In certain cases, bending the hydrophilic porous material comprises forcing the hydrophilic porous material into a mold having the desired shape. Additionally or alternatively, bending the hydrophilic porous material comprises inserting a material into a lumen of the hydrophilic porous material and bending the material into a desired shape (e.g., a "V" shape). Bending the hydrophilic porous material can also be achieved by physically deforming the hydrophilic porous material (e.g., bending a distal end at a desired angle relative to a proximal end).

[0167] In some embodiments, the article may be formed using thermoforming, for example, by placing a wire (e.g., nitinol, steel, etc.) within the lumen and heating the article to form it into the desired shape. Additionally or alternatively, the article can be placed within a metal housing (e.g., a tube, mold cavity, etc.) and heated to form the article into the desired shape. By restricting the dimensions of the initial component to the desired shape, the shape can be curved, straightened, compressed, or stretched to form the desired shape. Rounded edges can facilitate fluid flow, reduce wear, and reduce surface area, improving catheter placement, catheter life, and patient comfort.

[0168] In some embodiments, the molding method comprises forming a dual lumen article (e.g., a dual lumen catheter) from a first body portion including a first lumen and a second body portion including a second lumen. In some embodiments, forming the dual lumen article can be accomplished by swelling the first body portion to make it flexible and / or bendable and placing the second body portion within the first lumen of the first body portion.

[0169] Examples of solvents configured to swell the first body portion include, but are not limited to, water, dimethyl sulfoxide, and any combination thereof. For example, in some embodiments, the solvent comprises 0% w / w or more, 10% w / w or more, 20% w / w or more, 30% w / w or more, 40% w / w or more, 50% w / w or more, 60% w / w or more, 70% w / w or more, 80% w / w or more, 90% w / w or more, or 100% w / w or more of water. In certain embodiments, the solvent comprises 100% w / w or less, 90% w / w or less, 80% w / w or less, 70% w / w or less, 60% w / w or less, 50% w / w or less, 40% w / w or less, 30% w / w or less, 20% w / w or less, 10% w / w or less, or 0% w / w or less of water. Combinations of the above ranges are also possible (eg, greater than or equal to 10% w / w and less than or equal to 90% w / w).

[0170] In some embodiments, the solvent comprises 0% w / w or more, 10% w / w or more, 20% w / w or more, 30% w / w or more, 40% w / w or more, 50% w / w or more, 60% w / w or more, 70% w / w or more, 80% w / w or more, 90% w / w or more, or 100% w / w or more DMSO. In certain embodiments, the solvent comprises 100% w / w or less, 90% w / w or less, 80% w / w or less, 70% w / w or less, 60% w / w or less, 50% w / w or less, 40% w / w or less, 30% w / w or less, 20% w / w or less, 10% w / w or less, or 0% w / w or less DMSO. Combinations of the above ranges (e.g., 10% w / w or more and 90% w / w or less) are also possible.

[0171] In one preferred embodiment, the solvent is a homogeneous solution of DMSO. In another preferred embodiment, the solvent is a homogeneous solution of water.

[0172] In some embodiments, the solvent causes the first body portion to swell (e.g., absorb the solvent within the non-crosslinked, water-soluble polymer network of the body portion). One skilled in the art will appreciate that the swelling ratio (e.g., the rate at which a material's weight increases due to solvent absorption) can be used to quantify the degree of swelling, for example, of a hydrogel. According to some embodiments, the first body portion placed in the solvent may have a swelling ratio of 10% or more, 25% or more, 50% or more, 100% or more, 250% or more, 500% or more, 1000% or more, 2000% or more, or 3000% or more. In other cases, the body portion placed in the solvent may have a swelling ratio of 3000% or less, 2000% or less, 1000% or less, 500% or less, 250% or less, 100% or less, 50% or less, 25% or less, or 10% or less.

[0173] In some embodiments, the second body portion is heated and / or mechanically deformed until the outer diameter of the second body portion is smaller than the first inner diameter of the first lumen (e.g., in a swollen state), thereby allowing the second body portion to be placed within the first body portion. As described elsewhere herein, it is generally believed that heating increases the mobility of the polymer chains comprising the second body portion, allowing the second body portion to be manipulated (e.g., stretched and / or compressed, etc.). Any technique known to those skilled in the art may be used to reduce the outer diameter of the second body portion. For example, in some embodiments, the second body portion may be heated to stretch it, and additionally or alternatively, a smaller diameter material may be placed within the lumen of the hydrophilic porous material to radially compress the second body portion to the desired outer diameter.

[0174] In some embodiments, the outer diameter of the second body portion can vary along its axial dimension (e.g., central axis). For example, in certain embodiments, the second body includes a proximal end with a first outer diameter and a distal end with a second outer diameter dimension that is different from the first outer diameter dimension. Configurations in which the second outer diameter dimension is smaller than the first outer diameter dimension taper toward the distal end of the second body, and conversely, configurations in which the first outer diameter dimension is smaller than the second outer diameter dimension taper toward the proximal end of the second body. Other configurations are possible. For example, the outer diameter of the second body portion can increase and decrease periodically (e.g., sinusoidally) to form a wave-like shape. Other shapes and configurations are possible.

[0175] In some embodiments, assembling the dual lumen article includes inserting the second body portion into the lumen of the first body portion and drying the dual lumen article. Without being bound by theory, it is generally believed that drying the article removes absorbed solvent from the first body portion, causing the first body portion to shrink and trap the second body portion within the first body portion. In some embodiments, the dual lumen article is dried until the equilibrium moisture content is 5% w / w or less, 4% w / w or less, 3% w / w or less, 2% w / w or less, 1% w / w or less, 0.5% w / w or less, 0.25% w / w or less, 0.1% w / w or less, or 0.05% w / w or less.

[0176] In some embodiments, the dual-lumen article comprises one or more surface features (e.g., barbs, bulges, hooks, etc.) at the interface between the first body portion and the second body portion configured to mechanically reinforce the interface between the first body portion and the second body portion. In certain embodiments, the first body portion comprises the one or more surface features, while in other cases, the second body portion may comprise the one or more surface features. In some cases, the first body portion comprises one or more surface features configured to engage with one or more surface features on the second body portion (e.g., like a key and lock). In some embodiments, drying the article causes the one or more surface features to engage with the opposing surface, thereby mechanically reinforcing the interface between the first body portion and the second body portion.

[0177] Some aspects of the present disclosure generally relate to methods of inserting any of the articles described herein into a subject in need thereof. The articles described herein are at least partially comprised of a body comprising a first material including a hydrophilic, water-soluble polymer. In some embodiments, the article is an intravenous catheter. Without being bound by theory, it is believed that processing parameters increase chain entanglement between the hydrophilic, water-soluble polymer and non-covalent bonding (e.g., hydrogen bonding) between adjacent polymer chains, resulting in the formation of a physically crosslinked polymer network. Physically crosslinked hydrogels, like chemically crosslinked hydrogels, can absorb significant amounts of water within their crosslinked network. Thus, in some embodiments, the article can be inserted into a subject (e.g., intravenously) in a dehydrated, partially (de)hydrated, or fully hydrated (e.g., swollen) state.

[0178] In some embodiments, an article is dehydrated when it has a moisture content of 5% w / w or less. According to some embodiments, an article is (at least partially) hydrated when it has a moisture content of 5% w / w or more and 50% w / w or less. For example, in some embodiments, an article is (at least partially) hydrated when the moisture content is 5% w / w or more, 10% w / w or more, 20% w / w or more, 30% w / w or more, 40% w / w or more, or 50% w / w or more. In certain embodiments, an article is hydrated when the moisture content is 50% w / w or less, 40% w / w or less, 30% w / w or less, 20% w / w or less, 10% w / w or less, or 5% w / w or less.

[0179] In some embodiments, an article (e.g., an intravenous catheter) comprises a polymeric material including a first water-soluble polymer having a plurality of pores, a lumen, and a distal end having a tip shape suitable for intravenous insertion into a subject. Non-limiting examples of possible tip shapes include a bevel-tip needle stylet, a bevel-tip needle cannula, a lancet-point needle stylet, a back-bevel needle stylet, a back-bevel needle cannula, a trocar-tip needle stylet, a francis-tip needle cannula, or a conical-tip needle stylet. In some embodiments, the tip comprises a symmetrical shape, while in certain embodiments, the tip comprises an asymmetrical shape.

[0180] In some embodiments, at least a portion of the article is dehydrated and has a Young's modulus of 500 MPa or more, 750 MPa or more, 1 GPa or more, 2 GPa or more, 4 GPa or more, or 5 GPa or more. In some embodiments, at least a portion of the article is dehydrated and has a Young's modulus of 10 GPa or less, 5 GPa or less, 4 GPa or less, 2 GPa or less, 1 GPa or less, or 750 MPa or less. Combinations of the above ranges (e.g., 500 MPa or more and 10 GPa or less) are also possible. Other ranges are also possible. In some embodiments, an article having a portion with a Young's modulus of at least 500 MPa or more is inserted into a subject (e.g., intravenously) without the use of a needle or other venipuncture device. For example, a portion of the article (e.g., the tip of the article) can have a needle-like design and have a sufficient Young's modulus to enable the article to penetrate the skin, subcutaneous tissue, and / or vein wall of a subject (e.g., to facilitate needle-free insertion of a vascular catheter).

[0181] In some embodiments, at least a portion of the article may undergo rapid hydration upon insertion of the article into a subject (e.g., via fluid flow within the article (e.g., within a lumen of the article) or via exposure to bodily fluids, such as, for example, blood, of the subject). Advantageously, such articles allow for needleless insertion of an intravenous catheter into a subject, such that the article remains within the patient's body (e.g., functions as a catheter).

[0182] In some embodiments, the intravenous catheter is inserted in a dehydrated state. In some embodiments, the intravenous catheter has a first water content during insertion and a second water content after insertion. For example, the catheter may have a water content of 5% w / w or less during insertion and a water content of 5% w / w or more and 50% w / w or less after insertion. Without being bound by theory, it is generally believed that upon insertion into a subject's vein, the catheter absorbs blood components (e.g., serum, plasma, etc.) within a physically crosslinked network and then expands (e.g., increases in water content) within the vein to reach its final size.

[0183] In some embodiments, the intravenous catheter may expand to its final dimensions (e.g., EWC) in 5 seconds or more or 60 minutes or less. For example, in some embodiments, the intravenous catheter may expand to its final dimensions in 5 seconds or more, 10 seconds or more, 30 seconds or more, 1 minute or more, 5 minutes or more, 10 minutes or more, 20 minutes or more, 30 minutes or more, 40 minutes or more, 50 minutes or more, or 60 minutes or more. In certain embodiments, the intravenous catheter may expand to its final dimensions in 60 minutes or less, 50 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 10 minutes or less, 5 minutes or less, 1 minute or less, 30 seconds or less, 10 seconds or less, or 8 seconds or less. Combinations of the above ranges are also possible (e.g., 5 seconds or more and 60 minutes or less, 1 minute or more and 5 minutes or less, 5 minutes or more and 30 minutes or less). Other ranges are also possible. Advantageously, the mechanical properties of the article may be tailored to have a specific swelling time (e.g., time to swell to final dimensions at EWC), for example, using the methods described herein.

[0184] In some embodiments, the intravenous catheter is inserted in a hydrated or partially hydrated state. Thus, in some cases, the catheter may have a water content of 5% w / w or more and 50% w / w or less before insertion. If the catheter is not fully hydrated (e.g., less than 50%) before insertion, the catheter will continue to absorb fluid from the venous system until it reaches an equilibrium swelling ratio (e.g., 50%). In some embodiments, the catheter may have a water content of 5% w / w or more, 10% w / w or more, 20% w / w or more, 30% w / w or more, 40% w / w or more, or 50% w / w or more before insertion into a subject. In certain embodiments, the catheter may have a water content of 50% w / w or less, 40% w / w or less, 30% w / w or less, 20% w / w or less, 10% w / w or less, or 5% w / w or less before insertion into a subject. Combinations of the above ranges (e.g., 5% w / w or more and 50% w / w or less) are also possible.

[0185] In some embodiments, the inner diameter of the lumen is reduced after insertion into a patient. Based on the teachings herein, one skilled in the art will understand that the articles described herein, e.g., venous catheters, can be useful, for example, for administering bodily fluids (e.g., medications, crystalloids, colloids, etc.) to a subject in need thereof and / or withdrawing bodily fluids (e.g., blood). Importantly, inserting the devices / articles of the present invention into a subject's venous system does not cause substantial hemolysis and is therefore generally considered safe.

[0186] Extrusion processes for producing articles of the present invention are described in International Patent Application Publication Nos. WO 2018 / 237166 and WO 2017 / 112878, which are incorporated herein by reference in their entireties. In some embodiments, processes involving extrusion are used to produce high aspect ratio devices. An embodiment of a process for producing a material comprises heating a mixture comprising at least one water-soluble polymer and a solvent in a solvent-removing environment to a temperature above the melting point of the polymer solution forming the mixture to obtain a physically crosslinked matrix, and continuing to remove the solvent until the physically crosslinked matrix becomes a microporous or nanoporous solid material. The physical crosslinking can occur while the mixture is cooling and / or while the solvent is being removed. Additional polymers can be incorporated into the pores of the material.

[0187] 9A-9C illustrate an embodiment of an apparatus for producing porous solid materials. The illustrated apparatus 100 includes a syringe pump 102 that accepts at least one syringe 104, an optional heating jacket (not shown) for heating the syringe, a die head 106, a heating element 108, a power cable 109 for the die head 106 to provide the necessary heating for the die head 106 (details not shown in FIG. 9A), a dispensing spool 110 for a core tube 112, a suction spool 114 and motor (not shown) for the core tube, and a reservoir 116 for extrusion material 117, which has temperature control for cooling or heating, shown as a heat exchanger 118 with heat exchange pipes 120 within the reservoir 116. The die head 106 accepts the core tube 110, which passes through the die head 106. A supply line 122 from the syringe to the die head 106 feeds the apparatus 100. The system of this embodiment may further include a metering station, a jacketed vessel for heating and mixing the solution to be filled into the syringe, and a solvent removal environment for further drying the tubing after removal from the bath 116. The system may also include a heating station for heating and annealing the tubing or other extrusion, as needed. In addition to PTFE core tubes, wire, air, gas, non-solvent liquids, or other materials may be used for the core tube.

