COMPONENTS INCORPORATING BIOACTIVE MATERIAL

Abstract

There are provided methods of producing a component incorporating a bioactive material. In one embodiment the method comprises: (a) using a screw extruder to mix a polymeric material (I) with a bioactive material (II) and melt the polymeric material (I); and (b) making a component by moulding; and wherein the polymeric material (I) is of a type which includes: (i) phenyl moieties; (ii) ketone moieties; and (iii) ether moieties. Also provided are components comprising a polymeric material and a bioactive material.

Claims

1.-53. (canceled)

54. A method of producing a component incorporating a bioactive material wherein the method comprises: (a) using a twin-screw extruder to mix a polymeric material (I) with a bioactive material (II) and melt the polymeric material (I); and (b) making a component by moulding; wherein the polymeric material (I) comprises polyetheretherketone (PEEK) and the bioactive material (II) comprises hydroxyapatite (HA); wherein the bioactive material is introduced to the extruder at a point downstream of a point at which the polymeric material is introduced to the extruder; wherein the component comprises the PEEK in an amount of between 75% and 85% by weight of the component and the HA in an amount of between 15% and 25% by weight of the component; wherein the PEEK has a melt viscosity of at least 0.06 kNsm.sup.−2, as measured using capillary rheometry operating at 400° C. at a shear rate of 1000 s.sup.−1 using a tungsten carbide die, and wherein the HA is in the form of particles having a mean particle size of 10 μm or less; and wherein the component comprises a polymeric-material-bioactive material composite having a tensile strength of at least 80 MPa.

55. The method according to claim 54, wherein the polymeric material consists of polyetheretherketone (PEEK).

56. The method according to claim 54, wherein the component consists of PEEK and HA.

57. The method according to claim 54, wherein step (a) comprises producing discrete units of composite material.

58. The method according to claim 54, wherein the method comprises producing pellets of composite material in step (a) and making a part by moulding from the pellets in step (b).

59. The method according to claim 54, wherein step (b) comprises injection moulding.

60. The method according to claim 54, wherein the method comprises pelletizing the output from the extruder in step (a) and subsequently melting the pellets so formed to produce a component by injection moulding in step (b).

61. The method according to claim 54, wherein the component comprises a component for medical use.

62. The method according to claim 54, wherein the component comprises an implant adapted for bioactive fixation.

63. The method according to claim 54, wherein the component is adapted to bond to hard and/or soft tissue.

64. The method according to claim 54, wherein the component is a component which, when placed in a simulated body fluid (SBF) test for bioactivity, passes said test with the formation of new apatite (CaP) at the ratio close to the theoretical value for hydroxyapatite, which is 1.67.

65. The method according to claim 54, wherein the method comprises producing a component comprising a polymeric material-bioactive material composite having tensile strength and/or flexural strength which are at least 80% of the respective strength of the polymeric material.

66. The method according to claim 54, wherein the method comprises producing a component comprising a polymeric material-bioactive material composite having a tensile strength which is at least 85% of the respective strength of the polymeric material.

67. The method according to claim 54, wherein the method comprises producing a component comprising a polymeric material-bioactive material having an impact strength of at least 5 KJ m.sup.−2.

68. The method according to claim 54, wherein the method comprises producing a bioactive component comprising a polymeric material-bioactive material having an impact strength of no more than 10 KJ m.sup.−2.

69. The method according to claim 54, wherein the component comprises the PEEK in an amount of 80% by weight of the component and the HA in an amount of 20% by weight of the component.

70. The method according to claim 54, wherein at the extrusion end of the extruder, the extruder has a pelletizer.

71. The method according to claim 70, wherein the method comprises producing pellets having a diameter of 3.5 mm or less.

72. The method according to claim 70, wherein the method comprises producing pellets of composite material in step (a) and making a part by moulding from the pellets in step (b).

73. The method according to claim 54, wherein the component comprises a porous material comprising a material which is rendered porous using salt leaching or laser sintering.

