WO2018185302A1

WO2018185302A1 - Moulding and casting of composites

Info

Publication number: WO2018185302A1
Application number: PCT/EP2018/058891
Authority: WO
Inventors: Morten Østergaard ANDERSEN; Martin Bonde JENSEN; Casper SLOTS
Original assignee: Syddansk Universitet
Current assignee: Syddansk Universitet
Priority date: 2017-04-07
Filing date: 2018-04-06
Publication date: 2018-10-11
Anticipated expiration: 2019-10-07

Abstract

The present invention relates to moulding or casting processes for producing solid objects. The process involves a suspension which comprising a liquid non-aqueous substance and a material such as a ceramic. The suspension is liquid at elevated temperatures (e.g. above 40°C) but solid at lower temperatures (e.g. below 40°C). The solidified suspension may find direct use as a medical implant. In a preferred embodiment, 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.

Description

MOULDING AND CASTING OF COMPOSITES

Technical field of the invention

The present invention relates to a moulding or casting process for preparing solid objects. In particular, the present invention relates to a process for preparing medical implants and biotechnological objects and uses thereof.

Background of the invention

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. A common method is one where 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. Sintering is, however, a time consuming, expensive and wasteful process that also removes any beneficial organic compound present. It is to be understood that, while the powders are frequently composed of particulates with near spherical shape, their constituent materials may also take other shapes such as fibre or net shapes.

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. This could be an external prosthetic or sensor that needs to fit the outer surface of a patient, an implant that should fit a defect, recreate or modify an individual's anatomy or fit e.g. a standardized drill hole with a particular diameter. 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.

This could be pure or mixed cultures of one or more of the following including single celled organisms such as bacteria, archaea, algae, yeasts and other microorganisms as well as more complex life including fungi, plants and animals as well as cell cultures derived thereof.

Araki et al. (Journal of the American Ceramic Society., vol. 87, no. 10, 21 October 2004, pages 1859-1863) 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.

In some of these cases, it may be advantageous if 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

biocompatible as well as biodegradable in a living body or in nature. Hence, an improved process for preparing 3D objects would be advantageous, and in particular, a more efficient and/or faster and/or cheaper and/or reliable and/or less toxic and/or less wasteful and/or more environmentally friendly process would be advantageous. Summary of the invention

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). Thus, 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. In a preferred embodiment, 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.

Thus, 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

biotechnological uses. 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.

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. One example would be where a substance (e.g. a liquid, gas or air) passes (by diffusion, artificial forces or natural processes) through or near the device where cells and/or organisms that are living on, in or near it then capture, convert or degrade some of the compounds in the passing substance. Possibly, with resulting synthesis of new compounds that remain within the device, cells or organisms or which are released to the passing substance. Such devices may be used for industrial biotechnology, fermentation processes, biofuel production,

pharmaceutical production, enzyme production, waste processing, environmental remediation, environmental rehabilitation, ecosystems restoration, agriculture, aquaculture, capture of compounds or synthesis of compounds. One way of making such devices would be through casting or molding.

Thus, one aspect of the invention relates to a process for producing a (solid) object, the process comprising

a) providing a mould or cast;

b) providing a suspension 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;

c) placing said suspension in the mould or cast, at a temperature

above the melting temperature of the liquid non-aqueous substance, such as above 40°C;

d) solidifying said suspension by lowering the temperature to below the melting temperature of the liquid non-aqueous substance, such as below 30°C, to provide said solid object in the mould; e) removing said solid object from the mould or cast; and

f) providing the solid object.

In a preferred embodiment, 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. In a further preferred embodiment, the provided object is biocompatible and biodegradable. In a further preferred embodiment, the provided object is composed of compounds found in the human body, preferably exclusively. Another aspect of the present invention relates to a solid object obtained/obtainable by a process according to the invention.

Yet another aspect of the present invention is to provide a solid object

obtained/obtainable by a process according to the invention, for use as a medicament or a drug release system.

Still another aspect of the present invention is to provide a solid object

obtained/obtainable by 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

obtained/obtainable by a process according to the invention for use as a cell or organism supporting device for biotechnology applications.

