NON-BREAKING FILAMENT FOR SHAPING BONE AND DENTAL SUBSTITUTES

Abstract

Materials for additive manufacturing. More precisely, a non-breaking filament, preferably for 3D printing bone substitutes. The filament includes 50% to 99% in weight to the total weight of the filament (w/w) of a polymeric matrix and 1% to 50% w/w of tricalcium silicate. Also, a method and composition for preparing the filament. Additionally, the uses of the filament, such as for example in the dental field; especially, for providing suitable bone and dental substitutes.

Claims

1.-16. (canceled)

17. A filament comprising: 50% to 99% in weight to the total weight of the filament (w/w) of a polymeric matrix; and 1% to 50% w/w of tricalcium silicate.

18. The filament according to claim 17, further comprising dicalcium silicate, tricalcium aluminate, tricalcium oxide, gypsum and/or Portland cement.

19. The filament according to claim 17, wherein the polymeric matrix is made of at least one biocompatible polymer.

20. The filament according to claim 17, wherein the polymeric matrix is made of at least one biocompatible polymer selected from poly(lactic acid) or poly(lactide) (PLA), poly(glycolic acid) or poly(glycolide) (PGA), poly(lactide-co-glycolide) (PLGA), polycaprolactone (PCL), poly-(D,L)-lactide (PDLLA), polydioxanone (PDO), polyvinylalcohol (PVA), polyetherketoneketones (PEKK), polyetheretherketones (PEEK), polyetherimide (PEI) and any mixtures thereof.

21. The filament according to claim 17, wherein the amount of tricalcium silicate is ranging from 1% to 30% w/w.

22. The filament according to claim 17, wherein the amount of tricalcium silicate is ranging from 10% to 20% w/w.

23. The filament according to claim 17, wherein the amount of polymeric matrix is ranging from 70% to 99% w/w.

24. The filament according to claim 17, further comprising a radiopacifier.

25. The filament according to claim 24, wherein the radiopacifier is selected from zinc oxide, zirconium oxide, yttrium oxide, tin oxide, barium sulfate, tungsten oxide, bismuth oxide and barium oxide.

26. The filament according to claim 17, comprising 70% to 99% w/w of poly(lactide-co-glycolide) (PLGA) or polyetheretherketone (PEEK); and 1% to 30% w/w of tricalcium silicate.

27. The filament according to claim 17, having a diameter ranging from 1 mm to 10 mm.

28. A composition for manufacturing a filament according to claim 17, said composition comprising: 50% to 99% in weight to the total weight of the composition (w/w) of at least one biocompatible polymer; and 1% to 50% of tricalcium silicate; wherein said composition is under the form of rods, pellets or granules

29. The composition according to claim 28, wherein the biocompatible polymer selected from poly(lactic acid) or poly(lactide) (PLA), poly(glycolic acid) or poly(glycolide) (PGA), poly(lactide-co-glycolide) (PLGA), polycaprolactone (PCL), poly-(D,L)-lactide (PDLLA), polydioxanone (PDO), polyvinylalcohol (PVA), polyetheretherketones (PEEK), polyetherketoneketones (PEKK), polyetherimides (PEI) and any mixtures thereof.

30. A shaped body obtained by 3D printing using a fused filament deposition printer fed with a filament according to claim 17.

31. A bone substitute comprising a shaped body according to claim 30.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0254] FIG. 1A is a photograph showing a filament of the invention (PLGA with 30% C3S) wrapped around a coil. FIG. 1B is a photograph showing a filament of the invention (PEEK with (from bottom to top) 0%, 10%, 20% and 30% C3S) wrapped around a coil.

[0255] FIG. 2 is a microscopy cliché showing the filament without any C3S load (on the left) and with 10% w/w, 20% w/w or 30% w/w of C3S (from the left to the right).

[0256] FIG. 3 is a set of microscopy clichés showing the sections of the filaments of FIG. 2.

[0257] FIG. 4 is a set of microscopy clichés showing a filament of the invention (PLGA with 30% C3S) before (FIG. 4a) and after (FIG. 4b) two weeks immersed in a PBS solution.

