EP1869093A1 - Corps moule polymerise - Google Patents

Corps moule polymerise

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Publication number
EP1869093A1
EP1869093A1 EP06721201A EP06721201A EP1869093A1 EP 1869093 A1 EP1869093 A1 EP 1869093A1 EP 06721201 A EP06721201 A EP 06721201A EP 06721201 A EP06721201 A EP 06721201A EP 1869093 A1 EP1869093 A1 EP 1869093A1
Authority
EP
European Patent Office
Prior art keywords
shaped body
composition
mpa
composition according
bone
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.)
Withdrawn
Application number
EP06721201A
Other languages
German (de)
English (en)
Inventor
Robert Liska
Monika Schuster
Jürgen STAMPFL
Heinrich Gruber
Franz Varga
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.)
Technische Universitaet Wien
Original Assignee
Technische Universitaet Wien
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 Technische Universitaet Wien filed Critical Technische Universitaet Wien
Publication of EP1869093A1 publication Critical patent/EP1869093A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
    • C08F220/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing

Definitions

  • the invention relates to radiation-curable, biocompatible and bioresorbable compositions and their use in molding processes for the production of polymeric bone replacement support materials.
  • a substance can be introduced, which generates pores during curing.
  • This can be a foaming agent, or even a solid such as sodium chloride or sugar, which can be subsequently dissolved out.
  • WO 98/20893 describes a process in which monomer mixtures are cured in the presence of sugar cubes in a silicone mold and the sugar is then dissolved out with water.
  • the pore size and the Internal geometry can be controlled only within certain statistical limits in such methods and it is thus not possible to generate defined cellular structures.
  • RP rapid prototyping
  • WO 03/002490 A2 claims biomaterials based on poly (propylene fumarate) which are photocrosslinkable with diethyl fumarate. From these mixtures, prefabricated implants can either be prepared by means of molding techniques, or they are used as injectable formulations which are cured in vivo by photopolymerization.
  • the system poly (propylene fumarate) / diethyl fumarate has also been used in a stereolithographic process.
  • the production succeeded a prototype molding, which was not porous.
  • the mechanical stability of the moldings with a modulus of elasticity of about 200 MPa does not meet the mechanical material requirements for bone replacement materials, since a natural bone has a modulus of elasticity of about 2000 MPa.
  • a general disadvantage of these aliphatic polyesters based on glycolic acids or lactones is that the bonds are relatively hydrolysis-labile, i. that they are broken down relatively quickly in an aqueous environment.
  • the degradation proceeds hydrolytically and is not controllable by the autocatalytic nature.
  • the bone substitute disintegrates faster than new bone tissue can be formed.
  • high acid concentrations can occur, creating a milieu, which can lead to uncontrolled cell death and thus to necrotic tissue changes.
  • purely enzymatic degradation would be preferable, i. With a biomaterial that promotes growth of bone cells (osteoconductive), and thus also enzymes are formed by these cells, which degrade the polymer. In this way, the body's cells can effectively control the degradation of the implanted plastic. Polymers which are built up over hydrolytically more stable amide bonds are generally better suited.
  • hydrogels based on gelatin and polyethylene glycol are known as biomaterials obtained by radical copolymerization of Jeffamin-bis-methacrylamides and methacrylamide-substituted gelatin (Zimmermann, J .; Bittner, K., Stark, B .; Mülhaupt, R. Biomaterials; 2002; 23; 2127-2134). These hydrogels are characterized by good cell adhesion and proliferation.
  • Redox initiators or photoinitiators at temperatures below 4O 0 C cured Redox initiators or photoinitiators at temperatures below 4O 0 C cured.
  • WO 1998/55161 A1 describes materials for wound dressings based on crosslinked methacryl-modified gelatin, or copolymers thereof, with methacryl-modified polysaccharides (for example dextran or xanthan).
  • methacryl-modified polysaccharides for example dextran or xanthan.
  • these hydrogel films are soft materials which must have good absorbency for aqueous media, as this is a prerequisite for wound dressings and dressings.
  • biocompatible protein fibers and crosslinked fibers or fabrics for medical applications described which may optionally contain living cells.
  • the fibers are produced on the basis of polymerizable derivatives of proteins, for example elastin, collagen or gelatin or polymerizable derivatives of peptide sequences which are characteristic of these proteins.
  • the fibers are produced by electrospinning, with photochemical crosslinking subsequently taking place via the polymerizable groups with the aid of photoinitiators.
  • water-soluble polymers polyethylene oxide
  • E moduli in the range of 8 to 12 MPa are given for collagen PEO fibers.
