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WO2018185302A1 - Moulage et coulage de composites - Google Patents

Moulage et coulage de composites Download PDF

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Publication number
WO2018185302A1
WO2018185302A1 PCT/EP2018/058891 EP2018058891W WO2018185302A1 WO 2018185302 A1 WO2018185302 A1 WO 2018185302A1 EP 2018058891 W EP2018058891 W EP 2018058891W WO 2018185302 A1 WO2018185302 A1 WO 2018185302A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
process according
suspension
tcp
mould
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.)
Ceased
Application number
PCT/EP2018/058891
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English (en)
Inventor
Morten Østergaard ANDERSEN
Martin Bonde JENSEN
Casper SLOTS
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Syddansk Universitet
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Syddansk Universitet
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Filing date
Publication date
Application filed by Syddansk Universitet filed Critical Syddansk Universitet
Publication of WO2018185302A1 publication Critical patent/WO2018185302A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/34—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
    • C04B28/344—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders the phosphate binder being present in the starting composition solely as one or more phosphates
    • 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
    • A61L27/10—Ceramics or glasses
    • 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
    • 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
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • 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
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • 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
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • 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
    • A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses
    • 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 present invention relates to a moulding or casting process for preparing solid objects.
  • the present invention relates to a process for preparing medical implants and biotechnological objects and uses thereof.
  • Casting and moulding liquid, fluid or plastic materials is a well-known method for shaping objects.
  • a difference is typically thought to be that casting refers to the process of pouring a free flowing material into a cast whereas moulding requires pressure to drive a material into a mould.
  • the moulded materials of interest are solid powders (e.g. metal or ceramic powders) that are suspended in different liquid, fluid or plastic materials (commonly polymeric materials). Examples of such processes would be metal injection moulding and ceramic injection moulding.
  • the liquid, fluid or plastic materials, hereafter referred to as the suspension liquid are removed after casting or moulding by burning or evaporation for example in an oven (also known as debinding), the powder materials of interest are then typically sintered afterwards to fuse them into the desired object.
  • One class of objects where particular shapes are often required is within the field of medical devices where it would often be advantageous to shape those devices in a particular way so that they, for example, fit a patient, recreate a particular anatomy, or combine easier with other medical devices.
  • Implantable drug release depots, pharmaceutical pills and similar objects for drug delivery/formulation are different related applications where a particular shape may result in a faster or slower drug release and/or a greater or smaller drug dosage and where such properties may be tailored to a given recipient (a human patient or an animal).
  • Another type of device is those that function as supports for maintaining living cells (e.g. in vitro) and organisms that grow on, within or near the devices.
  • Araki et al. discloses a freeze casting technique including a sintering step.
  • US 6,642,285 Bl discloses a composition including a hydraulic cement for implantation in a human or animal body.
  • the devices could be made available quickly, which can be difficult to achieve. It would also be advantageous if the devices could be made available by cheaper methods requiring less equipment. It would also be advantageous if the devices could be made
  • the present invention relates to moulding or casting processes for producing solid objects.
  • the process involves a suspension comprising a liquid non-aqueous substance and a material such as a ceramic (the suspension liquid).
  • the suspension is liquid at elevated temperatures (e.g. above 40°C) but solid at lower temperatures (e.g. below 40°C).
  • the process may not require sintering before use of the produced object.
  • the solidified suspension may find direct use as a medical implant, a drug delivery device (e.g. a pill or depot) or as a biotechnological object.
  • the mould or cast is dissolvable in a solvent, which is a non-solvent for the solidified suspension, thereby providing an efficient and fast process for providing e.g. medical implants.
  • the invention also relates to objects obtainable/obtained by such process and uses of such objects. A general outline of the process of the invention is presented in figure 12.
  • an object of the present invention relates to the provision of solid objects by a fast and cheap casting or moulding process, preferably for medical or
  • Medical uses may include the use of the object as a medical implant in humans or animals to restore tissue or organ function, recreate or modify anatomy or serve as a scaffold in tissue engineering and regenerative medicine.
  • Other medical uses of the object include the use as a pharmaceutical and nutrient pill or depot that is, for example, taken orally, implanted surgically, inserted into a body cavity (e.g. rectum, uterus, ears, eyes, nose etc.) or mounted onto the skin e.g. as a patch.
  • a body cavity e.g. rectum, uterus, ears, eyes, nose etc.
  • Biotechnological uses may include the use of the object as bioreactors, adherence substrates, chemical release structures and/or nutrient feedstocks that may do one or more of the following : (1) retain, carry or support cells and/or organisms, (2) provide cells and/or organisms with an anchorage or adherence point and (3) provide cells and/or organisms with released bioactive compounds such as pharmaceuticals, pesticides, enzymes, nutrients, and antimicrobials.
  • a substance e.g. a liquid, gas or air
  • passes by diffusion, artificial forces or natural processes
  • Such devices may be used for industrial biotechnology, fermentation processes, biofuel production,
  • one aspect of the invention relates to a process for producing a (solid) object, the process comprising
  • ⁇ at least 5% by weight of the total suspension of a liquid nonaqueous substance selected from the group consisting of fatty acids, cholesterol, or derivatives thereof, such as glycerol esters, triglycerides, phospholipids and cholesteryl esters;
  • ⁇ 40-95% by weight of the total suspension (w/w) one or more materials selected from the group consisting of ceramic materials, proteins, and/or carbohydrates;
  • ⁇ optionally, 1-10% by weight of a one or more proteins or carbohydrate materials, such as gelatine;
  • the mould or cast is removed in step e) by dissolving it in a solvent that is a non-solvent for the solidified object, the solvent preferably being water or a water based solution, such as saline, pH buffers or alkaline or acidic solutions.
  • the provided object is biocompatible and biodegradable.
  • Yet another aspect of the present invention is to provide a solid object
  • Still another aspect of the present invention is to provide a solid object
  • a process according to the invention for use as a medical implant such as a bone or dental implant.
  • Still another aspect of the present invention is to provide a solid object
  • Figure 1 shows left: An empty latex mould and, right: the same mould filled with a MCP, TCP, gelatin and lauric acid suspension according to claim 1
  • Figure 2 shows suspensions in a latex mould with fibers.
