WO2007147625A2

WO2007147625A2 - Material system for 3d printing

Info

Publication number: WO2007147625A2
Application number: PCT/EP2007/005537
Authority: WO
Inventors: Stephan Irsen; Hermann Seitz; Barbara Leukers; Carsten Tille
Original assignee: Stiftung Caesar Center Of Advanced European Studies And Research
Priority date: 2006-06-23
Filing date: 2007-06-22
Publication date: 2007-12-27
Also published as: DE102006029298B4; WO2007147625A3; DE102006029298A1

Abstract

Material composition in the form of a dispersion for the production of granules by spray or fluid bed granulation, wherein the granules are suitable for 3-D matrix printing, comprising a dispersant, in particular water, a powdered calcium phosphate, in particular, hydroxylapatite, as base material and polymeric additives: a first additive being a binder which binds the calcium phosphate crystals on spray-drying, a second dispersion additive increases dispersibility whilst maintaining a sufficiently low viscosity, a third lubricant additive is a lubricant, in particular a water-soluble PEG, provided to improve the free-flowing nature of the prepared granules and a fourth additive is provided as print binder which is the binder for use in the 3D matrix printing.

Description

Material system for 3D printing

The present invention relates to a material composition in the form of a dispersion for the production of granules by means of spray granulation or fluidized bed granulation, the granules being particularly suitable for 3-D binder printing. For this purpose, at least one of the components of the granules binds off with liquid pressure binder. Such a composition comprises: a suitable dispersant, especially water, as a base material a powdered calcium phosphate, especially hydroxyapatite, and polymeric additives wherein a first additive is a binder that binds the calcium phosphate crystals in the granulation process and wherein a second dispersing additive maximizes the solids content the dispersion while maintaining a sufficiently low viscosity possible.

For about two decades, generative manufacturing techniques, known as "rapid prototyping" methods, have been used to translate 3D computer models into real components, a practice well-known in the automotive industry for producing an intuition pattern or function prototype as quickly as possible.

A relatively new field of application for these procedures is the medical field. In this case, for example, based on computer tomograms of a patient created three-dimensional data sets anatomical models are produced, which serve the physician, especially in the field of oral and maxillofacial surgery, as a planning aid for operations. The preparation of patient-specific implants by means of rapid prototyping ("RP") method is only in the phase of research, with the implementation Such implants offers the powder-based RP method of so-called 3D printing.

For example, WO 98/09798 A1 describes 3D printing as a method in which a powdered material system is bonded to one another in layers. The powdery material is applied to a construction field as a layer of defined thickness and printed with an adhesive, as in the case of an inkjet printer , This creates a layer of the component. As soon as a layer has been completed, the construction field is lowered by the amount of the layer thickness, new powder is applied and the next layer image is printed. The individual layers bond together and gradually build up to the model by repeating these steps.

In general, materials for the production of bone replacement implants can be divided into two groups. These are on the one hand the bio-inert materials, which include, for example, most metals, and on the other hand, the bioactive materials, including the materials that have an impact on the organism. Especially in the field of synthetic bone replacement, the bio-active materials are of particular interest because they ensure an improved ingrowth of the implant into the body's own tissue. Here just calcium phosphate ceramics have established themselves as a particularly preferred bioactive material. Hydroxylapatite (HA), which in its stoichiometric composition corresponds to the mineral portion of human bone, is a commonly used raw material for making implants for bone replacement.

Bone replacement materials having different compositions, particle size distributions, porosity and manufacturing methods are known. The production of ceramic shaped bodies as a bone substitute based on hydroxyapatite and 3D printing is described, for example, in WO 2004/098456 A2. The strength of the adhesion of compact ceramic implants is rarely particularly high. However, the integration behavior of the implants can be favorably influenced by a porosity of the implant, whereby the introduction of such a porosity has turned out to be problematic. Thus, the introduction of porogenic substances, such as polymeric fibers or water-soluble salts, in the ceramic molding, for example, from EP 253 506 A1 known. However, after the shaping, the porogens have to be removed from the molding again. Since the structural differences between the synthetic materials and natural bone are large and lead to only insignificant improvements in the properties with respect to the healing behavior, such implant body have not been able to prevail so far.