Brief description of the figures

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. (A) polylactic acid (PLA) fibers and (B) Polyvinyl alcohol (PVA).

Figure 3 shows left: composition B from example 2 after 24h PBS+BSA bath. Right: 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. (A)

Protein (Gelatine) and Carbohydrate (Alginic Acid Sodium Salt). (B) Cast Molds of Protein and Carbohydrate. Figure 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 is lauric acid, SA is stearic acid, AP is ammonium phosphate and 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 is lauric acid, SA is stearic acid, AP is ammonium phosphate and KP is potassium phosphate. The present invention will now be described in more detail in the following.

Detailed description of the invention

Process for producing a solid object

As described above, 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. Thus, a first aspect of the invention relates to a process for producing a solid object, the process comprising

a) providing a mould or cast;

b) providing a (biocompatible) suspension 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

carbohydrates;

c) placing said suspension in the mould or cast, at a temperature

f) providing the solid object.

As also mentioned above, a difference between casting and moulding is typically thought to be that "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. In the present context the words casting and

molding/moulding is used interchangeable but without excluding the other variant in each instance, unless explicitly mentioned.

In a preferred embodiment, the process does not involve a sintering step.

Sintering of a generated object may take place at different temperatures depending on the material. Thus, in yet an embodiment 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. Thus, in an embodiment, 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. In another preferred embodiment, said provided solid object comprises the solidified suspension.

In the present context, the term "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.

Step a) - mould or cast

If the cast is made from a soluble material such as a water-soluble 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.

Alternatively, if the 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.

Thus, in an embodiment 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. Example 3 and 5 provide examples of casting in water dissolvable moulds, wherein water is a non-solvent for the provided object. Thus, in a preferred embodiment, 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.

One could imagine a case where 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. If implanted, for example, the suspension liquid could be released to the body requiring it to be a biocompatible hydrophobic substance preferably already present in the human body. Without being bound by theory, endogenous hydrophobic compounds, such as fatty acids, triglycerides and phospholipids could be preferred. Thus, in a further embodiment, the mould is a 3D printed or milled. In yet an embodiment, 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. This could be made through a similar process to the soluble mould but could also be solidified against the surface of an object with the desired shape; this could be part of a patient or an inanimate object. Several medical devices could then be cast within the cast. If the reusable cast is made from a flexible elastic material, the medical device may be easily removed. The mould or cast may also be made of a flexible material to remove easily the solid object from the mould. Thus, in a further embodiment, the mould is made of an elastic material, such as rubber, latex, silicone, or a thermoplastic elastomer. Step b) - suspension

Different ceramic materials may find use in the process according to the invention as a material in the suspension intended to be solidified. In one embodiment, 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. Thus, in an embodiment 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, cement, portland cement, silica, barium titanate, lead zirconate titanium, zinc oxide, potassium niobate, lithium niobate, sodium tungstate, glass, geopolymers, sodium chloride, sodium nitrate, potassium nitrate, potassium chloride, magnesium chloride, calcium chloride, calcium nitrate, magnesium nitrate, strontium oxide, strontium

phosphate, calcium sulfate, barium sulfate, calcium carbonate, calcium phosphate, magnesium phosphate, magnesium sulfate, sodium carbonate, sod ium fluoride, strontium oxide, other salts of calcium, magnesium, sodium, potassium, silicon and strontium and mixtures thereof. While 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.

In a more specific embod iment, 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. In the example section, ceramic objects have been produced from TCP or TCP + MCP.

For casting implants for void filling or restoring or mod ifying the anatomy of a patient, 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.

Examples of such materials would be collagen, gelatine, hyaluronic acid, aggrecan, elastin, chitosan, alginate and calcium and magnesium salts like calcium phosphate and components of extracellular matrices. Thus, in an embodiment, the protein is selected from the group of collagen, elastin,

fibronectin, laminin and other proteins found in extracellular matrices of living organisms such as humans and mixtures and derivative thereof such as gelatine, demineral ized tissue and dehydrated tissue. Example 7 show cast molding of gelatine (protein) .

In another embod iment, 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. In yet an

embodiment, 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).

