GB2461125A - A silk membrane for bone graft material - Google Patents
A silk membrane for bone graft material Download PDFInfo
- Publication number
- GB2461125A GB2461125A GB0811628A GB0811628A GB2461125A GB 2461125 A GB2461125 A GB 2461125A GB 0811628 A GB0811628 A GB 0811628A GB 0811628 A GB0811628 A GB 0811628A GB 2461125 A GB2461125 A GB 2461125A
- Authority
- GB
- United Kingdom
- Prior art keywords
- membrane
- silk
- bone
- graft material
- bone graft
- 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.)
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- 239000012528 membrane Substances 0.000 title claims abstract description 66
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 58
- 239000000463 material Substances 0.000 title claims abstract description 39
- 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 abstract description 37
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 36
- 239000007787 solid Substances 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 8
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 4
- 229940078499 tricalcium phosphate Drugs 0.000 claims abstract description 4
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims abstract description 4
- 230000008929 regeneration Effects 0.000 claims abstract 2
- 238000011069 regeneration method Methods 0.000 claims abstract 2
- 108010022355 Fibroins Proteins 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 27
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 230000010478 bone regeneration Effects 0.000 claims description 9
- 238000003860 storage Methods 0.000 claims description 5
- 230000001172 regenerating effect Effects 0.000 claims 1
- 238000000576 coating method Methods 0.000 abstract description 9
- 239000011248 coating agent Substances 0.000 abstract description 7
- 239000012460 protein solution Substances 0.000 abstract description 7
- 239000000243 solution Substances 0.000 description 10
- 230000007547 defect Effects 0.000 description 8
- 238000005266 casting Methods 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 238000002791 soaking Methods 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 5
- 230000003239 periodontal effect Effects 0.000 description 4
- 238000011179 visual inspection Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 230000003416 augmentation Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229920002955 Art silk Polymers 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000004053 dental implant Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001523 electrospinning Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002121 nanofiber Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 230000004819 osteoinduction Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 108010028203 spidroin 2 Proteins 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
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
- A61L27/36—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
- A61L27/3641—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 site of application in the body
- A61L27/3645—Connective tissue
- A61L27/365—Bones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
- A61F2/2846—Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects
-
- 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
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
- A61L27/32—Phosphorus-containing materials, e.g. apatite
-
- 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
- A61L27/3604—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 human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Vascular Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Urology & Nephrology (AREA)
- Materials For Medical Uses (AREA)
Abstract
A silk membrane (60, 90) having two sides and coated selectively on one of the two sides with a bone graft material. The bone graft material is preferably either hydroxyapatite or B-tricalcium phosphate or a combination of these. The membrane can be made by applying synthetic bone material to a solid support, drying it then coating the synthetic bone material with a silk protein solution. When dry the membrane can be removed from the solid support. Alternatively, the silk protein solution can be applied to the solid support first then the synthetic bone material applied. The silk membrane has applications in the regeneration of bone (400), particularly in the mouth.
Description
Description
Field of the Invention
The present invention relates to a silk membrane for guided bone regeneration and a method for manufacture thereof.
Background of the invention
Guided bone regeneration (GBR) is a treatment that promotes the healing of bone defects by the exclusion of competing non-osteogenic soft tissue cells with the help of a barrier membrane. The banier membranes are refened to as GBR membranes. For example, in periodontal therapy of single or molar defects, the GBR membranes have been used by periodontal surgeons for over 20 years as barrier membranes. The GBR membrane is also relevant for oral and maxillofacial bone augmentation procedures such as sinus floor or large ridge augmentations which are frequently used to augment a patients bone mass before implanting dental implants.
T�itially the manufacture of the GBR membranes was by the use of a non-resorbable material such PTFE. Today, however, the non-resorbable GBR membranes have been substituted by bio-resorbable GBR membranes. The advantage of using bio-resorbable GBR membranes is that their use eliminates the need for a second operation for removal of the bio-resorbable GBR membrane after GBR therapy.
An example for the manufacture such a bio-resorbable GBR membranes from collagen has been described in European Patent No. EP 1023091 Bi by Ed Geistlich S�hne AG.
The use of synthetic bone graft materials, such as hydroxyapatite (HA) which can bond directly to bone, is also known in the art. Many organic materials, including silk and even spider drag line silk (Cao and Chuanbin, Langmuir 23, 10701-10705, 2007) have been used as templates to grow HA to form a mineralized structure. The mineralised structure can be used as a building block for bone implant fabrication.