[0188] In use, the polymer is heated in a suitable solvent, for example, in a jacketed vessel, and then loaded into a syringe 104. One or more types of polymer may be present, and radiopaque agents and other additives may be added. One or more syringes may be used for the same or different mixtures. The polymer syringe is heated to a predetermined temperature, for example, 80-95°C or less, and degassed prior to extrusion. The syringe 104 is attached to a syringe pump 102 equipped with a wrap heater to maintain the temperature during extrusion. The core 112 is passed through a die head 106, such as a heated external die head, and fed into an extrusion vessel 116, which is then attached to a motor-driven suction spool 114. The vessel temperature is controlled, for example, using a heat exchanger 118, such as a chiller. The extruded material may be extruded at temperatures ranging from -30°C to 75°C; other temperatures may be used; a commonly useful temperature setting for extrusion is 0°C. Those skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, including, for example, any of the following as upper or lower limits: −30, −25, −20, −15, −10, −5, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, and 75° C. The motor speed of the suction (e.g., puller) spool 114 can be controlled to adjust the outer diameter gauge size around the core 112. Adjusting the die size, material feed rate, tubing core diameter, and puller speed plays an important role in adjusting the final tubing gauge, for example, in an embodiment manufacturing a catheter. The polymer feed rate, in this embodiment, can be adjusted, for example, by controlling the syringe pump 102. A connector 122 connects one or more syringes to the die head 106. Many pumps and other tools are known for controlling the delivery of polymer solution. The present apparatus and method are applicable to drawing processes, although alternative feeding processes are also possible.

[0189] In some embodiments, a composition (e.g., a prepolymer composition) can be provided (e.g., for extrusion) prior to formation of the polymeric material. In some embodiments, the composition comprises an aqueous solution. The aqueous solution can include an osmotic agent at a concentration of from 0.01 M to 8 M. The aqueous solution can include from 0 to 50 wt. % (e.g., from 40 wt. % to 50 wt. %) of a radiopaque agent. The composition can further include a water-soluble polymer having a molecular weight of from 40 kDa to 5000 kDa, which can be present in the solution in an amount of from 10 to 50 wt. %.

[0190] In some embodiments, the composition forms a swellable polymeric material upon extrusion.

[0191] In some embodiments, the osmotic agent is present in the solution at a concentration of 0.01 M or more, 0.1 M or more, 0.5 M or more, 1 M or more, 2 M or more, 3 M or more, 4 M or more, 5 M or more, or 6 M or more. In some embodiments, the osmotic agent is present in the solution at a concentration of 8 M or less, 6 M or less, 4 M or less, 2 M or less, 1 M or less, 0.5 M or less, or 0.1 M or less. Combinations of the above ranges are also possible (e.g., 0.01 M or more and 8 M or less). Osmotic agents are described in further detail herein.

[0192] In some embodiments, the radiopaque agent is present in the solution in an amount of 0% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, or 45% or more (w / w). In some embodiments, the radiopaque agent is present in the solution in an amount of 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less (w / w). Combinations of the above ranges are also possible (e.g., 0% or more and 50% or less (w / w). Other ranges are also possible. Radiopaque agents are described in more detail below.

[0193] In some embodiments, the water-soluble polymer is present in the solution in an amount of 10 w / w% or more, 13 w / w% or more, 15 w / w% or more, 20 w / w% or more, 25 w / w% or more, 30 w / w% or more, 35 w / w% or more, 40 w / w% or more, or 45 w / w% or more. In some embodiments, the water-soluble polymer is present in the solution in an amount of 50 w / w% or less, 45 w / w% or less, 40 w / w% or less, 35 w / w% or less, 30 w / w% or less, 25 w / w% or less, 20 w / w% or less, 15 w / w% or less, or 13 w / w% or less. Combinations of the above ranges are also possible (e.g., 10 w / w% or more and 50 w / w% or less). In some embodiments, the water-soluble polymer is present in the solution in an amount of 13 w / w% or more.

[0194] In some embodiments, methods of forming polymeric materials and / or devices described herein comprise providing a mixture comprising a first water-soluble polymer and an osmotic agent (e.g., a salt), as described above. In some embodiments, the mixture is extruded. In some embodiments, the extruded mixture is extruded onto a core material to form a polymeric material disposed on the core material. In some embodiments, the formed polymeric material is exposed to a non-solvent for the polymeric material. In some embodiments, a solution comprising a second water-soluble polymer different from the first water-soluble polymer and, optionally, an osmotic agent is introduced into the polymeric material. In some embodiments, the polymeric material (e.g., after introducing the solution into the osmotic agent) is heated. In some embodiments, the solution is allowed to flow through the polymeric material. In some embodiments, the polymeric material can be dried.

[0195] In one exemplary set of embodiments, a method for forming a polymeric material and / or device described herein comprises physically assembling a body portion with one or more components. In some embodiments, the method comprises providing a mixture comprising a first water-soluble polymer and an osmotic agent (e.g., a salt), wherein the first water-soluble polymer is present in the mixture in an amount of 10 wt% or more (e.g., 13 wt% or more, or 13 wt% to 50 wt%) based on the total weight of the mixture, and performing the following steps: extruding the mixture onto a core material at atmospheric pressure and a temperature of 65°C or more (e.g., 65°C to 100°C) to form a polymeric material (e.g., a solid rod or gas) disposed on the core material; exposing the polymeric material to a non-solvent at a temperature of 8°C or less and -20°C or more for 15 minutes or more (e.g., 1 hour to 240 hours); contacting the polymeric material with a component comprising a second material different from the first water-soluble polymer and / or an osmotic agent (e.g., a salt) for 1 hour to 240 hours to form an integrated article; and heating the integrated article to a temperature of 25°C or more (e.g., 30°C or more, or 30°C to 65°C) for, for example, 1 hour or more (e.g., 1 hour to 48 hours, or 3 hours to 48 hours) to dry the polymeric material.

[0196] In some embodiments, the non-solvent comprises an alcohol. In some embodiments, the non-solvent is ethanol, methanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, decanol, dodecanol, dimethyl sulfoxide, ethyl acetate, acetate, propionate, ether, dimethylformamide, dimethylacetamide, acetone, acetonitrile, ethylene glycol, propylene glycol, glycerol, air, vacuum, or a combination thereof. Other non-solvents (e.g., solvents that are highly soluble in water but have a lower solubility for the water-soluble polymer compared to its solubility in water) can also be used.

[0197] In some embodiments, the extruding step is carried out at atmospheric pressure at a temperature of 65°C or more, 70°C or more, 75°C or more, 80°C or more, 85°C or more, 90°C or more, 95°C or more, 100°C or more, or 105°C or more. In some embodiments, the extruding step is carried out at atmospheric pressure at a temperature of 110°C or less, 105°C or less, 100°C or less, 95°C or less, 90°C or less, 85°C or less, 80°C or less, 75°C or less, or 70°C or less. Combinations of the above ranges (e.g., 65°C or more and 110°C or less) are also possible. Other ranges are also possible. One of ordinary skill in the art will recognize, based on the teachings herein, that additional pressures (e.g., greater than atmospheric pressure, less than atmospheric pressure) and / or temperatures are also possible.

[0198] In some embodiments, exposing the polymeric material to a non-solvent for the polymeric material is carried out at a temperature of 28° C. or less, 25° C. or less, 20° C. or less, 15° C. or less, 10° C. or less, 5° C. or less, 0° C. or less, −5° C. or less, −10° C. or less, or −15° C. or less. In some embodiments, exposing the polymeric material to a non-solvent for the polymeric material is carried out at a temperature of −20° C. or more, −15° C. or more, −10° C. or more, −5° C. or more, 0° C. or more, 5° C. or more, 10° C. or more, 15° C. or more, 20° C. or more, or 25° C. or more. Combinations of the above ranges are also possible (e.g., 28° C. or less and −20° C. or more). Other ranges are also possible.

[0199] In some embodiments, the step of exposing the polymeric material to the non-solvent for the polymeric material is carried out for 1 hour or more, 2 hours or more, 4 hours or more, 6 hours or more, 8 hours or more, 10 hours or more, 15 hours or more, 20 hours or more, 30 hours or more, 40 hours or more, 50 hours or more, 60 hours or more, 80 hours or more, 100 hours or more, 120 hours or more, 140 hours or more, 160 hours or more, 180 hours or more, 200 hours, or 220 hours or more (e.g., at a temperature of 28°C or less and -20°C or greater). In some embodiments, the step of exposing the polymeric material to the non-solvent for the polymeric material is carried out for 240 hours or less, 220 hours or less, 200 hours or less, 180 hours or less, 160 hours or less, 140 hours or less, 120 hours or less, 100 hours or less, 80 hours or less, 60 hours or less, 50 hours or less, 40 hours or less, 30 hours or less, 20 hours or less, 15 hours or less, 10 hours or less, 8 hours or less, 6 hours or less, 4 hours or less, or 2 hours or less. Combinations of the above ranges are also possible (e.g., 1 hour or more and 240 hours or less). Other ranges are also possible.

[0200] In some embodiments, the step of introducing the component comprising a second material different from the first water-soluble polymer and an optional osmotic agent (e.g., a salt) into the polymeric material comprises heating the polymeric material and component to a temperature of 25° C. or higher, 30° C. or higher, 35° C. or higher, 40° C. or higher, 45° C. or higher, 50° C. or higher, 55° C. or higher, or 60° C. or higher. In some embodiments, the polymeric material and component are heated to a temperature of 65° C. or lower, 60° C. or lower, 55° C. or lower, 50° C. or lower, 45° C. or lower, 40° C. or lower, 35° C. or lower, or 30° C. Combinations of the above ranges are also possible (e.g., 25° C. or higher and 65° C. or lower). Other ranges are also possible.

[0201] In some cases, it may be desirable to incorporate one or more biological molecules into the integrated article, as described in International Patent Application Publication No. WO 2020 / 132065. Thus, in some embodiments, a solution containing one or more compounds, a target agent (e.g., a therapeutic agent, a biological agent, etc.), and an optional osmotic agent may be flowed adjacent (e.g., directly adjacent) to the integrated article for a period of time. In some embodiments, the solution is flowed adjacent to the integrated article for 3 hours or more, 5 hours or more, 6 hours or more, 8 hours or more, 10 hours or more, 12 hours or more, 16 hours or more, 20 hours or more, 24 hours or more, 28 hours or more, 32 hours or more, 36 hours or more, 40 hours or more, or 44 hours or more. In some embodiments, the solution is flowed adjacent to the consolidated article for 48 hours or less, 44 hours or less, 40 hours or less, 36 hours or less, 32 hours or less, 28 hours or less, 24 hours or less, 20 hours or less, 16 hours or less, 12 hours or less, 10 hours or less, 8 hours or less, 6 hours or less, or 5 hours or less. Combinations of the above ranges are also possible (e.g., 3 hours or more to 48 hours or less). Other ranges are also possible. Combinations of the above temperatures and times are also possible.

[0202] In some embodiments, the method comprises annealing the consolidated article to a temperature of 80°C or higher (e.g., 80°C or higher and 250°C or lower) for 60 minutes or longer (e.g., 60 minutes or longer and 480 minutes or shorter). In some embodiments, the consolidated article is annealed at a temperature of 80°C or higher, 90°C or higher, 100°C or higher, 120°C or higher, 140°C or higher, 160°C or higher, 180°C or higher, 200°C or higher, 220°C or higher, or 240°C or higher. In some embodiments, the consolidated article is annealed at a temperature of 250°C or lower, 240°C or lower, 220°C or lower, 200°C or lower, 180°C or lower, 160°C or lower, 140°C or lower, 120°C or lower, 100°C or lower, or 90°C or lower. Combinations of the above ranges are also possible (e.g., 80°C or higher and 250°C or lower). Other ranges are also possible.

[0203] In some embodiments, the integrated article (e.g., body and components) is annealed for 30 minutes or more, 60 minutes or more, 80 minutes or more, 100 minutes or more, 120 minutes or more, 160 minutes or more, 200 minutes or more, 240 minutes or more, 280 minutes or more, 320 minutes or more, 360 minutes or more, 400 minutes or more, or 440 minutes or more. In some embodiments, the integrated article is annealed for 480 minutes or less, 440 minutes or less, 400 minutes or less, 360 minutes or less, 320 minutes or less, 280 minutes or less, 240 minutes or less, 200 minutes or less, 160 minutes or less, 120 minutes or less, 100 minutes or less, or 80 minutes or less. Combinations of the above ranges are also possible (e.g., 60 minutes or more and 480 minutes or less). Other ranges are also possible. Combinations of the above temperatures and times are also possible.

[0204] In some embodiments, the core material can be air, water, a non-solvent liquid, a solid, or a gas. In some cases, the core material can be removed after forming a polymeric material (e.g., a body portion) on the core material. In some cases, the core material can be physically removed and / or dissolved.

[0205] In exemplary embodiments, the method comprises using a mixture comprising at least one water-soluble polymer, a salt, and water (e.g., a solution described above and herein), wherein the at least one water-soluble polymer is present in the mixture in an amount of 10 wt% or greater, based on the total weight of the mixture, performing the following steps: heating the mixture to a temperature of 65°C or greater; after heating the mixture, cooling the mixture to a temperature at least 20°C below the melting point of the mixture; and mechanically shaping the mixture. In some embodiments, after cooling the mixture, the mixture may be extruded onto a core material at a temperature of 65°C or greater to form a polymeric material disposed on the core material. The method may comprise exposing the polymeric material to a non-solvent for the polymeric material at a temperature of 28°C or less for 4 hours or more; and removing at least a portion of the core material from the polymeric material.

