WO2024039331A1 - Produit bio-conforme doté de caractéristiques de réparation et de cicatrisation dans le cas de maladies et/ou fractures osseuses, et procédé d'obtention dudit produit - Google Patents
Produit bio-conforme doté de caractéristiques de réparation et de cicatrisation dans le cas de maladies et/ou fractures osseuses, et procédé d'obtention dudit produit Download PDFInfo
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- WO2024039331A1 WO2024039331A1 PCT/TR2023/050756 TR2023050756W WO2024039331A1 WO 2024039331 A1 WO2024039331 A1 WO 2024039331A1 TR 2023050756 W TR2023050756 W TR 2023050756W WO 2024039331 A1 WO2024039331 A1 WO 2024039331A1
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- Prior art keywords
- product
- value
- hydroxyapatite
- gram
- bone
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 64
- 208000020084 Bone disease Diseases 0.000 title claims abstract description 18
- 230000035876 healing Effects 0.000 title description 9
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 55
- 230000008569 process Effects 0.000 claims abstract description 31
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 230000008439 repair process Effects 0.000 claims abstract description 20
- 230000002068 genetic effect Effects 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 28
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 28
- 239000000976 ink Substances 0.000 claims description 20
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 19
- 239000011572 manganese Substances 0.000 claims description 19
- 239000000661 sodium alginate Substances 0.000 claims description 19
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- 229940005550 sodium alginate Drugs 0.000 claims description 19
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 17
- 229910052748 manganese Inorganic materials 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 11
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- 229940072056 alginate Drugs 0.000 claims 2
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
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- NEXSMEBSBIABKL-UHFFFAOYSA-N hexamethyldisilane Chemical compound C[Si](C)(C)[Si](C)(C)C NEXSMEBSBIABKL-UHFFFAOYSA-N 0.000 description 1
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- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
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- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
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- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
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- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
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- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- -1 sodium alginate compound Chemical class 0.000 description 1
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- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
-
- 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
-
- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3637—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the origin of the biological material other than human or animal, e.g. plant extracts, algae
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- 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
- B33Y70/00—Materials specially adapted for additive manufacturing
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Definitions
- BIO-COMPLIANT PRODUCT THAT HAS REPAIRING AND HEALING CHARACTERISTICS FOR BONE DISEASES AND/OR BREAKAGES, AND A METHOD FOR OBTAINING SAID PRODUCT
- the present invention belongs to bone tissue engineering technical field, relates to a bio- compliant product which is suitable for use in repair and/or treatment of bone breakages and/or bone diseases that are genetic or that occur afterwards and which enables realization of this repair or treatment processes in short durations.
- the present invention provides a method for the production of a bio- compliant product which is suitable for use in repair and/or treatment of bone breakages and/or bone diseases that are genetic or that occur afterwards and which enables realization of this repair or treatment processes in short durations.
- Bone In animals and humans, bone is the hardest one among the tissues that form the body. Bone is the tissue that functions as a support for organisms. Bones have a substantially hard structure since they are substantially rich in terms of calcium, this condition leads to brittleness of bones.
- Damages or breakages in bone tissues can take place due to genetic structure or events (accidents, impacts) that occur afterwards. Particularly in the advancing ages, bone tissues become more prone to damages or breakages in animals and humans. Said proneness substantially depends on feeding, living styles and genetic characteristics of persons.
- Proneness to breakages or damages in bone tissues can also result from genetic characteristics; the most common genetic bone diseases are for instance osteoporosis, rheumatoid arthritis, rachitism.
- the treatment of bone breakages has three phases. These phases are called as reactive phase where the cells that shall repair the breakage are collected at the breakage region, repair phase where the proteins produced by osteoblasts and condroblasts begin to harden by precipitation of calcium mineral thereon, and where the structure which provides fixation of the breakage called as ‘soft callus’ occurs, and re-development phase where the bone continues to return to its prior form. These phases must be realized respectively for eliminating or repairing the damages formed by bone diseases or the events that develop afterwards.
- Some methods are developed in the technical field for realization of treatment phases of bone breakages.
- the application of said methods shows change depending on damage intensity of bone diseases or the events that occur afterwards.
- the medical intervention and treatment are focused on supporting of the bone and at the same time, providing of the best conditions (immobilization) to the injured bone for optimum healing.
- the basic rule is the re-placement of broken parts and fixation thereof such that they do not move until healing. This process is named as “reduction”. Re-positioning of the bone without surgery is “closed reduction”.