Methods for producing porous implants by means of generative manufacturing methods, such as 3D binder printing, are described in DE 4 205 969 A1 and US Pat. No. 6,454,811 B1. These methods are suitable for the production of ceramic implants with an interconnecting porosity. There are different types of porosity:

While in 3D printing pores with diameters in the range between 100 microns and 800 microns are introduced into the implant ("macroporosity"), a "microporosity" can be generated with pores of size by about 100 microns by a suitable choice of the building material. While macroporosity is important for the process of vascularization, microporosity has a positive impact on cell adhesion and osteointegration of the implant. Pores with a diameter <2 μm, on the other hand, form a "nanoporosity" that influences the manufacturing process of 3D printed implants.

It is advantageous if the material of the implant comes as close as possible to the "gold standard", ie the autologous bone substitute.The aim of the current research is also to produce a resorbable bone substitute, which is replaced in the course of the healing process by the body's own bone high resorbability has in WO 2004/112855 A2 described alpha and beta tricalcium phosphate (TCP), but has the disadvantage of low mechanical strength and too rapid dissolution (absorption).

The object of the invention is first of all to provide a material composition in the form of a dispersion, which is particularly suitable for the production of granules to be used in 3D printing. The granules to be produced with it should also have a high compatibility and the implants made with it a great mechanical stability.

These objects are achieved by the material composition having the features of claim 1, the method of claim 6, and the granules of claim 9. Particular embodiments of the inventions are mentioned in the respective subclaims.

The concept essential to the invention is to provide a material composition for the production of granules, which is already optimized as such for later use in 3D printing. For this purpose, in addition to the known polymeric additives, a slip additive is provided as a lubricant, in particular an organic additive from the group of polyethylene glycols, which increases the flow or flowability of the finished granules. This ensures that the granules applied in a single layer in the printing process form a homogeneous and flat surface, so that the production of particularly high-quality implants is possible. In addition, the material composition is added to the later pressure binders in small amounts as an additive. This ensures that the interaction between the granules and the 3D printing binder is improved, which contributes to an increase in the resolution. In addition, this will demonstrably increase the strength of the printed implants.

In order to improve the material composition to be processed as a dispersion in view of the method of spray or fluidized bed granulation to be used therewith, the invention additionally makes use of a dispersing additive to reduce the viscosity of the dispersion. The reduced in their viscosity Dispersion means that the solids content can be significantly increased from about 20% (wt) to about 50% (wt). As a result, under the conditions of suitable granulation conditions, the "hollow granules" which normally occur during the granulation process can be avoided and porous granules are obtained which have an average round shape of the individual granules.

In order to further optimize the granules to be produced for the 3-D binder printing, a second idea essential to the invention is to provide a lubricant. These two additives, namely the dispersing additive and the lubricant lead to an increase in the flowability or flowability of the finished granules and thus ultimately to a better processability of the granules in the printing process.

In summary, the invention relates to the production and processing of bone substitute materials or combinations of materials consisting of a granulate and a matched binder liquid. These materials have optimized properties for the production of 3D printed porous articles using the abovementioned rapid prototyping methods which utilize the layered wetting of powdered materials. The materials according to the invention are optimized for this application.

As stated, the material composition uses a powdered calcium phosphate, especially hydroxyapatite, as the base material. It has proved to be particularly advantageous to subject the calcium phosphate no thermal pretreatment. It has been found that implants made of thermally untreated hydroxyapatite show a much better absorption behavior. The crystallite size of the material is the deciding factor. While non-pretreated hydroxyapatite (HA) is readily absorbable in preferably nanocrystalline form, the material loses its solubility in vivo by thermal treatment. So far, only the use of thermally treated HA material for use in 3D binder printing is known from the prior art. Other benefits of thermally untreated HA are the significantly better resolution for 3D printing. It can therefore be created implants with much finer details. In addition, it has been found that implants with higher porosity can be produced, which favors their osteointegration.

According to the invention, the granules are produced by spray granulation. For this purpose, an aqueous suspension of the raw materials is sprayed in a spray dryer in a heated air stream via nozzles and dried. The nature of the suspension is crucial to the resulting granules. In particular, the solids content of calcium phosphate, in particular HA, and the viscosity of the suspension affect the morphology and size of the resulting granules.