[0206] In some embodiments, the step of cooling the mixture comprises cooling to a temperature that is at least 20°C, at least 25°C, at least 30°C, at least 35°C, at least 40°C, at least 45°C, at least 50°C, at least 60°C, at least 70°C, at least 80°C, or at least 90°C below the melting point of the mixture. In some embodiments, the step of cooling the mixture comprises cooling to a temperature that is 100°C or less, 90°C or less, 80°C or less, 70°C or less, 60°C or less, 50°C or less, 45°C or less, 40°C or less, 35°C or less, 30°C or less, or 25°C or less below the melting point of the mixture. Combinations of the above ranges are also possible (e.g., at least 20°C or more and 100°C or less). Other ranges are also possible. The mixture may be cooled for any suitable period of time.

[0207] In some embodiments, the mixture can be mechanically shaped. In some embodiments, the composition (e.g., the mixture before extrusion) can be mechanically shaped by kneading, rolling, cutting, and combinations thereof.

[0208] In some embodiments, the mixture is mixed at a temperature of 80° C. or higher, 90° C. or higher, 100° C. or higher, 120° C. or higher, 140° C. or higher, 160° C. or higher, 180° C. or higher, 200° C. or higher, 220° C. or higher, or 240° C. or higher. In some embodiments, the mixture is mixed at a temperature of 250° C. or lower, 240° C. or lower, 220° C. or lower, 200° C. or lower, 180° C. or lower, 160° C. or lower, 140° C. or lower, 120° C. or lower, 100° C. or lower, or 90° C. Combinations of the above ranges are also possible (e.g., 80° C. or higher and 250° C. or lower). Other ranges are also possible.

[0209] In some embodiments, the method comprises adsorbing a compound of interest (eg, a drug) onto a polymeric material, as described above and herein.

[0210] In some embodiments, the polymeric materials and / or devices described herein may be exposed to and / or include a humectant. In some embodiments, at least a portion of the humectant is disposed on the surface (e.g., luminal and / or abluminal surfaces) of the polymeric material and / or device (e.g., body portion). For example, in some embodiments, a portion of the humectant 70 is disposed on the surface of the device 10. In some embodiments, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or all of the humectant is disposed on the surface of the polymeric material and / or device (e.g., body portion). In some embodiments, up to 100%, up to 90%, up to 80%, up to 70%, up to 60%, up to 50%, or up to 40% of the humectant is disposed on the surface of the polymeric material and / or device (e.g., body portion). Combinations of these ranges (e.g., 40% to 100%) are also possible.

[0211] In some embodiments, at least a portion of the humectant is present within the polymeric material and / or device (e.g., the body portion). In some embodiments, at least a portion of the humectant is present within the polymeric material and / or device (e.g., the body portion). For example, in some embodiments, some of the humectant 70 is present within the device 10 (e.g., absorbed into a substantial portion of the device). In some embodiments, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or all of the humectant is present within the polymeric material and / or device (e.g., the body portion). In some embodiments, up to 100%, up to 90%, up to 80%, up to 70%, up to 60%, up to 50%, or up to 40% of the humectant is present within the polymeric material and / or device (e.g., the body portion). Combinations of these ranges (e.g., 30-100%) are also possible.

[0212] In some embodiments, the humectant is a nonionic surfactant (i.e., a surfactant with a net uncharged hydrophilic head and a net uncharged hydrophobic tail) or a zwitterionic surfactant (i.e., a surfactant with a net uncharged hydrophilic head and a net uncharged hydrophobic tail). In some embodiments, the humectant is a nonionic surfactant selected from the group consisting of sugar alcohols, poloxamers, triacetin, α-hydroxy acids, polyethylene glycols, polypropylene glycols, ethylene glycols, propylene glycols, hexylene glycols, butylene glycols, glycerol, sorbitol, mannitol, xylitol, maltitol, erythritol, threitol, arabitol, ribitol, galactitol, fucitol, iditol, inositol, volemitol, maltitol, lactitol, maltotriitol, maltotetriitol, polyglycitol, and combinations thereof. In some embodiments, the humectant comprises an oil, such as vitamin E. In some embodiments, the humectant comprises a salt, such as sodium chloride, potassium chloride, and / or phosphocholine.

[0213] In some embodiments, the polymeric materials and / or devices described herein are exposed to and / or contain 0.1 wt.% or more, 0.5 wt.% or more, 1 wt.% or more, 5 wt.% or more, 10 wt.% or more, or 20 wt.% or more humectant. In some embodiments, the polymeric materials and / or devices described herein are exposed to and / or contain 30 wt.% or less, 25 wt.% or less, 20 wt.% or less, 15 wt.% or less, 10 wt.% or less, 5 wt.% or less, or 1 wt.% or less humectant. Combinations of these ranges (e.g., 0.1-30 wt.% humectant or 1-10 wt.% humectant) are also possible. Porous solids (e.g., those produced with the apparatus of Figures 1D-1F) can be annealed. Furthermore, porous solids can be processed (or fabricated) to further include polymer incorporated into the bulk, with or without prior annealing. In Figure 3A, a material 210 comprising a porous solid matrix 212 is desolvated and exposed to a mixture comprising a polymer in a dissolution solvent, which dissolves in the mixture to form a material 212 comprising a bulk-incorporated polymer 214. A cross-section of the matrix 212 (Figure 3B) shows an outermost region 216 where the pores of the matrix 212 are filled, an intermediate region 218 with a lower polymer density in the pores, less loading, and / or fewer occupied pores, and an interior region 220 that is not permeated by the polymer. The matrix can be solvated and / or desolvated before exposure to the mixture, but must be desolvated upon exposure to the mixture to allow the water-soluble polymer to migrate into the matrix.

[0214] In some embodiments, the method of moisturizing the device and / or polymeric material comprises placing the extruded segments in a solution containing a humectant (e.g., glycerol or poloxamer). In some embodiments, the solution contains 1% or more, 5% or more, 10% or more, 15% or more, 20% or more, or 25% or more w / w of the humectant. In some embodiments, the solution contains 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less w / w of the humectant. Combinations of these ranges are also possible (e.g., 1-35% w / w). In some embodiments, the solution includes a surfactant. In some embodiments, the solution includes PBS.

[0215] In some embodiments, the extruded segments are allowed to sit in the solution for a period of time. In some embodiments, the period is 1 hour or more, 2 hours or more, or 3 hours or more. In some embodiments, the period is 4 hours or less, 3 hours or less, or 2 hours or less. Combinations of these ranges are also possible (e.g., 3 hours, or 1-4 hours).

[0216] In some embodiments, the solution is maintained at a predetermined temperature while the extruded segments are exposed to the solution. In some embodiments, the temperature is 20°C or higher, 30°C or higher, 37°C or higher, 40°C or higher, 50°C or higher, or 60°C or higher. In some embodiments, the temperature is 70°C or lower, 60°C or lower, 55°C or lower, 50°C or lower, 40°C or lower, 37°C or lower, or 30°C or lower. Combinations of these ranges are also possible (e.g., 20-70°C, 37-55°C, or 45°C).

[0217] In some embodiments, after the extruded segments are removed from the solution, they can be dried (e.g., in a convection oven). In some embodiments, the extruded segments are dried at a specific temperature. In some embodiments, the temperature is 20°C or higher, 30°C or higher, or 40°C or higher. In some embodiments, the temperature is 50°C or lower, 40°C or lower, or 30°C or lower. Combinations of these ranges are also possible (e.g., 30°C, or 20-50°C). In some embodiments, the extruded segments are dried for a period of time. In some embodiments, the period of time can be 1 hour or higher, 2 hours or higher, or 3 hours or higher. In some embodiments, the period of time can be 4 hours or lower, 3 hours or lower, or 2 hours or lower. Combinations of these ranges are also possible (e.g., 3 hours, or 1-4 hours).

[0218] In some embodiments, biologically active agents may be incorporated into the article.

[0219] In some embodiments, the methods described herein do not involve a freeze-thaw process and / or a freezing process and / or a thawing process. Furthermore, these methods can be used to produce solid porous materials that exhibit little or no swelling, e.g., swelling of 0% to 100% w / w at EWC, even in the absence of a covalent crosslinker. Those skilled in the art will readily recognize that all ranges and values ​​between the explicitly defined boundaries are contemplated, including, for example, any of the following as upper or lower limits: 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 95, 100% w / w. Here, swelling is measured as % swelling = 100 × (total weight at EWC - dry weight) / dry weight, where dry weight is the weight of the material without water.

[0220] In some embodiments, extruded samples have horizontal chain orientation and alignment along the length of the sample (extrusion direction). Polymer chain orientation is induced by the extrusion process. Without being bound by theory, in some embodiments, this horizontal chain orientation and alignment along the length of the sample is believed to contribute to a greater increase in inner and / or outer diameter than the increase in length when the sample swells.

[0221] In some embodiments, it is useful to combine one or more of the following: extrusion of a hydrophilic polymer in a solvent, cold extrusion, and extrusion into a bath that rapidly removes the solvent from the extrudate. Additionally, in some embodiments, additional solvent removal and / or annealing processes provide further utility for producing desirable porous solids.

[0222] In some embodiments, requirements for nanoporous materials include a high polymer concentration of greater than about 10% w / w in the polymer-solvent mixture with a high level of crosslinking. Those skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, including upper or lower limits of 10, 12, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 95, or 99% w / w of polymer by total weight of the polymer-solvent mixture. In some embodiments, the polymer must be substantially solvated, meaning a true solution or at least half of the polymer is dissolved and the remainder is at least suspended. In some embodiments, polymer solvation contributes to polymer chain alignment and interpolymer crosslinking during extrusion. Without being bound by theory, it is likely that a high concentration of the starting polymer-solvent mixture facilitates this. Additionally, according to some embodiments, chain alignment that may occur as the material passes through the die is believed to promote intra-polymer crosslinking over inter-polymer crosslinking. When the extrudate or other formed mixture enters a desolvation environment (gas or liquid), in some embodiments, the pore structure may further collapse before the densely concentrated polymers are fully crosslinked, thereby improving chain proximity and further increasing crosslink density. Directly placing the extrudate or other formed material into the solvent removal environment is beneficial in some embodiments. In some embodiments, further solvent removal can continue to collapse the material until the structure and / or properties reach a desired endpoint. In some embodiments, an annealing process may further contribute to improved strength.

[0223] On the other hand, freezing increases strength by forcing the formation of ultra-dense microdomains, increasing chain proximity and improving crosslink density, while maintaining macroporosity due to the presence of ice crystals throughout the gel structure. Desolvation forces the formation of ultra-dense microdomains but does not create macropores. On the other hand, gels prior to dehydration or freezing possess macropores by the nature of the process. Furthermore, our research has shown that such nanoporous solids are stronger than macroporous materials.

[0224] Hydrogels can also be produced by lowering the polymer concentration in the polymer solvent mixture, typically less than 10% w / w. Those skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated. For example, upper or lower limits of 2%, 5%, 7%, 8%, 9%, or 10% w / w polymer concentration relative to the total weight of the polymer solvent mixture may be used. Additionally or alternatively, the polymer solvent mixture is not extruded into a solvent removal environment.

[0225] Microporous materials can be produced using process conditions intermediate between those of nanoporous solids and hydrogels. One embodiment prepares the material using conditions equivalent to those used to produce nanoporous materials, but stops solvent removal before reaching the nanoporous solid structure.

[0226] Extrusion of hydrophilic polymers in solvents is useful for producing high-strength materials. Using solvents as the starting material for extrusion (or extrusion molding) is uncommon, at least. Extrusion typically involves a solid material heated to a flowable temperature, extruded, and then cooled by various methods. For example, thermoplastic extrusion of pure PVA is considered possible. However, such extrusion lacks the polymer structure necessary to produce a porous solid, resulting in properties closer to traditional thermoplastic materials. The theory of operation suggests that pure PVA extrusion lacks the hydrogen bonding properties that occur in aqueous ionic solvents. At temperatures appropriate for PVA to flow during extrusion, a less cohesive material is produced at the die head, preventing the formation of continuous shapes. Forming extruded PVA into high-aspect ratio shapes, such as tubes, for use in extrusion processes has been difficult. PVA and other hydrophilic polymers have high viscosities and are difficult to dissolve. A narrow operating temperature range, e.g., 85–95°C, has been observed to be particularly useful. Below about 85°C, the PVA did not completely melt and reach a completely amorphous state suitable for extrusion. Above about 95°C, boiling and evaporative losses made the process inefficient. These temperature ranges could be offset by higher-than-atmospheric pressures, but pressurized systems are difficult to use and scale up. These processes are effectively carried out at temperatures below the boiling point of the polymer solvent material.

[0227] The flowing polymer-solvent mixture exhibited weak cohesion as it exited the die. The use of a core to support the mixture in the die allowed it to retain its shape through the die. This condition contrasts with typical core extrusion processes used in coating processes, such as wire coating for mobile phone chargers. Typical processes that avoid the use of solvents or high solvent concentrations result in relatively high cohesion as they exit the die, allowing the tube to easily hold together. They also do not rely on active bonds, such as hydrogen bonding in hydrophilic polymers, to form solid materials into a cohesive shape as they exit the die.

[0228] It was beneficial to send the formed polymer-solvent mixture to a solvent-removal environment. Most extrusion processes do not use bath temperatures below room temperature. Furthermore, the use of a solvent-removal bath is unusual compared to conventional processes. Baths and other solvent-removal environments help the extruded material solidify sufficiently to remain stable and concentric with the core; otherwise, the melt would teardrop-like. Furthermore, attempts to recover the melt at the end of extrusion would destroy it because it was still in a molten state. In conventional water-containing baths, PVA or similar hydrophilic polymer materials would lose their shape due to swelling, dissolution, or both. The molding process, in which a polymer-solvent mixture is prepared, cast in a mold, and then processed in a solvent-removal environment, does not offer the benefits of chain alignment seen in extrusion. However, with properly controlled temperature and solvent removal, materials with high strength and a well-defined pore structure can be obtained.

