WO2001044141A2 - Corps en ceramique poreux - Google Patents

Corps en ceramique poreux Download PDF

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Publication number
WO2001044141A2
WO2001044141A2 PCT/NL2000/000915 NL0000915W WO0144141A2 WO 2001044141 A2 WO2001044141 A2 WO 2001044141A2 NL 0000915 W NL0000915 W NL 0000915W WO 0144141 A2 WO0144141 A2 WO 0144141A2
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WO
WIPO (PCT)
Prior art keywords
ceramic body
porous ceramic
process according
slurry
porous
Prior art date
Application number
PCT/NL2000/000915
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English (en)
Other versions
WO2001044141A3 (fr
Inventor
Clayton Ellis Wilson
Walfridus Johannes Augustinus Dhert
Joost Dick De Bruijn
Original Assignee
Isotis N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Isotis N.V. filed Critical Isotis N.V.
Priority to AU32422/01A priority Critical patent/AU3242201A/en
Publication of WO2001044141A2 publication Critical patent/WO2001044141A2/fr
Publication of WO2001044141A3 publication Critical patent/WO2001044141A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • 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
    • B33Y70/10—Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B38/00—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof
    • C04B38/06—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by burning-out added substances by burning natural expanding materials or by sublimating or melting out added substances
    • C04B38/0615—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by burning-out added substances by burning natural expanding materials or by sublimating or melting out added substances the burned-out substance being a monolitic element having approximately the same dimensions as the final article, e.g. a porous polyurethane sheet or a prepreg obtained by bonding together resin particles
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
    • C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
    • C04B2111/00836—Uses not provided for elsewhere in C04B2111/00 for medical or dental applications

