Dental implant incorporating an apatite

Abstract

A dental implant comprises a composition which comprises a polymeric material which is preferably polyetheretherketone, and an apatite, for example a hydroxy-containing apatite. A prosthodontics device may comprise a dental implant made from polyetheretherketone, an abutment, also made from PEEK, and a crown, which is also made from PEEK by machining from a PEEK disc.

Claims

1. A method of making a dental implant, the method comprising: (i) selecting a composition which comprises a polymeric material and an apatite, wherein said polymeric material comprises a polymeric material which comprises a repeat unit of formula (I) ##STR00007## wherein t1 and w1 independently represent 0 or 1 and v1 represents 0, 1 or 2; wherein the ratio of the wt % of said polymeric material divided by the wt % of said apatite is in the range 1 to 9; (ii) forming said composition into a shape which defines said dental implant; and (iii) subjecting the implant to a humid atmosphere which comprises greater than 20% humidity for at least five days and a temperature in the range of 15 C. to 100 C. for at least five days.

2. A method according to claim 1, wherein the dental implant is configured to cooperate with a superstructure such that the superstructure is releasably securable to the dental implant.

3. A method according to claim 1 wherein the polymeric material has a repeat unit of formula I, wherein t1=1, v1=0 and w1=0.

4. A method according to claim 1, wherein the polymeric material has a melt viscosity (MV) of at least 0.09 kNsm.sup.2 to 0.5 kNsm.sup.2.

5. A method according to claim 1, wherein the level of crystallinity of the polymeric material, measured by DSC, is greater than 25%.

6. A method according to claim 1, wherein the ratio of the wt % of the polymeric material divided by the wt % of the apatite is in the range 2.3 to 9.

7. A method according to claim 1, wherein the ratio of the wt % of the polymeric material divided by the wt % of the apatite is in the range 3.8 to 4.2.

8. A method according to claim 1, wherein the composition includes at least 65 wt % of the polymeric material and includes at least 10 wt % of the apatite; and the sum of the wt % of the polymeric material and the apatite is in the range 90 to 100 wt %.

9. A method according to claim 1, wherein the apatite is a hydroxyapatite.

10. A method according to claim 1, wherein said apatite is a hydroxyapatite which consists essentially of calcium, phosphorous, oxygen and hydrogen moieties.

11. A method according to claim 1, wherein the D50 of said apatite, assessed using laser diffraction and based on a volume distribution, is less than 200 m.

12. A method according to claim 1, wherein the D50 of said apatite, assessed using laser diffraction and based on a volume distribution, is less than 20 m.

13. A method according to claim 1, wherein the dental implant is arranged to cooperate with a superstructure, wherein said implant includes a female or male element which is arranged to cooperate with a male or female element associated with said superstructure.

Description

(1) Specific embodiments of the invention will now be described, by way of example, with reference to the following figures, in which:

(2) FIG. 1 is a graph showing the results of grading of bone;

(3) FIG. 2 is a graph of Tensile Elongation v. Days from moulding for conditioned components;

(4) FIG. 3 is an exploded view of a prosthodontics device;

(5) FIG. 4 is an assembled view of the device of FIG. 3;

(6) FIG. 5 is a view of a one-piece implant/abutment component;

(7) FIG. 6 is a view of a combined, one-piece crown/abutment component;

(8) FIG. 7a is a view of a one-piece prosthodontics device; and

(9) FIG. 7b is a partially cut-away view illustrating how the device of FIG. 7a may be screwed into a patient's jawbone.

(10) The following materials are referred to hereinafter:

(11) Hydroxyapatite (HA) obtained from Plasma Biotal Ltd. It has a D.sub.50 measured by laser diffraction of 5.18 m, a surface area of 5.91 m.sup.2/g and a bulk density of 0.62 g/ml.sup.3.

(12) PEEK OPTIMA LTIpolyetheretherketone obtained from Invibio Ltd.

(13) In the figures, the same or similar parts are annotated with the same reference numerals.

(14) In the following examples, Example 1 describes the manufacture of composite material comprising polyetheretherketone (PEEK) and hydroxyapatite (HA); Example 2 provides a general procedure for making injection moulded components; Examples 3 to 6 describe preparation of composite materials comprising different levels of PEEK/HA; Example 7 describes bioactivity testing of PEEK/HA material; Example 8 provides results of pre-clinical studies; and Example 9 provides a method for improving mechanical properties of a PEEK/HA component. Thereafter, further embodiments are described with reference to FIGS. 3 to 8.