[0258] FIG. 5 is a photograph showing a 1-cent coin next to a cubic scaffold by 3D-printing using a fused filament deposition printer fed with a filament of the invention (made of PLGA loaded with 10% of C3S).

EXAMPLES

[0259] The present invention is further illustrated by the following examples.

Abbreviations

[0260] 3D: three-dimension, [0261] C3S: tricalcium silicate, [0262] ° C.: Celsius degree, [0263] PBS: phosphate buffer saline, [0264] PCL: polycaprolactone, [0265] PDLLA: poly(D, L-lactide), [0266] PDO: polydioxanone, [0267] PEEK: polyetheretherketone, [0268] PLGA: poly(lactide-co-glycolide), [0269] PVA: polyvinylalcohol, [0270] rpm: road per minute, and [0271] TGA: thermogravimetric analysis.

[0272] Part I: Chemistry

Example 1: Process for Manufacturing Non-Breaking and 3D Printable Filaments

[0273] General Protocol

[0274] First, C3S, under the form of particles or any other suitable form well-known by the skilled artisan, are dried for 2 hours at 150° C. and polymer is dried at least 2 hours under vacuum at a temperature ranging from 30° C. to 150° C. Then, the polymer and C3S are mixed in a twin screw extruder (apparatus: PHARMA 11 of Thermo Scientific) under laminar air flow to limit moisture intake (25° C. and 30% relative humidity). Finally, extrusion is implemented at a rate ranging from 5 rpm to 25 rpm and at a temperature ranging from 90° C. to 400° C. The diameter of the outlet filament is checked throughout the extrusion process. Starting from the temperature ranges given in this general protocol, the skilled artisan would be able to adapt the drying temperature and the extrusion temperature depending on the selected polymer(s).

[0275] This general protocol was implemented for manufacturing filaments of PEEK, PLGA, PVA, PCL, PDLLA or PDO, loaded with a C3S amount (1%, 5%, 10%, 20%, 30% or 50% in weight to the total weight of the filament). A TGA analysis confirms the C3S load for each filament obtained by the process of the invention.

[0276] According to the general protocol as described above, additional ingredients may be added when the polymer and C3S are mixed in a twin screw extruder. Such additional ingredients may be for example, dicalcium silicate, tricalcium aluminate, tricalcium oxide, gypsum, a radiopacifier such as zinc oxide, zirconium oxide, yttrium oxide, tin oxide, barium sulfate, tungsten oxide, bismuth oxide or barium oxide; and/or Portland cement.

Example 2: Characterization of the Filaments of the Invention

[0277] The filaments obtained from the process described in Example 1 were studied. The aim is to evaluate their pliability and checkup the C3S distribution in the filament.

[0278] 2.1. Non-Breaking Filament

[0279] In general, in the 3D printing field, polymer filaments are pliable and stored under filament coils. However, it is expected that addition of mineral compounds (such as tricalcium silicate) inside such filaments, stiffens the structure leading to the breakage of the filaments. Consequently, such filaments might be stored under coils and a fortiori, not be used in fused filament deposition.

[0280] In this experiment, the pliability of the filaments of the invention (loaded with C3S, (Yo given in weight of C3S to the total weight of the filament) was tested. For this purpose, the following filaments were wrapped around a coil and stored until used in 3D printing: [0281] PLGA with 1% C3S, [0282] PLGA with 5% C3S, [0283] PLGA with 10% C3S, [0284] PLGA with 20% C3S, [0285] PDLLA with 30% C3S, [0286] PEEK with 10% C3S, [0287] PEEK with 20% C3S, [0288] PEEK with 30% C3S, and [0289] PCL with 50% C3S.

[0290] The results (visible to the naked eye) showed that there is no breakings for all filaments loaded in C3S and wrapped around a coil. FIG. 1A shows an example of a filament coil of the invention made of PLGA with 10% C3S. FIG. 1B shows filaments made of PEEK with (from bottom to top) 0% wt., 10% wt., 20% wt. and 30% wt. of C3S; the PEEK filament without any C3S is used as a reference. Furthermore, the filament coils made of PLGA with 10% C3S were successfully used in 3D printing (see example 3).