  • WO 1991/08242 A1 describes graft copolymers obtained by grafting mixtures of peptides, proteins, vinyl monomers and crosslinkers onto insoluble finished polymers, e.g. Cellophane or polyethylene terephthalate be prepared by gamma radiation. This procedure results in flexible films with a biocompatible surface, from which implants for the blood vessel replacement can be made.
  • the object of the invention is to provide a radiation-curable composition which can be used by means of rapid prototyping for the production of any - especially cellular or porous - moldings with high mechanical strengths, similar to those of natural bones, and which are bioresorbable Support materials can be used for bone replacement.
  • the compositions must be liquid, biocompatible, non-toxic, and highly reactive.
  • the polymer formed in the RP method must also contain structural elements which ensure good adhesion of osteoblasts, ie bone-forming cells.
  • sufficient hydrolytic stability is required in order for the bone cell-induced enzymatic degradation to proceed preferentially.
  • the invention relates to a composition curable by polymerization with a) 10-80% by weight of a reactive diluent based on acrylic acid or methacrylic acid derivatives, b) 10-50% by weight of a liquid or in the formulation ( the composition) of soluble monomer of the general formula
  • R 2 H or -CH 3
  • radicals Y independently of one another represent hydrogen, -CH 3 , -CH 2 -CH (CH 3 ) 2 ,
  • the composition is a UV or visible light curable (polymerizable) composition containing as component b) 10-50% by weight of a liquid or formulation-soluble monomer of the general formula
  • n is an integer between 1 and 100
  • R 2 H or -CH 3
  • Z 1 is -O- (CH 2) x -C0-, -0- (CH 2 -CH 2 -0.)
  • R 1 is hydrogen or R 1 together with Y is the radical - (CH 2 ) 3 or -CH 2 -CH (OX) -CH 2 -, in which X has the above meaning,
  • R 2 H or -CH 3
  • the composition contains 0-60% of a filler or solvent.
  • acrylic or methacrylic esters and amides or mixtures thereof for example acrylic acid, methacrylic acid, hydroxyethyl acrylate, hexanediol diacrylate, polyethylene glycol diacrylates, pentaerythritol triacrylate, dimethylacrylamide, diethylacrylamide, polylactic acid block polyethylene glycol block polylactic acid diacrylate.
  • liquid derivatives such as N, N
  • the monomers listed under b) are special (meth) acryloylated amino acids, peptides or proteins. These can be substituted according to the invention at one or both terminal groups and / or laterally on correspondingly reactive amino acid units, such as lysine, serine, tyrosine, aspartic acid or glutamic acid residues.
  • Such monomers are known from the literature (E. Schacht, WO 98/55161, 1998) (Zimmermann, J .; Bittner, K., Stark, B .; Mülhaupt, R.
  • Biomaterials; 2002; 23; 2127-2134) but can also be prepared by reacting peptides with reactive (meth) acrylic acid derivatives, such as (meth) acryloyl chloride, anhydride or glycidyl ester.
  • reactive (meth) acrylic acid derivatives such as (meth) acryloyl chloride, anhydride or glycidyl ester.
  • peptides mixtures which are obtained by hydrolysis of naturally occurring proteins, such as gelatin, keratin, fibrin or casein, but also peptide mixtures obtained from rice, soy, wheat, potato, hen's egg, meat or fish can be used for these reactions .
  • Preference according to the invention is given to (meth) acryloylated peptides which contain collagen-specific amino acid building blocks (for example glycine, arginine, aspartic acid, glutamic acid, alanine, proline, hydroxylysine or hydroxyproline) and (meth) acryloylated gelatin hydrolysates having molecular weights of up to 10,000 ,
  • collagen-specific amino acid building blocks for example glycine, arginine, aspartic acid, glutamic acid, alanine, proline, hydroxylysine or hydroxyproline
  • acryloylated gelatin hydrolysates having molecular weights of up to 10,000
  • the polymerizable (meth) acryloyl radicals can also be bonded to the peptide via a spacer.
  • Corresponding reaction reagents are: 12-Methacryloyloxydodekanklad, mono (14-methyl-13-oxo-3,6,9, 12-tetraoxapentadek-14-en-l-yl) butane-1, 4-diacid esters (EP 324 455 A2 ) or commercially available acryloxy-polyethylene glycol-N-hydroxysuccinimides.
  • Suitable photoinitiators are all radical-forming type I and type II initiators (compare "Photoinitiators for free radical polymerization" by J. Crivello and K. Dietliker, Wiley / SITA London). Examples of these are benzil ketals, benzoins, hydroxyalkylphenones, aminoalkylphenones, acylphosphine oxides, bisacylphosphine oxides, titanocenes.
  • Type II initiators such as benzophenones, diketones, thioxanthones and ketocoumarins are used with suitable coinitiators. These are mostly tertiary amines such as 4-
  • DMAB Dimethylaminobenzoic acid ethyl ester
  • camphorquinone / DMAB 2-hydroxy-1- [4- (2-hydroxyethoxy) phenyl] -2-methyl-1-propanone (Irgacure 2959) or phenylbis (2,4,6-trimethylbenzoyl) phosphine oxide ( Irgacure 819).