EXAMPLE 1MANUFACTURE OF COMPOSITION COMPRISING POLYETHERETHERKETONE (PEEK) AND HYDROXYAPATITE (HA)

(15) Polyetheretherketone (PEEK) obtained in the form of PEEK-OPTIMA LTI (Invibio Biomaterial Solutions, UK) having a melt viscosity (MV) of 0.44 KNsm.sup.2 was dried to remove water (it absorbs water during storage). The PEEK was in the form of granules of approximately 3 mm by 2 mm size. Hydroxyapatite (HA) in the form of particles having mean particle size of about 5 m was selected.

(16) The PEEK and HA were mixed in a twin screw compounder (extruder) which heated the mixture to between 360 C. and 400 C. (with a temperature of 400 C. at the extruder output) to melt the PEEK. 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.

(17) 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 wt % of HA.

(18) 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. Laces of approximately 2 mm diameter were chopped to lengths of approximately 3 mm to define the PEEK and HA composite pellets.

EXAMPLE 2GENERAL PROCEDURE FOR MAKING INJECTION MOULDED COMPONENTS

(19) Pellets (e.g. those of Example 1) were injection moulded to produce a bioactive component. An injection moulding machine used 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.

(20) Mechanical properties, including Izod impact strength (Notched) (ISO 180), flexural strength (ISO 178), flexural modulus (ISO 178), tensile strength (ISO 527), and strain at break (ISO 527) of a test specimen were determined and the results are shown in Table 1.

EXAMPLES 3 TO 6

(21) 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 a different wt % of HA, as detailed in Table 1.

(22) TABLE-US-00001 TABLE 1 Example No. PEEK (wt %) HA (wt %) 3 80 20 4 70 30 5 60 40 6 50 50

(23) The PEEK and HA composite pellets produced were injection moulded as described in Example 2 to produce bioactive components. Mechanical properties of components made were determined and the results are shown in Table 2.

COMPARATIVE EXAMPLE 1

(24) 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 following the general procedure of Example 2. Mechanical properties were determined for comparison with the components of Examples 1 and 3 to 6 and the results are shown in Table 2.

(25) Results

(26) The results of the mechanical tests are detailed in Table 2 below:

(27) TABLE-US-00002 TABLE 2 Comparative Example Example 1 Example 3 Example 4 Example 5 Example 6 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 (%)

(28) It was found that PEEK could be successfully compounded with HA up to 50 wt % HA, without significant difficulties 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 (plots not shown) against the filler content and compared with those of the unfilled PEEK to determine optimum HA levels. From this it was concluded that 20 wt % of HA (Example 3) 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

EXAMPLE 7BIOACTIVITY TESTS

(29) PEEK containing 20% by weight HA (Example 3) was chosen for further bioactivity studies due to the limited effects on material mechanical properties compared to PEEK alone (Comparative Example 1).

(30) 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 controls comprising PEEK alone.

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

(32) TABLE-US-00003 Starting Materials MW Purity Formula [g/mol] [] Sol. A Sol. B Weights of starting materials [g/L] NaCl 58.44 99.5% 6.129 6.129 NaHCO.sub.3 84.01 99.5% 5.890 Na.sub.2HPO.sub.4 .Math. 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

(33) 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). 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.

(34) 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.

(35) 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.

(36) 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 PO 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.

(37) 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.

EXAMPLE 8ASSESSMENT OF DEGREE OF DIRECT IMPLANT-BONE CONTACT IN AN OVINE PRE-CLINICAL STUDY

(38) Cylindrical dowels of the composition of Example 3 and PEEK-OPTIMA were implanted in an established ovine model. Implants were placed in sheep tibia cortical bone for 4 weeks and 12 weeks. At the end of each time point, implants and surrounding bone were harvested and embedded in PMMA. Tissue sections were stained for histology using methylene blue and basic fuchsin. Histology images were graded on a semi-quantitative scale by two blinded observers to determine the percent bone ongrowth. At both the 4 week and 12 week time points, the percentage of direct bone contact was higher with the composition of Example 3 compared with PEEK-OPTIMA alone.