  • PVA polylactic acid
  • PVA Polyvinyl alcohol
  • Figure 3 shows left: composition B from example 2 after 24h PBS+BSA bath.
  • Composition C from example 2 after 24h PBS+BSA bath.
  • Figure 4 shows (A) a CAD model of the segmental jaw implant and (B) a CAD model of the corresponding implant mould
  • Figure 5 shows (A) 3D printing of the implant mould in PVA and (B) the implant, either 3D printed directly using traditional FDM and ABS plastic (left) or by casting TCP + MCP + gelatine in the soluble cast 3D printed using PVA (right).
  • Figure 6 SEM pictures of (A) TCP casted with stearic acid, solidified but not sintered and (B) TCP casted with stearic acid then debonded and sintered at 1300°C.
  • Figure 7 shows (A) an empty rectangular mould made by 3D printing PVA and (B) such moulds filled with different casting compositions
  • Figure 8 shows (A) the dissolution of 3D printed PVA moulds and (B) the resulting final objects
  • Figure 9 shows (A) casted objects that include the porogen sodium chloride, ((B), right) an image of a solid composition and ((B), left) a porous cast beam made with cotton candy strings and (C) Microscopy image of the solid (left) and cotton candy (right) samples
  • Figure 10 shows (A) Composition A (left), Composition B from example 6 (center) and a sample from example 5 (right), (B) Composition C (left) and Composition D (right) from example 6 and (C) Electrical measurement of sample D from example 6.
  • Figure 11 shows casting of proteins and carbohydrates with stearic acid.
  • FIG. 12 shows a flow diagram of an embodiment of the process according to the invention.
  • Figure 13 shows cumulative methylene blue release from casted non-sintered fatty acid/TCP composites over a week.
  • C12 is lauric acid
  • C14 is myristic acid
  • C16 is palmitic acid
  • C18 is stearic acid.
  • Figure 14 shows the pH in demineralized water wherein objects composed solely of fatty acids or of non-sintered fatty acids and a ceramic have been placed for 4 days.
  • LA lauric acid
  • SA is stearic acid
  • AP is ammonium phosphate
  • KP is potassium phosphate.
  • Figure 15 shows the compressive strength of casted pure fatty acids as well as of casted non-sintered objects made from fatty acids and TCP.
  • C12 is lauric acid
  • C14 is myristic acid
  • C16 is palmitic acid
  • C18 is stearic acid.
  • Figure 16 shows the weight changes in non-sintered fatty acid and TCP objects when immersed in cell culture medium with serum.
  • C12 is lauric acid
  • C14 is myristic acid
  • C16 is palmitic acid
  • C18 is stearic acid.
  • Figure 17 shows the viability of soil microorganism cultured in the presence of camphene, paraffin and lauric and stearic acid with or without ammonium phosphate and potassium phosphate.
  • LA lauric acid
  • SA is stearic acid
  • AP ammonium phosphate
  • KP potassium phosphate.
  • the present invention relates to a process for producing a solid object.
  • the process relates to providing materials (such as ceramics) in a specific suspension, wherein the suspension is positioned in a mould in a liquid state, the suspension is then cooled so that it solidifies and subsequently the mould is removed.
  • materials such as ceramics
  • a first aspect of the invention relates to a process for producing a solid object, the process comprising
  • ⁇ at least 5% by weight of the total suspension of a liquid nonaqueous substance selected from the group consisting of fatty acids, cholesterol, or derivatives thereof, such as glycerol esters, monoglycerides, diglycerides, triglycerides,
  • phospholipids glycerophospholipids, glycerol-ether lipids and cholesteryl esters
  • ⁇ 40-95% by weight (w/w) of the total suspension one or more materials selected from the group consisting of ceramic materials (such as TCP and/or MCP), proteins, and/or
  • ⁇ optionally, 1-10% by weight of a one or more proteins or carbohydrate materials, such as gelatine;
  • casting refers to the process of pouring a free flowing material into a cast whereas "molding” or “moulding” requires pressure to drive a material into a mould.
  • casting and moulding require pressure to drive a material into a mould.
  • molding/moulding is used interchangeable but without excluding the other variant in each instance, unless explicitly mentioned.
  • the process does not involve a sintering step.
  • Sintering of a generated object may take place at different temperatures depending on the material.
  • said sintering is to be understood as the heating of an entire object to a temperature in the range 150 to 3000°C, such as in the range 250 to 350°C, such as in the range 300 to 400°C, such as in the range 400 to 500°C, such as in the range 600 to 700°C, such as in the range 900 to 1000°C, such as in the range 1000 to 1200°C, such as in the range 1200 to 1400°C, such as in the range 1400 to 1700°C, or such as in the range 1700 to 2500°C.
  • the process does not involve a step including a temperature in the range 150 to 3000°C, such as in the range 250 to 350°C, such as in the range 300 to 400°C, such as in the range 400 to 500°C, such as in the range 600 to 700°C, such as in the range 900 to 1000°C, such as in the range 1000 to 1200°C, such as in the range 1200 to 1400°C, such as in the range 1400 to 1700°C, or such as in the range 1700 to 2500°C.
  • said provided solid object comprises the solidified suspension.
  • solid refers to an object which is not liquid.
  • a solid object according to the invention may still have some elasticity and plasticity e.g. to match that of natural tissues, such as bone or dental material.
  • the casted object may survive the dissolution of the cast if the liquid non-aqueous substance content is hydrophobic and non-soluble in the cast solvent.
  • suspension liquid is partly or fully soluble in the cast solvent it may dissolve along with the cast and leave behind the solid material of interest, that material would then be free to undergo reactions with or mediated by the cast or mould solvent.
  • This could for example be cementing, hydration or other chemical reactions that transform the powder into a solid material.
  • the mould or cast is removed in step e) by dissolving it in a solvent that is a non-solvent for the solidified object, the solvent preferably being water or a water-based solution, such as saline, enzymatic solutions, pH buffers or alkaline or acidic solutions.
