EP3240584A1 - Kraniofaziale implantate - Google Patents
Kraniofaziale implantateInfo
- Publication number
- EP3240584A1 EP3240584A1 EP14838826.7A EP14838826A EP3240584A1 EP 3240584 A1 EP3240584 A1 EP 3240584A1 EP 14838826 A EP14838826 A EP 14838826A EP 3240584 A1 EP3240584 A1 EP 3240584A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- implant
- implant according
- craniofacial
- loaded
- production stage
- 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- Withdrawn
Links
- 239000007943 implant Substances 0.000 title claims abstract description 65
- 238000004108 freeze drying Methods 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 239000012867 bioactive agent Substances 0.000 claims description 12
- 239000003102 growth factor Substances 0.000 claims description 12
- 229920000642 polymer Polymers 0.000 claims description 11
- 239000011148 porous material Substances 0.000 claims description 8
- 229910021536 Zeolite Inorganic materials 0.000 claims description 7
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims description 7
- 239000010457 zeolite Substances 0.000 claims description 7
- 239000001506 calcium phosphate Substances 0.000 claims description 6
- 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 claims description 6
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 6
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 6
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 6
- -1 BM4 Proteins 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229920000520 poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Polymers 0.000 claims description 3
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 3
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 3
- 230000000845 anti-microbial effect Effects 0.000 claims description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 2
- 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 2
- 239000004599 antimicrobial Substances 0.000 claims 5
- 230000004913 activation Effects 0.000 claims 2
- 229910010272 inorganic material Inorganic materials 0.000 claims 2
- 239000011147 inorganic material Substances 0.000 claims 2
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 claims 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 claims 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims 1
- 229930182566 Gentamicin Natural products 0.000 claims 1
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 claims 1
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 claims 1
- 229920000954 Polyglycolide Polymers 0.000 claims 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims 1
- 108010059993 Vancomycin Proteins 0.000 claims 1
- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 0.000 claims 1
- 229920001610 polycaprolactone Polymers 0.000 claims 1
- 229910052709 silver Inorganic materials 0.000 claims 1
- 239000004332 silver Substances 0.000 claims 1
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 claims 1
- 229960005256 sulbactam Drugs 0.000 claims 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 claims 1
- 229960003165 vancomycin Drugs 0.000 claims 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 claims 1
- 230000007547 defect Effects 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 9
- 239000000155 melt Substances 0.000 abstract description 2
- 238000007493 shaping process Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 description 19
- 210000000988 bone and bone Anatomy 0.000 description 18
- 238000013459 approach Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 239000000654 additive Substances 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920001432 poly(L-lactide) Polymers 0.000 description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
- 229920002530 polyetherether ketone Polymers 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 1
- 206010058046 Post procedural complication Diseases 0.000 description 1
- 208000035965 Postoperative Complications Diseases 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 239000003462 bioceramic Substances 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000004956 cell adhesive effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000004820 osteoconduction Effects 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
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
- A61L27/18—Macromolecular materials obtained otherwise than 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
- A61L27/50—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
- 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
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/64—Animal cells
-
- 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
- the present invention relates to development of a porous implant type which eventually melts off and replaced with new leaves growing tissue to cover craniofacial defects in the body and shaping of the same with rapid prototyping and lyophilization methods.
- craniofacial bone reconstruction is considered to be dependent on surgical skills, quality of adjacent soft tissues, size and location of the bone defect and choice of repair method.
- the methods include free and vascularized bone grafts, a variety of biomaterials and, more recently, the use of osteoinductive growth factors.
- the use of autologous bone for craniofacial reconstruction may be restricted due to limited amounts of donor bone.
- the need of remodelling the harvested bone into complex shapes may also complicate the surgery.
- significant bone resorption using free bone grafts and the enhanced morbidity and risks from harvesting bone grafts cannot be disregarded.
- Implantable materials need to fulfil the demands on biocompatibility with no or low side effects, including infiltration of leucocytes and fibrosis.
- the craniofacial implants are metallic, non biodegradable materials and the target is to develop highly porous, biodegradable implant materials that will erode in time and be replaced by the newly developing tissue.
- the current craniofacial implants do not carry growth ' enhancing compounds (e.g. growth factors) and antimicrobial compounds.
- Bone autograft is the golden standard as the implant material for repairing bone defects, simply because the risk of rejection and related immunological problems are minimal.
- the amount of autogenous bone available for transplantation is limited since it has to be harvested from the patient's own body which might be limited or unsatisfactory quality. Besides, harvesting involves postoperative complication risks, and the pain.
- the ideal biomaterial for maxillofacial and other types of bony reconstruction has to be biocompatible, capable of allowing tissue in-growth and provide a framework for cell adhesion and guidance during new bone development.
- the material needs to be malleable or processable, serve as a carrier medium for osteogenic proteins.
- a high initial stiffness would allow proper attachment of the defect edges or fit the defect site perfectly with sufficient strength to mimic the cranial bony tissue. This will need to be gradually resorbed and the stiffness decreased in parallel with the strength of the healing bone taking over the deficiency created by the resorbing implant.
- the present invention discloses a craniofacial implant material composition and also about the production approach. There are several patent documents disclosing similar invention and theses are listed as follows:
- FIG. 1 Sponge type implant.
- the present invention relates to defining biocompatible, biodegradable composite compositions, and the production and/or preparation of biomedical craniofacial implants that would be used in closing cracks or filling gaps in skull of patients with porous and biodegradable polymeric materials.