Silk fibroin is a well established biornaterial which has been used extensively in the field of tissue engineering research (Altrnann et al., Biomaterials 24, 401-416, 2003). Recently, nano-fibre GBR membranes manufactured from silk fibroin without further functionalisation have been reported by Kim et al. (Journal of Biotechnology 120, 327-339, 2005). However, most research activity has been focused on the functionalisation of silk fibroin with synthetic bone graft materials; this is in order to improve the bone regeneration potential. The state of the art today is the deposition of HA through a soaking method or a co-dispersion method in phosphate and calcium solutions. For example, Wang et al. (J. Mater. Sci. Mater. Med., 15, 26 1-265, 2004) deposited HA on silk fibroin microspheres through the co-dispersion of H3P04 and Ca(HO)2. Furuzono et al. (J Biomed Mater Res, 50, 344-352, 2000 and US Patent 6395037) have reported growth of HA crystals on silk fabrics through alternate soaking in a calcium chloride solution buffered with tris-(hydroxyrnethyl) aminomethane, HC1 (hydrochloric acid) and phosphate. Recently Kino et al. reported the preparation of multilayered HA/silk fibroin membranes through alternating lamination of silk fibroin and HA/silk fibroin membranes which were prepared by growing HA crystals in solution on silk fibroin membranes (Journal of Bioscience and Bioengineering 103, 514-520, 2007). Another soaking method of using silk scaffolds as template for growing HA crystals in mineralization solutions has been described in US Patent Application 2006/0 159837 by David Kaplan.
A disadvantage of the HA coating methods is the lack of directionality during the coating method which leads to indiscriminate coating of all silk fibroin surfaces in contact with the soaking solutions. The HA functionalised silk fibroin GBR membranes prepared through the soaking method lead to the presence of HA not only on the membrane surface that is in contact with the bone defect side, but also on the membrane surface of the opposite side which is supposed to serve as an efficient banier for soft gum tissue cells.
A further disadvantage of the soaking method described in the prior art is the limited control of the quality of the HA crystals grown on the silk fibroin surface. As demonstrated, for example by Furuzono et al. in J Biomed Mater Res, 50, 344-352, 2000. There is observed a great variation in shape and diameters of the HA crystals grown on silk fibroin material through the soaking method. This variation in shape and diameter of the HA crystals could be solved by inclusion of ready made, precisely manufactured nano-sized crystalline hydroxyapatite particles, for example prepared according to the technique described in US 7,169,372 B. Such hydroxyapatite particles are claimed to offer improved biocompatibility and resorption due to the uniform nano-scale dimensions and homogeneity. However, thus far, the inclusion and even distribution of nano-sized hydroxyapatite particles in silk materials has been a technical challenge as the nano-sized hydroxyapatite particles tend to form aggregates. For example, Li et al. (Biomaterials 2006, 27: 3115-3124), reported uneven distribution and formation of aggregated hydroxyapatite clusters on the silk fibroin materials prepared by electrospinning. For medical applications, an even distribution and precise control of hydroxyapatite particles is necessary for achieving optimal bone regeneration results.
There is therefore a need to be able to manufacture a directionally coated HA silk fibroin GBR membrane. There is also a need for a silk fibroin material which presents on its surface uniform and evenly distributed, nano-scale HA crystals with precisely controlled size and shape for bone regeneration.
Summary of the invention
The object of the invention is to improve the membranes used for guided bone regeneration.
A further object of the invention is to improve the growth of bone in a dental environment.
These and other objects of the invention are solved by providing a silk membrane with one side selectively coated with a ready made, synthetic, bone graft material.
These and other objects of the invention are also solved by a method comprising: providing a first layer of ready made, synthetic bone graft particles on a surface of a casting device, drying the first layer, adding a second layer of silk fibroin solution over the first layer, drying the second layer.
In an alternative aspect of the invention, these and other objects of the invention can also be solved by a method comprising: providing a first layer of silk fibroin solution on a surface of a casting device, adding a second layer of ready made, synthetic bone graft particles over the first layer whilst the first layer is wet followed by drying.
Any synthetic bone graft material in combination with any natural or artificial silk protein or silk derived peptide feedstock may be used for manufacturing of the described silk membrane.
Description of Figures
Figure 1 shows a first method for selectively coating a silk membrane with ready made synthetic bone graft materials.
Figure 2 shows a second method for selectively coating a silk membrane with ready made synthetic bone graft materials.
Figure 3 shows an example of the silk membrane made according to the first method and/or the second method.
Figure 4 shows an example of periodontal surgery canied out using the silk membrane of the invention.