  • a solvent that is a non-solvent for the solidified object
  • the solvent preferably being water or a water-based solution, such as saline, enzymatic solutions, pH buffers or alkaline or acidic solutions.
  • Example 3 and 5 provide examples of casting in water dissolvable moulds, wherein water is a non-solvent for the provided object.
  • the mould is made of water- dissolvable material, such as polyvinylalcohol (PVA), polylactic acid (PLA, soluble in alkaline solutions), sodium chloride or a carbohydrate like sucrose.
  • PVA polyvinylalcohol
  • PLA polylactic acid
  • soluble in alkaline solutions sodium chloride or a carbo
  • a CAD file of a desired medical device is derived from patient CT or MRI scanning data or from the CAD file of another medical device such as a drill. That CAD file may then be used to manufacture the medical device, which could be an implant, by fabricating a "negative" cast from water- soluble materials through e.g. subtractive or additive manufacturing (e.g. milling and 3D printing, respectively).
  • One or more powders that will eventually form the device are then combined with a hydrophobic suspension liquid and casted into the manufactured cast. After solidification of the casted material, the cast may be placed in an aqueous solvent and dissolved leaving the medical device.
  • the suspension liquid could potentially be part of the device for its entire usage or it could be released at a later time.
  • the suspension liquid could be released to the body requiring it to be a biocompatible hydrophobic substance preferably already present in the human body.
  • endogenous hydrophobic compounds such as fatty acids, triglycerides and phospholipids could be preferred.
  • the mould is a 3D printed or milled.
  • the mould shape is derived from human or animal scanning data, such as a CT-scan, an MRI-scan or a 3D surface scan e.g. by using a laser 3D scanner. A related method would involve a reusable cast.
  • the mould is made of an elastic material, such as rubber, latex, silicone, or a thermoplastic elastomer.
  • ceramic material refers to any solid inorganic material that is not exclusively composed of metals regardless of how it was made and whether it has been sintered first.
  • the ceramic material is selected from the group consisting of TCP (tricalciumphosphate), MCP (monocalciumphosphate), DCP (dicalciumphosphate), tetracalciumphosphate, hydroxylapatite, alpha-TCP, beta-TCP, bioglass, titanium oxide (titania), aluminium oxide (alumina), zirconium oxide (zirconia), yttrium oxide (yttria), yttria stabilized zirconia, indium oxide, indium tin oxide, boron nitride, silicon carbide, boron carbide, tungsten carbide, beryllium oxide, zeolite, cerium oxide (ceria), tungsten disilicide, sodium silicide, platinium silicide, zirconium nitride, tungsten nitride, vanadium nitride, tantalum nitride, niobium nitride, silicon boride, clay, earth, soil
  • materials such as soil and earth also include other components than ceramics, such as organics, their d ry mass is predominantly ceramic in that their major constituents are ceramic grains of e.g . metal oxides, metal carbonates and metal sulfates such as silicon d ioxide, aluminium oxide, iron oxide etc.
  • the ceramic material comprises cement forming materials such as one or more calcium phosphate materials, such as monocalcium phosphate (MCP) together with tricalcium phosphate (TCP) or d icalcium phosphate (DCP) together with tetracalcium phosphate.
  • MCP monocalcium phosphate
  • TCP tricalcium phosphate
  • DCP d icalcium phosphate
  • the solid materials may be components that are able to form a cell supporting matrix upon implantation, either immediately or through later degradation, chemical reactions, remodeling or repurposing by the body.
  • the protein is selected from the group of collagen, elastin,
  • Example 7 show cast molding of gelatine (protein) .
  • the carbohydrate is selected from the group of alginate, gellan gum, agarose, chitin, pectin, cellulose, chitosan, hyaluronic acid, heparan sulfate, chondroitin sulfate, keratan sulfate and mixtures and derivative thereof such as gelatin, demineralized tissue and dehydrated tissue.
  • the carbohydrate is selected from the group of alginate, gellan gum, agarose, chitin, pectin, cellulose, chitosan, hyaluronic acid, heparan sulfate, chondroitin sulfate, keratan sulfate and mixtures and derivative thereof such as gelatin, demineralized tissue and dehydrated tissue.
  • the material is a mixture of carbohydrate and protein such as a proteoglycan.
  • Example 7 show cast molding of Alginic Acid Sodium Salt (a carbohydrate).
  • the suspension comprises in the range 50-95% of the ceramic materials, such as TCP and/or MCP, and/or proteins, and/or
  • carbohydrates such as 50-95%, such as 60-95%, such as 70-95%, such as 80- 95%, such as 85-95%, such as 90-95%, such as 80-85%, such as 80-84%, such as 80-83%, such as 80-82%, such as 81-85%, such as 82-85%, or such as such as 83-85%.
  • the casted material may contain pharmaceuticals such as antibiotics, anti-cancer drugs, antibodies or growth factors as well as their drug delivery and/or release systems. These may be the entire part of, or the partial part of, the solid materials, the suspension liquid (if the pharmaceuticals or their delivery and/or release systems are fatty acids, cholesterol or derivatives or conjugates thereof) or they be a third component in the suspension in addition to other solid materials and suspension liquids.
  • Example 9 shows the release of a pharmaceutical
  • the provided solid material comprises nutrients that stimulate the growth of one or more organisms.
  • the particle size of the provided materials may vary.
  • the particle size of the one or more materials are in the range 1 nm - 1 mm, such as below 500 Mm, below 354 ⁇ " ⁇ , below 250 Mm, below 149 Mm, below 105 Mm, below 74 Mm, below 44 Mm, below 10 Mm, below 1 Mm, below 500 nm, or such as below 100 nm, preferably below 10 Mm.
  • part of the solid material comprises a soluble porogen that may dissolve to leave porosities either in an aqueous solution or in the body of a living organism such as a human.
  • the porogen is selected from the group consisting of soluble polymers like polyvinylalcohol, soluble salts like sodium chloride, and soluble carbohydrates like sucrose. Similar to the non-aqueous liquid, it is of course preferred that the ceramic materials and/or protein material, and/or carbohydrate material is biocompatible. Thus, in an embodiment the ceramic materials and/or protein material, and/or carbohydrate material is biocompatible.