- Surgical intervention may be needed particularly for the treatment of breakages resulting from genetic-based bone diseases.
- the kind of the needed treatment depends on whether the breakage is “open” or “closed” or the place and the intensity of the breakage.
- a broken bone of the backbone is treated in a different manner from a broken leg bone or a broken hip.
- these surgical operations that are in the form of bone transfer are recently realized by placement of the bio-compliant parts that enable shortening of disease healing processes to the damaged bone tissues. For this reason, research and development specialists make studies which enable realization of healing phases formed by bone damages at the optimum values and which enable shortening of treatment durations and in a manner not forming any toxic effect for the biological organism.
- the present invention relates to a bio-compliant product which provides treatment and/or repairing for bone diseases and breakages.
- the present invention relates to a bio-compliant product which enables realization of the phases, needed for healing of bone damages that are genetic or that occur afterwards, in an optimum manner.
- the present invention relates to a method for production of bio- compliant product that enables realization of the phases, needed for healing bone damages that are genetic or that occur afterwards, in an optimum manner.
- the present invention relates to gaining antibacterial and anti- oxidative characteristics to a bio-compliant product that enables realization of the phases, needed for healing of bone damages that are genetic or that occur afterwards, in an optimum manner.
- the subject matter belongs to bone tissue engineering technical field, relates to a bio-compliant product which is suitable for use in repair or treatment of bone breakages or bone diseases that are genetic or that occur afterwards and which enables realization of this repair or treatment processes in short durations, and is explained with references to examples without forming any restrictive effect only in order to make the subject more understandable.
- the subject matter product is placed to the regions, where damaged bones in viable organisms exist, by means of a surgical operation, and afterwards, it provides realization of healing processes of bone damages and provides repairing of the damaged region. Accordingly, there are some characteristics expected from the product; the most important one is that the product must be bio-compliant. In the invention, while “a bio-compliant product” is being mentioned, the natural or synthetic materials used for fulfilling or supporting the functions in viable tissues in human body are mentioned. Another important characteristic is that the bio-compliant product placed to the damaged bone region must enable realization of the phases which provide treatment and repair of said damaged region.
- the subject matter product comprises components that have bio-compliant characteristics and that provide treatment and repair of bone diseases. Accordingly, the subject matter product is a composite material.
- the composite material comprises at least one matrix and at least one supportive and/or at least one supplementary auxiliary component.
- composite material describes the materials formed by combining two or more different materials for collecting the best characteristics thereof in a single material at the macro-level.
- matrix describes the component where the composite material forms the main component and where the other components are encircled together and in the desired form.
- the subject matter product comprises hydroxyapatite component as the matrix component.
- “Hydroxyapatites” are bio-ceramics used frequently since they increase bioactivity and mechanical characteristics of bioactive glass, alumina and calcium phosphate composite material. Hydroxyapatite forms 70% of the inorganic phase of natural bone, and is used in various biomedical areas like tissue engineering, controlled drug release. Hydroxyapatite provides a strong connection for accommodating hard tissues since it is chemically similar to the inorganic component of the bone tissue.
- hydroxyapatite has disadvantages like late degradation, single bone induction performance, low mechanical resistance; and functioning of hydroxyapatite as a composite material component in a single manner is not preferred in the art due to these disadvantages. Accordingly, the present invention owners have considered that the hydroxyapatite exists as matrix component in the composite material in order to use technical advantages thereof.
- the subject matter product comprises at least one supportive and/or supplementary component.
- the subject matter product comprises a natural and/or synthetic polymer material as at least one reinforcing and/or supportive component.
- the polymer material can be a hydrogel.
- the subject matter product comprises at least one polymer material as the supportive and/or supplementary component; it comprises sodium alginate compound as said polymer material.
- Sodium alginate is a natural polymer material as also known in the art. Again as known in the art, sodium alginate can be preferred as component in bone tissue engineering.
- the present invention owners expect that the sodium alginate natural polymer material functions as a supplementary/supportive component in the composite material and provide contribution to improvement of bio-compliancy and muco-adhesion characteristics of the composite material. Since sodium alginate is a natural polymer material, it is supported that and not prevented that the subject matter product has low toxicity and high bio-compliancy characteristics.
- the subject matter product comprises manganese element.
