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EP4626956A1 - Matériau d'hydrogel ayant des propriétés de transport améliorées pour l'encapsulation d'organismes vivants - Google Patents

Matériau d'hydrogel ayant des propriétés de transport améliorées pour l'encapsulation d'organismes vivants

Info

Publication number
EP4626956A1
EP4626956A1 EP23828926.8A EP23828926A EP4626956A1 EP 4626956 A1 EP4626956 A1 EP 4626956A1 EP 23828926 A EP23828926 A EP 23828926A EP 4626956 A1 EP4626956 A1 EP 4626956A1
Authority
EP
European Patent Office
Prior art keywords
hydrogel
solution
carboxymethyl
polyanion
poly
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23828926.8A
Other languages
German (de)
English (en)
Inventor
David Henry
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Corning Inc
Original Assignee
Corning Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Corning Inc filed Critical Corning Inc
Publication of EP4626956A1 publication Critical patent/EP4626956A1/fr
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/0052—Preparation of gels
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B11/00—Preparation of cellulose ethers
    • C08B11/02—Alkyl or cycloalkyl ethers
    • C08B11/04—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals
    • C08B11/10—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals substituted with acid radicals
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0021—Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
    • C08J3/246—Intercrosslinking of at least two polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
    • C08L1/08—Cellulose derivatives
    • C08L1/26—Cellulose ethers
    • C08L1/28—Alkyl ethers
    • C08L1/286—Alkyl ethers substituted with acid radicals, e.g. carboxymethyl cellulose [CMC]
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/04—Alginic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/04—Enzymes or microbial cells immobilised on or in an organic carrier entrapped within the carrier, e.g. gel or hollow fibres
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/02—Foams characterised by the foaming process characterised by mechanical pre- or post-treatments
    • C08J2201/026—Crosslinking before of after foaming
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/02—Foams characterised by the foaming process characterised by mechanical pre- or post-treatments
    • C08J2201/03—Extrusion of the foamable blend
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2205/00—Foams characterised by their properties
    • C08J2205/02—Foams characterised by their properties the finished foam itself being a gel or a gel being temporarily formed when processing the foamable composition
    • C08J2205/022—Hydrogel, i.e. a gel containing an aqueous composition
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2205/00—Foams characterised by their properties
    • C08J2205/04—Foams characterised by their properties characterised by the foam pores
    • C08J2205/042—Nanopores, i.e. the average diameter being smaller than 0,1 micrometer
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2301/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
    • C08J2301/08—Cellulose derivatives
    • C08J2301/26—Cellulose ethers
    • C08J2301/28—Alkyl ethers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/04—Alginic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2401/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
    • C08J2401/08—Cellulose derivatives
    • C08J2401/26—Cellulose ethers
    • C08J2401/28—Alkyl ethers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
    • C08J2405/04—Alginic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
    • C08J2405/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Definitions