[0229] Porous solids are highly lubricious, can be used in a hydrated state, and can easily be bonded to other materials. For example, catheter extensions, luer locks, suture wings, and the like are useful. In some embodiments, copolymer extrusions are useful where the second polymer is present in a range of 0.1% to 10% w / w of the first polymer, or up to 10% w / w, or even up to 5% w / w. One of skill in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, including, for example, any of the following as upper or lower limits: 0.1, 0.2, 0.4, 0.5, 0.8, 1, 2, 3, 4, 5, 6, 8, 10% w / w.

[0230] In some embodiments, the salt helps to control the strength of the material. Without being limited to a particular theory, it is believed that the salt is part of the physical crosslinks, acting as a low molecular weight crosslinker between the polymer chains.

[0231] Some embodiments of the polymer blend include at least one first hydrophilic polymer and at least one second hydrophilic polymer in a solvent extruded as described herein. Examples include one or more combinations of PVA, PAA, PEG, PVP, polyalkylene glycols, hydrophilic polymers, and combinations thereof. Exemplary concentrations include 1 part of the at least one second hydrophilic polymer per 10,000 parts of the first hydrophilic polymer. Those skilled in the art will readily recognize that all ranges and values ​​between the explicitly defined boundaries are contemplated, and any of the following can be used as upper or lower limits, for example: 1, 2, 10, 100, 1000, 1500, 2000, 2500, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10,000 parts. Exemplary concentrations of polymers in a polymer-solvent mixture include a first polymer present at a first concentration and one or more additional polymers present at a second concentration, where the first polymer concentration and the additional polymer concentration are independently selected from 0.1 to 99%, e.g., 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 33, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95% w / w. Additionally, non-hydrophilic polymers and / or non-hydrophilic blocks in block polymers may be present, with the concentration of such polymers and / or such blocks generally being less than about 10% w / w, e.g., 0.1, 0.2, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10% w / w.

[0232] Some embodiments include porous matrices prepared with water-soluble polymers that lose no more than 20-90% w / w of the water-soluble polymer under comparable conditions, and one of skill in the art will readily recognize that all ranges and values ​​between the explicitly defined boundaries (e.g., 20, 25, 30, 33, 40, 50, 60, 70, 80, 90% w / w) are contemplated.

[0233] In some embodiments, materials incorporated into the bulk may exhibit a monolayer on the surface. The term monolayer refers to a layer of a single molecule thickness. A monolayer does not rely on the cohesive forces between the molecules of the monolayer for its stable presence on the surface. At least one water-soluble polymer forms the monolayer. In contrast, the thickness of even a thin self-crosslinked polymer coating corresponds to the thickness of the network formed by the crosslinked polymer. For example, it may be possible to form a crosslinked PVA coating on a surface, but such a coating relies on the interconnections between PVA molecules to necessarily form a crosslinked network. Thus, embodiments include a water-soluble polymer present on the surface of a porous solid, but without covalent bonds to the surface, and the polymer is not part of the network.

[0234] Those skilled in the art, upon reading this disclosure, will be able to apply the principles, given their known understanding of extrusion and other forming technologies, to develop alternative processes and equipment that achieve the same end product as described herein. Scaled-up embodiments of the process may be adapted, for example, to a multi-zone screw extruder, feeding the solvent mixture through appropriate injectors or hoppers, with each zone controlled for cold extrusion. For example, functions such as syringe pumps may be replaced by appropriately metered and controlled liquid or solid polymer feeding systems.

[0235] As described elsewhere herein, the present disclosure provides guidance for joining a body to one or more components. In some embodiments, a body comprising a polymer is softened by heating and contacted with one or more components under pressure. Alternatively or additionally, the components are softened and contacted with the body under pressure. In other embodiments, the body (or components) is softened using a solvent comprising a water-soluble polymer and contacted with the component (or body) under pressure. Without being bound by theory, it is generally believed that softening the body (or components) softens the polymer, promoting interdiffusion of polymer chains at the joint under pressure to form a unified article.

[0236] In some embodiments, bonding may be performed with bodies and / or components in a desolvated state (e.g., dehydrated or dry, EWC of 5% w / w or less), partially hydrated, or fully hydrated (EWC of about 50% w / w). In preferred embodiments, bonding is performed in a desolvated state.

[0237] Without being bound by any particular theory, it is generally believed that heating the joint between the body and / or component in a desolvated state creates a polymer melt at the joint (e.g., the polymer is above its glass transition temperature but below its melting point). When pressure is applied to the joint, polymer chains from the body flow freely into the component, and polymer from the component flows freely into the body. Upon cooling, the polymer chains of the body become physically entangled and united within the bulk of the component, and the polymer chains of the component become physically entangled and united within the bulk of the body. For example, in some cases, the polymer chains of the component may become entangled within the porous bulk structure of the body.

[0238] Bulk incorporation not only modifies the surface of the body and / or component, but also modifies the subsurface, e.g., at least 1-5000 μm. One of ordinary skill in the art will readily recognize that all ranges and values ​​between the explicitly defined boundaries are contemplated, e.g., 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, 100, 250, 500, 750, 1000, 2000, 3000, 4000, or 5000 μm.

[0239] Alternatively or additionally, the interface can be softened using a solvent containing a water-soluble polymer, which can be configured to swell or rehydrate the porous body and / or components. For example, the body (e.g., a porous hydrophilic material) can be exposed to a solvent containing a solvating polymer (e.g., poly(vinyl alcohol)), which can draw these polymers into the pores when the porous matrix is ​​desolvated. The solvent has an affinity for the matrix and is drawn in as the matrix absorbs the solvent. The solvent in the mixture with the bulk-incorporated polymer can be selected to have an affinity for the matrix and be absorbed into the desolvated matrix, but it need not be the same as the solvent in the matrix. Generally, the hydrophilic solvent in the mixture is at least partially desolvated and absorbed into the hydrophilic porous matrix containing the hydrophilic solvent. For bulk incorporation, those skilled in the art can adjust various solvents as needed to create appropriate conditions.

[0240] A hydrophilic solvent is a solvent that is freely miscible with water at 20°C or that is present in a mixture at a concentration that makes it freely miscible with water.

[0241] Desolvation refers to a matrix that is solvent-free, e.g., completely dry, or below the EWC (solvation coefficient) for the solvent contained in the matrix. If the solvent in the matrix is ​​not water, the EWC can be calculated for the material based on measurements in the solvent; that is, in the appropriate context, the term EWC can be used for solvents other than water. For example, a hydrophilic matrix may be solvated in an aqueous solution of an alcohol and have an EWC for that solvent. Embodiments include desolvation weights for porous solids between 1 and 100, and one of skill in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated: 1, 5, 10, 15, 20, 33, 40, 50, 60, 70, 80, 90, 95, 99, 100% w / w refers to the total weight of removable solvent.

[0242] Without being bound by any particular theory, it is believed that a porous material is desolvated (dehydrated if the porous material's solvent is water) and exposed to a polymer in a solution that dissolves the porous material, drawing the polymer into the pores. Thus, the polymer forms a physical bond with the matrix material that defines the pores, and in practice, is permanently incorporated into the bulk of the material by both at least partially filling the pores and physically bonding with the matrix. Alternatively or additionally, the polymer may have a hydrodynamic radius that causes the polymer to exhibit a diameter that exceeds the pore opening diameter, so that the polymer is permanently incorporated into the pores of the material, particularly when the material is used in aqueous or physiological solutions. Generally, if a bulk-incorporated polymer is solvated by a polymer that wets the pores of the porous solid, the polymer may be drawn into the pores of the matrix as it dissolves. When a hydrophilic porous matrix is ​​below the EWC of the matrix, a mixture containing a bulk-incorporated polymer may be drawn in because the polymer's solvent is compatible with the matrix material, e.g., to wet the pores of the material. For example, a hydrophilic solvent will typically wet the pores of a hydrophilic matrix.

[0243] Materials comprising porous matrices of non-covalently bound polymers are preferred embodiments because they can be manufactured with a high degree of control over pore size and material properties, including the ability to select nanoporous, microporous, or other characteristic pore sizes. The matrix can include physically crosslinked water-soluble polymers that define the pores. The solids concentration of these water-soluble polymers can be at least 33% w / w of the matrix at the equilibrium water content (EWC) of the matrix, although other concentrations can be used.

[0244] Thus, one embodiment of a process for incorporating a polymer into a porous material comprises providing a material comprising a porous hydrophilic matrix containing one or more water-soluble polymers (also referred to herein as matrix polymers) physically crosslinked to each other to form a matrix. The matrix-containing material is exposed to a solvent containing one or more polymers solvated in a solvent (also referred to as bulk-incorporation polymers, preferably the polymers are water-soluble, and the solvent is also referred to as a conditioning mixture or bulk-incorporation mixture), where the matrix is ​​below the EWC and is hydrophilic with respect to the solvent prior to exposure to the solvent. The material comprising the bulk-incorporation polymers is desolvated prior to exposure to the solvent.

[0245] In some embodiments, the bulk incorporation process results in an outer region of filled pores, a middle region where the pores are mostly or nearly filled, and an inner region where there is little or no polymer penetration. Bulk incorporation modifies not only surface pores but also subsurface pores, e.g., at least or within the range of 1-5000 μm. Those skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, e.g., 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, 100, 250, 500, 750, 1000, 2000, 3000, 4000, or 5000 μm. The percentage of pores containing polymer can be analyzed as previously described, and the penetration graded by percentage cutoffs, e.g., the first zone is 100% of the pores filled, the second zone is 50% of the pores filled, and the third zone is 0% of the pores filled.

[0246] The bulk incorporation process is preferably carried out using a porous matrix made from a water-soluble polymer, although it may be made using a matrix made solely from PVA, which does not have hydrophobic domains in the polymer. The polymer may form a matrix with physical crosslinks. Thus, embodiments include materials including a matrix without hydrophobic domains, a matrix made from a water-soluble polymer without hydrophobic domains, or a matrix without a water-insoluble polymer. However, when a hydrophilic matrix is ​​made using a water-soluble polymer with physical crosslinks, some hydrophobic domains can be tolerated without destroying the matrix formed thereby. In embodiments of the present invention, the hydrophobic content of the polymer forming the porous matrix is ​​0, 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, or 15% w / w.

[0247] A porous matrix consisting essentially of water-soluble polymers refers to a matrix containing up to 3% w / w of polymers that are crosslinked to form the matrix. For example, RO agents such as salts are not polymers that are crosslinked to form the matrix. A porous matrix consisting essentially of physically crosslinked polymers refers to a matrix that does not contain agents that form covalent bonds between polymers, or a matrix that contains such agents in small amounts, where no more than about 6% (referring to the number of polymers) of the polymers are crosslinked to each other by such agents, e.g., a stoichiometric ratio of polymer number to bifunctional crosslinker of at least 100:3. Similarly, a matrix that is essentially free of covalent bonds refers to a matrix made from crosslinked polymers, where no more than about 6% (referring to the number of polymers) of the polymers that are not covalently bonded to each other are crosslinked. The number of covalent bonds in the matrix can similarly be limited to a stoichiometric ratio of 100:3 to 100:100, e.g., 100 to 3, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100. For example, in hydrogels made by free radical polymerization, typically 100% of the polymers are covalently bonded to each other, with a polymer:covalent bond stoichiometry of 100:100.

[0248] As previously mentioned, porous solids can be manufactured with a controlled pore size range and can be manufactured to provide a matrix with no pores larger than a specific diameter. Diameters can be measured in appropriate conditions, such as by EWC in distilled water. Thus, embodiments include polymers encapsulated in porous matrices that contain no pores larger than 1-5000 μm. Those skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, such as 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 50, 100, 200, 250, 300, 400, 500, 750, 1000, 2000, 3000, 4000, or 5000 μm.

[0249] Porous solids can contain other materials, such as radiopaque (RO) agents, added to but not part of the matrix, as described elsewhere herein. RO agents typically contribute little to the crosslinking that provides the matrix strength. Similarly, other materials, such as wires and reinforcing materials, may be present within the matrix without being part of it. A matrix made with physical crosslinks is a type of matrix that can be made from materials that define pores with a diameter. This contrasts with hydrogels, which typically have polymer strands separated from one another and connected in a mesh network structure, formed, for example, using free radical polymerization or by the reaction of monomers and polymers in solution. Such mesh networks typically cannot be expected to stably incorporate polymers within the pores without covalent bonding using a polymer imbibition process. Porous materials are described in detail herein and may be freely selected for use with bulk-incorporated polymers in accordance with the present disclosure. Porous materials may be selected to have the bulk properties described herein.

[0250] The polymer incorporated into the bulk can be any of the polymers described elsewhere herein for the porous solid. Examples include water-soluble polymers. Examples of water-soluble polymers include polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylic acid (PAA), polyacrylamide, hydroxypropyl methacrylamide, polyoxazoline, polyphosphate, polyphosphazene, poly(vinyl acetate), polypropylene glycol, poly(N-isopropylacrylamide) (PNIPAM), polysaccharides, sulfonated hydrophilic polymers (e.g., sulfonated polyphenylene oxide, Nafion®, sulfobetaine methacrylate), and iodinated versions thereof (e.g., PVA-I, PVP-I), or versions with additional pendant groups, copolymers thereof, and combinations thereof. The solvent can contain one or more polymers, meaning polymers of different chemical compositions, such as PVA and PEG. The term "polymer" refers to one or more polymers.

[0251] The solubility of the water-soluble polymer for incorporation into the porous matrix or bulk can be selected, for example, to be at least 1, 2, 5, or 10 g / 100 ml in water at 20°C. The polymer can be selected from linear or branched polymers. Examples include polymers or hydrophilic polymers with molecular weights of, for example, 40k to 5,000k daltons. Those skilled in the art will readily recognize that all ranges and values ​​within explicitly defined ranges are contemplated. For example, any of the following molecular weights can be used as upper or lower limits: 40k, 50k, 100k, 125k, 150k, 250k, 400k, 500k, 600k, 750k, 800k, 900k, 1 million, 1.5 million, 2 million, 2.5 million, and 3 million. The molecular weight of the polymer can be selected taking into account the available pore size of the porous solid. Nanoporous or microporous materials are preferred.