The following is a recipe of an HA suspension that is particularly suitable for making granules for 3D printing. The absolute quantities reflect the relations and can be converted accordingly for other quantities:

215 g of HA are dissolved as a solid in 285 g of water. To lower the viscosity and increase the solids content 10 g dispersing additive are added, wherein the commercially available by the company room and black dispersing "DP 75" (an abbreviation of Dolapix ^® PC 75), a polyelectrolyte, is particularly suitable. Alternatively, for As a binder, 10 g of PVP K30 (polyvinylpyrrolidone) are added to achieve optimized granule strength, and 17.5 g of PEG 20000 (polyethylene glycol) are added to improve processability in the printer, with 20,000 being the average chain length In addition, add 4 g of GDX4 and 3 g of PVA5 solution (polyvinyl alcohol), the numbers refer to the concentration of the aqueous solution, the composition of the GDX4 3D binder is shown below, and the two solutions improve the print image in 3D Printing process and the strength of the produced green body.

Quantity ranges are given in the following table:

GDX4 is the binder that will later be used as a printing binder in the 3D printing process. In essence, the binder should have a viscosity of <12 mPas and high adhesiveness. The composition is described in the following table:

^* eg PEG monolaurate ("Polyethylenglykolmonoaulat")

It has been found that the order of addition is of great importance for the quality of the suspension. The following table gives an example of an advantageous sequence of steps in the preparation of a suspension:

The processing of the suspension can be carried out in a spray granulator. Here, a "MiniGlatt" spray granulator was operated with a two-fluid nozzle and a nozzle diameter of 0.5 mm The following process parameters have proven particularly suitable: the temperature is 95 ° C, the spray pressure 1 bar, the fluidization air 0.5 bar and the feed rate of the suspension 6 g / min.

If the 3D printed, porous implants are to be subjected to a sintering process to increase the strength as 3D printed green bodies, then it has proven advantageous to add to the granules an inorganic component which increases the sintering activity of the granular material. This is of particular importance, since the 3D printed green bodies are sintered "without pressure", whereby, as is otherwise customary in ceramic technology, no precompression can take place The sintering aid can be added to the composition before the granules are produced or mixed under the finished granules The sintering aids should either generate a liquid phase during sintering or increase the diffusion rate of the HA.

The following materials are to be preferred as sintering aids. The materials are grouped according to their material classes. Suitable oxides are oxides, fluorides and chlorides, such as CaF ₂ , LiCl, NaCl, KCl, MgCl _2, CaCl ₂ , MgO, Na ₂ CIO ₃ , CaCO ₃ , Na ₄ P ₂ O ₇ , Na ₅ P ₃ O ₀ , β NaCaPO ₄ , Na ₃ PO ₄ (NaPO ₃ ) _n , KH ₂ PO ₄ , and K ₄ P ₂ O ₇ . Carbonates, such as CaCO ₃ , and borides, such as H ₃ BO ₃ are also suitable as sintering aids.

Due to the later use as biomaterial, the biocompatibility of the material is of particular importance. Here is the good biocompatibility of HA known. In general, it should be ensured that all the additives used are biocompatible, which is the case in the recipes according to the invention.

For the use in the 3D printer, the wettability of the granule surface is of crucial importance. It has a direct influence on the quality of the components to be created in terms of their mechanical strength and their surface quality. The wettability can be improved either by adding surface-active substances, in particular surfactants, or by adding a certain proportion of the pressure binder.

With regard to the highest possible strength of the later component, it is particularly advantageous to provide a specific particle size distribution of the granules in the granules. This can be used to create a particularly dense sphere package in the 3D printer. In order to allow a high density of the granules during processing in the 3D printer, the material should have a two or more modal distribution. In general, the individual granules should have a size between 10 .mu.m and 100 .mu.m, and it has proven advantageous if the biocompatible ceramic granulate is distributed bi-modally and in each case a maximum of the "Gaussian" distributed particle size in the range between 10 .mu.m and 30 .mu.m This distribution guarantees a high strength of the produced green parts and the required surface quality of the component In principle, the two modes should be in a diameter ratio of between 1: 3 and 1: 10. The recipes for the production of Granulate spray granulation is optimized for the bimodal distribution in the granules, eliminating the need to subsequently classify the granules and mix granules of different sizes.

In order to achieve optimal integration of the 3D printed implants in the surrounding bone tissue, it is advantageous if the porosity of the implants and the material is as high as possible. The prior art describes a so-called macroporosity in the range between 100 μm and 700 μm. This is introduced into the material by the 3D printing process. Furthermore, a microporosity with a pore diameter between 3 .mu.m and 20 .mu.m than for the Biointegration considered particularly advantageous. This porosity can be realized by the granulation according to the recipe of the invention.