Definitions

  • the invention relates to a method of preparing a porous ceramic body and to a body obtainable by said method.
  • the invention further relates to the use of said body as a scaffold m tissue engineering.
  • Regeneration of skeletal tissues has been recognized as a new means for reconstruction of skeletal defects arising from abnormal development, trauma, tumors and other conditions requiring surgical intervention.
  • Autologous bone grafting is considered the gold standard of bone transplantation with superior biological outcomes.
  • autologous bone stocks are limited and often insufficient, particularly when large skeletal defects are encountered.
  • Allografts are used as alternative materials but are associated with immunologically mediated complications and risks of disease transmission. Additional disadvantages of autograft and allograft materials include their limited potential for molding or shaping to achieve an optimum fit with bone voids.
  • Variation of the scaffold design as three-dimensional superstructures has been demonstrated as an approach to optimize the functionality of bone regeneration materials so that these materials may be custom designed for specific orthopedic applications m the form of void fillers, implants, or implant coatings.
  • void fillers, implants, or implant coatings In attempt to develop a skeletal cell and tissue carrier, which could provide optimal spatial conditions for cell migration and maintenance by the arrangement of structural elements such as pores and fibers, the feasibility of using "live” material is under investigation.
  • live material could take the form of an open-porous implant system together with living tissue. In other words, this is so-called hard tissue engineering.
  • H 2 0 2 hydrogen peroxide
  • an HA slurry is made by mixing HA powder with water and a H 2 0 2 solution. Then, samples of the slurry are put m oven, under elevated temperature. H 2 0 2 decomposes and 0 2 is released from the bulk material, leaving a porous structure.
  • H 2 0 2 decomposes and 0 2 is released from the bulk material, leaving a porous structure.
  • th s technique is still widely used m both clinical applications and research areas.
  • porous ceramics made by this H 2 0 2 method has an intrinsic shortcoming: it possesses only "laminar porosity".
  • the manufacturing route comprises preparing an HA slurry (slip) by mixing HA powder under stirring with water, a deflocculant and binder agents.
  • a kind of foam sponge
  • the slurry will be sucked into the foam.
  • a layer of ceramic will be coated on all the struts of the sponge after removing the extra slurry by squeezing the samples. Then the samples will be dried m microwave oven and finally sintered m a furnace.
  • This method is often referred to as a positive replica method.
  • Slip-casted materials are highly porous; they have a reticulate structure.
  • the ceramic due to the inner flaws m the ceramic, which are left after the sponge is burnt off, the strength of the material can not be increased to meet the requirement of tissue engineering application.
  • coral HA has gained a wide interest m biomate ⁇ al spheres.
  • An example of such a material is Interporeo, which has a high porosity and excellent microporous surface structure.
  • Interporeo which has a high porosity and excellent microporous surface structure.
  • it is an expensive material and, more importantly, its mechanical strength is insufficient for tissue engineering applications.
  • porous ceramics there are several known methods of preparing porous ceramics.
  • porous ceramic which are to be used for skeletal regeneration, hard tissue repairing, and even for hard tissue engineering purpose.
  • the pore size should be m the range of 100 to 300 microns, and the pores should be fully interconnected. This specification gives rise to a desire for a more suitable porous ceramic (tissue carrier or 3-D scaffold) .
  • the present invention provides an improved method for preparing a porous ceramic body.
  • the method leads to a ceramic body having defined and controllable pore or channel size, pore or channel geometry, pore or channel mterconnectivity, net shape and architecture. These and other structural or architectural features may be deliberately designed into the ceramic body using this method. Cavities with the shape of tunnels or channels may advantageously facilitate the flow of culture medium through the ceramic body when it is used as a scaffold m tissue engineering and cells seeded onto it are being cultured. Furthermore, with the addition of designed structural features, the mechanical properties, particularly the compressive strength, of the ceramic body may be superior to those of ceramic bodies prepared by the above discussed, known methods.
  • a process for preparing a porous ceramic body according to the invention is based on a negative replica method. More m detail, the present method comprises the steps of :
  • the present method has the advantage that a ceramic body is obtained which has a porous structure consisting of interconnected pores. Moreover, a particularly high porosity can be achieved while maintaining superior mechanical properties.
  • a ceramic body obtainable by the present method possesses a specific surface microstructure on all surfaces, including within the pores or channels.
  • the surface of the ceramic body including the surface within the pores, has a certain advantageous rugosity.
  • a good attachment of cells is obtained when cells are seeded onto the body, e . g . m tissue engineering applications.
  • the ceramic body may give rise to osteomduction.
  • the above described ceramic materials prepared by a slip- casting method have been found not to have this feature.
  • the present method involves the use of rapid prototyping to prepare the negative structure for the negative replica method.