  • the ceramic materials and/or protein material, and/or carbohydrate material is biocompatible and/or biodegradable.
  • the ceramic materials and/or protein material, and/or carbohydrate material is biodegradable in the human (or animal) body or in other living organisms.
  • Most proteins are biodegradable, examples of biodegradable ceramic materials include MCP, DCP, TCP, calcium sulphate, bioglass and examples of biodegradable carbohydrates include hyaluronic acid and glycogen.
  • Example 8 shows the biocompatibility of a mixture of stearic acid and tricalcium phosphate in a mice study.
  • the suspension comprises two or more ceramic materials and/or two or more carbohydrate materials and/or two or more protein materials. Many materials react in or with water but can remain stable for longer in a nonaqueous suspension liquid, this enables such suspensions to be made, stored and distributed prior to casting them.
  • the liquid non-aqueous substance forming part of the suspension may comprise fatty acids.
  • the liquid non-aqueous substance comprises one or more fatty acids or derivatives thereof.
  • the one or more fatty acids or derivative thereof comprises at least one acid group from the group consisting of carboxylic acid, phosphonic acid and sulfonic acid group attached to at least one C5-C30 hydrocarbon.
  • the hydrocarbon is a saturated or unsaturated aliphatic hydrocarbon group or an aromatic hydrocarbon group or a mixture thereof.
  • the fatty acid comprises at least one carboxylic acid and the hydrocarbon is a saturated or unsaturated C5-C30 aliphatic
  • the fatty acid or derivative thereof is a compound of Formula (I) : o
  • R is a saturated or unsaturated C5-C30 aliphatic hydrocarbon group
  • Z is selected from the group consisting of carbon (C), S(O), and P(OH).
  • the saturated or unsaturated C5-C30 aliphatic hydrocarbon group is unbranched.
  • the saturated or unsaturated Cs- C30 aliphatic hydrocarbon group is branched.
  • the saturated or unsaturated aliphatic hydrocarbon group is a C6-C30 aliphatic hydrocarbon group, such as a C7-C30, C8-C30, C9-C30, C10-C30, C10-C25, C10-C20 aliphatic hydrocarbon group.
  • the one or more fatty acids are selected from the group consisting of caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid, myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, a-linolenic acid, arachidonic acid,
  • eicosapentaenoic acid eicosapentaenoic acid, erucic acid, and docosahexaenoic acid
  • pentadecanoic acid heptadecanoic, nonadecanoic, preferably a fatty acid with a melting temperature above 25°C, even more preferably a fatty acid with a melting point above 40°C, even more preferably a saturated fatty acid with a chain length of at least 12 carbon atoms, even more preferably the one or more fatty acids are selected from lauric acid, myristic acid, palmitic acid or stearic acid.
  • the liquid nonaqueous substance is biocompatible.
  • the liquid nonaqueous substance is selected from the group consisting of biocompatible and/or lipids that are endogenous to organism it contacts (e.g. the human or animal bodies but could also be other living organisms).
  • the preferred lipids being of the classes free fatty acids, mono-, di-, or triglycerides, phospholipids, other fatty acid conjugates, other fatty acid esters, ethers or cholesterol or its derivatives, Such as stearic acid, palmitic acid, myristic acid, lauric acid, arachidic acid, elaidic acid, monostearin, distearin, tristearin, dipalmitoylphosphatidylcholine,
  • dipalmitoylphosphatidylserine dipalmitoylphosphatidylserine, cholesterol, cholesterol esters and bile acids.
  • the suspension is free of non-biocompatible compounds and/or non-biodegradable compounds, such as paraffin, non-polar waxes, addition polymers, camphene, and compounds that are purely aromatic and/or aliphatic hydrocarbons.
  • non-biocompatible compounds and/or non-biodegradable compounds such as paraffin, non-polar waxes, addition polymers, camphene, and compounds that are purely aromatic and/or aliphatic hydrocarbons.
  • the suspension comprises in the range 5-50% fatty acid by weight of the total suspension, such as in the range 10-50% such as in the range 10-40%, such as 10-30% such as 12-30%, such as 15-30%, such as 15-20%, such as 15-18% or such as 15-17%.
  • the suspension comprises a mixture of 50-85% (w/w) ceramic material and 15-50% (w/w) fatty acid, such as a mixture of 50-85% (w/w) TCP and 15-50% (w/w) stearic acid, lauric acid, myristic acid or palmitic acid or a mixture of 50-85% (w/w) TCP and MCP (preferable in a stoichiometric ratio) and 15-50% (w/w) stearic acid, lauric acid, myristic acid and/or palmitic acid.
  • the compositions may further comprise 1-10% by weight of a one or more proteins and/or carbohydrate materials (see also below).
  • the suspension comprises a mixture of 80-85% (w/w) ceramic material and 15-20% (w/w) fatty acid, such as a mixture of 80-85% (w/w) TCP and 15-20% (w/w) stearic acid, lauric acid, myristic acid or palmitic acid or a mixture of 80-85% (w/w) TCP and MCP and 15-20% (w/w) stearic acid, lauric acid, myristic acid or palmitic acid.
  • fatty acid such as a mixture of 80-85% (w/w) TCP and 15-20% (w/w) stearic acid, lauric acid, myristic acid or palmitic acid.
  • the suspension is free or substantially free of water (especially if a water dissolvable mould is used).
  • the suspension comprises less than 10% by weight water, such as less than 5%, preferably such as less than 1%, more preferably the suspension is non-aqueous.
  • the liquid non-aqueous substance is not volatile.
  • the liquid non-aqueous substance has a vapour pressure at room temperature of no more than 17.5 mmHg.
  • the size of the molecules in the liquid non-aqueous substance may also vary.
  • the volatility and solubility of the suspension liquid may be too high if it is composed of molecules with low molecular weights. If it is composed of molecules with high molecular weights, the suspension liquid may be too viscous and/or difficult and/or slow to dissolve and disperse e.g. in the body after implantation via for example the albumin system.