- Manganese is one of the most apparent trace elements that exist in bone, and exists approximately at a value 1.7-3 ppm in bone. Manganese has an important duty in arrangement of the metabolism of bones and muscles. Moreover, manganese deficiency leads to weakening of osteoblast activities and delay of osteogenesis and this leads to bone deformation, growth inhibition, reduction in movement coordination and even bone loss. Manganese element partially takes part in carbohydrate synthesis metabolism of muco-polysaccharides and provides contribution to the growth and development of the bone. Manganese provides adhesion of cells like integrins to each other among the molecules that function in cell adhesion.
- Manganese increases stimulation of protein osteocalcin that binds calcium to bones, moreover, it increases alkaline phosphatase activity and improves collagen type I production and provides extra-cellular matrix of the bone to be shaped again.
- the present invention owners have decided that manganese element must exist in the product due to said characteristics.
- manganese element also provides contribution to the antimicrobial characteristics of the final product.
- Antimicrobial activity tests have been applied to final product samples and the antimicrobial activity of the manganese element is searched.
- the samples which are to be examined are added into 5 ml Luria-Bertani liquid growth medium, and the bacteria culture shall be left to incubation at 37°C for 24 hours. After 24 hours, the series shall be diluted, and afterwards, spreading culturing shall be realized to Tryptic Strain Agar growth medium, and colony counting shall be realized after incubation at 37°C for a night. Inhibition % proportion shall be calculated by comparing with bacteria control that does not include sample therein.
- Test shall be made on gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria. These bacteria have been selected since they are prone to lead to multiple infections during implantation and surgical treatments. As seen in Table 1 , antibacterial test has been made by using Staphylococcus aureus bacteria which is a gram positive bacteria. As a result of this test, it is seen that the bacteria inhibition is 0% in frameworks that do not have Mn, bacteria inhibition proportion is 100% in bone frameworks that have 10% Mn proportion, and bacteria inhibition is 88% in bone frameworks that have 5% Mn proportion. Antibacterial characteristic is provided by adding Mn element to the structure.
- the antibacterial test is planned to be made on Escherichia coli which is a gram negative bacteria.
- Mn proportion shall be determined also by taking into consideration that it does not lead to toxic effect in the cells in the study to be made.
- Table 1 Results of the antibacterial test made by using gram positive bacteria of bone frameworks comprising 5-10% Mn element pressed as a result of pre-study.
- the subject matter product is a composite material for providing the desired characteristics; and comprises hydroxyapatite as the matrix component and comprises sodium alginate and manganese as the supplementary/supportive component.
- the present invention relates to a method for production of the product comprising hydroxyapatite as the matrix component and comprising sodium alginate and manganese as the supplementary/supportive component. Accordingly, in the invention, the operation principle of 3 dimensional printers is used as the method, the following processes are realized respectively;
- 3D printer technology is the process of production of a designed virtual object from materials like polymer, composite and resin by subjecting said materials to thermal or chemical process. Accordingly, the most critical step of the present invention is obtaining the bio-ink to be used in 3D printers.
- the bio-ink must have a form that is suitable to be processed in 3D printer, and the final product to be obtained must have the desired mechanical and bioactive characteristics. Accordingly, the existence percent of the components that exist in the bio-ink is substantially important. Accordingly, the invention owners have made studies about the percent that has to exist in the product for each component. Accordingly, preferably water is used as solvent for providing homogenous structure to the components in obtaining bio-ink.
- hydroxyapatite/water (g%/ml) between solvent and hydroxyapatite which is the matrix component is at a value between 90% and 120%.
- the proportion of hydroxyapatite/water is 100% and above, the most optimum values are between 105% and 115%.
- sodium alginate must exist at the weight proportions in a manner providing muco-adhesive characteristic in the final product, at the same time, it has limited existence proportion for obtaining bio-ink with the desired form together with the solvent and hydroxyapatite.
- the invention owners have determined that sodium alginate/hydroxyapatite (gram/gram%) is at a value between 0.06% and 0.1 %. This value is preferably between 0.075% and 0.09%.
- manganese element that is for providing the desired performances, exists at a value between 2% and 10% by weight in accordance with total bio-ink weight. It is very important that manganese element that is at a value between 2% and 10% by weight exists in the bio-ink. While it is possible that the desired technical effects can be observed under said value, it has been detected by means of the studies that manganese can have toxic effect above the given value. Accordingly, for preparing the bio-ink, the following process steps are provided:
- pre-products are obtained by utilizing 3D technology of the bio-ink samples obtained in a prior process step. Accordingly, determination of specific parameters in 3D printers for the obtained bio-ink has become the study subject. Accordingly, 3D technology has been used by using 3D printer parameters given in Table 2.