  • Fillers which can be used are all known biocompatible and bioinert organic polymers or inorganic materials. These may be soluble or dispersed in the liquid monomer mixture in the form of powders, fibers and the like. Examples of these are polyvinylpyrrolidone, polyvinyl alcohol, casein, keratin, gelatin, cellulose esters and ethers, chitosan, starch derivatives, hyaluronic acid derivatives, poly- ⁇ -hydroxy acid-based polyesters, poly- ⁇ -caprolactone, polypropylene fumarates, polycarbonates, polyanhydrides, polyphosphazenes, aluminum oxide, Zirconia, or Ti, (Ta, Nb) Alloys. Especially preferred according to the invention are hydroxyapatite, tricalcium phosphate, bone meal, algipore, polyethylene glycol, polyesters based on lactic acid and glycolic acid, keratin fibers, and fibrin glue.
  • the present invention relates to the use of the composition for the preparation of polymers or the process for the preparation of the polymers by polymerization of the composition.
  • thermal or photoinitiators can be used for polymerization.
  • the polymer is preferably a shaped body which is shaped in particular either by polymerization of the composition in a mold or by rapid prototyping (lithographic or stereolithographic rapid prototyping).
  • the constituents of the composition are preferably dissolved in organic solvents, with a water content of ⁇ 10%, preferably ⁇ 1%, most preferably ⁇ 0.1% (in% by weight, and, possibly, a fluid constituent may also occur as solvent ).
  • the present invention relates to moldings consisting of the polymerized composition having an E-modulus greater than 500 MPa.
  • Such a molded article is obtainable by the described method.
  • the shaped body preferably has an E-modulus greater than 500 MPa, preferably greater than 1000 MPa, in particular greater than 1500 MPa, especially preferably greater than 2000 MPa, most preferably greater than 5000 MPa or greater than 10000 MPa.
  • the modulus of elasticity (also: Young's modulus) is a material characteristic value from materials engineering that describes the relationship between stress and strain in the deformation of a solid body with linear elastic behavior.
  • the modulus of elasticity is abbreviated to modulus of elasticity.
  • the amount of elastic modulus is greater, the more resistance a material opposes to its deformation. Thus, a high modulus material is stiff, a low modulus material is compliant.
  • the modulus of elasticity is defined as the slope of the graph in the stress-strain diagram at uniaxial loading within the linear elasticity range.
  • the composition is responsible for the hardness, which is preferably absorbed in anhydrous organic solvents - since there is no water-related swelling or shrinkage.
  • the composition In the polymerization of the selected components of the composition, it also does not water. (Moisture may be tolerated to a small extent depending on the hardness to be achieved.)
  • the composition has ⁇ 10%, preferably ⁇ 1%, most preferably ⁇ 0.1% of water (in% by weight).
  • the components b) are not water-soluble (at most heterogeneously dispersible) but are soluble (homogeneously) in organic solvents.
  • Macromolecular structures as described by Anseth (Biomaterials 2003: 2485) or published in EP 1 142 596 A1 achieve only a modulus of 500 MPa.
  • Bismethacrylates of a polyorthoester have only a modulus of about 40 MPa (Kellomaki, M., Heller, J .; Tormala, P. Processing and properties of two different poly (ortho esters); Journal of Materials Science: Materials in Medicine (2000) 8-17 MPa (Cohn, D .; Hotovely-Salomon, A. Biodegradable multiblock PEO / PLA thermoplastic elastomers: molecular design and properties, polymer (II), 11 (6), 345-355), PEG-lactide bismethacrylate. 2005), 46 (7), 2068-2075).
  • the present invention now provides compositions which polymerize to much cheaper moldings (see Examples, below).
  • the surface of the shaped body is modified.
  • the formulation contains, for example, methacrylic anhydride
  • the surface can easily be modified by means of aminolysis. Suitable substances that are thus accessible are added (from the composition) or alternatively, are peptides that improve the adhesion of osteoblasts or precursors of osteoblasts. These include peptides with RGD sequences, preferably collagen I or collagen IV-like peptides.
  • the surface is preferably modified by covalently bonded proteins, peptides, amino acids or oligonucleotides.
  • the shaped body has a cellular or porous structure.
  • the cells have a wall thickness or pore size of 150-500 microns, in particular by 200 microns.
  • 200 ⁇ m corresponds to the average striae diameter of trabecular bone.
  • Pore diameters of between 150 ⁇ m to 500 ⁇ m, in particular 350 to 500 ⁇ m, are optimal for the attachment of osteoblasts.
  • This can be effected by specific forms in which the composition is polymerized, in particular those forms which consist of soluble materials, after which, after dissolution in a suitable solvent, the molding remains (molding).
  • such a structure can be constructed by means of the rapid prototyping method.
  • the solid shaped body is built up layer by layer from a solution or fluid composition of the starting materials (monomers), e.g. by slightly raising a lifting plate in a container with the starting composition from the bottom and light from below (a specific image of the respective layer to be polymerized) being radiated through the light (or UV) permeable bottom of the container, whereby at the illuminated areas the composition polymerizes. By further raising the plate and illuminating the next layer is built up, etc.