  • a hydrogel comprises: a crosslinked network of a polyanion, a polycation, and a carboxymethyl polysaccharide; wherein the hydrogel comprises an average pore size of at least 100 nm.
  • the hydrogel of aspect (1) wherein the polyanion comprises at least one of alginic acid salt, pectic acid salt, pectinic acid salt, amidated pectin, or gellan gum.
  • the hydrogel of aspect (1) or (2) is provided, wherein the polyanion comprises a molecular weight of at least 250 kDa.
  • the hydrogel of any of aspects (l)-(3) is provided, wherein the polycation comprises at least one of chitooligosaccharide, polylysine, polyarginine, polyomithine, poly(vinylbenzyl trialkyl ammonium), poly(4-vinyl-N-alkyl-pyridinium), poly(acryloyl-oxyalkyl-trialkyl ammonium), poly(acrylamidoalkyl-trialkyl ammonium), poly(diallyldimethyl-ammonium), or poly(diallyldimethylammonium chloride).
  • the hydrogel of any of aspects (l)-(4) is provided, wherein the polycation comprises a molecular weight of 10 kDa or less.
  • the hydrogel of any of aspects (l)-(5) is provided, wherein the polycation comprises a molecular weight of 5 kDA or less.
  • the hydrogel of any of aspects (l)-(6) wherein the carboxymethyl polysaccharide comprises at least one of carboxymethyl dextran, carboxymethyl starch, carboxymethyl cellulose, carboxymethyl hyaluronic acid, carboxymethyl inulin, or carboxymethyl guar.
  • the hydrogel of any of aspects (l)-(8) is provided, wherein a weight ratio of the polyanion to the carboxymethyl polysaccharide is from 3 : 1 to 1 : 1.
  • hydrogel of any of aspects (l)-(10) is provided, wherein hydrogel is a spherical capsule.
  • the hydrogel of aspect (11) is provided, wherein the spherical capsule comprises an average diameter of from 0.5 mm to 5 mm.
  • a method of forming a hydrogel comprising: forming a first solution comprising a polyanion and a carboxymethyl polysaccharide; adding the first solution to a second solution comprising polycation to form a hydrogel comprising an average pore diameter of at least 100 nm.
  • the method of any of aspects (17)-(19) wherein forming the first solution further comprises adding a third solution comprising 0.5 wt% to 5 wt% of the polyanion to a fourth solution comprising from 0.5 wt% to 5 wt% of the carboxymethyl polysaccharide.
  • the method of any of aspects (17)-(22) is provided, wherein the polyanion comprises a molecular weight of at least 250 kDa.
  • the method of any of aspects (17)-(23) is provided, wherein the polycation comprises at least one of chitooligosaccharide, polylysine, polyarginine, polyomithine, poly(vinylbenzyl trialkyl ammonium), poly(4-vinyl-N-alkyl- pyridinium), poly(acryloyl-oxyalkyl-trialkyl ammonium), poly(acrylamidoalkyl-trialkyl ammonium), poly(diallyldimethyl-ammonium), or poly(diallyldimethylammonium chloride).
  • the polycation comprises at least one of chitooligosaccharide, polylysine, polyarginine, polyomithine, poly(vinylbenzyl trialkyl ammonium), poly(4-vinyl-N-alkyl- pyridinium), poly(acryloyl-oxyalkyl-trialkyl ammonium), poly(acrylamidoalkyl
  • the method of any of aspects (17)-(24) is provided, wherein the polycation comprises a molecular weight of 10 kDa or less.
  • a weight ratio of the polyanion to the polycation is from 2: 1 to 1 : 1.
  • the method of aspect (29) is provided, wherein the spherical capsule comprises an average diameter of from 0.5 mm to 5 mm.
  • the method of any of aspects (17)-(28) comprises continuously extruding the first solution into the second solution to form a cylindrical tube.
  • the method of aspect (31) is provided, further comprising flattening the cylindrical tube to form a ribbon.
  • the method of aspect (33) comprises filtering the first solution.
  • dissolving the hydrogel further comprises incubating the hydrogel in a solution of dextran sulfate.
  • the method of aspect (39) is provided, wherein the dextran sulfate has a molecular weight of 5 kDa or less.
  • the method of aspect (39) is provided, wherein the solution of dextran sulfate further comprises at least one of an anti-clumping agent or alginate lyase.
  • FIGS. 1A and IB depict process flow diagrams of methods for forming porous hydrogels, according to an exemplary embodiment
  • FIG. 3 includes SEM images of the porosity of spherical capsules prepared using various ratios of FITC-labeled carboxymethyl dextran to alginate, including exemplary embodiments of the present disclosure
  • FIG. 4 includes images of the porosity of spherical capsules of the same type shown in FIG. 3 that were dried using an ethanol/water gradient, according to an exemplary embodiment
  • the porous hydrogel is a crosslinked network of a polyanion, a polycation, and a carboxymethyl saccharide.
  • the inventor surprisingly and unexpectedly found that using a high ratio of the carboxymethyl saccharide relative to the polyanion (> 0.5:1) to form the porous hydrogel produced relatively large and uniform pores.
  • Conventional hydrogels typically have pores that are in the range of tens of nanometers up to a few hundred nanometers, which limits the use of these hydrogels in studying transport of large molecules, extracellular vesicles (EV), and viral particles, among others.
  • the organisms encapsulated within the porous hydrogel can be harvested from the hydrogel by incubating the hydrogel in low molecular weight (e.g., 5 kDa or less) dextran sulfate, which competes with the polyanion to link with the polycation, thereby causing dissolution of the hydrogel.
  • the dextran sulfate solution is a 10% solution.
  • the low molecular weight dextran sulfate can be used in conjunction with an anti-clumping agent (such as GIBCOTM available from ThermoFisher Scientific, Waltham, MA).
  • alginate lyase can also be used to digest the alginic acid polyanion.
  • the third solution containing alginate was combined with a plurality of fourth solutions containing different carboxymethyl polysaccharides. Preparation of the fourth solutions is described below.
  • CM cellulose A 2% by weight aqueous carboxymethyl (CM) cellulose was prepared by dissolving 0.8 g of CM cellulose in 39.2 g deionized water.