  • This has the great advantage that a very accurate method is provided m which any architecture or geometry, regardless of its complexity, may be achieved.
  • the design of the negative structure may be carried out using a computer, a very flexible operating method is provided. New designs can be optimized quickly at relatively low costs.
  • This is particular advantageous m view of the intended application of the porous ceramic body as a scaffold for tissue engineering. Tissue engineering by its very nature, particularly when involving the use of patient specific cell cultures, requires but also provides a custom solution for each patient. The possibilities range from simply altering the overall size of an existing design for proper fit to offering a completely custom implant through integration of 3D medical imaging data ⁇ e . g.
  • a porous structure of an organic material is prepared. It is necessary that the organic material is substantially insoluble in water, so that the integrity of the structure is not affected when it is filled with the (aqueous) slurry of ceramic material. Of course it is further necessary that the organic material is processable in a rapid prototyping protocol, which will be further discussed below.
  • Another important requirement that has to be met by the organic material is that it should be removable by thermal decomposition. It is preferred that the organic material decomposes into volatile and/or gaseous residues upon exposure to temperatures above 200°C or 400°C. Depending on the envisaged application of the ultimate ceramic body, it is desirable that substantially no charred or tar- like residues are formed upon thermal decomposition, respectively remain within the porous structure of the ceramic body after sintering.
  • an organic solvent may or may not be present. It will be clear that, if an organic solvent is to be used, it should be chosen such that it does not substantially interfere with the characteristics of the organic phase recited above. Without wishing to be exhaustive, the following suitable materials for use in the organic phase can be mentioned waxes, shellac, fatty acids, fats, epoxy resins, polyurethane resins, polyester resins, polyvmyl resins, poly (meth) acrylate resins, elastomers, thermoplastics and combinations thereof.
  • thermoplastic Protobuild m
  • ModelMaker II 3D modeling system m the ModelMaker II 3D modeling system.
  • suitable materials for use m the organic phase have been, and will be, developed by rapid prototyping system and material manufacturers and developers .
  • the formulation of these materials is typically proprietary, however, the skilled person will be able to readily identify suitable materials by the material properties and characteristics described above.
  • the porous structure of the organic material is prepared using rapid prototyping
  • rapid prototyping refers to a class of technologies that can automatically construct physical models from Computer-Aided Design (CAD) data. These 'three dimensional printers' allow designers to quickly create tangible prototypes of their designs, rather than just two dimensional pictures. At least six different rapid prototyping techniques are commercially available, each with unique strengths . Because RP technologies are being increasingly used m non-prototyping applications, the techniques are often collectively referred to as solid free- form fabrication, computer automated manufacturing, or layered manufacturing.
  • the object to be built is modeled using a Computer-Aided Design (CAD) software package.
  • CAD Computer-Aided Design
  • NURBS Modeling for Windows which may be run on any suitable type of computer. It is possible to use a pre-existing CAD file or one can create a file expressly for prototyping purposes .
  • the various CAD packages use a number of different algorithms to represent solid objects.
  • STL stereolithography, the first RP technique
  • the second step is to convert the CAD file into STL format.
  • This format represents a three dimensional surface as an assembly, or mesh, of planar triangles.
  • the file contains the coordinates of the vertices and the direction of the outward normal of each triangle. For rapid prototyping it is important that the meshed surface is completely closed (watertight) .
  • CAD file is designed so that the rapid prototyping process will produce a negative replica of the desired ceramic body.
  • Structural or architectural properties that may be defined during CAD file creation include, but are not limited to, pore or channel size, pore or channel geometry, pore or channel mterconnectivity, porosity, net shape and architecture, as well as variations of these parameters within a design.
  • a pre-processing program prepares the STL file to be built.
  • Several programs are available and most allow the user to adjust the size, location and orientation of the model. Build orientation is important for several reasons. First, properties of rapid prototypes vary from one coordinate direction to another. For example, prototypes may be weaker and less accurate m the vertical directions than m the horizontal plane. In addition, part orientation partially determines the amount of time required to build the model . Placing the shortest dimension m the vertical direction reduces the number of layers, thereby shortening build time.
  • the pre-processing software slices the STL model into a number of layers of a thickness which can suitably be controlled, depending on the desired accuracy. Typically, the thickness of the layers will be between 0.01 and 0.7 mm.
  • the program may generate an auxiliary structure to support the model during the build. Supports are useful for delicate features such as overhangs, internal cavities and thm-walled sections .
  • the fourth step of the RP process is the actual construction of the part.
  • RP machines build one layer at a time from polymers, paper, or other materials. Most machines are fairly autonomous, needing little human intervention.