  • the advantage of the rapid prototyping method is that a targeted geometry of the shaped article can be made which is precisely adapted to medical needs, e.g. For example, after the removal of a bone tumor, the bone hole can be precisely measured (tomography) and then an exactly matching shaped body can be produced by means of the imaging method.
  • Salt leachincr NaCl particles and polymer are mixed in solution. The solvent is evaporated, the polymer over
  • Fiber Bonding Polyglycolic acid (PGA) fibers are immersed in a solution of polylactic acid (PLA). The solvent is evaporated and the resulting network is heated above the melting point of PGA (network fused), PLA is dissolved and the
  • 3D - printinc ⁇ with porogen PGA, PLA powder with NaCl, w.o., 95%
  • the shaped body is preferably modified by bound proteins, peptides, amino acids or oligonucleotides.
  • these are bone morphogenic proteins (BMP), cytokines, growth factors (e.g., TGF- ⁇ , PTH), cell differentiation factors, collagens or collagen fragments, preferably BMPs and collagens, especially type II collagen.
  • BMPs are known from the literature, in particular BMP-I (US 5,108,922), BMP-2 and BMP-3 (US 5,116,738 and US 5,013,649), BMP-4 (US 5,013,649), BMP-5 (US 5,106,748), BMP-6 ( US 5,187,076) and BMP-7 (US 5,108,753).
  • nucleic acids or oligonucleotides which promote bone growth are disclosed, for example, in EP 741 785. These proteins or oligonucleotides may also be administered separately in the medical application. Preferably, the surface is modified by hydroxyapatite coating.
  • the present invention relates to moldings for medical use, in particular as a bone substitute or bone replacement part, in particular as an implant. This is especially for the treatment of Bone damage, such as tumor-related Knochenaushöhlungen, beneficial.
  • the moldings are degradable after a certain time, which, without being limited to any particular theory, is caused by slow water penetration into the polymer.
  • the invention also relates to the use of a shaped body according to the invention for the production of an implant for the treatment of bone damage.
  • compositions of the invention which can be used by the rapid prototyping method for the production of mechanically stable bone substitute materials and compared with polymers of the prior art.
  • Methacylic anhydride MSA
  • GMl Methacylic anhydride
  • GM2 Methacylic anhydride
  • GM3 Methacylic anhydride
  • DS The average degree of substitution (DS) of methacryloyl-substituted lysine units was determined by NMR:
  • GMl 1.03 g yellow solid
  • DS 5% GM2: 1.27 g yellow oil
  • DS 47% GM3: 1.18 g yellow oil
  • DS 52%
  • Diethylene glycol or polyethylene glycol 400 were stirred overnight with CaCl 2 and filtered off. Methacrylic acid chloride was freshly distilled before use.
  • the mixtures were poured into a silicone mold and cured under nitrogen atmosphere on a UV system.
  • the resulting test pieces were extracted to remove residual monomer with organic solvents and water in an ultrasonic bath.
  • the extracted polymer forms were sterilized by irradiation with UV light.
  • osteoblast-like cells called MC3T3-E1 were used.
  • the adherent cells were first detached from each other with pronase and from the bottom of the Petri dish. They were then mixed with freshly prepared nutrient medium and distributed evenly on the individual test specimens in the multiwell.
  • the nutrient medium consisted of commercially available Dulbecco's Modified Eagle's Medium (DMEM, which originally contained 1000 mg / l glucose and was supplemented with further glucose up to a concentration of 4500 mg / l) supplemented with 10% FCS (fetal cow serum). , 30 ⁇ g / ml gentamycin (broad spectrum antibiotic), L-glutamine and ascorbic acid.
  • DMEM Dulbecco's Modified Eagle's Medium
  • FCS fetal cow serum
  • FCS fetal cow serum
  • the multiwell with the cells was incubated at 37 ° C. Using a microscope, it was possible to observe whether the cells can survive and adhere. If live cells were present after 2 weeks of culture, they were fixed with a solution of 4% paraformaldehyde and 0.5% Triton in PBS, washed several times with PBS buffer 7 and with a solution of 4, 6-diamidino-2-phenylindole (DAPI, 5 ⁇ g / ml) in PBS buffer 7 .
  • DAPI 4, 6-diamidino-2-phenylindole
  • Biodegradability studies were performed at 37 ° C. in PBS buffer at a pH of 7.0.
  • the PBS buffer was changed every 12 hours in the first week, then every 3 days to keep the pH constant. Samples were taken after 1, 3, 7, 21 and 30 days.
  • the mechanical stiffness of the materials was determined by determining the modulus of elasticity by means of dynamic mechanical Analysis determined. Corresponding values for the modulus of elasticity are given in the following table:
  • formulations 6 to 9 according to the invention were able to achieve substantially higher and permanent stiffness values and, at the same time, excellent cell adhesion in comparison to known polymers 1-4 prepared according to the prior art.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • Veterinary Medicine (AREA)
  • Materials Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Composite Materials (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Macromonomer-Based Addition Polymer (AREA)