  • the CM cellulose had a molecular weight of 90 kDa. Sonication was used to facilitate the dissolution.
  • the second solution of 1% by weight of COS was provided in a 150 mL beaker equipped with a magnetic stir bar. Stirring speed was set to 100 rpm. A syringe, having a 34-gauge, blunt-end needle, was used to drip First solution A (alginate/FITC-labeled CM dextran) into the second solution of COS. The drips were dropped from a height of about 3 cm. After 5 minutes of crosslinking time, the spherical capsules were collected using a fiber mesh strainer and were washed with pure water. The spherical capsules are shown in FIG. 2. The capsules had an average diameter in the range of 1.8 mm to 2 mm.
  • the spherical capsules were frozen and broken in liquid nitrogen.
  • the broken capsules were kept at -80 °C for 2 hours and then freeze-dried for 16 hours (using an Alpha 2-4 LD Freeze Dryer available from Martin Christ Gefriertrocknungsanlagen GmbH, Germany).
  • the freeze-dried capsules were observed using a scanning electron microscope (Phenom Pure available from ThermoFisher Scientific, Waltham, MA).
  • Surface porosity as a function of FITC-labeled CM dextran content is shown in FIG. 3. Images (a)-(e) of FIG. 3 include increasing amounts of FITC-labeled CM dextran relative to alginate.
  • Image (a) contains no FITC-labeled CM dextran (0: 1 ratio), and image (e) contains a 1 : 1 ratio of FITC-labeled CM dextran to alginate.
  • Images (b), (c), and (d) contain ratios of 0.25: 1, 0.5: 1, and 0.75: 1 ratios of FITC-labeled CM dextran to alginate, respectively.
  • image (c) some porosity emerges at a ratio of 0.5: 1 of FITC- labeled CM dextran to alginate, and a large amount of porosity is present in image (e), depicting a ratio of 1 : 1 FITC-labeled CM dextran to alginate.
  • FIG. 4 provides an SEM image of the capsules at increasing magnification, and the images demonstrate that the porosity remains uniform and that the pore size remains large, indicating that the porosity is not a function of thermally induced phase separation from freeze drying.
  • Example 2 the capsules of Example 2 were prepared starting with the second solution of 1% by weight of COS provided in a 150 mL beaker equipped with a magnetic stir bar. Stirring speed was set to 100 rpm. A syringe, having a 34-gauge, blunt- end needle, was used to drip First solution B (alginate/CM dextran) into the second solution of COS. The drips were dropped from a height of about 3 cm. After 5 minutes of crosslinking time, the spherical capsules were collected using a fiber mesh strainer and were washed with pure water. FIG. 5 depicts the spherical capsules produced. The spherical capsules are substantially the same as the spherical capsules produced using First Solution A, but the capsules lacked the fluorescence caused by the FITC labeling.
  • First solution B alginate/CM dextran
  • Example 1 was repeated with the exception that the First Solution A of alginate/FITC-labeled CM dextran was made with 1.5% by weight alginate and 1% by weight of FITC-labeled CM dextran. First Solution A was dripped in the second solution of 1% by weight COS and allowed to crosslink for 5 minutes. As shown in FIG. 8, the porosity of the spherical capsules produced was in the range of 4 pm to 40 pm.
  • Example 1 was again repeated with the exception that the third solution of 1% alginate was dissolved at 80 °C, and First Solution A (containing alginate and FITC-labeled CM dextran) was autoclaved for 30 minutes at 121 °C to sterilize it.
  • FIG. 9 is an SEM image of the porosity of the spherical capsules. As can be seen, the pores have a large size and are uniform across the surface.
  • First Solution A (containing alginate and FITC-labeled CM dextran) was continuously extruded from a syringe with a 32-gauge needle into the second solution of 1% by weight COS to form microtubes.
  • the microtubes were left in the second solution for 5 minutes to crosslink, withdrawn from the solution using a nylon mesh, and washed with water.
  • FIGS. 10, 11, and 12 depict increasing magnifications of a microtube prepared according to this method, showing the dimensions of the microtubes.
  • the nylon mesh can be seen in the background behind the microtubes.
  • FIG. 13 provides a further magnification of the microtubes showing the porosity of the microtube surface. As can be seen in FIG. 13, the pores are substantially uniform across the surface and have a size of about 2 pm.
  • Spherical capsules were prepared according to Example 1 with the exception that the second solution of 1% by weight of COS was replaced with 4% by weight of calcium chloride. The mixture of the solutions formed capsules, but no surface porosity was observed. From this, the inventor surmised that the replacement of COS with calcium chloride affects the crosslinking behavior of the solutions. In particular, a relatively low molecular weight polycation, such as COS, promotes formation of large pores, whereas the ionotropic crosslinking using inorganic anions does not promote large porosity.
  • a relatively low molecular weight polycation such as COS, promotes formation of large pores, whereas the ionotropic crosslinking using inorganic anions does not promote large porosity.
  • Example 1 was again repeated with the exception that the second solution of 1% by weight of COS was replaced with 1% by weight PDADMAC.
  • PDADMAC is an effective crosslinker known to form capsules with cellulose sulfate.
  • no capsules were obtained with First Solution A (alginate and FITC-labeled CM dextran).
  • This comparative example demonstrates the importance of the low molecular weight polycation, such as COS, in crosslinking the alginate/FITC-labeled CM dextran.
  • hydrogels from a crosslinked network of polyanion, polycation, and carboxymethyl polysaccharide that have large pore sizes.
  • the hydrogel contains naturally derived materials and no synthetic components and can be used to encapsulate living organisms.
  • the pores are large enough to allow for diffusion of large molecules from within the hydrogel to outside the hydrogel so that the hydrogel can be used, e.g., as a bioreactor.