74. Pellets comprising 75 to 85% by weight of polyetheretherketone and 15 to 25 wt % of hydroxyapatite, wherein said pellets define a composite material having the following properties: a tensile strength of at least 80 mPa, when measured in accordance with ISO 527; a flexural strength of at least 150 mPa, when measured in accordance with ISO 178; a flexural modulus of 6 GPa or less, when measured in accordance with ISO 178; an impact strength of at least 5 JKm-2, when measured in accordance with ISO 180; a strain at break of at least 8%, when measured in accordance with ISO 527.

Description

EXAMPLE 1

[0224] A bioactive component was manufactured by using a screw extruder to mix a polymeric material (polyetheretherketone) with a bioactive material (hydroxyapatite) and melt the polymeric material. The extruded composite was formed into pellets which were then used to make said component by injection moulding.

[0225] Polyetheretherketone (PEEK) obtained in the form of PEEK-OPTIMA® (Invibio Biomaterial Solutions, UK) was dried to remove water (it absorbs around 0.5% by weight of water during storage). The PEEK was in the form of granules of approximately 3 mm by 2 mm size. The dried PEEK was mixed with hydroxyapatite (HA) obtained from Plasma Biotal Ltd., UK in the form of particles having mean particle size of 5 μm.

[0226] The PEEK and HA were mixed in a twin screw compounder (extruder) which also heated the mixture to between 360° C. and 400° C. (with a temperature of 400° C. at the extruder output) to melt the PEEK This resulted in the PEEK polymer being in the fluid state within the extruder. The PEEK was introduced to the extruder at a point upstream from the introduction of HA to the extruder. The PEEK was heated and conveyed through the extruder such that the PEEK was in a molten state within the extruder before the HA was added. The mixture of HA and molten PEEK was then conveyed further through the extruder to mix the PEEK and HA. A PEEK and HA composite was extruded from the extruder and pelletized.

[0227] The PEEK and HA were added to the extruder in a ratio such that the output of the extruder was a PEEK and HA composite which comprised 10% by weight of HA.

[0228] The extruder comprised a normal screw profile fabricated from stainless steel with a minimum L/D ratio of 45:1. At the extrusion end a twin hole die with a 4 mm orifice and pelletizer was used. The main screw rotation speed was set at 150-250 rpm. The screws were intermeshing counter rotating screws having a length of around 1 m and a diameter of around 40 mm

[0229] The PEEK and HA composite pellets produced by the extruder were laces of approximately 2 mm diameter which were chopped to lengths of approximately 3 mm. These were fed to an injection moulding machine and injection moulded to produce a bioactive component. The injection moulding machine comprised a heated barrel through which the pellets were conveyed by a screw. The barrel was heated to temperatures of between 360° C. and 375° C. such that the polymeric material within the pellets melted as they were conveyed through the barrel such that a melt was produced. The melt was then injected through a nozzle into a mould with the mould tool being heated to between 200° C. and 220° C.

[0230] Mechanical properties, including impact strength (ISO 180), flexural strength (ISO 178), flexural modulus (ISO 178), tensile strength (ISO 527), and strain at break (ISO 527), were determined and the results are shown in Table 1.

EXAMPLE 2

[0231] The method of Example 1 was repeated but the ratio of PEEK to HA was adapted such that the output of the extruder was a PEEK and HA composite which comprised 20% by weight of HA.

[0232] The PEEK and HA composite pellets produced by the extruder were injection moulded to produce a bioactive component.

[0233] Mechanical properties, including impact strength (ISO 180), flexural strength (ISO 178), flexural modulus (ISO 178), tensile strength (ISO 527), and strain at break (ISO 527), were determined and the results are shown in Table 1.

EXAMPLE 3

[0234] The method of Example 1 was repeated but the ratio of PEEK to HA was adapted such that the output of the extruder was a PEEK and HA composite which comprised 30% by weight of HA.

[0235] The PEEK and HA composite pellets produced by the extruder were injection moulded to produce a bioactive component.