In a further embodiment, 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

(methylene blue) from cast fatty acid/tricalciumphosphate objects. In yet an embodiment, the provided solid material comprises nutrients that stimulate the growth of one or more organisms.

The particle size of the provided materials may vary. Thus, in yet an embodiment, the particle size of the one or more materials are in the range 1 nm - 1 mm, such as below 500 Mm, below 354 μη"ΐ, 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.

It may also be advantageously if part of the suspension comprised one or more materials, which could be dissolved to provide pores in the solid object. Thus, in yet an embodiment, 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. In yet an embodiment, 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.

Similar, it is preferred that the ceramic materials and/or protein material, and/or carbohydrate material is biocompatible and/or biodegradable. Thus, in an embodiment 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.

In yet an embodiment, 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. Thus, in an embodiment, the liquid non-aqueous substance comprises one or more fatty acids or derivatives thereof. In yet an embodiment 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.

In yet another embodiment, the hydrocarbon is a saturated or unsaturated aliphatic hydrocarbon group or an aromatic hydrocarbon group or a mixture thereof. In a further embodiment, the fatty acid comprises at least one carboxylic acid and the hydrocarbon is a saturated or unsaturated C5-C30 aliphatic

hydrocarbon group. In yet a further embodiment, the fatty acid or derivative thereof is a compound of Formula (I) : o

wherein

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). In an embodiment, the saturated or unsaturated C5-C30 aliphatic hydrocarbon group is unbranched. In a further embodiment, the saturated or unsaturated Cs- C30 aliphatic hydrocarbon group is branched. In yet an embodiment, 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.

In a preferred embodiment, 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, 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.

When the provided object is to be used in contact with a living organism e.g. an implant in a human or animal body, it is of course preferred that the liquid nonaqueous substance is biocompatible. Thus, in an embodiment 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, cholesterol, cholesterol esters and bile acids.

In a related embodiment, 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.

In an embodiment, 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%.

In yet an embodiment, 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. In a preferred embodiment, the compositions may further comprise 1-10% by weight of a one or more proteins and/or carbohydrate materials (see also below).

In yet an embodiment, 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.

It may be preferred that the suspension is free or substantially free of water (especially if a water dissolvable mould is used). Thus, in an embodiment, 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.

It may also be advantageously of the liquid non-aqueous substance is not volatile. Thus, in an embodiment, 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. Thus, in an embodiment, 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.

As mentioned above, the suspension may comprise additional components, which may improve the provided object. Thus, in an embodiment, 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. 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.

In cases with medical devices, the solid powder material in the casted object may be many different compounds depending on the use case. For casting devices for collecting biopotential measurements, the device may need to comprise electrically conductive materials like metals or inorganic carbon materials

(graphite, graphene etc.). Thus, to add additional features to the provided object, such as being able to lead an electrical current, metal may be added to the suspension. Thus, in an embodiment 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.

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).

Preferred compositions according to the invention may comprise:

• 20-45% (w/w) Monocalcium phosphate (MCP) + 20-40% (w/w) Tricalcium Phosphate (TCP) + 20-50% (w/w) Laurie acid.

• 20-45% (w/w) MCP + 20-40% (w/w) TCP + 2-10% (w/w) gelatine + 20- 50% (w/w) lauric acid.

• 40-70% (w/w) TCP + 5-20% (w/w) stearic acid.

These preferred combinations may be adjusted to comprise additional components according to the invention.

Step c) - placing said suspension in the mould or cast:

As mentioned above, the suspension is placed in the mould or cast at a

temperature above the melting temperature of the liquid non-aqueous substance. Thus, in an embodiment, 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

As also mentioned above, the suspension is solidified by lowering the temperature to below the melting temperature of the suspension. Thus, in an embodiment, the solidification step d) is carried out by lowering the temperature to below the melting temperature of the liquid non-aqueous substance. In yet an embodiment, 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. When used as a medical implant it is of course desired that the solidified objects stays solidified after implantation for a certain period of time, before being substantially degraded.