[0291] 2.2. C3S Distribution

[0292] The aim is to check up if the distribution of tricalcium silicate inside the filaments is homogenous in view of achieving good biological and physicochemical properties.

[0293] In the Raw Filament

[0294] First, a microscopy cliché (FIG. 2) has been realized of: [0295] a filament without any C3S load (FIG. 2 on the left); and [0296] filaments of the invention made of PLGA, loaded with 10%, 20% or 30% of C3S (% w/w) respectively.

[0297] FIG. 2 shows that a filament without any C3S load is translucent. To the contrary, the filament is more and more opaque when the C3S amount increases. These observations were confirmed by thermogravimetric analysis. The result of FIG. 2 evidences a C3S distribution on the whole outer surface of the filament.

[0298] Microscopy clichés of the sections of these filaments have been realized. The results of FIG. 3 confirm the homogenous distribution of C3S inside the filament of the invention.

[0299] Thus, both results evidence the homogenous distribution of C3S inside the filaments.

[0300] On the Filament after its Immersion in a PBS Solution

[0301] Then, the filaments of the invention (with a C3S load) have been placed in a PBS solution during 2 weeks, at 37° C. FIG. 4a shows a cliché of a filament of the invention (PLGA with 30% C3S) before its immersion in the PBS solution and FIG. 4b shows the same filament after two weeks in the PBS solution.

[0302] FIG. 4b shows the presence of crystals on the whole surface of the filament. A X-Ray analysis of these crystals demonstrated that these crystals are hydroxyapatite resulting from the reaction between phosphate of the PBS solution and the C3S particles present on the loaded filament.

[0303] In conclusion, microscopy clichés (FIGS. 4a and b) and X-ray analysis evidence that the process of the invention provides filaments with C3S particles well-distributed in the filament of the invention.

[0304] 2.3. Others Characteristics of the Filament of the Invention

[0305] The aim is to provide filaments for manufacturing bone substitutes either by molding or by 3D printing. For this goal, the filaments must have some mechanical parameters close to those of the cortical or the spongious bones.

[0306] In this experiment, the compressive strength, the tensile strength and the Young's modulus of the filaments have been determined and compared to reference value ranges. These reference value ranges [“bone ref.”] corresponds to the limit values of cortical and spongious bones.

[0307] The results are presented in the following table:

TABLE-US-00001 10% 20% 30% 30% 30% 30% 30% 10% 20% 30% C3S- C3S- C3S- C3S- C3S- C3S- C3S- C3S- C3S- C3S- Bone loaded loaded loaded loaded loaded loaded loaded loaded loaded loaded ref. PLGA PLGA PLGA PVA PCL PDLLA PDO PEEK PEEK PEEK Young's 0.1-30.sup.  3.9 4.3 5.2 8 1.1 6 1.8 5.6 6.1 6.3 modulus (GPa) Tensile strength 10-150 51.5 46.8 51.4 73 17 43 33 76.2 76.8 76.1 (MPa) Compressive  2-230 71.7 74 86.8 142 28 78 53 139 138 156 strength (MPa)

[0308] The results show that for all the filaments loaded with C3S, the values of Young's modulus, tensile strength and compressive strength are in the reference value ranges of cortical and spongious bones.

[0309] Thus, the filaments of the invention feature mechanical parameters suitable for their use in the manufacture of bone substitutes.

[0310] Part II: Uses

Example 3: Manufacturing of an Object by Fused Filament Deposition (FFD)

[0311] The filaments of the invention have been used for manufacturing objects by filament fused deposition.

[0312] The aim is to finely execute the manufacturing of a shaped object of small dimensions.

[0313] FIG. 5 shows a cubic scaffold obtained by 3D-printing using a fused filament deposition printer fed with a filament of the invention (made of PLGA loaded with 10% of C3S).

[0314] We can notice that the cubic scaffold is homogenously executed with regular holes of a diameter of about 200 μm.

[0315] In conclusion, this experiment evidences that: [0316] the filament of the invention may be stored on a filament coil without any breakage issue and is 3D-printable; and [0317] objects of small dimensions may be successfully 3D-printed from a filament coil of the invention.