Abstract

Compositions polymérisables qui contiennent 10-80 % en poids d'un diluant réactif à base de dérivés d'acide acrylique ou d'acide méthacrylique, et 10-50 % en poids d'un monomère liquide ou soluble dans la composition, correspondant à la formule chimique indiquée, ledit monomère pouvant contenir des restes d'acide aminé ou des séquences peptidiques, en particulier celles qui sont spécifiques du collagène. Ces éléments structuraux permettent la dégradation enzymatique des polymères de la composition.
EP06721201A 2005-04-14 2006-04-10 Corps moule polymerise Withdrawn EP1869093A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT0062605A AT501700B1 (de) 2005-04-14 2005-04-14 Mit strahlung härtbare, biologisch abbaubare zusammensetzungen und deren verwendung als stützmaterialien für den knochenersatz
PCT/AT2006/000143 WO2006108202A1 (fr) 2005-04-14 2006-04-10 Corps moule polymerise

Publications (1)

Publication Number Publication Date
EP1869093A1 true EP1869093A1 (fr) 2007-12-26

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Country Link
US (1) US8022155B2 (fr)
EP (1) EP1869093A1 (fr)
JP (1) JP2008535979A (fr)
AT (1) AT501700B1 (fr)
CA (1) CA2604492A1 (fr)
WO (1) WO2006108202A1 (fr)

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EP3154771A1 (fr) * 2014-06-16 2017-04-19 SABIC Global Technologies B.V. Polycarbonates réticulables pour procédés de fabrication par extrusion de matériau
US11566133B2 (en) * 2016-06-17 2023-01-31 Universidad De Los Andes Gelatin polymer derived from natural sources of cold-adapted marine species and uses thereof
US10953597B2 (en) 2017-07-21 2021-03-23 Saint-Gobain Performance Plastics Corporation Method of forming a three-dimensional body
EP3866730A4 (fr) * 2018-10-16 2022-07-06 The Schepens Eye Research Institute, Inc. Bioadhésif pour réparation de tissus mous

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US8022155B2 (en) 2011-09-20
WO2006108202A1 (fr) 2006-10-19
AT501700B1 (de) 2011-03-15
AT501700A1 (de) 2006-10-15
WO2006108202A8 (fr) 2007-01-18
JP2008535979A (ja) 2008-09-04
CA2604492A1 (fr) 2006-10-19

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