Step e) - removing said solid object from the mould or cast

As also explained under step a) The object can be removed (or freed) from the cast in different ways. Thus, in an embodiment, step e) (removing the mould) 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. In a related embodiment, the liquid is an aqueous liquid such as water, with the proviso that the mould is dissolvable in the aqueous liquid. In a related embodiment, the liquid dissolves the mold and the liquid component of the suspension leaving the solid. In a further embodiment, 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.

Step f) - provided object

The provided object according to the process of the invention may have different sizes. Thus, in an embodiment the provided object has a volume of at least 1 cm³, such as at least 10 cm³, such as in the range 1-1000 cm³ or such as 1-100 cm³.

In yet an embodiment the provided object comprises a solidified form of the suspension of step b). As mentioned below, different steps can be introduced to increase porosity in the provided object. Thus, in yet an embodiment, the provided object is porous. The provided objects according to the process of the invention may find uses in different technical fields. Thus, in an embodiment, 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.

A preferred use of the provided object is medical use. Thus, in a preferred embodiment, the solid object is a medical implant, such as a bone or dental implant. In yet an embodiment, 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.

Another preferred use of the provided object is in biotechnology such as industrial, energy, agricultural, aquacultural or environmental biotechnology. Thus, in a preferred embodiment, the solid object is a support structure for living cells or organisms that may be prokaryotes, eukaryotes or archaea. In yet an

embodiment, 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.

As mentioned above the provided object may comprise metal able to lead a current. Thus, in an embodiment, 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.

Additional steps

It may be possible to add additional steps to the process to improve the provided objects in different ways. For some objects such as tissue engineering implants one may add further solids, such as non-soluble fibres to increase the mechanical properties of the final object. Thus, in an embodiment, 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). In one embodiment, said fibres provide tensile strength to the provided object. In a related embodiment, 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.

Alternatively, 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. Such pore forming materials could be soluble salt like sodium chloride, soluble polymers like polyvinyl alcohol or soluble carbohydrates such as sucrose. Thus, in another embodiment, 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. In a related embodiment 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. Thus, in an embodiment, 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. In yet an embodiment, 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

On the other hand, to be able to provide quickly and cheaply e.g. 3D implant, it may be advantageous if the object could be made available quickly without the need for e.g. debinding or sintering. Thus, in an alternative embodiment, 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.

In a more specific embodiment, 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.

In a more specific embodiment, the process is an extrusion moulding process. In a more specific embodiment, the process is a matrix moulding process.

In a more specific embodiment, the process is a rotational moulding process. In a more specific embodiment, the process is a thermoforming process.

In a more specific embodiment, the process is a vacuum forming process. Object obtained/obtainable by the process

The process according to the invention results in provided objects which special characteristics. Thus, an aspect of the invention relates to a solid object obtained/obtainable by a process according to the invention. In a special aspect, the process further comprising the step of placing living cells on/or in the solid object. Preferably, this is done in vitro.

In yet an aspect, the invention relates to the use of the (provided) solid object as a growth enhancer for living organisms.

Medical uses

In yet an aspect according to the invention the obtained/obtainable (provided) objects are for use as a medicament. Biodegradable objects (such as medical implants) cannot be reused and can therefore be considered medicaments. Thus, the object may be ready for use directly after step f) without further processing steps, such as sintering or similar.

In yet a further aspect, the obtained/obtainable (provided) objects are for use as a medical implant, such as a bone implant.

In a special aspect 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

In a further aspect, the invention relates to a kit comprising :

- a suspension 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;

- (optionally) 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.

Preferably, 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.

In a further preferred embodiment, the suspension in its solidified form (object) is biocompatible and biodegradable.

In yet an embodiment, the kit further comprises instructions for moulding or casting an object according to the process of the invention. Solid/solidified object

Yet an aspect of the invention relates to a solid/solidified object comprising

- at least 5% by weight of 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;

- 40-95% by weight (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. Such object may be obtained by the process of the invention.

In yet a further aspect, 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.

All patent and non-patent references cited in the present application, are hereby incorporated by reference in their entirety. The invention will now be described in further details in the following non-limiting examples.

Examples

Example 1

Casting with reusable mould

Materials and methods

5.5 g monocalcium phosphate (MCP), 7.5g tricalcium phosphate (TCP), 1.3g gelatin and 7.2g lauric acid (LA) (14.3g solid (67% w/w) and 7.2g liquid (33% w/w) was heated to 50°C in a water bath and then mixed to provide a suspension.