[0252] The polymer incorporated into the bulk may be selected to be the same as the polymer forming the porous matrix, to be the same as at least one of the polymers that make up the matrix, or to be different.

[0253] The bulk polymer concentration in the solvent can be any concentration that allows the polymer to dissolve, based on the solvent at the start of the process, keeping in mind that undissolved polymer or other unsolvated materials will not enter the pores. In some embodiments, the concentration is 1-50% w / w. One of skill in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 33, 35, 40, 50% w / w.

[0254] The solvent may be selected to solvate the polymer and provide a solvent that is absorbed into the porous solid. For hydrophilic matrices, hydrophilic solvents are generally preferred. The solvent may be water, an organic solvent, an aqueous solvent, or a solvent that does not contain these (e.g., an organic solvent-free solvent). In some embodiments, the concentration of water is 0-99 w / w%, e.g., 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 95, or 99 w / w%.

[0255] The temperature of the conditioning mixture should not exceed the melting point of the porous solid matrix, and can range from, for example, 10 to 100°C, such as 10, 20, 30, 37, 40, 50, 60, 70, 80, or 90°C.

[0256] The exposure time is preferably the time necessary for the porous solid in the mixture to reach the EWC. In some embodiments, the time may include 2, 4, 6, 8, 10, 12, 16, 20, 24, and 48 hours. Agitation and temperature may be manipulated to affect the exposure time, for example, to accelerate the attainment of the EWC or to control the viscosity of the mixture. Salinity and / or osmolality may be adjusted as needed, for example, for solubility, viscosity, and / or EWC.

[0257] The Examples provide guidance regarding salt concentrations in the conditioning mixture. Exemplary salt concentrations are 0.1-2% w / w. Generally, singly charged cations with small atomic radii penetrate deeper into porous solids, while cations with large atomic radii reduce penetration. Examples of salts include salts containing monovalent cations, divalent cations, or other cations, such as sodium, potassium, lithium, copper, and quaternary ammonium (NR4 + , where R is hydrogen, an alkyl group, or an aryl group), magnesium, calcium, copper, iron, or zinc salts. Generally, physiological pH buffers are useful for the mixtures. The pH can be adjusted to increase or decrease penetration into the matrix, and the solvent may or may not contain buffer salts. Example pHs are 4-10, e.g., 4, 5, 6, 7, 8, 9, or 10.

[0258] The viscosity of a conditioning mixture based on a water-soluble polymer and a solvent is affected by pH (high pH, ​​high viscosity), polymer concentration and / or molecular weight, and the branched structure of the polymer, with increases in any of these generally leading to increased viscosity. Generally, the higher the viscosity, the less penetration of the bulk-incorporated polymer into the porous solid. One embodiment is a porous material comprising a water-soluble polymer trapped in the pores of a porous matrix. The matrix may include physically crosslinked water-soluble polymers that crosslink with each other to form the matrix and define the pores. The matrix may have the characteristics disclosed herein, such as polymer content, weight percent of polymer, strength, Young's modulus, coverage, pore size, etc.

[0259] Surface coverage of the water-soluble polymer in the porous matrix can be complete. Complete coverage, with no underlying surface pores observed under SEM observation conditions, is indicative of coverage in EWC. Coverage can be less than 100%, for example, 50-100%. One skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, such as 50%, 60%, 70%, 80%, 90%, 95%, 98%, 99%, 99.9%, or 100%.

[0260] Bulk incorporation can reduce the physical properties of the porous solid. Thus, embodiments include porous solids (e.g., as disclosed herein) that, upon treatment with a water-soluble polymer, exhibit a 1-20% decrease in Young's modulus and / or tensile strength compared to the same material not treated with the water-soluble polymer. Those skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, e.g., 1, 2, 3, 4, 5, 7, 9, 10, 12, 15, or 20%. Stability testing of water-soluble polymers involves immersing a test device in a physiologically representative fluid (e.g., PBS) at body temperature and placing the test device directly into a pump head in a circulating peristaltic loop at a flow rate of 10-12 mL / s, 150 rpm, and a volumetric flow rate of 0.1225 cm for 24 hours. 3 / s / cm 2 This test involves mechanical sample compression at 100000 cycles at 1000 rpm for approximately 500,000 cycles. While the test identified a maximum loss of 25%, other test criteria, such as 0-50% w / w loss, e.g., 1, 5, 10, 15, 20, 25, 30, 40, or 50% w / w loss, may be used. Alternatively, other tests may be performed, such as 0-5% w / w loss, e.g., 1, 2, 3, 4, or 5% w / w loss, after 1-52 weeks of static exposure to excess PBS, e.g., 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, or 52 weeks.

[0261] In some aspects, the present disclosure relates to porous materials (e.g., porous hydrophilic materials, bodies, etc.). Provided herein are processes for producing biocompatible porous solids, such as microporous or nanoporous solid materials, that have low protein adsorption properties and can serve as the basis for non-biofouling devices. By varying the starting polymer concentration, molecular weight, solvent removal, molding process, and curing / annealing process, surface properties with reduced protein adsorption and other properties can be achieved. Some embodiments include extruding polymer mixtures to produce various continuous shapes. The mixtures can be further cured and annealed. These processes can be used to produce tough, highly lubricious materials. Embodiments include polymer mixtures extruded into single- or multi-lumen shapes with various diameters and wall thicknesses.

[0262] One embodiment of a method for producing a nanoporous solid material comprises heating a mixture containing a polymer and a solvent (polymer mixture), extruding the mixture into a solvent-removing environment, and removing the solvent from the crosslinked matrix until a nanoporous solid material is formed. Depending on the process, one or more of these steps may be combined. Additionally, cooling the mixture as it exits the die may be useful. Without being bound by any particular theory of operation, it is believed that crosslinking of the polymer during passage through the die initially forms a porous matrix that is not a true nanoporous solid material because, although there are spaces between the polymer strands, it lacks a pore structure. Once the solvent is removed under appropriate conditions, the crosslinked structure becomes a nanoporous solid. Crosslinking begins when the polymer mixture is extruded through the die and as the mixture cools. Crosslinking can continue while the solvent is being removed. The transition to a nanoporous material occurs simultaneously with solvent removal and is generally considered complete, or substantially complete (greater than 90%), at this stage. The resulting material can be further processed by annealing with or without additional solvents or plasticizers. This process, and other extrusion or other forming processes and / or materials described herein, including bulk incorporation processes, may not include one or more of covalent crosslinking agents, agents that promote covalent crosslinking, radiation to crosslink polymer chains, freezing, thawing, freeze-thaw cycles, one or more freeze-thaw cycles, ice crystal formation, foaming agents, surfactants, hydrophobic polymers, hydrophobic polymer segments, reinforcements, wires, braids, non-porous solids, and fibers.

[0263] Porous materials can be produced by an extrusion process that includes forcing a polymer mixture through a die into a cooling environment. The cooling environment can also be a solvent removal environment. If the solvent is water, the cooling environment is a dehydration environment. The die can have a core extending therethrough, whereby the polymer mixture can be formed around the core. Additionally, a solvent removal environment and / or an annealing environment can be used.

[0264] The extrusion process of the polymer solvent mixture can be performed as cold extrusion. Cold extrusion refers to a process that involves passing the polymer solvent mixture through a die, and does not require heating the polymer solvent mixture above its boiling point throughout the entire process, from preparing the polymer solvent mixture to extrusion. Therefore, in cold extrusion, the die head is kept below the boiling point of the polymer solvent mixture. Many solvents can be used, but water is often a useful solvent, and in this case, the die head temperature is kept below 100 ° C., although lower temperatures can be useful as mentioned above.

[0265] The term "polymer mixture" refers to a polymer in solution or dissolved or suspended in a solvent. The solvent may include, for example, water, an aqueous solution, an organic solvent, or a combination thereof. Heating the polymer mixture may involve heating the mixture to a temperature above the melting point of the polymer. Generally, a solution changes from a cloudy state to a clear state when the melting point is reached. An aqueous solution may contain, for example, 10 to 100% (w / w or v / v) water by volume. One skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges, such as 10, 20, 30, 40, 50, 60, 70, 80, or 90%, or at least one of these, are contemplated.

[0266] Extrusion is a useful process for shaping materials. Other shaping processes, such as molding, casting, or thermoforming of polymer-solvent mixtures, can also be used. Typically, the polymer-solvent mixture is prepared without boiling and formed into a shape that is exposed to controlled solvent removal conditions to produce nanoporous or microporous materials according to the guidance provided herein. Annealing processes can be included. Hydrogels that are not microporous or nanoporous materials can also be produced.

[0267] The heated polymer mixture can be molded or otherwise shaped as it cools, or it can be cooled immediately after being molded / formed. "Molding" is a broad term that refers to the transition of a material from an amorphous molten state into a final product or an intermediate shape for further processing. Molding encompasses casting, laminating, coating, injection molding, pultrusion, and extrusion. Molding can be performed using an injection molding apparatus, where the mold is constructed of a thermally conductive material that can be easily heated to increase the flowability of the injected polymer mixture and then rapidly cooled in a cooling environment. In other embodiments, the molding process can be achieved by extruding the polymer mixture through a die to form a continuous material.

[0268] Cooling the polymer mixture can include cooling an extruded material, such as when passing the polymer material through a die. Examples of cooling include a liquid bath at a temperature at least 20°C below the boiling point of the polymer mixture or below the Tm of the polymer mixture, such as 20, 30, 40, 50, 60, 70, 80, 90, 100, or 110°C below the boiling point or Tm of the polymer, or a bath or other environment at a temperature between -50 and 30°C. Those skilled in the art will readily recognize that all ranges and values ​​between the explicitly defined boundaries are contemplated, and may use any of the following as upper or lower limits: -50, -45, -25, -20, -10, -5, -4, 0, 15, 20, 25, or 30°C. Cooling can be performed in a solvent-removing environment. Freezing temperatures can be avoided. Without being bound by a particular theory of operation, the polymer chains are cooled to a temperature that promotes intermolecular hydrogen bonding and stabilizes chain motion. This can occur at temperatures as high as 30°C, but even higher if time permits. The bath can be aqueous, adjusted with salt or other osmotic agents to achieve an osmotic pressure that removes the solvent from the aqueous material at a relatively low osmotic pressure through osmotic pressure and diffusion. The bath can also be other solvents that freeze at lower temperatures than water, in which case temperatures below 0°C can be used without freezing the solvent or material. For example, when using a hydrophilic copolymer in combination with PVA, temperatures above 20°C can be used, as crosslinking and chain immobilization occur at much higher temperatures.

[0269] The solvent removal environment refers to an environment that significantly accelerates solvent removal compared to drying at room temperature. Such an environment can be an unheated environment, i.e., an environment at room temperature or below (e.g., 20°C or below). Such an environment can be a vacuum environment (e.g., a vacuum chamber), a salt bath, or a bath that removes solvent from the polymer mixture. For example, a method can be used in which the aqueous polymer mixture is introduced into an ethanol bath to replace the water with ethanol. The ethanol can then be removed. The salt bath can be, for example, a high-salt bath (1M to 6M). The duration of the solvent removal environment and / or the cooling process can be independently selected from 1 to 240 hours. One skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated, and that, for example, 1, 2, 5, 10, or 24 hours, or 1, 2, 5, 7, or 10 days can be used as upper or lower limits. The salt can be a salt that dissociates to form monovalent, divalent, or trivalent ions.

[0270] One or more solvent removal environments may be used, or one environment may be temperature controlled. A cooling bath may be used followed by solvent removal in an oven or vacuum oven. Before or after cooling or solvent removal, cleaning may be performed by immersion in a series of solvents, e.g., varying concentrations, salt solutions, ethanol, or other solvent ratios.

[0271] One embodiment is an extruded material that has undergone a solvent removal process involving exposure to a salt bath, where the material is immersed in a series of HO baths (new or replacement) for a period of time (e.g., 2-48 hours, 4-24 hours) to remove excess salt from the cast material or end-user device. The material is then removed from the wash step and dehydrated to remove excess water. Dehydration can be performed using temperatures ranging from 20°C to 95°C, for example. Dehydration is typically performed at 37°C for 24 hours or more.

[0272] In one embodiment, the extruded or otherwise molded polymer mixture is immersed in a bath of high salt concentration (1M-6M) for a time inversely proportional to the salt concentration; the higher the salt concentration, the shorter the immersion time required. For example, immersion in a 6M NaCl solution for 16-24 hours. After immersion, the material is rinsed from the salt solution. This strengthens the material and allows it to be removed from the mold left behind from the initial molding. Alternatively, after immersion in the salt or other bath, the material is immersed in a water bath and dehydrated to remove excess water. Dehydration can be performed at temperatures ranging from 20-95°C. Dehydration can be performed at 37°C for 4 hours or more, 24 hours or more, or for a range of 2-150 hours. One skilled in the art will readily recognize that all ranges and values ​​within the explicitly stated ranges are contemplated. For example, upper or lower limits can be specified as 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, 144, or 150 hours. For example, it has been confirmed that dehydration at 40°C for 6 to 24 hours is effective.

[0273] In another embodiment, NaCl is added to the starting polymer solution at a concentration of 0.1-3M by volume of the final polymer mixture. The polymer is dissolved in the heated solution under stirring and then heated above its melting point. Dry NaCl is slowly added to the solution under stirring until completely dissolved. The slightly cloudy solution is then injected into the feed and formed into shapes by injection molding, casting, extrusion, and / or stretch molding. Quenching occurs at the end of each step to rapidly reduce the temperature and form a solid material. In this embodiment, additional salt soaks are not required. After the material hardens, it can be removed from the molding process, rinsed with water to remove salt, and dehydrated, if desired.