Detailed Description of the Invention
For a complete understanding of the present invention and the advantages thereof, reference is now made to the following detailed description taken in conjunction with the Figures.
It should be appreciated that the various aspects of the invention discussed herein are merely illustrative of the specific ways to make and use the invention and do not therefore limit the scope of invention when taken into consideration with the claims and the following detailed description. It will also be appreciated that features from one aspects of the invention may be combined with features from another aspect of the invention.
The teachings of the cited documents should be incorporated by reference into the description.
In particular the teachings of the Applicant's International Patent Application PCT/EP2007/OO 1775 are incorporated by reference.
A first method for the production of a silk membrane is shown in overview in Figure 1. In a first step 100, a ready made, synthetic bone graft material 10 is applied as a thin coat to a solid support 20. The solid support 20 can be made out of glass or PTFE or other materials suitable for use with proteins.
In the next step 110, the ready made, synthetic bone graft material 10 is dried on the solid support 20 to form a first layer 30. Examples of the synthetic bone graft material 10 include, but are not limited to, hydroxyapatite and B-tricalcium phosphate.
In the next step 120, a silk protein solution 40 is prepared with a silk protein content of between 0.3 % and 30 % (w/w), (as described in the applicants' international application PCT/EP2007/001775). The silk protein solution 40 is then transferred on top of the first layer 30.
lii the next step 130, the silk protein solution 40 is dried on the first layer 30 to form a second layer 50.
In the final step 140, the now formed uni-directionally coated silk fibroin membrane 60 is removed from the solid support 20 and transferred into a storage container (not shown) and stored until further use.
In a further aspect of the present invention, the uni-directionally coated silk fibroin membrane may be sterilised inside the storage container through y-radiation.
A second method of production of a silk membrane according to an aspect of the present invention, is shown in overview in Figure 2.
In a first step 200, a silk protein solution 40 is prepared with a silk protein content between 0.3 % and 30 % (w/w), (as described in the applicants' International Patent Application PCT/EP2007/001775). The silk protein solution 40, is then applied to the solid support 20 to form a first layer 70.
In the next step 210, the ready made, synthetic bone graft material 10 is applied to the first layer 70 when the first layer 70 is still wet.
lii the next step 220, the synthetic bone graft material 10 is dried on the first layer 70 to form a second layer 80.
In the final step 230, the now formed uni-directionally coated silk fibroin membrane 90 is removed from the solid support 20 and transfened into a storage container (not shown) and stored until further use.
In a further aspect of the present invention, the uni-directionally coated silk fibroin membrane may be sterilised inside the storage container through y-radiation.
A uni-directionally coated silk membrane 60 or 90 produced by either one of the methods described is shown in Figure 3.
The use of a uni-directionally coated silk membrane 60 or 90 formed by either one of the methods (100, 200) in periodontal surgery is shown in Figure 4. A section of bone 400 carries a bone defect 415 which requires GBR therapy. The uni-directionally coated silk membrane 60 or 90 produced by either one of the methods described above is placed in the position 415 with one of the sides 30 or 80 coated with the bone graft material 10 in contact with the bone 400. A non-coated side 50 or 70 is placed away from and not in contact with the bone 400.
Bone growth is guided through osteoinduction stimulated by the bone graft material 10 coated on side 30 and 80 in contact with bone 400.
The following examples of specific aspects for canying out the present invention are for illustrative purposes only, and are not intended to limit the scope of the present invention in any way.
Examples:
Example 1
Nano-crystalline hydroxyapatite paste (bone graft material -10) was applied evenly as a thin layer to the bottom of a casting form (solid support 20) with dimensions 10 x 10 x 0.05 mm and left to dry at room temperature for 12 hours. The hydroxyapatite layer formed at the bottom of the casting form was then covered with silk fibroin solution (40) produced with the apparatus described in international patent application PCT/EP2007/00 1775 and left to dry for 12 hours at room temperature. The resulting hydroxyapatite/silk membranes (60) were removed from the casting form and stored at room temperature until further use.
Mechanical handling tests demonstrated that the hydroxyapatite layer was bound firmly to the silk fibroin membrane, even after incubation in water for 24 hours. The one-sided coating of the silk membrane with the hydroxyapatite was easily detectable upon visual inspection as a rough, non-light reflecting surface. The opposite surface of the silk membrane was easily detectable upon visual inspection as shiny, light reflecting surface.