The suspension was then placed into an elastic latex mould using a spatula Figure

1, left: before addition of suspension; Figure 1, right: after addition of suspension.

Upon cooling the suspension solidified and the provided solid object could be flipped out of the elastic cast by bending the cast.

Insertion of fibers

Fibers of PLA or PVA were inserted in the suspension in the mould after casting

(figure 2).

Results

It was found that, within the first minutes after casting, fibers (1.75mm diameter) of polylactic acid (PLA) (figure 2A) and polyvinyl alcohol (PVA) (figure 2B) could be inserted into the suspension.

Conclusion

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). In addition, fibers providing tensile strength and water dissolvable fibers providing porosity could be inserted in the object. It is noted that 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

Compression testing of Casted Calcium Phosphate cement

Materials and methods

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

Tricalcium Phosphate (TCP) + 15 g Lauric acid.

• 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

gelatine.

After casting, 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.

Results

All three compositions were casted fine, but composition 2 suffered cracks after the 24h PBS+BSA bath. None of the samples were sintered. 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. T- Testing revealed no difference in elastic modulus but the cemented composition (composition 3) had a significantly higher compressive strength (p = 0.008). The ± symbol refers to standard deviation. See also figure 3.

Conclusion

In a simulated bodily environment, the lauric acid is presumably dissolved by albumin allowing water to contact the TCP and MCP which then undergo a chemical reaction and form DCP. This reaction may result in minor cracks in the object unless another component like gelatine is included. This is likely due to the fact that DCP is highly brittle on its own and prone to cracking, the presence of a component like gelatine likely modifies the impact, flexural and/or tensile strength of the material allowing it to resist cracking during the formation of DCP. The end result is the formation of a cement object in the casted shape presumably with none or little of the lauric acid present and with a higher mechanical strength. This cementing step can be carried out before implantation, or it may take place after implantation in a living organism such as a human body. Example 3

Casting a segmented Jaw part.

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). A mixture of 14.25g MCP + 10.75g TCP + 17g Laurie 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.

Conclusion

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.

Example 4

TCP casting, sintering and compression testing

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. When testing with a T-Test there were differences between non-sintered and sintered samples in stress at break (p = 0.0018) but not in elastic modulus.

Conclusion

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

Beams of cement and copper.

Three mixtures were produced consisting of:

^■ 14.25 g Monocalcium phosphate + 10.75 g Tricalcium Phosphate + 15 g Laurie acid;

^■ 14.25g MCP + 10.75g TCP + 17g Laurie acid + 2.5g gelatine;

^■ 25 g TCP + 5 g Stearic acid

The compositions were mixed in a water bath at 70°C. The mixtures were then poured into the 3D printed PVA moulds (Figure 7A). After the mixtures had solidified (Figure 7B) the moulds was placed in a 40°C hot demineralized water bath with stirring (Figure 8A) until the PVA moulds were dissolved (Figure 8B). Furthermore, to investigate whether it was possible to create pores in the casted objects, two methods were tested. One where the material was added sodium chloride (Figure 9A) and one it was added sugar strings created on a cotton candy machine (Figure 9B), both added prior to casting. Under light microscopy, pores in the samples casted with sugar strings were observed (Figure 9C).

Conclusion

It is possible to design pores in the objects by mixing porogens such as soluble fibres (e.g. cotton candy) or particulates (e.g. sodium choride) in the suspension prior to casting.

Example 6

A conductive material

The mixture was then tested with a conductive metal.

Mixture of:

A. 18g TCP + 18g Copper + 5g Stearic acid

B. 18g TCP + 18g Copper + 5g Laurie acid

C. 14,25 g MCP + 10,75 g TCP + 5g Copper 12, 5g Laurie acid

D. 14,25 g MCP + 10,75 g TCP + 5g Copper 12, 5g Laurie acid

The four batches were mixed in a 70°C water bath and then moulded in the cylindrical latex mould (Figure 10A). Mixture D was then suspended in 37°C solution PBS for 24h (Figure 10B). Electrical resistance was then measured on sample D, the sample was found to conduct electricity (Figure IOC).