  • the majority of the molecules in the liquid non-aqueous substance have molecular weights higher than 100 g/mol, in another embodiment it is lower than 1000 g/mol and in the preferred embodiment it is in the range of 100 g/mol to 1000 g/mol.
  • the suspension may comprise additional components, which may improve the provided object.
  • the suspension further comprises 1-10% by weight of a one or more proteins and/or carbohydrate material, selected from the group consisting of agar, carrageenan, starch, alginate, chitosan, chiton or an extracellular matrix component or a derivative thereof, such as collagen, gelatin, proteoglycans, heparan sulfate, chondroitin sulfate, keratan sulfate, hyaluronic acid, elastin, calcium phosphate mineral, fibronectin, laminin, aggrecan or enzymes such as alkaline phosphatase and transglutaminases.
  • a one or more proteins and/or carbohydrate material selected from the group consisting of agar, carrageenan, starch, alginate, chitosan, chiton or an extracellular matrix component or a derivative thereof, such as collagen, gelatin, proteoglycans
  • gelatine As shown in example 2, the addition of gelatine improved the provided object by reducing cracking of the object after exposure for 24 hours to a liquid resembling in vivo conditions. Without being bound by theory, it is believed that gelatine (or a similar material), modifies the mechanical properties of the object so that it can withstand strains and/or stresses that may be caused by the hydration of the ceramic and/or the formation of a cement.
  • the solid powder material in the casted object may be many different compounds depending on the use case.
  • the device may need to comprise electrically conductive materials like metals or inorganic carbon materials
  • the suspension further comprises an electrically conductive material such as metal or a metal alloy, such as copper, aluminum, silver, gold, platinum, titanium, tantalum, surgical steel and/or inorganic carbon materials such as graphite or graphene etc.
  • an electrically conductive material such as metal or a metal alloy, such as copper, aluminum, silver, gold, platinum, titanium, tantalum, surgical steel and/or inorganic carbon materials such as graphite or graphene etc.
  • Example 6 shows that the addition of copper to the suspension, allows for the production of solid objects being able to lead an electrical current.
  • the metal may be present in amount in the range 5-40% (w/w) such as 5-30%, such as 5-20%.
  • the precise amount of metal depend on the desired use and the selected metal (or metals).
  • compositions according to the invention may comprise:
  • the suspension is placed in the mould or cast at a
  • step c) is carried out at a temperature in the range 50- 300°C, preferably such as 50-100°C, or in the range of 60-95°C, such as 70- 90°C.
  • step d) - solidification
  • the suspension is solidified by lowering the temperature to below the melting temperature of the suspension.
  • the solidification step d) is carried out by lowering the temperature to below the melting temperature of the liquid non-aqueous substance.
  • step d) is carried out at a temperature in the range 1-49°C, such as 1-45°C, or in the range of 1-37°C, such as preferably 1-25°C or more preferably 1-15°C.
  • the lowering of the temperature may be aided by various means such as by using cooling channels in the mold, using a fan, ice, dry ice, liquid nitrogen or by placing the filled mold in cold space such as in a freezer.
  • step e) comprises positioning the solidified object, present inside the mould, in a liquid dissolving the mould, but which do not dissolve or substantially dissolve the solidified object.
  • the liquid is an aqueous liquid such as water, with the proviso that the mould is dissolvable in the aqueous liquid.
  • the liquid dissolves the mold and the liquid component of the suspension leaving the solid.
  • the solid is able to form a cement in the liquid.
  • Example 3 and 5 provide example of casting in water dissolvable moulds, wherein water is a non-solvent for the provided object. Both examples also likely result in the formation, at least partially, of a cement via the reaction of TCP with MCP to form DCP.
  • the provided object according to the process of the invention may have different sizes.
  • the provided object has a volume of at least 1 cm 3 , such as at least 10 cm 3 , such as in the range 1-1000 cm 3 or such as 1-100 cm 3 .
  • the provided object comprises a solidified form of the suspension of step b).
  • different steps can be introduced to increase porosity in the provided object.
  • the provided object is porous.
  • the provided objects according to the process of the invention may find uses in different technical fields.
  • the object comprises ceramics and is selected from the group consisting of whole items, parts or components of medical devices, medical implants, tooth or bone replacement materials, pills, drug depots, nutrients, agricultural objects, aquacultural objects, environmental objects, sensors, actuators, thermal insulation, electric insulation, acoustic insulation, armour, weapon systems, refractory materials, engines, power plants, electronics, turbines, wind turbines, heterogeneous chemical catalysts,
  • bioreactors immobilized bioreactors, other living cell supports, buildings, bridges, roads, dams, infrastructure, art, pottery, robots, aircraft, UAVs, spacecraft, cars, ships and other manned or unmanned vehicles.
  • the solid object is a medical implant, such as a bone or dental implant.
  • the object comprises proteins, carbohydrates and/or ceramic materials, and is selected from the group consisting of whole items, parts or components of medical devices, medical implants, and tooth or bone replacement materials.
  • the solid object is a support structure for living cells or organisms that may be prokaryotes, eukaryotes or archaea.
  • the object comprises proteins, carbohydrates and/or ceramic materials, and is selected from the group consisting of whole items, parts or components of bioreactors, nutrient feedstocks, containers or adherence structures for cells and organisms, immobilized bioreactors and living cell supporting and/or contacting structures.
  • the provided object may comprise metal able to lead a current.
  • the provided object is able to lead an electrical current.
  • Such objects may find use as sensors, actuators, batteries, electrical power sources, fuel cells, microbial fuel cells etc.
  • Fatty acids, glycerol -fatty acid compounds and phospholipids are all natural lipids that may be used by different organisms including humans. They may be used by cells directly to build up their cell membranes, they may be metabolised into other compounds and they may also provide an energy rich nutrient source. As such, if the provided object is made with a natural liquid non-aqueous substance it has the added benefit of providing nearby cells and organisms with an energy dense nutrient as it degrades.
  • the process comprises a step of positioning fibres in the moulded object, said fibers being inserted before solidifying step d), such as before step c), during step c) or after step c).