- Table 2 Parameter values used in 3D printer in the subject matter method
- the sintering process is applied for combining powder particles of pre-product samples, obtained by means of 3D technology, with the help of thermal energy.
- the pre-product becomes a final product.
- Table 3 Degree and duration parameters that can be used for the sintering processes
- sintering parameters arranged as b) given in Table 3 are used. Accordingly, the pre-products have been sintered for 1 hour at 350°C, for 1 hour at 650°C and for 2 hours at 1200°C.
- Another innovative characteristic of the present invention is that the coating process is realized on the obtained final product in order to obtain and/or improve antibacterial and anti- oxidative characteristics. It is very important that said coating is bio-compliant material.
- the subject matter product is coated with cardamom oil.
- the coating material namely cardamom oil
- electro-spraying method is used in the present invention. Accordingly, the invention owners have determined suitable coating process parameters or electro-spraying method. The following processes are realized respectively,
- PLA polylactic acid
- PLA is dissolved in DCM at a value between 1% and 10% by weight. In the most preferred application, PLA is dissolved at a value between 2% and 6% by weight.
- the obtained solution is sprayed onto the final product, where sintering processes are applied, by means of electro-spraying method. Accordingly, the device used in electrospraying process has flow speed at a value between 15 and 25 pl/min and has a voltage value between 10 kV and 20 kV.
- MC3T3-E1 mouse osteoblast cells have been obtained from Atihm University Metallurgy and Material Engineering Department (Ankara, Turkey) for realizing cell culture studies.
- DMEM/F-12 Modified Pteridium Medium of Dulbecco/ Nutrient Mixture F-12
- FBS Fetal Bovine Serum
- L glutamine penicillin/streptomycin
- BSA Bovine Serum Albumin
- PBS Phosphate buffered saline
- the samples have been incubated for 21 days (at 37°C 5% CO 2 ), and the growing medium DMEM/F-12 has been prepared by using FBS (10% volume/volume), penicillin streptomycin solution (1% volume/volume), L-glutamine (1% volume/volume).
- FBS 10% volume/volume
- penicillin streptomycin solution 1% volume/volume
- L-glutamine 1% volume/volume
- the biological characterization of the prepared material has been realized by MTT test for determining cell viability, Alizarin Red Dyeing for determining calcium accumulation, and Alkaline Phosphate Activity for determining differentiation. Additionally, the adhesion, growth and augmenting of the cells cultured to the prepared samples have been examined by means of SEM.
- the viability of the osteoblast MC3T3-E1 cells sintered and cultured onto raw HA bone frameworks and powder pellets has been realized with MTT determination on 1 st , 7 th , 14 th and 21 st days. After incubation (5% CO 2 , 37°C), the medium has been removed, and the samples have been washed with PBS solution three times. After the rinsing process, the samples that exist on the 24-well plates have been transferred to a new medium with 96 wells comprising 90 pL new medium and 10 pL MTT solution. MTT solution has been added to well plaques, and afterwards, all samples have been incubated 3 hours more.
- MTT solution is removed and 200 pL DMSO has been added for dissolving formazan crystals. Finally, the growth medium is taken from the wells, and the absorbance values of the solutions have been measured at 540 nm by means of micro-plate reader.
- dyeing solution shall be added onto the samples and shall be waited for 30 minutes in a dark medium.
- the samples have been centrifuged at 200 rpm.
- the absorbance values of the solutions have been measured at 405 nm by means of micro-plate reader.
- ALP activity of the cultured HAP frameworks has been examined on 7 th , 12 th and 21 st days of the culture in order to determine the differentiation.
- nitro blue tetrazolium and 5-bromo-4 chloro-3-indolil phosphate tablet has been dissolved in 10 mL pure water. Then, this prepared solution has been waited for 2 hours at room temperature in a dark medium.
- the samples that exist in the culture have been removed from the incubator and have been put to the medium, and the cells have been washed with PBS solution for three times. 10% formalin solution shall be added to the samples and has been kept for 60 seconds for fixing the cells. Then, the formalin solution has been removed and the cells have been washed three times with PBS solution.
