MEDICAL MATERIALS AND DEVICES

Abstract

Provided herein is a composite material for use in orthopaedic applications, and an orthopaedic implant made from such material, the composite material comprising a polymeric matrix material and further comprising a filler material comprising TiO.sub.2 and reduced graphene oxide. Also provided herein is a cranial prosthesis comprising a peripheral frame portion defining an aperture, and a removable insert portion for closing the aperture. Further provided is a cranial prosthesis comprising a core layer and a first skin layer, the first skin layer having a lower porosity than the core layer. The medical materials and devices disclosed herein may provide improved materials for use in orthopaedic applications, prostheses which offer improved access for revision surgery, and prostheses which offer improved bone integration and mechanical properties.

Claims

1. An orthopaedic device comprising a composite material, the composite material comprising: a polymeric matrix material; and filler material comprising a TiO.sub.2-reduced graphene oxide nanocomposite.

2. The orthopaedic device according to claim 1 wherein the polymeric matrix material is selected from polyphenylsulphone, polycarbonate urethane, a PAEK (polyaryletherketone) polymer, polycaprolactone, poly-L-lactic acid, polyvinyl acetate or poly(lactic-co-glycolic acid).

3. The orthopaedic device according to claim 2 wherein the polymeric matrix material is polyphenylsulphone.

4. The orthopaedic device according to claim 1 wherein the amount of filler material is from 0.05 wt % to 80 wt % based on total weight of the composite material.

5. The orthopaedic device according to claim 1 wherein the amount of TiO.sub.2 is less than 3 wt % based on total weight of the composite material.

6. The orthopaedic device according to claim 1 wherein the combined amount of TiO.sub.2 and reduced graphene oxide is less than 3 wt % based on total weight of the composite material.

7. The orthopaedic device according to claim 1 wherein the ratio of TiO.sub.2 to reduced graphene oxide in the filler material is between 50:50 and 99:1 by weight.

8. The orthopaedic device according to claim 7 wherein the ratio of TiO.sub.2 to reduced graphene oxide in the filler material is 80:20 by weight.

9. The orthopaedic device according to claim 1 wherein the filler material further comprises hydroxyapatite.

10. The orthopaedic device according to claim 9 wherein the amount of hydroxyapatite is from 1 wt % to 70 wt % based on total weight of the composite material.

11. The orthopaedic device according to claim 1 wherein the TiO.sub.2-reduced graphene oxide nanocomposite is in a photoactivated state.

12. The orthopaedic device according to claim 11 wherein the photoactivated state is achieved by irradiation of the TiO.sub.2-reduced graphene oxide nanocomposite with ultraviolet or gamma radiation.

13. The orthopaedic device according to claim 12 wherein the radiation is gamma radiation applied at a dose of 8-40 kGy.

14. The orthopaedic device according to claim 13 wherein the gamma radiation is applied at a dose of 25 kGy.

15. (canceled)

16. The orthopaedic device according to claim 1 wherein the orthopaedic device is a cranial prosthesis.

17. The orthopaedic device according to claim 1 wherein the orthopaedic device is an articulating implant having one or more bearing surfaces.

18. The orthopaedic device according to claim 1 wherein the orthopaedic device has variable porosity.

19-36. (canceled)

37. The orthopaedic device according to claim 16 wherein the cranial prosthesis has variable porosity.

38. The orthopaedic device according to claim 17 wherein the articulating implant has variable porosity.

Description

SUMMARY OF THE FIGURES

[0069] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0070] FIG. 1 is a schematic plan view of a cranial prosthesis according to one embodiment of the present invention;

[0071] FIG. 2 is a schematic exploded view of a cranial prosthesis according to one embodiment of the present invention;

[0072] FIG. 3 is a schematic cross-sectional view of a cranial prosthesis according to one embodiment of the present invention;

[0073] FIG. 4 is schematic cross-sectional view of a portion of a cranial prosthesis according to one embodiment of the present invention;

[0074] FIG. 5 is an oblique posterior view of a spinal prosthesis according to one embodiment of the present invention;

[0075] FIG. 6 is an oblique posterior view of a pair of members forming a part of a spinal prosthesis according to FIG. 5;

[0076] FIG. 7 is an oblique anterior view of a pair of members forming a part of a spinal prosthesis according to FIG. 5.

DETAILED DESCRIPTION OF THE INVENTION

[0077] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.