  • said fibres provide tensile strength to the provided object.
  • said fibres are selected from the group consisting of PLA, PCL, PLLA, PLGA, PGA, PDO, PHBV, PVA, PHB, other polyesters and other polymers that degrade over time in the human body.
  • Porosity in the provided objects may also be desired. Such porosity may be introduced either by designing the mould so that is has “threads” hanging in the volume to be occupied by the casted material. These would penetrate the casted material and would leave pores in it after the cast has been dissolved.
  • part of the solid material could be a material that is soluble in an aqueous solvent, for example in the form of particles or fibers, when added to the solvent such shapes would dissolve to form holes and channels in the object, respectively.
  • pore forming materials could be soluble salt like sodium chloride, soluble polymers like polyvinyl alcohol or soluble carbohydrates such as sucrose.
  • said fibres are dissolvable in a solvent, which is a non-solvent for the solidified object, and generate pores in the final object after being dissolved.
  • said dissolvable fibers are made of one or more substances selected from the group consisting of polymers, carbohydrates or salts such as polyvinylalcohol, sucrose or sodium chloride.
  • the process according to the invention may also comprise other additional steps.
  • the process further comprises one or more processing steps selected from the group consisting of debinding, sintering, cementing, crosslinking, sterilization, autoclaving, cell seeding, coating with substances, milling or subtractive manufacturing or porogen leaching.
  • the process does not involve a processing step to remove the liquid non-aqueous substance prior to use, examples of such processes include such as debinding, washing, evaporation, thermolysis and freeze drying
  • the process does not involve any further processing steps selected from the group consisting of debinding, sintering, cementing, sterilization, autoclaving, milling or subtractive manufacturing or porogen leaching.
  • the process is an injection moulding process. In a more specific embodiment, the process is a compression moulding process. In a more specific embodiment, the process is a blow moulding process.
  • the process is an extrusion moulding process. In a more specific embodiment, the process is a matrix moulding process.
  • the process is a rotational moulding process. In a more specific embodiment, the process is a thermoforming process.
  • the process is a vacuum forming process. Object obtained/obtainable by the process
  • an aspect of the invention relates to a solid object obtained/obtainable by a process according to the invention.
  • the process further comprising the step of placing living cells on/or in the solid object. Preferably, this is done in vitro.
  • the invention relates to the use of the (provided) solid object as a growth enhancer for living organisms.
  • the obtained/obtainable (provided) objects are for use as a medicament.
  • Biodegradable objects such as medical implants
  • the object may be ready for use directly after step f) without further processing steps, such as sintering or similar.
  • the obtained/obtainable (provided) objects are for use as a medical implant, such as a bone implant.
  • the process further comprising the step of placing the solid object on or within the body of a living organism such as a human. Kits
  • the invention relates to a kit comprising :
  • a liquid nonaqueous substance selected from the group consisting of fatty acids, cholesterol, or derivatives thereof, such as glycerol esters, triglycerides, phospholipids and cholesteryl esters;
  • materials selected from the group consisting of ceramic materials, proteins, and/or carbohydrates;
  • ⁇ optionally, 1-10% by weight of a one or more proteins or carbohydrate materials, such as gelatine;
  • a cast or mould for receiving the suspension to be solidified in the mould or cast as an object; wherein the said suspension has a melting temperature above 30°C, such as preferably above 40°C, or more preferably above 50°C or such as above 60°C.
  • the kit also further comprises a solvent that is a solvent for the mould or cast, but is a non-solvent for the solidified object, the solvent preferably being water or a water based solution, such as saline, enzyme solutions, pH buffers or alkaline or acidic solutions.
  • a solvent that is a solvent for the mould or cast, but is a non-solvent for the solidified object, the solvent preferably being water or a water based solution, such as saline, enzyme solutions, pH buffers or alkaline or acidic solutions.
  • the suspension in its solidified form (object) is biocompatible and biodegradable.
  • the kit further comprises instructions for moulding or casting an object according to the process of the invention.
  • a non-aqueous substance selected from the group consisting of fatty acids, cholesterol, or derivatives thereof, such as glycerol esters, triglycerides, phospholipids and cholesteryl esters;
  • the solid/solidified object is for use as a medical implant, such as a bone implant. It should be noted that embodiments and features described in the context of one of the aspects of the present invention also apply to the other aspects of the invention.
  • MCP monocalcium phosphate
  • TCP tricalcium phosphate
  • LA lauric acid
  • Fibers of PLA or PVA were inserted in the suspension in the mould after casting
  • Solid objects can be produced using the process of the invention (liquid : 33% w/w lauric acid, solid : 67% w/w MCP, TCP and Gelatin).
  • fibers providing tensile strength and water dissolvable fibers providing porosity could be inserted in the object.
  • the exemplified process extends to both ceramic and protein materials.
  • the combination of MCP and TCP was used as the chemicals react in the presence of water to form DCP cement. When suspended in lauric acid, this reaction does not happen and the chemicals can be combined and casted. But when the lauric acid is removed from the casted object prior to or after implantation water is able to penetrate to the MCP and TCP which then forms stabile DCP cement. This allows the casted structure to be retained even after the lipid content has been removed.
  • Example 2
  • 18 cylinders (0 20mmm, h : 20mm) were made with 3 different compositions by mixing them in a 70°C water bath and then casting them in a cylindrical elastic reusable latex mould, the compositions were solidified by cooling.
  • composition 1 14.25 g Monocalcium phosphate (MCP) + 10.75 g
  • composition 2 14.25 g MCP + 10.75g TCP + 15 g Lauric acid.
  • composition 3 14.25g MCP + 10.75g TCP + 17g Lauric acid + 2.5g
  • compositions 2 and 3 were suspended in a 37°C warm solution (30 mL PBS + BSA) for 24h.
  • the bath was included to represent the environment in the human body.
  • compositions 1 and 3 were then compression tested.
  • Composition A had an elastic modulus of 80 ⁇ 45 MPa and a compressive strength of 5.2 ⁇ 0.8 MPa whereas composition C had an elastic modulus of 134 ⁇ 63 MPa and a compressive strength of 6.6 ⁇ 0.5 MPa.