(39) Results are provided in FIG. 1 which shows the grading of bone in contact for components made from Comparative Example 1 and Example 3 materials.

(40) Granules comprising the material of Example 3 may advantageously be used to produce prosthodontics devices, for example implants, using a range of methods, for example: (i) Milling of discs made from the material of Example 3 using CAD-CAM technology as described in WO2013/070493. (ii) Injection moulding (iii) Compression moulding. (iv) Use of dental press system (casting).

(41) It has been found that components made from a composition comprising PEEK and HA can be conditioned yielding components of improved mechanical properties. This is discussed in the following example.

EXAMPLE 9

(42) Injection moulded sample components comprising PEEK (80 wt %) and HA (20 wt %) were conditioned at 23 C. and 50% humidity for a length of time as indicated in FIG. 1. At each time point, tensile elongation at break of five samples. Measurements of tensile elongation at break were conducted in accordance to ISO527. A substantial increase in tensile elongation at break was observed for the conditioned samples when compared with the initial moulded samples.

(43) The embodiments described hereinafter address the second object of preferred embodiments of the invention, with reference to FIGS. 3 to 8.

(44) In a first embodiment, a prosthodontics device 2, shown in FIG. 3, comprises a dental implant 4 which includes an outer screw-threaded region 6 which enables the implant to be threaded into a bore (not shown) which is drilled in a patient's mandible or maxilla. The implant 4 includes an internal screw-threaded region (not shown) which is arranged to screw-threadedly engage screw-threaded region 8 of an abutment 10. Abutment 10 includes a head 12 which includes a bore 14 which includes an internal screw-threaded region (not shown). A crown 16 is arranged to be secured to the abutment 12 by engagement of a screw (not shown) in a bore (not shown) defined in the prosthetic tooth, the screw extending and being secured in the internal screw-threaded region of the abutment. The assembled structure is shown in FIG. 4.

(45) The dental implant 4 may be made from polyetheretherketone (PEEK) (PEEK-OPTIMA LT1 obtained from Invibio Limited). It may be made by injection moulding, by compression moulding or by machining of a rod made from PEEK. It may be a commodity item which need not be customized for a particular patient. It may though be provided in a range of different sizes.

(46) The abutment 10 may also be made from PEEK as described for the implant 4. It also may be a commodity item which need not be customized, at least at the time of manufacture, for a particular patient. It may also be provided in a range of different sizes. Alternatively, in some cases, the abutment may be customized for particular patients and made by a CAD-CAM process

(47) The implant and abutment may be assembled as follows:

(48) Firstly, a bore is drilled into the patient's mandible or maxilla and the implant 4 is screwed into the bore. It is then left for several weeks to osseointegrate. A temporary abutment or healing cap might be used during this healing phase of the gum and oseointegration of the implant. In this case, once osseointegrated, the abutment 10 is screw-threadedly secured to the implant so the head 12 of the abutment extends above the patient's mucosa. If an immediate loading approach is taken, the final abutment is screwed into the implant after implant placement and before osseointegration has taken place. Once osseointegrated, the abutment 10 is screw-threadedly secured to the implant so the head 12 of the abutment extends above the patient's mucosa. Subsequently, a dentist may, if appropriate, mill the abutment to adjust it and/or facilitate attachment of the crown. Such milling with the abutment in situ in a patient's mouth is readily possible.

(49) Next, a mould is taken of the appropriate part of the patient's mouth which includes the abutment 10 using a standard impression tray. The mould is then poured with dental plaster and allowed to set. The mould is then scanned to collate relevant CAD data which is input into an 5-axis CAD-CAM machine. The machine then produces the crown 16 from a PEEK disc. Thus, like the implant 4 and abutment 10, the crown 16 is made from PEEK.

(50) Prior to assembly, the crown 16 may be finished by application of dental veneers to define an aesthetically acceptable prosthetic tooth. Thereafter, the crown is secured in position on the abutment. This may be achieved by engagement of a screw with both the crown and abutment (via bore 14) in conjunction, optionally, with cements. Advantageously, since both the crown and abutment are made from PEEK a cement may be selected which is optimised for adhesion to PEEK rather than a compromise cement being selected as would be the case if the crown and abutment were made from different materials.