- the production of two different types of implants with designed or random pore sizes and pore size distribution are prepared by two different methods:
- bioactive agents like antibiotics, growth factors are added into these implants. Besides with the added antibiotics, the implants will be freer of infection and with the growth factors their integration will be better. Since there will be no need for revisions surgeries, no risks due to new surgery, trauma of the procedure; the pain and the cost of the surgical procedure will be avoided. Under optimum circumstances, patients' own osteoblasts or bone marrow are added to the porous implant to obtain a tissue engineering product.
- the implant material should be easily processed into various craniofacial components such as screws and plates. Since a metallic implant will not grow with the patient, a biodegradable material that would induce cell growth into the implant and gradually will go away is what is needed. Thus, a certain level of porosity is needed. Depending on the defect type this porosity is between 70 to 90%. Typical pore size range is ca. 100-300 urn, because otherwise cells do not properly fill the gaps of the implant.
- CT computerized tomography
- the polymers to be used in rapid prototyping are selected based on their chemical and mechanical properties such as melting temperature, molecular weight, hydrophilicity, presence of cell adhesive groups or moieties in addition to their rate of degradation in this invention.
- the ability to vary the degradation rate of biocompatible relatively short length polyesters such as polylactide (PLA) and polyglycolide (PGA) by copolymerization or blending in addition to their FDA (fused deposition modeling) approval has made these materials a natural choice for bone repair.
- PCL poly(E-caprolactone)
- T m 60° C
- PLGA poly(E-caprolactone)
- PLLA poly(E-caprolactone)
- freeze drying produces much higher porosity materials, because the wall thickness of the spongy structures are much lower than the fibers used in additive manufacturing (several tens or hundreds of microns vs several micrometers or nanometers.
- the composition of the implant material is also modified according to the needs.
- the candidate molecule groups to fulfil these functions are growth factors, antibiotics and minerals with chemistries similar to bone mineral component.
- PCL or another polyester such as poly(L-lactide), PLGA, PHBV
- chloroform or dichloromethane is dissolved in chloroform or dichloromethane to produce a 5-10% w/v solution.
- the solution is frozen at -20°C of the freezer compartment of the refrigerator or at the deep freeze at -80°C until completely solid (overnight).
- the solid polymer solution is then taken to a lyophilizer and allowed to dry under vacuum in frozen state.
- the resultant sponge is the highly porous implant material without any bioactive agent.
- mineral/ceramic components such as hydroxyapatite, tricalcium phosphate or zeolite, or antibiotics, or growth factors
- they are suspended in the initial polymer solution at a concentration of up to 40%(w/w) with respect to the polymer.
- the minerals, or the bioactive agents are entrapped with the walls of the sponge. They will release their content gradually with a rate depending on the degradation and hydration rate of the polymer (controlled by polymer crystallinity, molecular weight and chemistry) and function by increasing cell integration into the pores.
- the sponge is exposed to oxygen plasma at 13.56 Hz 5-10 Watts for 15 s to 10 min.
- an aqueous solution of the bioactive agent (5-20% (w/v) depending on the viscosity of the solution) is applied immediately so that the radicals created on the sponge surface are not deactivated by the medium. After drying under vacuum or air drying the sponge is ready to use.
- bioactive agents l.i.i.i.
- Another approach to incorporation of bioactive agents into the sponge structure is to place zeolite in an aqueous solution of the bioactive agent (5-20% w/v depending on the viscosity of the solution) and then apply vacuum-air cycles to remove the air within the pores of the zeolite and replace them with the drug solution. Then the method l.i. is applied. Upon drying the bioactive agent loaded zeolite is incorporated into the sponge walls as was explained above.
- Patient specific implant is prepared by using the MR or CT image of the defect site and then feeding this information to a rapid prototyping device that extrudes a polymeric material upon application of heat and pressure.
- the product is in the form of fibers that have a geometry based on the computer mode selected to fill the contours defined by the CT image. These could be in the form of grids the organization of different layers with respect to each other could be varied depending on the porosity needed. With this approach a solid polymeric device is obtained upon cooling of the extruded polymer.
- the construct is made by extrusion through rapid prototyping as above and then approach l.i.i. is applied to coat the bioactive agents on the surface of the construct.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2014/000524 WO2016108769A1 (en) | 2014-12-29 | 2014-12-29 | Craniofacial implants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP3240584A1 true EP3240584A1 (de) | 2017-11-08 |
Family
ID=52544549
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP14838826.7A Withdrawn EP3240584A1 (de) | 2014-12-29 | 2014-12-29 | Kraniofaziale implantate |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP3240584A1 (de) |
| WO (1) | WO2016108769A1 (de) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108030960B (zh) * | 2017-12-22 | 2021-04-13 | 重庆医科大学附属永川医院 | 一种促进骨创伤愈合的植入材料及其制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008106625A2 (en) * | 2007-02-28 | 2008-09-04 | University Of Notre Dame Du Lac | Porous composite biomaterials and related methods |
| WO2009120886A2 (en) * | 2008-03-28 | 2009-10-01 | Drexel University | Design and manufacturing of bioactive implanted surgical fixation devices using injection molding of gradient cellular strucures |
| US9492375B2 (en) * | 2008-07-23 | 2016-11-15 | Warsaw Orthopedic, Inc. | Foam carrier for bone grafting |
-
2014
- 2014-12-29 WO PCT/TR2014/000524 patent/WO2016108769A1/en not_active Ceased
- 2014-12-29 EP EP14838826.7A patent/EP3240584A1/de not_active Withdrawn
Non-Patent Citations (2)
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| None * |
| See also references of WO2016108769A1 * |
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| WO2016108769A1 (en) | 2016-07-07 |
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