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  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
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  • Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Des modes de réalisation de la divulgation concernent un hydrogel. L'hydrogel est formé à partir d'un réseau réticulé d'un polyanion, d'un polycation et d'un polysaccharide de carboxyméthyle. L'hydrogel a une taille de pore moyenne d'au moins 100 nm. La divulgation concerne également un procédé de formation d'un hydrogel. Dans le procédé, une première solution comprenant un polyanion et un polysaccharide de carboxyméthyle est formée. La première solution est ajoutée à une deuxième solution comprenant un polycation pour former un hydrogel ayant un diamètre de pore moyen d'au moins 100 nm.
EP23828926.8A 2022-11-30 2023-11-27 Matériau d'hydrogel ayant des propriétés de transport améliorées pour l'encapsulation d'organismes vivants Pending EP4626956A1 (fr)

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PCT/US2023/081069 WO2024118457A1 (fr) 2022-11-30 2023-11-27 Matériau d'hydrogel ayant des propriétés de transport améliorées pour l'encapsulation d'organismes vivants

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US6060534A (en) * 1996-07-11 2000-05-09 Scimed Life Systems, Inc. Medical devices comprising ionically and non-ionically crosslinked polymer hydrogels having improved mechanical properties
ITPD20060203A1 (it) * 2006-05-22 2007-11-23 Univ Degli Studi Trieste Idrogeli di miscele di polisaccaridi per l'ingegneria tissutale e la veicolazione di composti attivi
CN107753421B (zh) * 2017-11-07 2021-02-09 天津大学 一种抗生物粘附聚电解质水凝胶及制备方法及应用

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