Two-component system for the in situ preparation of an artificial cartilage
The invention relates to a two-component system for the in situ preparation of a polymer network by polymerizing acrylate monomers in the presence of a redox initiator couple comprising an activator and an initiator, the system comprising —a first container with a first component, which first component comprises the activator; and —a second container with a second component, which second component comprises the initiator; wherein the activator and/or the initiator is dissolved in an aqueous buffer solution; and wherein one or both containers further comprise —a water soluble acrylic monomer having one acrylate group; and —a water soluble acrylic monomer having two or more acrylate groups; and —at least one glycosaminoglycan; and wherein the combined water content in both containers is at least 50 wt. %, based on the total weight of the contents of both containers.
1 . A two-component system for the in situ preparation of a polymer network by polymerizing acrylic monomers in the presence of a redox initiator couple comprising an activator and an initiator, the system comprising
a first container that contains a first aqueous buffer solution comprising the activator; and
a second container that contains a second aqueous buffer solution comprising the initiator;
wherein one or both of the first aqueous buffer solution and the second aqueous buffer solution further comprise
a water soluble acrylic monomer having one acrylate group; and
a water soluble acrylic monomer having two or more acrylate groups; and
at least one glycosaminoglycan;
wherein the combined water content in both containers is at least 50 wt. %, based on the total weight of the contents of both containers, and
wherein the acrylic monomer in the first container is completely dissolved in the first aqueous buffer solution and the acrylic monomer in the second container is completely dissolved in the second aqueous buffer solution.
2 . The two-component system according to claim 1 , wherein the contents of the first container and the contents of the second container are completely water-soluble.
3 . The two-component system according to claim 1 , wherein one or both containers further comprise an antibacterial agent selected from an aminoglycoside and glycopeptide.
4 . The two-component system according to claim 1 , wherein the at least one glycosaminoglycan is selected from the group of heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate and hyaluronic acid.
5 . The two-component system according to claim 1 , comprising acrylic monomer selected from the group of 2-hydroxyethyl methacrylate, acrylamide, 2-carboxyethyl acrylate, 2-(dimethylamino) propyl acrylate, methacrylamide, [2-(acryloyloxy)ethyl]trimethylammonium chloride, N-[Tris(hydroxymethyl)methyl]acrylamide, 3-sulfopropyl acrylate, a salt thereof, 2-(diethylamino)ethyl methacrylate, diacetone acrylamide and N-[3-(dimethylamino)propyl]methacrylamide.
6 . The two-component system according to claim 1 , wherein at least one acrylic monomer having two or more acrylate groups is a poly(1,3-glycerolate) diacrylate or a poly(ethylene glycol) diacrylate.
7 . The two-component system according to claim 1 , comprising a diacrylate having a number average molecular mass (M n ) of 10,000 g/mol or lower, in particular a number average molecular mass (M n ) in the range of 100-1500 g/mol, wherein said number average molecular mass (M n ) is determined by SEC according to DIN 55672-1.
8 . The two-component system according to claim 1 , wherein the activator is selected from the group of N,N-dimethyl-p-toluidine, N,N-bis(2-hydroxyethyl)-p-toluidine, 2-(diethylamino)ethyl methacrylate, 2-(dimethylamino)propyl acrylate, N-[3-(dimethylamino)propyl]methacrylamide and tetramethylethylenediamine.
9 . The two-component system according to claim 1 , wherein the initiator is selected from the group of ammonium persulfate, cumene hydroperoxide and dibenzoyl peroxide.
10 . The two-component system according to claim 1 , wherein the composition of the first container and the second container is chosen in such manner that the entire amount of acrylic monomers is completely dissolved in aqueous buffer solution in the first container or in the second container; and
the polymerization product that forms upon mixing the first aqueous buffer solution and the second aqueous buffer solution exhibits phase separation of the polymerization product and the first and second aqueous buffer solution.
11 . The two-component system according to claim 1 , wherein the pH of the buffer solution in each container is in the range of 7.2 to 7.6.
12 . The two-component system according to claim 1 , wherein the activator comprises a tertiary amino group.
13 . The two-component system according to claim 1 for treatment of a chondral defect or a bone-related disease or condition.
14 . A polymer network comprising
a cross-linked polymer of two or more acrylic monomers comprising a water soluble acrylic monomer having one acrylate group and a water soluble acrylic monomer having two or more acrylate groups;
water that is contained in the cross-linked polymer; and
at least one glycosaminoglycan that is contained in the cross-linked polymer;
wherein the polymer network has a free volume fraction of at least 0.50, wherein the free volume fraction (FVF) is calculated as
FVF=(1 −m d /m g )
wherein m d is the mass of the cross-linked polymer after evaporation of all the water that is contained in it, and m g is the mass of the cross-linked polymer when it is saturated with water, wherein the cross-linked polymer is dissolved in the water to form a hydrogel.
15 . The polymer network according to claim 14 , wherein the cross-linked polymer is permeable for human blood cells.
16 . The polymer network according to claim 14 for treatment of a chondral defect or a bone-related disease or condition.
17 . The two-component system of claim 1 , wherein the first aqueous buffer solution and the second aqueous buffer solution are adapted to react to produce a polymer network having a free volume fraction of at least 0.60.
18 . The two-component system according to claim 1 , wherein the composition of the first container and the second container is chosen in such manner that the entire amount of acrylic monomers is completely dissolved in aqueous buffer solution in the first container or in the second container; and
the polymerization product that forms upon mixing the first aqueous buffer solution and the second aqueous buffer solution is a hydrogel.
19 . The two-component system of claim 1 , wherein:
the contents of the first container consist of the first aqueous buffer solution, which is completely water-soluble; and
the contents of the second container consist of the second aqueous buffer solution, which is completely water-soluble.
20 . The two-component system of claim 1 , wherein the monomer contained in the first container consists of water soluble acrylic monomers, and the monomer contained in the second container consists of water soluble acrylic monomer.
21 . The polymer network of claim 14 , wherein the cross-linked polymer is derived from acrylic monomers consisting of water soluble acrylic monomers having one acrylate group and water soluble acrylic monomers having two or more acrylate groups.
22 . A two-component system for the in situ preparation of a polymer network by polymerizing acrylic monomers in the presence of a redox initiator couple comprising an activator and an initiator, the system comprising
a first container that contains a first aqueous buffer solution comprising the activator; and
a second container that contains a second aqueous buffer solution comprising the initiator;
wherein one or both of the first aqueous buffer solution and the second aqueous buffer solution further comprise
a water soluble acrylic monomer having one acrylate group; and
a water soluble acrylic monomer having two or more acrylate groups; and
at least one glycosaminoglycan;
wherein the combined water content in both containers is at least 50 wt. %, based on the total weight of the contents of both containers, and wherein the total amount of water soluble acrylic monomer is at least 5.0 weight percent of the first and second aqueous buffer solutions.
23 . The two-component system of claim 22 , wherein the total amount of water soluble acrylic monomer is at least 15.0 weight percent of the first and second aqueous buffer solutions.
24 . The two component system of claim 22 , wherein
the water soluble acrylic monomer having one acrylate group has a solubility of at least 20 weight percent; and
the water soluble acrylic monomer having two or more acrylate groups has a solubility of at least 20 weight percent.
25 . The two-component system of claim 22 , adapted for the in situ preparation of a polymer network that is a hydrogel.