  • the techniques that can be use are primarily stereolithography, laminated object manufacturing, selective laser sintering, fused deposition modeling, solid ground curing, and mk et printing. These techniques are known per se, and m principle any of them may be used m the context of the invention. Preferably, however, use is made of mk et printing, e . g.
  • the final step of the rapid prototyping protocol is post -processing . This involves removing the prototype from the machine and detaching any supports. Some photosensitive materials need to be fully cured before use. Prototypes may also require minor cleaning and surface treatment. In accordance with the invention, this final step preferably comprises the removal of the support material as described by the manufacturer and a light rinse m water to remove loose debris .
  • the porous organic structure is filled with a ceramic slurry.
  • the ceramic material of which the slurry s prepared can m principle be any material of which it is desired to prepare a porous body of. In other words, the choice for a particular ceramic material will depend on the objective application of the final product . In view of the envisaged application of the porous body as a scaffold m tissue engineering, m accordance with the invention it is preferred that the ceramic material is a calcium phosphate.
  • Highly preferred calcium phosphates may be chosen from the group of octacalcium phosphate, apatites, such as hydroxyapatite and carbonate apatite, whitlockites, ⁇ -t ⁇ calcium phosphate, ⁇ - t ⁇ calcium phosphate, sodium calcium phosphate, and combinations thereof.
  • an additive m the aqueous slurry may be desired to incorporate an additive m the aqueous slurry.
  • additives are binders, surfactants, pH controlling agents, deflocculants, and the like.
  • binder a water soluble polymer such as a cellulose derivative (e.g. carboxymethylcellulose (CMC) ) may be used, preferably m an amount of between 0.05 and 0.5 wt.%, based on the weight of the slurry.
  • a pH controlling agent may suitably be employed to control the solubility of the ceramic material. It will be clear that it is to be avoided that (a significant amount of) the ceramic material dissolves m the aqueous phase. The skilled person will be able to determine whether there is a need for the use of a certain additive, based on his general knowledge .
  • the concentration of the ceramic material m the slurry will depend on the solubility of the chosen ceramic material m water. Generally, said concentration will be chosen between 50 and 80 wt.%, preferably between 55 and 75 wt.%, based on the weight of the slurry.
  • the slurry may be prepared by admixing water and the ceramic material under stirring until a homogeneous slurry is obtained.
  • a foaming agent may conveniently be included m the ceramic slurry.
  • the foaming agent may be present m the organic phase m amounts of up to 10 wt.%.
  • a preferred example of a foaming agent is a combination of sodium bicarbonate and citric acid, which agents may suitably be employed m a weight ratio of between 1 : 2 and 1:5.
  • combustible particulate matter such as pine tree branches or rigid polymeric fibers
  • combustible particulate matter such as pine tree branches or rigid polymeric fibers
  • This matter is meant to decompose when the organic phase is removed by thermal decomposition.
  • a ceramic body is obtained which has additional discrete cavities m its structure which have the shape and size of the particulate matter that has been removed.
  • the filling of the porous organic structure with the ceramic slurry is preferably carried out by pulling the slurry through the porous structure by creating a vacuum using for instance a syringe.
  • the porous organic structure may preferably be wrapped m a suitable material such as parafilm and mounted on Y 2 of an mime tubing filter.
  • the syringe need only provide sufficient vacuum to enable the filling on the organic structure. It is also possible to push the slurry through the mold, again by using a syringe. It can be envisaged that virtually any vacuum or pressure source, including commercial vacuum and injection molding machines, may be used for this purpose .
  • the structure and tubing filter are preferably removed as a single piece.
  • a drying step is carried out m order to dry the ceramic material.
  • the drying is carried out for a duration of at least 5 hours at atmospheric conditions. If a more thorough drying is desired, the structure may be placed a low temperature oven at 50°C for this purpose.
  • the dried structure is subsequently placed m a furnace m order to thermally decompose, and remove, the organic material.
  • Suitable conditions will depend on the nature of the organic material.
  • thermal decomposition will be achieved at a temperature between 200 and 800°C.
  • the heating may be prolonged for a duration of up to 24 or even 36 hours.
  • a porous ceramic body is obtained which may find application m itself.
  • the ceramic body is sintered. Sintering may be performed at a temperature between 800 and 1400°C, preferably between 1000 and 1300°C.
  • the thus obtained ceramic body has superior mechanical properties.
  • it has a very high strength
  • the compressive strength will preferably be at least 10 MPa
  • the ceramic body has the structural and architectural properties as designed m the CAD file.
  • tissue engineering is intended to refer to any process wherein cells are seeded onto the scaffold material and cultured there, either in vi tro or m vivo, to form tissue of a desired type.
  • tissue cells of various types may be used ranging from stem cells to all sorts of differentiated cells. Due to its mechanical properties, the present porous ceramic body is particularly useful for tissue engineering bone tissue or for repair of defects at non-load bearing sites, but also at load bearing sites.