[0274] The term "annealing" in the context of semicrystalline polymers or solid porous materials refers to heat treatment at an annealing temperature equivalent to the melting point of the polymer or polymers in the material. This temperature is typically below the melting point on the absolute temperature scale, within approximately 0-15% of the melting point. Plasticizers and other additives can affect the melting point, usually by lowering it. For example, for pure PVA, the annealing temperature is within approximately 10% of the PVA melting point; if other substances are present, the annealing temperature is typically lower. The principle of operation is that annealing combines stress relief and an increase in the crystalline domain size of the annealed material. Unlike metals, annealing improves the strength of the annealed material. Annealing can be performed under one or more conditions: in air, in a gas, or in the absence of oxygen or water (e.g., in nitrogen, vacuum nitrogen, under argon, with an oxygen scavenger, etc.). For example, experiments have been conducted on the annealing of dehydrated PVA nanoporous materials. Annealing is used to increase the crystallinity of the PVA network, further reduce the pore size of the PVA network, and reduce the adsorption properties of the final gel surface. Annealing can be performed at temperatures ranging from 100 to 200 °C, for example. In a preferred embodiment, this step is performed by immersing the dehydrated gel in a mineral oil bath. Bulk incorporation of a polymer into the porous solid can also involve the annealing process described previously for the porous solid. Annealing can be performed after exposing the desolvated porous solid to a mixture containing the bulk-incorporated polymer. The Tg of the material can be increased or decreased depending on the residual solvent content and / or the presence of a bulk-incorporated second hydrophilic polymer. Therefore, as previously described, the annealing process conditions can be adjusted depending on the substrate temperature, time, heating rate, and cooling rate.

[0275] Annealing can be performed in gas or liquid at atmospheric, elevated, or low (vacuum) pressure. The liquid can be a low-molecular-weight polymer (up to 2000 Da) or other material (e.g., mineral oil). Examples of low-molecular-weight polymers include silicone oil, glycerin, polyols, and polyethylene glycols less than 500 Da. A useful embodiment is annealing in a glycerin bath, e.g., at 140°C for 1-3 hours. The glycerin further reduces the fouling properties of the gel through interaction and neutralization of the free hydroxyl end groups of the PVA network. The annealed nanoporous material is cooled, removed from the annealing bath, and the bath medium is washed off by a series of extended immersions. The product is then dehydrated and ready for terminal sterilization.

[0276] Various types of dies may be used, such as vertical, rectangular, horizontal, and spiral extrusion heads, single-polymer extrusion heads that extrude a single polymer, and multi-layer extrusion heads that simultaneously extrude multiple polymer or other layers. Continuous and cyclic heads may also be used. Various materials may be incorporated into or as layers, such as reinforcing materials, fibers, wires, braided materials, braided wires, braided plastic fibers, and the like. Similarly, these materials may be excluded. Furthermore, porous solids may be fabricated to have specific properties, such as Young's modulus, tensile strength, solids content, polymer composition, porous structure, or solvent content, that are known and therefore measurable to the exclusion of various other materials. Thus, embodiments include materials disclosed herein that are described based on the properties of the material, without consideration of the various other materials incorporated. For example, a nanoporous solid may have a known, constant Young's modulus, even with reinforcing wires that provide additional strength to the material.

[0277] The core can be used in an extrusion die. The core can be air, water, liquid, solid, non-solvent, or gas. Those skilled in the art who read this disclosure will understand that various extrusion processes can be used with these various types of cores. Cores made of polytetrafluoroethylene tubing (PTFE) are useful. In some embodiments, the core is a wire.

[0278] Multilumen tubing has multiple channels running through its profile. These extrusions can be custom designed to fit device designs. Multilumen tubing has a variety of outer diameters (OD), numerous custom inner diameters (ID), and various wall thicknesses. This tubing is available in a variety of shapes, such as round, oval, triangular, square, semicircular, and crescent. These lumens can be used for guidewires, fluids, gases, wires, and various applications. The number of lumens in a multilumen tubing is limited only by the size of the OD. In some embodiments, the OD can be as large as 0.5 inches, the ID as small as 0.002 inches, and the web and wall thickness can be as thin as 0.002 inches. Tight tolerances of + / - 0.0005 inches can be maintained. Those skilled in the art will readily understand that all ranges and values ​​between the explicitly stated boundaries are contemplated, for example, any of the following may be used as upper or lower limits for OD and / or ID: 0.002, 0.003, 0.004, 0.007, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 inches. Tolerances may be, for example, 0.0005 to 0.1 inches. Those skilled in the art will readily understand that all ranges and values ​​between the explicitly stated boundaries are contemplated, for example, any of the following may be used as upper or lower limits: 0.0005, 0.001, 0.002, 0.003, 0.006, 0.01, 0.02, 0.03, 0.06, 0.8, 0.9, and 1 inch.

[0279] Braided tubing can be manufactured in a variety of configurations. For example, it can be braided using round or flat wire as thin as 0.001 inches, with single or double wire ends. A variety of materials can be used to manufacture braided tubing, such as stainless steel, beryllium copper, silver, and monofilament polymers. Braids can be wrapped around many thermoplastic substrates, such as nylon and polyurethane, at various wire counts per inch. The advantages of braided catheter shafts are their high torque capacity and kink resistance. By varying several factors during the braiding process, the properties of the tubing can be tailored to meet performance requirements. Once braiding is complete, a second extrusion can be performed over the braided tubing to encase the braid and create a smooth finish. Wall thicknesses as thin as 0.007 inches can be achieved when braided tubing is required.

[0280] The devices, catheters, kits, and methods described herein may be administered to any suitable subject. As used herein, the term "subject" refers to an individual organism, such as, for example, a human or an animal. In some embodiments, the subject is a mammal (e.g., a human, a non-human primate, or a non-human mammal), a vertebrate, a laboratory animal, a livestock animal, an agricultural animal, or a companion animal. Non-limiting examples of subjects include humans, non-human primates, cows, horses, pigs, sheep, goats, dogs, cats, or rodents, such as mice, rats, hamsters, birds, fish, or guinea pigs. Generally, the present invention is intended for use in humans. In some embodiments, the subject may exhibit health benefits, for example, from administration of the device.

[0281] End-user products, intermediate products, or materials-containing products can be manufactured with a desired aspect ratio, such as at least 3:1, for the materials described herein, including nanoporous materials, microporous materials, and hydrogels. The aspect ratio increases as the length of the device increases and the width narrows. Those skilled in the art will readily recognize that all ranges and values ​​within the explicitly defined ranges are contemplated, including, for example, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 50:1, 100:1, and 1000:1, as upper and lower limits. High aspect ratios are highly advantageous for certain devices, such as many types of catheters. In principle, thin tubes can be continuously extruded without length limitations. Such devices include, for example, tubes, rods, cylinders, and devices with square, polygonal, or circular cross sections. Any of these may have one or more lumens. These devices may be made of a single material, substantially a single material, or multiple materials including the various layers already described or reinforcements, fibers, wires, braided materials, braided wires, braided plastic fibers.

[0282] In particular, the extrusion process provides for concentrically positioned lumens, as opposed to eccentrically positioned, which means the lumen is off-center. When there are multiple lumens, the lumens are symmetrically positioned, as opposed to eccentrically positioned lumens resulting from an inadequately controlled process. Embodiments include the aforementioned devices having an aspect ratio of at least 3:1, in which the lumens are not eccentrically positioned or one lumen is concentric with the longitudinal axis of the device.

[0283] For example, porous solids, such as nanoporous materials, microporous materials, and high-strength hydrogels, can be used to fabricate catheters and medical fibers. These can be fabricated with bulk-incorporated polymers and can have various characteristics as described above. Examples of catheters include central venous catheters, hub catheters, peripherally inserted central catheters, midline catheters, peripheral catheters, tunneled catheters, dialysis access, hemodialysis, vascular access ports, peritoneal dialysis, urinary catheters, neurocatheters, peritoneal catheters, intra-aortic balloon pumps, diagnostic catheters, interventional catheters, and drug delivery catheters, shunts, wound drains (external drains, including ventricular, ventriculoperitoneal, and lumboperitoneal), and infusion ports. Porous solids can be used to fabricate permanently or temporarily implantable devices, including fully implantable and percutaneously implantable devices. Porous solid materials can be used to fabricate blood-contacting or bodily fluid-contacting devices (external and / or intracorporeal devices, including blood-contacting implants). Examples of such devices include drug delivery devices (e.g., insulin pumps), tubing, contraceptive devices, feminine hygiene devices, endoscopes, implants (including those smaller than 6 mm in diameter), pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, leads for cardiovascular devices, ventricular assist devices, catheters (including cochlear implants, endotracheal tubes, tracheostomy tubes, drug delivery ports and tubing), implantable sensors (intravascular, percutaneous, intracranial), ventilator pumps, and ophthalmic devices, including drug delivery systems. Catheters can include tubular nanoporous materials with fasteners for connecting to other devices (e.g., Luer fasteners or fittings). Radiopaque agents can be added to materials, fibers, or devices. The term radiopaque agent refers to agents (e.g., barium sulfate, bismuth, or tungsten) commonly used in the medical device industry to impart radiopacity to materials. The RO agent may be added, for example, at 5-50% w / w of the total solids weight, such as 5, 10, 20, 30, 40, or 50%.

[0284] Medical fibers made from porous solid materials include applications such as sutures, threads, medical fabrics, braids, meshes, knitted or woven meshes, nonwoven fabrics, and devices based thereon. These fibers have excellent strength and flexibility. They can be used to fabricate materials that are resistant to fatigue and wear.

[0285] In some embodiments, the devices described herein are or are configured for use with medical devices such as catheters, hubs, cuffs, balloons, shunts, wound drains, infusion ports, drug delivery devices, tubing, contraceptive devices, feminine hygiene devices, endoscopes, grafts, pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization devices, cardiovascular device leads, ventricular assist devices, endotracheal tubes, tracheostomy tubes, implantable sensors, ventilator pumps, and ophthalmic devices. In some embodiments, the catheter is selected from the group consisting of a central venous catheter, a peripheral central venous catheter, a midline catheter, a peripheral catheter, a tunneled catheter, a dialysis access catheter, a urinary catheter, a neurocatheter, a percutaneous transluminal angioplasty catheter, and / or a peritoneal catheter. Other suitable uses are described in more detail below.

[0286] In some embodiments, the devices and compositions described herein are administered to a subject. In some embodiments, the device can be administered orally, rectally, vaginally, nasally, intravenously, subcutaneously, or urethrally. In some cases, the device can be administered into a subject's body cavity, epidural space, vein, artery, orifice, external orifice, and / or abscess. Non-limiting examples of orifices include wounds. Non-limiting examples of wounds include wound openings formed for venous access through the skin (e.g., as an insertion site).

[0287] The term "medically acceptable" generally refers to a highly purified material that is free of contaminants and non-toxic. The term "consisting essentially of," when used in the context of biomaterials or medical devices, refers to a material or device that contains no more than 3% w / w of other materials or components, and this 3% does not imply that the material or device is unsuitable for its intended medical use. Equilibrium moisture content (EWC) refers to the amount of water a material contains before it begins to decompose, at a constant wet weight. Materials with high solids content are generally observed to reach equilibrium moisture content in 24 to 48 hours. Distilled water is used to measure EWC unless otherwise specified.

[0288] The term w / v refers to weight per volume (e.g., g / L or mg / mL). The terms biomaterials and biomedical materials are used interchangeably herein and include biomedically acceptable materials intended for use in the biomedical field, such as implants, catheters, blood-contacting materials, tissue-contacting materials, diagnostic assays, medical kits, tissue sample processing, or other medical purposes. Additionally, these materials are suitable for, but are not limited to, biomedical applications and may be manufactured as general-purpose materials. Physiological saline refers to a phosphate buffer solution with a pH of 7-7.4 and equivalent to the physiological osmolality of humans at 37°C.

[0289] The term molecular weight (MW) is measured in g / mol. The MW of a polymer refers to the weight-average MW unless otherwise specified. If the polymer is part of a porous solid, the term MW refers to the polymer before crosslinking. If the distance between crosslinks is specified, the term refers to the weight-average MW between the crosslinks unless otherwise specified. The abbreviations k, M, and G stand for thousand, million, and billion, respectively, so 50kMW stands for 50,000 MW. Dalton is also a unit of MW, and when used with polymers, it also refers to the weight-average MW.

[0290] The publications, journals, patents, and patent applications referenced herein are incorporated herein for all purposes, and in the event of a conflict, the present specification shall control. The features of the embodiments described herein may be used in any combination as needed to create an operable process or product.

[0291] As used herein, the term "therapeutic agent," also referred to as "drug," refers to an agent that is administered to a subject to treat or prevent a disease, disorder, or other clinically recognized condition, and that has a clinically significant effect on the subject's body to treat and / or prevent the disease, disorder, or condition.

[0292] As used herein, when a component is described as being "adjacent" to another component, the component may be directly adjacent to (e.g., in contact with) the other component, or there may be one or more intervening components. A component that is "directly adjacent" to another component means that there are no intervening components.

[0293] "Subject" refers to any animal, such as, for example, a mammal (e.g., a human). Non-limiting examples of subjects include humans, non-human primates, cows, horses, pigs, sheep, goats, dogs, cats, or rodents, such as mice, rats, hamsters, birds, fish, or guinea pigs. The present invention is generally intended for use in humans. In some embodiments, a subject may exhibit a health benefit, for example, from administration of an autonomous righting device.

[0294] As used herein, "fluid" refers to the ordinary meaning, i.e., liquid or gas. Fluids cannot maintain a fixed shape and flow within an observable time frame, filling the container in which they are contained. Thus, fluids may have any suitable viscosity that allows for flow. When two or more fluids are present, one skilled in the art may independently select each fluid from essentially any fluid (liquid, gas, etc.). [Example]

[0295] Example Example 1 The following example generally illustrates the formation of a catheter tip according to some embodiments described herein.