[0236] Mechanical properties, including impact strength (ISO 180), flexural strength (ISO 178), flexural modulus (ISO 178), tensile strength (ISO 527), and strain at break (ISO 527), were determined and the results are shown in Table 1.

EXAMPLE 4

[0237] The method of Example 1 was repeated but the ratio of PEEK to HA was adapted such that the output of the extruder was a PEEK and HA composite which comprised 40% by weight of HA.

[0238] The PEEK and HA composite pellets produced by the extruder were injection moulded to produce a bioactive component.

[0239] Mechanical properties, including impact strength (ISO 180), flexural strength (ISO 178), flexural modulus (ISO 178), tensile strength (ISO 527), and strain at break (ISO 527), were determined and the results are shown in Table 1.

EXAMPLE 5

[0240] The method of Example 1 was repeated but the ratio of PEEK to HA was adapted such that the output of the extruder was a PEEK and HA composite which comprised 50% by weight of HA.

[0241] The PEEK and HA composite pellets produced by the extruder were injection moulded to produce a bioactive component.

[0242] Mechanical properties, including impact strength (ISO 180), flexural strength (ISO 178), flexural modulus (ISO 178), tensile strength (ISO 527), and strain at break (ISO 527), were determined and the results are shown in Table 1.

COMPARATIVE EXAMPLE

[0243] Polyetheretherketone (PEEK) obtained in the form of PEEK-OPTIMA® (Invibio Biomaterial Solutions, UK) was used in an injection moulding machine and injection moulded to produce a component corresponding structurally to that of Examples 1 to 5.

[0244] Mechanical properties, including impact strength (ISO 180), flexural strength (ISO 178), flexural modulus (ISO 178), tensile strength (ISO 527), and strain at break (ISO 527), were determined for comparison with the components of Examples 1 to 5 and the results are shown in Table 1.

[0245] PEEK was successfully compounded with HA up to 50% fill by weight, without significant issue and with no reaction observed between the two components. The mean mechanical values for impact strength, flexural strength, flexural modulus, tensile strength, and strain at break were plotted against the filler content and compared with those of the unfilled PEEK to determine optimum HA levels.

[0246] From this it was concluded that 20% by weight of HA (Example 2) gave the optimum level to allow HA to be present at sufficient levels to provide desirable bioactivity to the component without significant detriment to the physical properties.

TABLE-US-00002 TABLE 1 Comparative Example Example 1 Example 2 Example 3 Example 4 Example 5 Property (No HA) (10% HA) (20% HA) (30% HA) (40% HA) (50% HA) Impact 7.33 7.4 6.1 5.2 4.6 4.6 Strength (KJ/m2) Flexural 162.45 156.1 156.0 154.2 139.2 118.8 strength (MPa) Flexural 3.96 4.33 4.72 5.61 6.67 8.02 modulus (GPa) Tensile 99.25 88.7 88.7 81.8 73.5 75.5 Strength (MPa) Strain at 35.8 24.09 8.8 3.98 2.24 1.27 Break (%)

[0247] Bioactivity Tests

[0248] PEEK containing 20% by weight HA (Example 2) was chosen for further bioactivity studies due to the limited effects on material mechanical properties compared to PEEK alone (comparative example).

[0249] Bioactivity of the PEEK/HA was determined by the ability to form apatite on the surface of the material in a simulated body fluid SBF using SBF-JL2 as prepared and described in Bohner and Lemaitre (Bohner M, Lemaitre J./Biomaterials 30 (2009) 2175-2179) and compared with PEEK controls.