- substrate solution has been added to the wells, and has been incubated for 10 minutes at room temperature and measurement has been taken at 405 nm by means of the micro-plate reader.
- the subject matter product belongs to bone tissue engineering technical field, and as a result of the tests made, it has been detected that the subject matter product is suitable for use in bone diseases that are genetic or that occur afterwards and/or in repair of breakages and/or in treatment of breakages, and these repair or treatment processes take place in short durations.
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Abstract
La présente invention a trait au domaine technique de l'ingénierie tissulaire osseuse et concerne un produit bio-conforme approprié pour être utilisé dans la réparation et/ou le traitement des fractures osseuses et/ou de maladies osseuses d'origine génétique ou survenant ultérieurement, et qui permet la réalisation des processus de réparation ou de traitement sur des courtes durées. Dans un autre aspect, la présente invention concerne un procédé de production d'un produit bio-conforme approprié pour être utilisé dans la réparation et/ou le traitement des fractures osseuses et/ou de maladies osseuses d'origine génétique ou survenant ultérieurement, et qui permet la réalisation des processus de réparation ou de traitement sur des courtes durées.
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TR2022/012983A TR2022012983A2 (tr) | 2022-08-17 | 2022-08-17 | Kemi̇k rahatsizliklari ve/veya kirilmalari i̇çi̇n onarici ve tedavi̇ edi̇ci̇ özelli̇kte bi̇youyumlu bi̇r ürün ve söz konusu ürünün eldesi̇ i̇çi̇n bi̇r yöntem |
TR2022/012983 | 2022-08-17 |
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Citations (6)
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US20170027168A1 (en) * | 2015-07-27 | 2017-02-02 | Stephan HEATH | Methods, products, and systems relating to making, providing, and using nanocrystalline (nc) products comprising nanocrystalline cellulose (ncc), nanocrystalline (nc) polymers and/or nanocrystalline (nc) plastics or other nanocrystals of cellulose composites or structures, in combination with other materials |
US20170128627A1 (en) * | 2015-11-02 | 2017-05-11 | Amrita Vishwa Vidyapeetham | Porous composite fibrous scaffold for bone tissue regeneration |
JP2020055839A (ja) * | 2010-08-12 | 2020-04-09 | マイクロビオン コーポレーション | 農業用、工業用およびその他の使用のための消毒薬としてのビスマス−チオール |
US20210138071A1 (en) * | 2017-11-10 | 2021-05-13 | Cocoon Biotech Inc. | Silk-based products and methods of use |
CN114634762A (zh) * | 2022-03-17 | 2022-06-17 | 东莞市人民医院 | 金属离子介导的蛋白质涂层、其制备方法及其应用 |
CN115192777A (zh) * | 2022-07-15 | 2022-10-18 | 江西理工大学南昌校区 | 可降解羟基磷灰石/左旋聚乳酸牙槽骨植入物及制备方法 |
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2022
- 2022-08-17 TR TR2022/012983A patent/TR2022012983A2/tr unknown
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- 2023-08-01 WO PCT/TR2023/050756 patent/WO2024039331A1/fr unknown
Patent Citations (6)
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JP2020055839A (ja) * | 2010-08-12 | 2020-04-09 | マイクロビオン コーポレーション | 農業用、工業用およびその他の使用のための消毒薬としてのビスマス−チオール |
US20170027168A1 (en) * | 2015-07-27 | 2017-02-02 | Stephan HEATH | Methods, products, and systems relating to making, providing, and using nanocrystalline (nc) products comprising nanocrystalline cellulose (ncc), nanocrystalline (nc) polymers and/or nanocrystalline (nc) plastics or other nanocrystals of cellulose composites or structures, in combination with other materials |
US20170128627A1 (en) * | 2015-11-02 | 2017-05-11 | Amrita Vishwa Vidyapeetham | Porous composite fibrous scaffold for bone tissue regeneration |
US20210138071A1 (en) * | 2017-11-10 | 2021-05-13 | Cocoon Biotech Inc. | Silk-based products and methods of use |
CN114634762A (zh) * | 2022-03-17 | 2022-06-17 | 东莞市人民医院 | 金属离子介导的蛋白质涂层、其制备方法及其应用 |
CN115192777A (zh) * | 2022-07-15 | 2022-10-18 | 江西理工大学南昌校区 | 可降解羟基磷灰石/左旋聚乳酸牙槽骨植入物及制备方法 |
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