[0296] "Soft" material at the tip To reduce trauma during insertion, the tip is fused (glued or heat-bonded) with a low-hardness material. The injection-molded or extruded PVA tip is ground down and then annealed / heat-treated at 120°C and bonded to a PVA tube that is annealed / heat-treated at 150°C. Bonding is achieved by using PVA glue (10% PVA in water), drying, and annealing at 120-150°C. Bonding is achieved by using high frequency or localized heating and water as a solvent to reflow the material at the required bond points.

[0297] "Hard" material at the tip The tip is fused (glued or heat-bonded) with a high-hardness material to facilitate insertion into the skin, subcutaneous layer, and vessel wall (artery or vein). The PVA tip, which is injection molded or extruded and then ground, is annealed / heat-treated at 170°C and bonded to a PVA tube that is annealed / heat-treated at 150°C. Bonding is achieved by PVA glue (10% PVA in water), drying, and annealing at 120-150°C. Bonding is achieved by high-frequency or localized heating and using water as a solvent to reflow the material at the required bond points.

[0298] Example 2 The following examples relate to the molding of catheters with shape memory. Shape formation was observed at temperatures above 70°C, 90°C, 120°C, 150°C, and 170°C (increasing temperature exposure generally results in a stiffer and more pronounced memory to the underlying mandrel shape). Shape memory was achieved using a stainless steel mandrel bent to a specific desired shape, radius, or curvature. Straight or curved catheter tubing was extruded and partially hydrated with water, a salt solution (sodium chloride or phosphate-buffered saline), or an alcohol-water solution (85% ethanol / 15% water) until it was soft enough to be attached to straight, curved, bent, looped, or spiral catheter tubing. Shape memory can be induced by drying (<90°C) and then annealing at 120°C (>90°C). Figures 14A-14C are photographs showing examples of molded catheters. Figure 14A is a photograph of a partially hydrated straight catheter. Figure 14B is a photograph of a partially hydrated straight catheter (in 2.2% sodium chloride solution) mounted on a formed mandrel. Figure 14C (top) shows the formed mandrel. Figure 14C (bottom) is a photograph of an example catheter that, with the mandrel removed, was dried at 95°C for 90 minutes, annealed at 150°C for 90 minutes, and then rehydrated in 1x phosphate-buffered saline (37°C).

[0299] When attempting to reshape the lumen from a circular to a D-shape, hydrating the catheter and drying it at various temperatures imparts an aspect ratio similar to the shape of the underlying mandrel to varying degrees, typically proportional to the temperature (see Figures 15A-15C).

[0300] [Table 1]

[0301] While several embodiments of the present invention have been described and illustrated herein, those skilled in the art will readily conceive of various other means and / or structures for performing the functions and / or obtaining the results and / or one or more advantages described herein, and each such variation and / or modification is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the specific application(s) to which the teachings of the present invention are applied. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation equivalents to the specific embodiments of the invention described herein. Accordingly, it is to be understood that the foregoing embodiments are illustrative only and that, within the scope of the appended claims and their equivalents, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, device, material, kit, and / or method described herein. Furthermore, any combination of two or more of these features, systems, devices, materials, kits, and / or methods is also within the scope of the present invention, unless such features, systems, devices, materials, kits, and / or methods are mutually inconsistent.

[0302] The indefinite expressions "a" and "an," as used in the specification and claims, should be understood to mean "at least one," unless expressly indicated to the contrary.

[0303] The term "and / or," as used in the specification and claims, should be understood to mean "either or both" of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Elements other than those specifically identified by the "and / or" clause may optionally be present, whether associated with those elements or not, unless expressly stated to the contrary. Thus, as a non-limiting example, a reference to "A and / or B," when used in conjunction with open-ended language such as "comprising," can refer, in one embodiment, to A without B (optionally including elements other than B); in another embodiment, to B without A (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements), etc.

[0304] As used herein and in the claims, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" should be interpreted as inclusive, i.e., including at least one, including two or more, of a number or list of elements, and optionally including additional unlisted items. Only terms clearly indicated to the contrary, such as "only one of" or "exactly one of," or, as used in the claims, "consisting of," mean including exactly one element of a plurality of elements or a list of elements. In general, the term "or" as used herein should be interpreted as indicating exclusive alternatives (i.e., "not either / or") only when preceded by terms indicating exclusivity, such as "either," "one of," "only one of," or "exactly one of." "Essentially consisting of," when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0305] As used herein and in the claims, the phrase "at least one" when used in reference to a list of one or more elements should be understood to mean at least one element selected from any one or more elements in the list of elements, but does not necessarily include at least one of every element specifically listed in the list of elements, and does not exclude any combination of elements in the list of elements. This definition allows for the optional presence of elements other than those specifically identified in the list of elements to which the phrase "at least one" refers, whether associated with those elements or not. Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B" or, equivalently, "at least one of A and / or B") can refer in one embodiment to at least one (optionally multiple) A in the absence of B (and optionally including elements other than B); in another embodiment to at least one (optionally multiple) B in the absence of A (and optionally including elements other than A); in yet another embodiment to at least one (optionally multiple) A and at least one (optionally multiple) B (and optionally including other elements), etc.

[0306] In the claims and the foregoing specification, all transitional phrases such as, for example, "comprising," "including," "carrying," "having," "containing," "involving," and "holding" shall be understood to be open-ended, i.e., to mean "including, but not limited to." Only the transitional phrases "consisting of" and "consisting essentially of" shall be closed or semi-closed transitional phrases, respectively, as defined in U.S. Patent Office Manual of Patent Examining Procedure Section 2111.03.

[0307] As used herein, terms relating to, for example, the shape, orientation, arrangement, and / or geometric relationships of one or more devices, structures, forces, fields, flows, directions / trajectories, and / or subcomponents thereof, and / or combinations thereof, and / or other tangible or intangible elements characterized by such terms, unless otherwise defined or indicated, should not be understood to require absolute adherence to the mathematical definition of such terms, but rather to indicate the closest possible fit to the mathematical definition of such terms within the scope of characterizing the subject matter, and to be understood to the extent understood by one of ordinary skill in the art to which the subject matter most closely relates. Examples of such terms relating to shape, orientation, and / or geometric relationships include, but are not limited to, shapes such as, for example, circle, square, circle / circle, rectangle / rectangle, triangle / triangle, cylinder / cylinder, ellipse / ellipse, (n)polygon / (n)polygon, etc.; angular orientations such as, for example, perpendicular, orthogonal, parallel, perpendicular, horizontal, collinear, etc.; contours and / or trajectories such as, for example, plane / plane, coplanar, hemisphere, hemisphere, line / line, hyperboloid, paraboloid, flat, curve, line, arc, sinusoid, tangent / tangent, etc.; direction such as, for example, north, south, east, west, etc.; surface and / or bulk material properties and / or spatial / temporal resolution and / or distribution such as, for example, smooth, reflective, transparent, clear, opaque, rigid, impermeable, uniform, inert, non-wettable, insoluble, stable, unchanging, constant, homogeneous, etc.; and many others that will be apparent to one of ordinary skill in the relevant art. As an example, a fabricated device described herein as "square" need not have its faces or sides perfectly flat or straight and intersect at exact 90-degree angles (indeed, such a device may exist only as a mathematical abstraction), but rather, the shape of such a device should be construed as approximating a mathematically defined "square" to the extent that it is typically achievable and actually achieved with the described fabrication techniques, as would be understood by one of ordinary skill in the art or as specifically described.As another example, two or more fabricated devices described herein as "aligned" need not have their faces or sides perfectly aligned (indeed, such devices may exist only as a mathematical abstraction), but rather, the arrangement of such devices should be interpreted as approximating the mathematically defined "aligned" to the extent that one skilled in the art would understand or that is specifically described and is typically achievable and realized in the described fabrication techniques.

Claims

1. An article, a body portion comprising a first material including a water-soluble polymer; a component physically integrated with the body portion, the component comprising a second material different from the first material; below: i) the first material has a Young's modulus of elasticity of 500 MPa or more in a dehydrated state and a Young's modulus of elasticity of 300 MPa or less or 5 MPa or more in a state of equilibrium moisture content; ii) the first material is configured to swell from a dehydrated state to a equilibrium hydration state by an amount of 5% to 50% w / w within 60 minutes at 25°C; iii) the first material is free of covalent crosslinks between the water-soluble polymer forming the first material, and / or iv) the first material comprises pores each having a diameter of 1 μm or less; An article having one or more of the following.

2. An article, a hydrophilic porous polymeric material comprising a water-soluble polymer; and a component physically integrated with the hydrophilic porous polymeric material; the hydrophilic porous polymeric material comprises a plurality of pores, the hydrophilic porous polymeric material being free of covalent crosslinks between the water-soluble polymers; the component includes a second material different from the first material; the component comprises a plurality of fibers; At least a portion of said plurality of fibers are embedded within said hydrophilic porous polymeric material.

3. An article, a body portion and a component physically integrated with the body portion such that at least a portion of the component is embedded within the body portion; The article, wherein the body portion comprises a first material including a water-soluble polymer, the first material comprising a plurality of pores, and the component comprises a second material different from the first material.

4. 1. A method of forming an integrated article, comprising:

1. A polymer mixture comprising at least one water-soluble polymer and a solvent, said polymer mixture having a concentration of at least one water-soluble polymer of at least 10% w / w, comprising the steps of: heating the polymer mixture to achieve a temperature above the melting point of the polymer mixture; extruding the polymer mixture into a body; and removing solvent from the extruded body at a temperature above the freezing point of the solvent until the body becomes porous; performing the body is a porous body comprising the at least one water-soluble polymer, the porous body being made without a covalent crosslinking agent that forms covalent bonds between the polymers extruded to make the porous body; The method of claim 1, wherein during the step of extruding the polymer mixture, a component is integrated with the body portion, the component comprising a second material different from the first material, thereby forming the integrated article.

5. 1. A method of forming an integrated article, comprising: exposing the body portion to a solvent; Optionally, heating the body to a temperature of 100°C or less; contacting the body portion with the component in the presence of the solvent such that the component physically integrates with the body portion, thereby forming the integrated article; cooling the integrated article; and The method, wherein the body comprises a first material including a water-soluble polymer such that the water-soluble polymer softens in the presence of the solvent.

6. 1. A method of forming an integrated article, comprising: exposing the body portion to a solvent; contacting the body portion with the component in the presence of the solvent such that the component integrates with the body portion, thereby forming the integrated article; at least partially drying the consolidated article; and The method, wherein the body comprises a first material including a first water-soluble polymer, and the solvent comprises water and a second water-soluble polymer.

7. An article, a body portion comprising a first material including a water-soluble polymer; a solution coating disposed on a portion of a surface of the body; a component in physical contact with the solution coating such that the component is adhered to the body portion through the solution coating; Equipped with The article, wherein the solution coating comprises water and polyvinyl alcohol, the polyvinyl alcohol being present in the solvent in an amount of at least 0.1 wt % and at most 25 wt %.

8. 10. The article or method of any preceding claim, wherein the solvent comprises the water-soluble polymer at a concentration that is less than the concentration of the water-soluble polymer used to form the first material.

9. 10. The article or method of any preceding claim, wherein the solvent comprises water and polyvinyl alcohol, and the polyvinyl alcohol is present in the solvent in an amount of at least 0.1 wt % and at most 25 wt %.

10. 10. The article or method of the preceding claim, wherein the solvent has a hydrolysis level of 80% or greater, such that the solvent contains 20% or less acetate groups.

11. 10. The article or method of the preceding claim, wherein the solvent comprises water.

12. 10. The article or method of the preceding claim, wherein the solvent comprises water and the water-soluble polymer.

13. 10. The article of the preceding claim, wherein the article comprises a lumen.

14. 10. The article of the preceding claim, wherein the article comprises a hemodialysis catheter, a peripherally inserted central catheter (PICC), a central venous catheter, a midline catheter, a peripheral catheter, a urinary catheter, a neurocatheter, a peritoneal catheter, and / or an infusion port.

15. The article of the preceding claims, wherein the article is configured for use with a medical article such as, for example, a catheter, a balloon, a shunt, a wound drain, an infusion port, a drug delivery article, a tube, a contraceptive article, a feminine hygiene article, an endoscope, an implant, a pacemaker, an implantable cardioverter-defibrillator, a cardiac resynchronization article, a cardiovascular article lead, a ventricular assist article, an endotracheal tube, a tracheostomy tube, an implantable sensor, a ventilator pump, and an ophthalmic article.

16. 10. The article or method of the preceding claim, wherein the polymeric material does not include a covalent crosslinker.

17. 10. An article or method according to the preceding claims, wherein the polymeric material has a Young's modulus at equilibrium water content (EWC) of 5 to 100 MPa.

18. 10. An article or method according to the preceding claim, wherein the article comprises a plurality of interconnected pores.

19. 10. The article or method of the preceding claim, wherein the component comprises a plurality of fibers.

20. 10. An article or method according to the preceding claim, wherein the component is a catheter cuff.

21. 10. An article or method according to any preceding claim, wherein the body comprises a second material containing the first water-soluble polymer at a concentration that is less than the concentration of the first water-soluble polymer in the first material.

22. 10. The article or method of the preceding claim, wherein the water-soluble polymer can be loaded with a water-insoluble compound selected from the group consisting of a therapeutic agent, a bioactive compound, a fabric, a metal mesh, a color indicator, a radiopaque material, and a reactive indicator.

23. 10. An article or method according to the preceding claim, wherein the water-soluble polymer incorporates a conductive indicator that aids in the detection of P waves in an electrocardiogram.

24. 24. The article or method of claim 23, wherein the conductive indicator comprises silver powder that is insoluble in physiological fluids entrained in PVA.

25. 10. The article or method of the preceding claim, wherein the water soluble polymer is incorporated into a fabric selected from the group consisting of Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (atactic, syndiotactic, isotactic), and polyethylene (LLDPE, LDPE, HDPE).

26. The article or method of the preceding claim, wherein the intended use of the article or method is selected from the group consisting of a bandage, tissue in-growth, stent, shunt, braided tube, and wall stent, and is bonded to another PVA substrate.

27. 10. The article or method of any preceding claim, wherein the first and second water-soluble polymers are bonded together to create a new shape or to strengthen the one or more components physically integrated with the body portion.