  • the surface of a ceramic body according to the invention further has highly advantageous properties beneficial to cells with which it comes into contact.
  • the negative replica of the ceramic body is prepared using rapid prototyping, it is m fact built up of discernible layers. It has been found that at the interfaces of these layers, a certain roughness is produced.
  • the ceramic body is a replica of the body prepared m the rapid prototyping, it will possess the same, albeit the positive of the negative, type of roughness. This roughness has been found to be very beneficial to cells, m particular to the proliferation of cells.
  • the ceramic body is used as a scaffold for tissue engineering bone
  • the cells that are seeded onto the scaffold in vi tro or the cells that come into contact with or m the vicinity of the rough surface of the scaffold in vivo show a higher proliferation rate than the same cells would show when the surface would be smooth.
  • the roughness encompasses at least two elements.
  • the present ceramic body may be crushed to form a granulate of a desired porous structure.
  • the granulate so obtained may find application for example oral surgery and plastic surgery of the face, as well as spine surgery and orthopedics.
  • the mean diameter of the particles of the granulate are between 2 and 3.5 mm.
  • EXAMPLE A ceramic (hydroxyapatite) scaffold was desired for use m a critical size segmental defect of the goat femur.
  • the design specifications were as follows. Overall shape and dimensions: Hollow cylinder Inner (hole) diameter: 10.0 mm
  • the Rhinoceros NURBS Modeling for Windows software was used to design a negative replica mold (organic phase) according to the above specifications. A shrinkage of 20% for the ceramic material during drying and sintering, described later, was accounted for in the computer aided design process.
  • the design specifications for the negative replica mold were as follows.
  • Inner (hole) diameter 12.5 mm
  • Outer diameter 25.0 mm
  • Length 31.25 mm
  • struts were arrange in a "log pile" manner with each layer of struts (logs) perpendicular to the two adjacent layers. Within each layer the struts were spaced 750 ⁇ m apart, the same distance as the thickness of the struts, yielding the 50% overall porosity. Alternating layers were aligned.
  • the Rhinoceros NURBS Modeling for Windows software was used for computer aided design of the sub-molds according to the above specif cations. This software package was also used to convert the CAD file to the STL file format required for rapid prototyping and to edit the STL mesh as needed to create a closed (watertight) model. A computer rendered image of one sub-mold section is showing m Figure 1.
  • the STL file of a single sub-mold was sent via the internet to a rapid prototyping service bureau for per- processing and printing.
  • the ModelWorks software (Sanders Prototype, Inc.) was used to pre-process the STL model for printing using the ModelMaker II 3D printing system (Sanders Prototype, Inc.).
  • the STL sub-mold model was arranged and oriented in the print envelope.
  • the STL models were sliced in 53 ⁇ m thick slice/print layers.
  • the slice/print layer thickness may be varied from as little as 13 ⁇ m to as much as 150 ⁇ m using the ModelWorks software and ModelMaker II printer. Thinner slice/print layers produce better resolution but require longer to print than thicker slice/print layer.
  • the software automatically determined the placement of thermoplastic build (ProtoBuild) and wax support (ProtoSupport ) materials.
  • the sub-mold models were then printed. When printing was complete the printed models were removed from the machine. The wax support material was removed using and special solvent (BioAct). The remaining build material defined the negative replica sub- molds and they were designed. The cleaned sud-molds were sent via regular post to our facility.
  • Figure 2 shows the top and bottom surface of one of the sub-molds as received from the service bureau.
  • the sub-molds were prepared for filling with hydroxyapatite slurry by first stacking and aligning the five sub molds to form a single complete mold. Alignment was facilitated by placing a tight fitting rectangular piece of cardboard into the rectangular alignment hole of the sub- molds. The five sub-molds were pressed together by hand and then circumferentially wrapped with several layers of parafilm. The ends of the assembled mold were left unobstructed. One end of the mold was placed against the filter side of one half of an ime tubing filter. An additional wrap of parafilm held the filter to the mold and formed and air tight seal. The other side of the tubing filter attached to a 60 ml disposable syringe. HA powder, purchased commercially and calcined at
  • FIG. 4A shows the end of a hydroxyapatite cylinder which was produced by stacking five of the molds shown in figures 1 and 2.
  • Figure 4B shows a side view of this cylinder. Scanning electron microscopy of scaffolds produce by this method show several interesting features. Impressions of the layer mold morphology were present m the sintered ceramic scaffold.
  • FIGS. 5A and B show the advantageous surface microstructure of the cylinder shown m figures 4A and B.
  • the shrinkage of the resulting sintered scaffold was as expected, between 20 and 22%.
  • FT-IR analyses showed that scaffolds produced by this method were pure HA.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Ceramic Engineering (AREA)
  • Materials Engineering (AREA)
  • Structural Engineering (AREA)
  • Dermatology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Composite Materials (AREA)
  • Civil Engineering (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Manufacturing & Machinery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Prostheses (AREA)
  • Porous Artificial Stone Or Porous Ceramic Products (AREA)