(51) The arrangement described may have a number of advantages which may include the following: (i) Since the implant 4 and abutment 10 are made from a strong flexible material (i.e. PEEK), the combination will be flexible which may provide improved mouth feel; (ii) The flexibility of the implant and/or abutment 10 may reduce stress shielding (i.e. the implant working loose); (iii) Wear, for example, fretting wear between the implant and abutment and/or between abutment and crown may be reduced; (iv) Ease of precision manufacture of the components; (v) By virtue of (iv) and the nature of the material used, the combination of implant 4, abutment 10 and crown 16 may be cheaper to manufacture, supply and fit to a patient; (vi) By virtue of the ability to mill the abutment in situ, minor adjustments may be made in situ, reducing time and expense of fitting the prosthodontics device; (vii) The flexibility of the implant and/or abutment 10 may provide a shock absorbing benefit and preserve the underlining bone; (viii) Complete metal free solution, which might provide an alternative to patients that are allergic to metal ions and that cannot accept a metal dental implant.

(52) In a second embodiment, a single component may define both the implant and abutment. The component may be as shown in FIG. 5. The component may be produced in a single piece, for example by machining a rod, or by moulding (e.g. injection or compression moulding). Thus, there is no means of releasably securing the implant and abutments parts of the component. The component may be made from PEEK.

(53) In use, the component is screwed into the mandible or maxilla and allowed to osseointegrate. Then the crown is prepared and fitted as described for the first embodiment.

(54) Provision of the component may be feasible due to the precision with which it may be made coupled with the possibility of a dentist being able to mill the abutment in situ. Use of the component may also be advantageous for the reasons referred to under points (i) to (viii) for the first embodiment. Furthermore, as the component may be specific to each patient, it may be adapted to follow a patient's gum line in a more exact manner, with smaller margins. The ability to design the patient gum line into the abutment should allow for an immediate improved aesthetic result.

(55) In a third embodiment, illustrated in FIG. 6, there is provided a combined component 20 which incorporates an abutment part which includes a screw-threaded region 8 for cooperation with an implant which may be as described in FIG. 3. The abutment part is suitably shaped to engage the implant in the same manner as the abutment 10 engages the implant 4 of FIG. 3. The component 20 also includes a crown part 22.

(56) In the third embodiment, an implant is screwed into the mandible or maxilla as described with reference to FIG. 3 and the component 20 may subsequently be engaged with the implant.

(57) The third embodiment may have advantages as described for the other embodiments. In addition, since the prosthodontics device comprises only two components (i.e. implant and component 20), it may be significantly cheaper to manufacture compared to other devices.

(58) In a fourth embodiment, shown in FIGS. 7a and 7b, a one-piece component 40 includes a threaded implant part 42 and a crown part 44. The component 40 is made in one-piece from PEEK using a CAD-CAM machine as described in the first embodiment. This involves: digitally scanning a patient's mouth and bone situation; planning the implant location and its insertion digitally; design of the component; testing the component in digital articulators (which are based upon the patient's digital scan) and simulate the behaviour of the component 40 in the patient's mouth; and milling to define component 40. As illustrated in FIG. 5b, the component includes a bore providing access to and allowing cooperation with a tool 46 by means of which the component can be screwed into the mandible or maxilla. The dimensions of the component 40 are such that it can be rotated to screw it into the mandible or maxilla without being blocked by teeth adjacent to the gap in which the component is to be placed. After insertion, the bore may be closed and the crown part 44 finished by conventional means.

(59) Components as described (e.g. in FIGS. 3 and 5) may be used to secure bridges carrying multiple crowns and/or teeth in position. For example, first and second implants (e.g. both being the same as implant 4 of FIG. 1) may be secured at spaced apart positions within a patient's mouth. Respective abutments 10 may then be secured to the implants 4. A mould may then be taken as described according to the first embodiment and a bridge incorporating crowns, and being arranged to engage the abutments, may be made from PEEK, using a CAD-CAM machine as described in the first embodiment. Thus, both the implant, bridge and crowns are made from PEEK. The bridge may be secured in position by screws which are engaged with the bridge and implants. The assembly may be finished by conventional techniques.

(60) 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.