  • the ⁇ symbol refers to standard deviation. See also figure 3.
  • a section of a jaw was segmented in Meshmix (Figure 4). This section was then inverted and 3D printed in polyvinylalcohol (PVA) to create a mould ( Figure 5).
  • PVA polyvinylalcohol
  • a mixture of 14.25g MCP + 10.75g TCP + 17g Why acid + 2.5g gelatine was then mixed in a water bath at 70°C. The mixture was then poured into the 3D printed PVA mould. After the mixture had solidified the mould was suspended in 40°C of demineralized water bath until the PVA was dissolved.
  • Dissolvable moulds (dissolvable in water in this example) can be used with the invention.
  • the MCP and TCP may form DCP cement during the mould dissolution step saving processing time. It is possible to cast an object such as an implant with a shape derived from scanning data using the invention. This may be done by 3D printing a soluble mould with a negative shape to the desired object and then casting that object in this mould.
  • a mixture of 25g TCP and 5g stearic acid was heated and cast into cylindrical elastic latex moulds (cavity height 2cm, diameter 2cm) and solidified by cooling. The implants were then removed and half of the samples were debinded at 400°C for 1 hour and then sintered at 1300°C for 2 hours. The sintered and non-sintered samples were visualized with scanning electron microscopy (figure 6) and were then compression tested. The SEM pictures reveal that the non-sintered samples had TCP particles suspended in a solid matrix of stearic acid whereas the TCP had fused together in the sintered samples.
  • the non-sintered samples had an elastic modulus of 417 ⁇ 185 MPa and a stress at break of 6.6 ⁇ 2.7 MPa whereas the sintered samples had an elastic modulus of 505 ⁇ 100 MPa and a stress at break of 23.8 ⁇ 10.3 MPa.
  • p 0.0018
  • Example 4 demonstrates that other lipids, here stearic acid, and ceramics, here only TCP without MCP, may be used in the invention. It also demonstrates that such non-cement forming compositions may have sufficient strength (6.6 MPa) to be used as implants. Strength may be increased further with sintering.
  • Example 5 demonstrates that other lipids, here stearic acid, and ceramics, here only TCP without MCP, may be used in the invention. It also demonstrates that such non-cement forming compositions may have sufficient strength (6.6 MPa) to be used as implants. Strength may be increased further with sintering.
  • Example 5 demonstrates that other lipids, here stearic acid, and ceramics, here only TCP without MCP, may be used in the invention. It also demonstrates that such non-cement forming compositions may have sufficient strength (6.6 MPa) to be used as implants. Strength may be increased further with sintering.
  • Example 5 demonstrates that other lipids, here stearic acid, and ceramics
  • porogens such as soluble fibres (e.g. cotton candy) or particulates (e.g. sodium choride) in the suspension prior to casting.
  • the mixture was then tested with a conductive metal.
  • Samples composed of stearic acid (5g) and tricalcium phosphate (25g) were divided into two groups, of which one was sintered at 400°C for lh and 1100°C for 2h, the other group was left non-sintered. Both groups were crushed to a non- homogenous granulate using a mortar and pestle, 40mg powdered material was placed in 1 ml_ syringes where the tips had been cut off, the syringe openings were blocked with cotton and the syringes were autoclaved to 120°C. The syringes were kept dry until shortly before the operation when they were added 200 ⁇ _ saline solution. The powder from each syringe was in a sub-cutaneous pockets on the back of NOD-SCID mice. Each mouse carried 4 implant pockets each with identical implants.
  • the H&E staining showed that the implants were fully cellularized with cells residing both on and between the implant granulate, vascularization had occurred as evidenced by the presence of blood vessels inside the implants. Sirius red staining showed that collagen was deposited throughout the implants and when viewed in polarization light it was evident that the collagen was in many places organized.
  • non-sintered (stearic acid and TCP) as well as sintered (TCP only) implants are highly biocompatible, support cell growth, vascularization and new bone formation in vivo.
  • lOg fatty acid (stearic, palmitic, myristic or lauric) was melted in a water bath, thereafter 9,9g TCP and 0,lg methylene blue was added to the melted fatty acid. The mixture was stirred to a homogeneous paste. The paste was then added to the mold (the top of a disposable plastic Pasteur pipette was used at a mold). When solidified by cooling the cast was cut out of the mold and was weighed and measured. The cast was submerged into a 50ml tube, with 20ml PBS water and placed at 37 degrees Celsius.
  • Objects can be cast that contain and release a compound e.g. a drug (methylene blue is amongst other things used as a pharmaceutical to treat
  • methemoglobinemia and infections in humans and animals and used in
  • the release rate can be controlled by picking a fatty acid with a longer tail length.
  • the cast objects could be used a biodegradable controllable release pills, depots, implants or other medical devices for treating sick patients or animals.
  • Stearic or Why acids alone or with ammonium phosphate and/or potassium phosphate was cast the following way: lOg fatty acid (stearic or lauric) was melted in a water bath, thereafter lOg ammonium phosphate or potassium phosphate or 5g ammonium phosphate + 5g potassium phosphate was add to the melted fatty acid. The mixture was stirred to a homogeneous paste. The paste was then added to the mold (the top of a disposable plastic Pasteur pipette was used at a mold). When solidified the cast was cut out of the mold was weighed. The casted objects were submerged into a 50ml tube, with 20ml demineralized water and placed in an oven at 37 degrees. After 1 and 4 days the samples were observed and the pH of the water was measured with pH paper or a pH meter, at day 1 and 4, respectively (figure 14).
  • the fatty samples had pH levels of 5 and the samples with fatty acids and ammonium phosphate and/or potassium phosphate had pH levels of between 5 and 6.
  • the addition of ammonium phosphate and/or potassium phosphate significantly increased the pH of the water to pH 7 whereas the pure fatty acids further reduced it to about 4.
  • the lauric acid samples were
  • the casting method is applicable to a wide range of ceramic materials also those that are water soluble (potassium phosphate and ammonium phosphate are both water soluble ceramics).