Abstract

Cette invention se rapporte à un procédé servant à préparer un corps en céramique poreux et se basant sur la méthode des répliques négatives. Cette invention concerne en outre un corps céramique obtenu par ce procédé et son utilisation comme échafaudage pour le génie tissulaire.
PCT/NL2000/000915 1999-12-16 2000-12-13 Corps en ceramique poreux WO2001044141A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU32422/01A AU3242201A (en) 1999-12-16 2000-12-13 Porous ceramic body

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP99204378.6 1999-12-16
EP99204378 1999-12-16
EP00202704.3 2000-07-28
EP00202704 2000-07-28

Publications (2)

Publication Number Publication Date
WO2001044141A2 true WO2001044141A2 (fr) 2001-06-21
WO2001044141A3 WO2001044141A3 (fr) 2002-03-07

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10258773A1 (de) * 2002-12-16 2004-07-08 SDGI Holding, Inc., Wilmington Knochenersatzmaterial
DE10350570A1 (de) * 2003-10-30 2005-06-16 Bego Semados Gmbh Verfahren zur Herstellung von Knochenersatzmaterial sowie Knochenersatzmaterial
US7094371B2 (en) 2000-08-04 2006-08-22 Orthogem Limited Porous synthetic bone graft and method of manufacture thereof
EP2258291A3 (fr) * 2002-07-23 2013-09-11 Fondel Finance B.V. Élément support à fixer sur un os
US8747791B2 (en) 2008-11-13 2014-06-10 Catalymedic Inc. Calcium phosphate porous material with small amount of remaining aromatic hydrocarbon
US10286102B2 (en) 2010-05-11 2019-05-14 Howmedica Osteonics Corp Organophosphorous, multivalent metal compounds, and polymer adhesive interpenetrating network compositions and methods
CN109809810A (zh) * 2019-03-07 2019-05-28 华南理工大学 一种具有非均质多孔仿生天然骨结构的生物活性陶瓷支架及其制备方法
US11065601B2 (en) 2015-12-18 2021-07-20 University Of Canterbury Separation medium
CN114318255A (zh) * 2021-12-09 2022-04-12 贵研铂业股份有限公司 一种由易氧化金属镀膜保护制备的高致密NiV合金溅射靶材及其制备方法
CN114750412A (zh) * 2022-06-16 2022-07-15 季华实验室 结合3d打印制备无分层结构材料的方法

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JPS56166843A (en) * 1980-05-28 1981-12-22 Mitsubishi Mining & Cement Co Filler for bone broken section and void section
US5284695A (en) * 1989-09-05 1994-02-08 Board Of Regents, The University Of Texas System Method of producing high-temperature parts by way of low-temperature sintering
US5824250A (en) * 1996-06-28 1998-10-20 Alliedsignal Inc. Gel cast molding with fugitive molds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5740051A (en) 1991-01-25 1998-04-14 Sanders Prototypes, Inc. 3-D model making

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7094371B2 (en) 2000-08-04 2006-08-22 Orthogem Limited Porous synthetic bone graft and method of manufacture thereof
EP2258291A3 (fr) * 2002-07-23 2013-09-11 Fondel Finance B.V. Élément support à fixer sur un os
DE10258773A1 (de) * 2002-12-16 2004-07-08 SDGI Holding, Inc., Wilmington Knochenersatzmaterial
DE10350570A1 (de) * 2003-10-30 2005-06-16 Bego Semados Gmbh Verfahren zur Herstellung von Knochenersatzmaterial sowie Knochenersatzmaterial
US8747791B2 (en) 2008-11-13 2014-06-10 Catalymedic Inc. Calcium phosphate porous material with small amount of remaining aromatic hydrocarbon
US10286102B2 (en) 2010-05-11 2019-05-14 Howmedica Osteonics Corp Organophosphorous, multivalent metal compounds, and polymer adhesive interpenetrating network compositions and methods
US11065601B2 (en) 2015-12-18 2021-07-20 University Of Canterbury Separation medium
CN109809810A (zh) * 2019-03-07 2019-05-28 华南理工大学 一种具有非均质多孔仿生天然骨结构的生物活性陶瓷支架及其制备方法
CN114318255A (zh) * 2021-12-09 2022-04-12 贵研铂业股份有限公司 一种由易氧化金属镀膜保护制备的高致密NiV合金溅射靶材及其制备方法
CN114318255B (zh) * 2021-12-09 2022-09-16 贵研铂业股份有限公司 一种由易氧化金属镀膜保护制备的高致密NiV合金溅射靶材及其制备方法
CN114750412A (zh) * 2022-06-16 2022-07-15 季华实验室 结合3d打印制备无分层结构材料的方法

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