Example 2
A silk fibroin solution (40) produced with the apparatus described in international patent application PCT/EP2007/001775 was applied evenly as a thin layer to the bottom of a casting form with dimensions 10 x 10 x 0.05 mm. A hydroxyapatite powder (bone graft material -10) obtained through drying of nano-crystalline hydroxyapatite paste was applied evenly as a thin layer on top of the silk fibroin solution when the silk fibroin solution was still wet and left to dry for 12 hours at room temperature. The resulting hydroxyapatite/silk membranes (90) were removed from the casting form and stored at room temperature until further use.
Mechanical handling tests demonstrated that the hydroxyapatite coating was bound firmly to the silk fibroin membrane, even after incubation in water for 24 hours. The one-sided coating of the silk membrane with the hydroxyapatite was easily detectable upon visual inspection as rough, non-light reflecting surface. The opposite surface was easily detectable upon visual inspection as shiny, light reflecting surface.
Example 3
For use in oral surgery, a bone (400) defect (415) is exposed by standard dental surgery procedures, such as mucoperiosteal flap or sinus lift operation. The silk membrane (60, 90) prepared according to Example 1 or Example 2 is adapted to the required size with adequate cutting instruments (scissors, scalpels). After cutting, the silk membrane (60, 90) is wetted in water for 30 seconds. The silk membrane (60, 90) is then applied over the bone defect (415) with the rough, non-light reflecting surface facing the bone and the shiny, light reflecting surface facing away from the bone. The rough, non-light reflecting surface is the coated surface and the shiny, light reflecting surface is the non-coated surface of the silk membrane (60, 90). If required, the silk membrane (60, 90) is fixed with standard surgical fixation methods, such as suturing or bioresorbable pins at the bone defect site. The bone (400) defect site (415) is then closed with standard dental surgery procedures.
Claims (8)
- Claims 1. A silk membrane (60, 90) having two sides and coated selectively on one of the two sides with a bone graft material (10).
- 2. The silk membrane (60, 90) according to claim 1 wherein the bone graft material (10) is hydroxyapatite.
- 3. The silk membrane (60, 90) according to claim 1 wherein the bone graft material (10) is B-tricalcium phosphate.
- 4. The silk membrane (60, 90) according to claim 1 wherein the bone graft material (10) is a combination of hydroxyapatite and B-tricalcium phosphate.
- 5. A method (100) for manufacturing a bone regeneration membrane (60) selectively coated with bone graft material (10), comprising: -applying (100) a bone graft material (10) to a solid support (20); -drying (110) the bone graft material (10) on the solid support (20) to form a first layer (30), -applying (120) a silk fibroin solution (40) to the first layer (30), -drying (130) the silk fibroin solution (40) on the first layer (30) to form a second layer (50) thereby forming a uni-directionally coated silk fibroin membrane (60) with the bone graft material (10).
- 6. A method (200) for manufacturing a bone regeneration membrane (90) selectively coated with bone graft material (10), comprising: -applying (200) a silk fibroin (40) solution to a solid support (20) to form a first layer (70), -applying (210) the bone graft material (10) to the first layer (70) when the first layer (70) is still wet, -drying (220) the bone graft material (10) on the first layer (70) to form a second layer (80) thereby forming a uni-directionally coated silk fibroin membrane (90) with the bone graft material (10).
- 7. The method of claim 5 or 6, further comprising storage of the bone regeneration membrane (230).
- 8. A method for regenerating bone (400) comprising: placement of a first side of a silk membrane (60, 90) on a regeneration site (415), wherein a coated side (30, 80) of the silk membrane (60, 90) is placed adjacent to the bone generation site (415) and is in contact with the bone (400) and wherein a non-coated side (50, 70) of the silk membrane 60, 90) is not in contact with the bone is (400).