[0250] The SBF-JL2 was produced using a dual-solution preparation (Sol. A and Sol. B) having the following composition for 2 L of final fluid:

TABLE-US-00003 Starting Materials MW Purity Weights of starting materials [g/L] Formula [g/mol] [—] Sol. A Sol. B NaCl 58.44 99.5% 6.129 6.129 NaHCO.sub.3 84.01 99.5% 5.890 Na.sub.2HPO.sub.4•2H.sub.2O 177.99 99.0% 0.498 CaCl.sub.2 110.99 95.0% 0.540 Volume of HCl solution (mL/L) HCl 1.00M Aq. Sol. [mL/L] 0.934 0.934

[0251] Use of this in vitro method of examining apatite formation as a means of predicting in vivo bone bioactivity is both widely used and accepted (Kokubo T, Takadama H. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 2006; 27(15):2907-2915) and Bohner and Lemaitre relates to a variant method. Samples were immersed in SBF for 1, 3 and 7 days on a rotating platform at 37° C. with 5% CO.sub.2 and 100% humidity. X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were used to analyze the bioactive elements present on the surface of the specimens following immersion in SBF.

[0252] SEM analysis of the surface of PEEK controls and PEEK/20% HA composite revealed the formation of spherical crystals on the surface after immersion in SBF. These were more numerous and apparent on the PEEK/20% HA samples and these were observed as early as 1 day post-immersion in SBF, suggesting increased apatite formation.

[0253] Detailed Ca2p and P2p XPS spectra revealed that although Ca and P were identified on the surface of both materials, only elemental ratios present on the PEEK/20% HA samples were conducive to bone formation with a Ca/P ratio of 1.66, close to the theoretical value for hydroxyapatite. Meanwhile, the ratios of the depositions on the control PEEK were more variable (>1.67), and indicative of non-hydroxyapatite calcium phosphate formations.

[0254] Following immersion in SBF for 1 day, ATR-FTIR surface analysis was performed on PEEK/20% HA and control PEEK samples to semi-quantify the degree of apatite deposition and detect functional groups. A significant peak was observed at 1015 cm.sup.−1, most likely arising from the structural P—O bond of phosphate groups. The ratio of absorption at 1015 cm.sup.−1 to 1645 cm.sup.−1 (characteristic of PEEK) was measured and showed an increased ratio on PEEK/20% HA samples compared with control PEEK, confirming the XPS findings indicating greater apatite formation on the PEEK/20% HA samples.

[0255] Surprisingly it has been found that despite the low proportion of HA in the component (only 20% by weight) sufficient HA is available at the surface of the component to impart bioactive properties to the component and promote apatite formation. Without wishing to be bound by theory it is believed that the surface availability of HA and the effectiveness of the low level of HA in promoting apatite formation is due to the use of a screw extrusion method to produce PEEK and HA composite pellets. This is an unexpected effect of using a screw extrusion and pelletization process.

[0256] It will be appreciated that preferred embodiments of the present invention may allow the manufacture of a bioactive component which comprises a polymeric material incorporating a bioactive material and which may benefit from bioactive properties of the bioactive material whilst retaining desirable physical properties of the polymeric material.

[0257] The compounding of PEEK with HA according to preferred embodiments of the present invention may produce bioactive components that are unexpected in a number of ways:

[0258] The components produced may still be mechanically strong.

[0259] Examples with lower levels of HA (such as example 2 with 20% by weight of HA) may retain most of the properties of PEEK, yet the dispersion at the surface may show uniformity and a lot of HA presence.

[0260] The components may be bioactive. For example when the component comprising 20% by weight HA was placed in a simulated body fluid test for bioactivity, it passed that test with the formation of new apatite (CaP) at the ratio of 1.66 (theoretical value for HA ratio is 1.67) versus controls that did not have this ratio.

[0261] The HA:PEEK interface may be good. This has been a short-coming of previous processes.

[0262] The HA may show up near the surface at good uniformity and in sufficient amounts to confer bioactivity.

[0263] A relatively low concentration of HA (for example 20% by weight) may create a sweet spot of mechanical strength and bioactivity whilst retaining the flexibility of using industrial relevant manufacturing methods.

[0264] The bioactivity conferred may be afforded by a compound that may be created without any adverse reactions.

[0265] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0266] All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.

[0267] Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0268] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.