28. 30. The article or method of claim 27, wherein bonding comprises hydrating and heating the first and second water-soluble polymers that bond to the overlapping joint.

29. 10. An article or method according to any preceding claim, wherein upon heating, the first water-soluble polymer flows into the second water-soluble polymer.

30. 10. An article or method according to any preceding claim, wherein upon heating, the second water-soluble polymer flows into the first water-soluble polymer.

31. 10. The article or method of any preceding claim, wherein combining further comprises cooling the first and second water-soluble polymers.

32. 10. The article or method of the preceding claim, wherein cooling the polymer forms the unitary article.

33. 10. The article or method of the preceding claim, wherein the water-soluble polymer is hydrated in solution until an equilibrium % hydration is achieved.

34. 10. The article or method of the preceding claim, wherein the equilibrium % hydration is between about 0.1% and 100%.

35. 10. The article or method of the preceding claim, wherein the solution comprises phosphate buffered saline at a concentration of about 0.1M to 10M.

36. 10. The article or method of the preceding claim, wherein the bonding is performed using a specially configured split die bonder, RF welder, or hot air station.

37. An article or method according to the preceding claims, wherein the bonding temperature is between 60 and 95°C.

38. An article or method according to the preceding claims, wherein the bonding time is between 15 seconds and 5 minutes.

39. 10. An article or method according to any preceding claim, wherein the bonding is performed using FEP heat shrink tubing formed into a size and shape suitable for hot air treatment.

40. 10. An article or method according to any preceding claim, wherein bonding further comprises compressing the bond to increase chain entanglement of the materials being bonded.

41. 1. A method for reforming the shape of a hydrophilic porous material, comprising: bending the hydrophilic porous material containing the lumen in a desired shape; heating the hydrophilic porous material to 90°C or higher in the bent state; and a) bending the hydrophilic porous material comprises forcing the hydrophilic porous material into a mold having the desired shape; and / or b) bending the hydrophilic porous material comprises inserting a material into the lumen of the hydrophilic porous material to thereby provide the desired shape; and / or c) bending the hydrophilic porous material comprises physically deforming the hydrophilic porous material; In any of the cases (a) to (c), i) the hydrophilic porous material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or less in an equilibrium water content state; ii) the hydrophilic porous material is configured to swell from a dehydrated state to an equilibrium moisture content state by an amount of 5% to 50% w / w within 60 minutes at 25°C; iii) the hydrophilic porous material is free of covalent crosslinks between the water-soluble polymers forming the hydrophilic porous material; and iv) the hydrophilic porous material comprises pores each having a diameter of 1 μm or less; A method that satisfies one or more of the above.

42. An article, an elongated tube containing a first material comprising a water-soluble polymer; the elongated tube having a first portion and a second portion; the first portion has a radius of curvature that is different from a radius of curvature of the second portion in a relaxed state of the elongate tube; below: v) the first material has a Young's modulus of elasticity of 500 MPa or more in a dehydrated state and a Young's modulus of elasticity of 300 MPa or less and 5 MPa or more in a state of equilibrium moisture content; vi) the first material is configured to swell from a dehydrated state to an equilibrium moisture content state in an amount of 5% to 50% w / w within 60 minutes at 25°C; vii) the first material is free of covalent crosslinks between the water-soluble polymers forming the first material; and viii) the first material comprises pores each having a radius of 1 μm or less; A method that satisfies one or more of the above.

43. 1. A dual lumen article, comprising: a first body portion including a first material including a water-soluble polymer; and a second body portion including a second material different from the first material; the first body portion includes a first lumen having a first inner diameter; the second body portion includes a second lumen, a first portion of the second body portion having an outer diameter smaller than the first inner diameter of the first lumen, and a second portion of the second body portion having a second inner diameter approximately equal to the first inner diameter; the second body portion is at least partially disposed within the first body portion; below: ix) the first material has a Young's modulus of elasticity of 500 MPa or more in a dehydrated state and a Young's modulus of elasticity of 300 MPa or less and 5 MPa or more in a state of equilibrium moisture content; x) the first material is configured to swell from a dehydrated state to an equilibrium moisture content state by an amount of 5% to 50% w / w at 25°C within 60 minutes; xi) the first material is free of covalent crosslinks between the water-soluble polymers forming the first material; and xii) the first material comprises pores each having a diameter of 1 μm or less; A method that satisfies one or more of the above.

44. 1. A method of forming a dual lumen article, comprising: swelling a first body portion in a solvent, the first body portion including a first material including a water soluble polymer, the first body portion including a first lumen having a first inner diameter; heating and / or mechanically deforming a second body portion, the second body portion comprising a second material different from the first material, such that the second body portion has an outer diameter smaller than the first inner diameter of the first lumen; inserting the second body portion into the lumen of the first body portion, thereby forming the dual lumen article; drying the dual lumen article so that the first body portion shrinks; The method comprising:

45. 10. The article or method of any preceding claim, further comprising one or more surface features (e.g., valves, bulges) at an interface between the first body portion and the second body portion, the one or more surface features configured to mechanically reinforce the interface between the first body portion and the second body portion.

46. 10. The article or method of any preceding claim, further comprising one or more surface features (e.g., valves, bulges) at an interface between the first body portion and the second body portion, the one or more surface features configured to mechanically reinforce the interface between the first body portion and the second body portion.

47. 10. An article or method according to the preceding claims, wherein the article is formed using thermoforming.

48. 10. An article or method according to the preceding claims, wherein thermoforming occurs at a temperature of 90°C or greater.

49. 10. The article or method of the preceding claim, wherein thermoforming comprises placing a wire in the lumen of the article, placing the article in a mold, and thermally heating the mold to a designed shape.

50. 10. An article or method according to the preceding claims, wherein the article shape is curved, straightened, compressed or stretched by restricting the dimensions of the initial component to the desired shape.

51. An article or method according to the preceding claims, wherein the edges of the article are rounded to facilitate fluid flow, reduce wear, reduce surface area, and aid in placement, catheter longevity, and patient comfort.

52. 10. The article or method of the preceding claim, wherein the solvent comprises water.

53. 10. The article or method of the preceding claim, wherein the solvent comprises water and the water-soluble polymer.

54. 10. The article or method of any preceding claim, wherein the solvent comprises the water-soluble polymer at a concentration less than the concentration of the water-soluble polymer used to form the first material.

55. 10. The article or method of any preceding claim, wherein the solvent comprises water and polyvinyl alcohol, and the polyvinyl alcohol is present in the solvent in an amount of at least 0.1 wt % and at most 25 wt %.

56. 10. The article or method of the preceding claim, wherein the solvent has a hydrolysis level of 80% or greater, such that the solvent contains 20% or less acetate groups.

57. 10. The article of the preceding claim, wherein the article comprises a lumen.

58. 10. The article of the preceding claim, wherein the article comprises a hemodialysis catheter, a peripherally inserted central catheter (PICC), a central venous catheter, a midline catheter, a peripheral catheter, a urinary catheter, a neurocatheter, a peritoneal catheter, and / or an infusion port.

59. The article of the preceding claims, wherein the article is configured for use with a medical article such as, for example, a catheter, a balloon, a shunt, a wound drain, an infusion port, a drug delivery article, a tube, a contraceptive article, a feminine hygiene article, an endoscope, an implant, a pacemaker, an implantable cardioverter-defibrillator, a cardiac resynchronization article, a cardiovascular article lead, a ventricular assist article, an endotracheal tube, a tracheostomy tube, an implantable sensor, a ventilator pump, and an ophthalmic article.

60. 10. The article or method of the preceding claim, wherein the polymeric material does not include a covalent crosslinker.

61. 10. An article or method according to the preceding claims, wherein the polymeric material has a Young's modulus at equilibrium water content (EWC) of 5 to 100 MPa.

62. 10. An article or method according to the preceding claim, wherein the article comprises a plurality of interconnected pores.

63. 10. The article or method of the preceding claim, wherein the component comprises a plurality of fibers.

64. 10. An article or method according to the preceding claim, wherein the component is a catheter cuff.

65. 10. An article or method according to any preceding claim, wherein the body comprises a second material containing the first water-soluble polymer at a concentration that is less than the concentration of the first water-soluble polymer in the first material.

66. 10. The article or method of the preceding claim, wherein the water-soluble polymer can be loaded with a water-insoluble compound selected from the group consisting of a therapeutic agent, a bioactive compound, a fabric, a metal mesh, a color indicator, a radiopaque material, and a reactive indicator.

67. 10. An article or method according to the preceding claim, wherein the water-soluble polymer incorporates a conductive indicator that aids in the detection of P waves in an electrocardiogram.

68. 24. The article or method of claim 23, wherein the conductive indicator comprises iron powder that is insoluble in physiological fluids entrained in PVA.

69. 10. The article or method of the preceding claim, wherein the water soluble polymer is incorporated into a fabric selected from the group consisting of Dacron® (polyethylene terephthalate, also known as polyester), electrospun PVA, cotton, wool, polypropylene (atactic, syndiotactic, isotactic), and polyethylene (LLDPE, LDPE, HDPE).

70. The article or method of the preceding claim, wherein the intended use of the article or method is selected from the group consisting of a bandage, tissue in-growth, a stent, a shunt, a braided tube, and a wall stent, and is bonded to another PVA substrate.

71. 10. The article or method of any preceding claim, wherein the first and second water-soluble polymers are bonded together to create a new shape or to reinforce one or more components physically integrated with the body portion.

72. 30. The article or method of claim 27, wherein bonding comprises hydrating and heating the first and second water-soluble polymers to bond at an overlapping joint.

73. 10. An article or method according to any preceding claim, wherein upon heating, the first water-soluble polymer flows into the second water-soluble polymer.

74. 10. An article or method according to any preceding claim, wherein upon heating, the second water-soluble polymer flows into the first water-soluble polymer.

75. 10. The article or method of any preceding claim, wherein combining further comprises cooling the first and second water-soluble polymers.

76. 10. The article or method of the preceding claim, wherein cooling the polymer forms the unitary article.

77. 10. The article or method of the preceding claim, wherein the water-soluble polymer is hydrated in solution until an equilibrium % hydration is achieved.

78. 10. The article or method of the preceding claim, wherein the equilibrium % hydration is between about 0.1% and 100%.

79. 10. The article or method of the preceding claim, wherein the solution comprises phosphate buffered physiological solution at a concentration of about 0.1M to 10M.

80. 10. The article or method of the preceding claim, wherein the bonding is performed using a specially configured split die bonder, RF welder, or hot air station.

81. 10. An article or method according to the preceding claims, wherein the bonding temperature is between 60°C and 95°C.

82. An article or method according to the preceding claims, wherein the bonding time is between 15 seconds and 5 minutes.

83. 10. An article or method according to any preceding claim, wherein the bonding is performed using FEP heat shrink tubing formed into a size and shape suitable for hot air treatment.

84. 10. The article or method of any preceding claim, wherein bonding further comprises compressing the bond to increase chain entanglement of the bonded materials.

85. 1. A venous catheter, comprising: a polymeric material comprising a first water-soluble polymer having a plurality of pores; Lumens and a distal end having a tip shape suitable for intravenous insertion into a subject; Equipped with The polymeric material has a moisture content of less than 5 wt. % and greater than or equal to 0.1 wt. % in a dehydrated state, and the polymeric material is configured to swell from the dehydrated state to an equilibrium moisture content state by an amount of greater than or equal to 50 wt. % within 60 minutes at 25°C.

86. 10. A system comprising a venous catheter according to the preceding claims and components configured to administer therapeutic agents and / or fluids to a subject and / or withdraw bodily fluids from said subject.

87. inserting an intravenous catheter into a vein, the intravenous catheter comprising a polymeric material including a first water-soluble polymer having a plurality of pores, a lumen, and a distal end having a tip shape suitable for intravenous insertion into a subject, wherein during the inserting, the catheter has a water content of 5 wt% or less; expanding the intravenous catheter to a water content of not less than 5 w / w% and not more than 50 w / w%; The method comprising:

88. inserting an intravenous catheter into the vein; the intravenous catheter comprises a polymeric material including a first water-soluble polymer having a plurality of pores, a lumen, and a distal end having a tip shape suitable for intravenous insertion into a subject; the polymeric material has a water content of 5 w / w% or more and 50 w / w% or less; below: i) the polymeric material has a Young's modulus of 500 MPa or more in a dehydrated state and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium hydrated state; ii) the polymeric material does not have covalent crosslinks between the water-soluble polymers forming the polymeric material; and iii) the polymeric material contains pores having a diameter of 1 μm or less; A method that satisfies one or more of the above.

89. 10. A catheter or method according to the preceding claim, wherein the polymeric material is free of covalent crosslinkers.

90. 10. A catheter or method according to any preceding claim, wherein the article comprises a plurality of interconnected pores.

91. 10. A catheter or method according to the preceding claim, wherein the polymeric material has a Young's modulus of 500 MPa or more in a dehydrated state, and a Young's modulus of 300 MPa or less and 5 MPa or more in an equilibrium hydrated state.

92. 10. A catheter or method according to the preceding claim, wherein the intravenous catheter is adapted to be inserted into a subject in a dehydrated state.

93. 10. A catheter or method according to the preceding claim, wherein the intravenous catheter is configured to be inserted into a subject in an at least partially hydrated state.

94. 10. A catheter or method according to the preceding claims, further comprising administering a fluid to the subject via the intravenous catheter.

95. 10. A catheter or method according to the preceding claims, further comprising withdrawing blood from the subject via the venous catheter.

96. 10. A catheter or method according to the preceding claims, wherein the intravenous catheter exhibits hemolysis of 10% or less.

97. 10. A catheter or method according to any preceding claim, wherein the intravenous catheter has a softening rate that reduces insertion force by at least 99% in a three-point ratio relative to the final hydrated state.

98. 10. A catheter or method according to the preceding claim, wherein the distal end of the catheter is pointed.

99. 10. A catheter or method according to the preceding claims, wherein the proximal end of the catheter is hubbed.

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