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0811628A GB2461125A (en) | 2008-06-25 | 2008-06-25 | A silk membrane for bone graft material |
| PCT/EP2009/055866 WO2009156226A2 (en) | 2008-06-25 | 2009-05-14 | A silk membrane for bone graft material and a method for manufacture thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0811628A GB2461125A (en) | 2008-06-25 | 2008-06-25 | A silk membrane for bone graft material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0811628D0 GB0811628D0 (en) | 2008-07-30 |
| GB2461125A true GB2461125A (en) | 2009-12-30 |
Family
ID=39683123
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0811628A Withdrawn GB2461125A (en) | 2008-06-25 | 2008-06-25 | A silk membrane for bone graft material |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2461125A (en) |
| WO (1) | WO2009156226A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111298198A (en) * | 2019-04-18 | 2020-06-19 | 上海交通大学医学院附属第九人民医院 | A double-layer absorbable bionic barrier film and its preparation method and application |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008106485A2 (en) | 2007-02-27 | 2008-09-04 | Trustees Of Tufts College | Tissue-engineered silk organs |
| CA2688431C (en) | 2007-05-29 | 2016-07-05 | Trustees Of Tufts College | Method for silk fibroin gelation using sonication |
| CN101970023A (en) | 2008-02-07 | 2011-02-09 | 塔夫茨大学信托人 | 3-dimensional silk hydroxyapatite compositions |
| US8501172B2 (en) | 2008-09-26 | 2013-08-06 | Trustees Of Tufts College | pH-induced silk gels and uses thereof |
| US9074302B2 (en) | 2009-09-28 | 2015-07-07 | Trustees Of Tufts College | Methods of making drawn silk fibers |
| CA2774643A1 (en) | 2009-09-29 | 2011-04-07 | Trustees Of Tufts College | Silk nanospheres and microspheres and methods of making same |
| WO2011109691A2 (en) | 2010-03-05 | 2011-09-09 | Trustees Of Tufts College | Silk-based ionomeric compositions |
| EP2611473A4 (en) | 2010-09-01 | 2014-08-13 | Tufts College | BIOMATERIALS BASED ON SILK FIBROIN AND POLYETHYLENE GLYCOL |
| CA2815285C (en) | 2010-10-19 | 2019-12-31 | Trustees Of Tufts College | Silk fibroin-based microneedles and methods of making the same |
| WO2012145652A1 (en) | 2011-04-20 | 2012-10-26 | Trustees Of Tufts College | Dynamic silk coatings for implantable devices |
| GB201118000D0 (en) * | 2011-10-19 | 2011-11-30 | Orthox Ltd | An implantable repair device |
| CN102512712B (en) * | 2011-12-22 | 2014-12-10 | 南京工业大学 | Silk fibroin multilayer functional film with gradient structure and preparation method thereof |
| CN102847194A (en) * | 2012-09-17 | 2013-01-02 | 浙江星月生物科技股份有限公司 | Stent type silk fibroin film insoluble in water, and preparation and application of stent type silk fibroin film |
| CN102847198A (en) * | 2012-09-17 | 2013-01-02 | 浙江星月生物科技股份有限公司 | Silk fibroin film insoluble in water, and preparation and application of silk fibroin film |
| CN103738932B (en) * | 2013-12-13 | 2016-04-20 | 苏州大学 | A kind of nanometer hydroxyapatite and preparation method thereof |
| CN103656756B (en) * | 2013-12-13 | 2014-12-31 | 苏州大学 | Nano-hydroxyapatite/silk fibroin composite membrane material and preparation method thereof |
| KR101602797B1 (en) * | 2015-10-21 | 2016-03-11 | 대한민국 | Artificial biomembrane using silk matrix and Method for manufacturing thereof |
| CN108969802A (en) * | 2018-07-19 | 2018-12-11 | 浙江大学 | A kind of double induction hydroxyapatite silk fibroin composite membrane coating preparation methods with rush osteogenesis function |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060257377A1 (en) * | 2005-03-11 | 2006-11-16 | Wake Forest University Health Services | Production of tissue engineered digits and limbs |
| WO2008134541A2 (en) * | 2007-04-25 | 2008-11-06 | Musculoskeletal Transplant Foundation | Reinforced biological mesh for surgical reinforcement |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0516846D0 (en) * | 2005-08-17 | 2005-09-21 | Knight David P | Meniscal repair device |
| EP1852470A1 (en) * | 2006-05-03 | 2007-11-07 | Technische Universität München | Multilayer Silk Protein Films |
-
2008
- 2008-06-25 GB GB0811628A patent/GB2461125A/en not_active Withdrawn
-
2009
- 2009-05-14 WO PCT/EP2009/055866 patent/WO2009156226A2/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060257377A1 (en) * | 2005-03-11 | 2006-11-16 | Wake Forest University Health Services | Production of tissue engineered digits and limbs |
| WO2008134541A2 (en) * | 2007-04-25 | 2008-11-06 | Musculoskeletal Transplant Foundation | Reinforced biological mesh for surgical reinforcement |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111298198A (en) * | 2019-04-18 | 2020-06-19 | 上海交通大学医学院附属第九人民医院 | A double-layer absorbable bionic barrier film and its preparation method and application |
| CN111298198B (en) * | 2019-04-18 | 2022-03-01 | 上海交通大学医学院附属第九人民医院 | A double-layer absorbable bionic barrier film and its preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0811628D0 (en) | 2008-07-30 |
| WO2009156226A2 (en) | 2009-12-30 |
| WO2009156226A3 (en) | 2010-09-16 |
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