Conclusion Other materials, such as metals, may be combined with the invention by adding them to the casting material. Such materials may be used to modify the properties, here electrical properties, of the resulting object.

Example 7

Cast Molding of Proteins and Carbohydrates

Materials and methods

7 gram of stearic acid was mixed with 12,5 grams of the protein gelatine (figure 11A, left) in a beaker. 7 grams of stearic acid was mixed with 12 grams of the carbohydrate Alginic Acid Sodium Salt (figure 11A, right) in a beaker. The beakers was then placed in a water bath at 90°C until liquidation of the stearic acid. The powders were then stirred in to suspension in the liquidated Stearic Acid. Both suspensions was the cast in to rectangular PVA molds and solidified by cooling (figure 11B).

Conclusion

It is possible to cast solid objects with proteins or carbohydrates using the process of the invention.

Example 8

Biocompatibility of implants in mice

Materials and methods

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 μΙ_ 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.

Results

The weights and appearance of the mice was monitored for 8 weeks. For both groups, it was observed that the mice looked fine, behaved normally and that there was no weight loss during the 8 weeks of implantation. 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.

Conclusion

In sum, the 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. Example 9

Fatty acid + TCP Methylene blue release

Materials and methods

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. Measurements of released methylene blue were done spectrophotometrically at: t=60, t= 120, t=180, t=240, t=24h, t=48h, t=4d and t=7d. From each tube 200μΙ was added to a 96 well plate that was read on a biotek epoch plate reader (figure 13). After measuring the 50ml tube was emptied of PBS water and 20ml fresh PBS water was added after each measurement. Results

Lauric acid released its contents and dissolved/melted within 24 hours. The remaining samples stayed intact and drug release correlated with the fatty acid chain length. At day 4, cumulative release was 5.0, 8.9 and 10.0, respectively, for myristic, palmitic and stearic acid.

Conclusion

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

aquaculture to control parasite infections in fish). 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.

Example 10

Casting of phosphate minerals and control of pH

Materials and methods

Stearic or Laurie 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).

Results

After 1 day, 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. At day 4, 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

disintegrating but the other samples were intact after 4 days of water immersion. Conclusion

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.

Example 11

Mechanical strength as a function of lipid content

Materials and Methods

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

determined on a Zwick testing machine (figure 15).

Results

The stearic acid and stearic acid/TCP castings were significantly stronger that the other fatty acids and fatty acid/TCP castings, respectively.

Conclusion

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.

Example 12

Resorption of material

Materials and methods

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.

Results Sintered TCP gains 20% upon first reading and the weight gain remained throughout the period, likely due to water absorption in and onto the ceramic. The lauric acid (C12) samples gained weight the first 4 hours and then disintegrated, likely due to the dissolution of lauric acid. 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 palmitic (C16) and stearic acid (C18) samples had only gained 5.0% and 4.8% weight, respectively, on day 28.

Conclusion

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.

Example 13

Stimulating growth of soil organisms with cast substrates

Materials and Methods

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. 150μΙ_ of the liquid from the tubes were added 50μΙ_ resazurin (0.036%) and was incubated for 30 minutesat 37°C before the absorbance at 492nm was read using an Epoch plate reader.

Results

A higher viability was observed within the pure fatty acid samples compared to that in the camphene and paraffin samples. Lauric acid (C12) gave rise to a higher viability than stearic acid (C18). The addition of ammonium phosphate and ammonium phosphate+potassium phosphate both led to much higher viabilities than using the pure fatty acids.

Conclusion

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.

Claims

1. A process for producing a solid object, the process comprising

a) providing a mould or cast;

b) providing a biocompatible suspension comprising :

- at least 5% by weight (w/w) of the total suspension of a

liquid non-aqueous substance selected from the group consisting of fatty acids, glycerol esters, triglycerides, phospholipids 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, proteins, and/or carbohydrates;

^■ optionally, 1-10% by weight of a one or more proteins or carbohydrate materials, such as gelatine.

c) placing said suspension in the mould or cast, at a temperature

above the melting temperature of the liquid non-aqueous substance, such as above 40°C, or above 50°C;

f) providing the solid object. wherein said provided solid object comprises the solidified suspension.