It is also advantageous for the strength of the later implants, when the vast majority of individual granules are made of solid material. The term "solid material" means that they have as little as possible a cavity, as most known granules have.Such hollow spheres are the "natural" results of the known spray-drying and result from an evaporation inside the granule. The recipes for the production of granules according to the invention by means of spray drying are optimized with regard to the creation of "balls" of solid material, the stability is not affected and it is advantageous for the weight if this solid material has a "spongy" microporosity in the range between 10 and 50%. As already mentioned, this microporosity promotes the ingrowth of the surrounding tissue into the implant.

The advantages of the invention are summarized again below:

The material composition according to the invention leads to granules which are distinguished by a particular flowability, which can therefore be handled well in the printing process, in particular during recoating, ie during the application of a layer "Granules are characterized by their interaction with the binder. The granules have a particularly round shape and smooth surface compared to those known from the prior art.

In addition, the granules are characterized by its adhesive power. The granules can also produce a high resolution and an excellent print image because of the bimodal distribution. The green bodies produced are of particular strength and can be easily post-processed, in particular sintering. The manufactured implants have a high strength with excellent porosity. Above all, the shrinkage behavior of the implants during sintering is predictable and, depending on this, is about 25%. The implants with their created porosity have very good biocompatibility and osteoactivity.

Claims

claims

1. Material composition in the form of a dispersion for the production of granules by spray or fluidized bed granulation, wherein the granules are suitable for the 3-D binder printing, comprising a dispersant, in particular water, a powdered calcium phosphate, in particular hydroxyapatite, as

Base material and polymeric additives:

wherein a first additive is a binder that binds the calcium phosphate crystals in the spray-drying,

wherein a second dispersing additive increases the dispersibility while maintaining sufficiently low viscosity, characterized by

a third slip additive as a lubricant, in particular a water-soluble PEG, for increasing the flowability of the finished granules,

a fourth additive as a binder, which is the binder to be used for 3-D binder printing.

2. Material composition according to claim 1, characterized in that the calcium phosphate is untreated as such and has undergone no thermal pretreatment in the form of a heating above 700 ⁰ C.

3. Material composition according to claim 1, characterized in that the dispersing additive is a condenser from the group of sterically effective condenser, in particular "DP 75" or Na polyacrylate

4. Material composition according to claim 1, characterized in that the slip additive is a water-soluble polymer of the group of polyethylene glycols having a chain length between 15,000 and 25,000.

5. Material composition according to claim 1, characterized by a sintering aid for increasing the diffusion rate in the finished product produced by 3-D binder printing, wherein the sintering aid in particular CaF ₂ , LiCl, NaCl, KCl, MgCl ₂ , CaCl ₂ , MgO, Na ₂ CIO ₃ , CaCO ₃ , Na ₄ P ₂ O ₇ , Na ₅ P ₃ Oi ₀ , β-NaCaPO ₄ , Na ₃ PO ₄ (NaPOs) _n , KH ₂ PO ₄ , K ₄ P ₂ O ₇ , CaCO ₃ , or H ₃ BO is ₃ .

6. A process for the preparation of the composition according to claim 1, characterized in that first the dispersing additive is dissolved in water, that the calcium phosphate is slowly stirred, that is dispersed and the final dispersion, in particular more than 15

Minutes, that the slip additive, in particular PEG, and the binder, in particular the PVP K30, is added and the suspension is dispersed, that the pressure binder, in particular PVA5 or GDX4, and the

Suspension is dispersed.

7. The method according to claim 6, characterized in that the sintering aid is added.

8. A process for the preparation of granules from the composition according to claim 1, characterized in that the suspension with a temperature between 9O ⁰ C and 10O ⁰ C fed to a spray dryer and sprayed with a spray pressure of about 1 bar.

9. granules made with the material composition according to claim 1 and in particular with the method according to claim 8, characterized in that the individual granules have a size between 10 .mu.m and 100 .mu.m, that the majority of the individual granules are made of solid material and have no cavity that the individual granules have a bimodal particle size distribution,. where the two modes differ in diameter and the diameter ratio is between 1: 3 and 1:10.

10. Granules according to claim 9, characterized by a subsequently added sintering aid.

11. Granules according to claim 9, characterized in that the solid material has a porosity between 10% and 50%.

12. Use of the granulate according to claim 9 for a material system for 3D printing, wherein a fourth additive added as a binder, in particular GDX-4 or PVA-5.

13. Use of the material system according to claim 12 for the production of an implant by means of 3D pressing.