  • the experiment shows that the release and dissolution of such water soluble ceramics may be slowed by embedding them in the fatty acid matrix.
  • the pH change between day 1 and 4 for the ceramic samples clearly indicate they are still dissolving at this time point. Based on example 9, this release rate can likely be tailored by choosing fatty acids with different chain lengths. As they are released and dissolve, the ceramics may change the pH. It may in some cases, such as in some medical use cases, be desirable with an object that does not acidify its surroundings, incorporating a pH regulating ceramic allows one to control pH.
  • Elastic cylindrical molds (internal cavity was 2 cm high and 2 cm in diameter) were 3D printed in a flexible resin on a Form2 3D printer. Different fatty acid compositions with and without TCP were then made, melted and cast into the molds. After solidification, the compressive mechanical properties were
  • the stearic acid and stearic acid/TCP castings were significantly stronger that the other fatty acids and fatty acid/TCP castings, respectively.
  • the fatty acid tail length may be used to control the mechanical strength of the casted object, longer equals stronger. Furthermore, the addition of ceramic material to the fatty acid increases the strength of the casted material over that of a pure fatty acid.
  • TCP 5 g of TCP was mixed with either 25 g of lauric acid, 25 g of myristic acid, 25 g palmitic acid or 25 g stearic acid under stirring and heated to create four different materials. Six pieces of each material were made, additionally, six pieces were made and sintered at 400° C for 1 hour and 1100° C for 2 hours to yield sintered TCP. All pieces were weighed individually before being transferred to sterile 12 well trays in a LAF bench. Each well received 2 ml of cell medium containing 10% foetal bovine serum and 1% pen/strep. At 1 hour, 4 hours, 6 hours, 1 day, 2 days, 1 week, 2 weeks and 4 weeks each piece was weighed individually to determine the rate of degradation (figure 16). At each recording, the entire cell medium in each well was replaced with fresh medium.
  • the myristic acid (C14) sample did not gain weight the first 2 days but had a significantly higher weight than the palmitic and stearic acid samples at day 7, 14 and 28, it had gained 12.5% weight on day 28, indicating increasing absorption of water likely due to dissolution of the hydrophobic fatty acid.
  • the degradation rate of the lipid/ceramic suspension can be tailored using the chain length of the fatty acid, the longer the length of the fatty acid, the slower the degradation.
  • the dissolution process seems to involve absorbance of water as indicated by the weight gain, possibly as a replacement for dissolved lipid.
  • Pieces of the casted materials made as in example 10, were weighed and were placed in 50 mL tubes. Control groups contained nothing, paraffin or camphene. The samples were added a weight controlled inoculum (lmL / 30mg material) of organisms from washed topsoil (the inoculum is likely to contain a mix of bacteria, archaea, fungi, plants and other organisms). After 4 days, the viability within the tubes was measured using resazurin. 150 ⁇ _ of the liquid from the tubes were added 50 ⁇ _ resazurin (0.036%) and was incubated for 30 minutesat 37°C before the absorbance at 492nm was read using an Epoch plate reader.
  • the fatty acids may be metabolized as nutrients by microorganisms that reside in soil and more so than paraffin and camphene.
  • the fatty acids likely function as a source of carbon.
  • the availability of this nutrient source may be controlled by controlling the solubility of the fatty acid. A longer fatty acid will have lower solubility and give a slower release of this nutrient.
  • the ceramic component may be used as a source of additional nutrients by the organisms providing them with, for example, a source of nitrogen, potassium and phosphate.

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Abstract

La présente invention concerne des procédés de moulage ou de coulage pour la production d'objets solides. Le procédé concerne une suspension qui comprend une substance liquide non aqueuse et un matériau tel qu'une céramique. La suspension est liquide aux températures élevées (par exemple au-dessus de 40 °C) mais solide aux températures inférieures (par exemple en-dessous de 40 °C). La suspension solidifiée peut trouver une utilisation directe comme implant médical. Dans un mode de réalisation préféré, le moule ou le produit coulé peut être dissous dans un solvant, qui est un non-solvant pour la suspension solidifiée, fournissant ainsi un procédé efficace et rapide pour fournir par exemple des implants médicaux. L'invention concerne également des objets pouvant être obtenus/obtenus par un tel procédé et les utilisations de tels objets.
PCT/EP2018/058891 2017-04-07 2018-04-06 Moulage et coulage de composites Ceased WO2018185302A1 (fr)

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CN110317973A (zh) * 2019-07-03 2019-10-11 北京科技大学 一种生物可降解LiZn4-Zn复相材料及其制备方法
CN111690417A (zh) * 2020-06-12 2020-09-22 中国铁道科学研究院集团有限公司铁道建筑研究所 一种用于高含水率黏土填料的改良剂、路基填筑施工方法
CN112919927A (zh) * 2021-03-25 2021-06-08 华南理工大学 一种多孔轻质水泥基保温材料及制备方法
KR20230053937A (ko) * 2021-10-15 2023-04-24 장경철 시트러스계 오일이 함유된 다공성 생분해성 지지체의 제조방법, 상기 다공성 생분해성 지지체를 이용한 항균 실리콘 드레싱제 제조방법
US11998654B2 (en) 2018-07-12 2024-06-04 Bard Shannon Limited Securing implants and medical devices
CN118903542A (zh) * 2024-07-25 2024-11-08 北京理工大学 一种智能压电硬质骨支架的制备方法及应用

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KR20230053937A (ko) * 2021-10-15 2023-04-24 장경철 시트러스계 오일이 함유된 다공성 생분해성 지지체의 제조방법, 상기 다공성 생분해성 지지체를 이용한 항균 실리콘 드레싱제 제조방법
KR102675441B1 (ko) * 2021-10-15 2024-06-14 장경철 시트러스계 오일이 함유된 다공성 생분해성 지지체의 제조방법, 상기 다공성 생분해성 지지체를 이용한 항균 실리콘 드레싱제 제조방법
CN118903542A (zh) * 2024-07-25 2024-11-08 北京理工大学 一种智能压电硬质骨支架的制备方法及应用

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