2. The process according to claim 1, wherein 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.

3. The process according to any of the preceding claims, wherein the liquid nonaqueous substance has a vapour pressure at room temperature of no more than 17.5 mmHg.

4. The process according to any of the preceding claims, wherein the process does not involve any processing steps selected from the group consisting of debinding, sintering, cementing, sterilization, autoclaving, milling or subtractive

manufacturing or porogen leaching.

5. The process according to any of the preceding claims, wherein the process does not involve a sintering step.

6. The process according to any of the preceding claims, wherein the process does not involve cementing step.

7. The process according to any of the preceding claims, wherein the provided object is biocompatible and biodegradable.

8. The process according to any of the preceding claims, wherein the provided object is composed of compounds found in the human body, preferably

exclusively.

9. The process according to any of the preceding claims, wherein the liquid nonaqueous substance is composed of lipids that are endogenous to the organisms it contacts.

10. The process according to any of the preceding claims, wherein the suspension is free of non-biocompatible compounds and/or non-biodegradable compounds, such as paraffin, non-polar waxes, camphene, addition polymers, and compounds that are purely aromatic and/or aliphatic hydrocarbons.

11. The process according to any of the preceding claims, wherein 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, cell culture medium or alkaline or acidic solutions.

12. The process according to any of the preceding claims, wherein 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.

13. The process according to claim any of the preceding claims, wherein 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, cement, portland cement, silica, barium titanate, lead zirconate titanium, zinc oxide, potassium niobate, lithium niobate, sodium tungstate, glass, geopolymers, sodium chloride, sodium nitrate, potassium nitrate, potassium chloride, magnesium chloride, calcium chloride, calcium nitrate, magnesium nitrate, strontium oxide, strontium phosphate, calcium sulfate, barium sulfate, calcium carbonate, calcium phosphate, magnesium phosphate,

magnesium sulfate, sodium carbonate, sodium fluoride, strontium oxide, other salts of calcium, magnesium, sodium, potassium, silicon and strontium and mixtures thereof.

14. The process according to any of the preceding claims, wherein 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 dicalcium phosphate (DCP) together with

tetracalcium phosphate.

15. The process according to any of the preceding claims, wherein 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%, or such as 70-95%.

16. The process according to any of the preceding claims, wherein the protein is selected from the group of collagen, elastin, fibronectin, laminin and other proteins found in extracellular matrices of living organisms such as humans and mixtures and derivative thereof such as gelatine, demineralized tissue and dehydrated tissue.

17. The process according to any of the preceding claims, wherein 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 demineralized tissue and dehydrated tissue.

18. The process according to any of the preceding claims, wherein the liquid nonaqueous substance comprises one or more fatty acids.

19. The process according to any of the preceding claims, wherein the one or more fatty acids are selected from the group consisting of lauric acid, stearic acid caprylic acid, capric acid, myristic acid, palmitic 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, 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, stearic acid, myristic acid, or palmitic acid.

20. The process according to any of the preceding claims, wherein the suspension comprises in the range 5-50% fatty acid by weight of the total suspension, such as in the range 10-50%, or such as in the range 10-40%.

21. The process according to any of the preceding claims, wherein 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 and 15-50% (w/w) stearic acid, lauric acid, myristic acid and/or palmitic acid.

22. The process according to any of the preceding claims, wherein 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.

23. The process according to any of the preceding claims, wherein suspension comprises 1-10% by weight of gelatin.

24. The process according to any of the preceding claims, wherein the provided solid material comprises pharmaceuticals such as antibiotics, anti-cancer drugs, antibodies or growth factors as well as their drug delivery and/or release systems.

25. The process according to any of the preceding claims, wherein the provided solid material comprises nutrients that stimulate the growth of one or more organisms.

26. A solid object obtained/obtainable by a process according to any of claims 1- 25.

27. The solid object according to claim 26, for use as a medicament.

28. The solid object according to claim 26, for use as a medical implant, such as a bone implant.

29. Use of the solid object according to claim 26, as a growth enhancer for living organisms.