[0078] FIGS. 1 to 3 show various representations of a cranial prosthesis 100 embodying a number of different aspects of the present invention.

[0079] The cranial prosthesis comprises a single peripheral frame portion 101 defining a single central aperture 103. In other words, the prosthesis is a two-part prosthesis. The peripheral frame portion here comprises the entire periphery of the prosthesis 100. The frame portion is an irregular shape selected to match a cranial defect of an intended recipient of the prosthesis, and accordingly improve cosmesis of a cranioplasty using the implant. The frame portion has four integrated fixation lugs 105 which are approximately evenly distributed about the perimeter of the peripheral frame portion 101. Each lug has a hole 107 for receiving a screw (not shown) for fixing the lug to the skull of a recipient of the prosthesis in a manner well known to the skilled person. Providing integrated fixation lugs gives improved intraoperative ease, as it removes the requirement for provision and attachment of separate fixation plates: the prosthesis can be attached directly to the skull of the recipient.

[0080] The prosthesis comprises a removable insert portion 109 which is of a shape suitable for closing the aperture 103. Here, the removable insert portion entirely closes the aperture 103 when it is located within the aperture, such as after implantation of the prosthesis. The removable insert portion also has four integrated fixation lugs 111 for removably attaching the insert portion 109 to the peripheral frame portion 101. The integrated fixation lugs 111 and the shape of the peripheral frame portion 101 are selected to provide an appropriate degree of keying between the lugs and the frame which can assist in correct location of the insert within the aperture. In a similar manner to the lugs 105 of the peripheral frame portion, each fixation lug 111 of the insert portion has a hole 115 receiving a screw (not shown) for fixing the lug to the peripheral frame portion. Here, the (countersunk) holes 107, 115 have chamfered edges to allow for recessing of a screw head into the hole. The holes 107, 115 could alternatively be counterbored.

[0081] The fixation lugs 111 of the insert portion attach to the peripheral frame portion 101 at recessed fixation points comprising suitably shaped ledges 113 by which the fixation lugs of the insert portion can be supported. Because the ledges 113 are recessed from the surface of the peripheral frame portion, the outer surface of the insert lies flush with the outer surface of the peripheral frame portion when it is closing the aperture 103. This can be seen most clearly in FIG. 3.

[0082] The peripheral frame portion and the insert portion have different porosities represented by the different density of hashing in FIG. 3. Here, the peripheral frame portion has a higher porosity than the insert portion. By providing a prosthesis where the porosity is graduated laterally across the implant in an in-plane direction, the prosthesis is able to provide suitable bone integration at the peripheral frame portion (which has a bone-contacting edge 117) whilst also providing a satisfactory mechanical strength. Furthermore, bone integration into the insert portion is discouraged due to its lower porosity. The recessed fixation ledges 113 of the peripheral frame portion have a lower porosity than the rest of the peripheral frame portion. This allows for the ledges to have suitable mechanical strength for holding a screw in place.

[0083] The cranial prosthesis shown in FIG. 1-3 is advantageously made from a material according to Example 1, below. That is, the prosthesis is formed from 29.5-34.5 wt % PPSU reinforced composite containing 65-70 wt % HAP nanoparticle and 0.5 wt % reduced graphene oxide/titanium dioxide nanocomposite based on total weight of the composite material, the reduced graphene oxide/titanium dioxide nanocomposite having a TiO.sub.2:rGO ratio of 80:20 by weight. In this way, the prosthesis can provide suitable promotion of osseointegration in combination with antibacterial capability.

[0084] FIG. 4 is a schematic cross-sectional view of a portion of a cranial prosthesis 200 according to one embodiment of the present invention. The cranial prosthesis 200 has a core layer 201, a first skin layer 203 and a second skin layer 205. The skin layers are disposed on opposite sides of the core layer 201 in a symmetrical arrangement. The different porosities of the different layers of the prosthesis (as represented by the density of hashing) provide a through-thickness porosity graduation. The skin layers have a lower porosity than the core layer, thus more closely matching or mimicking the structure and morphology of cranial bone, in which the central trabecular bone layer has greater porosity than the surrounding layers of cortical bone.

[0085] Here, the core layer is thicker than each of the skin layers, being approximately twice as thick as each skin layer. The skin layers are of approximately equal thickness. This arrangement also mimics that of cranial bone, where the central trabecula bone layer is typically thicker than the cortical bone layers.

[0086] FIGS. 5 to 7 show various oblique views of a spinal prosthesis 300 and members forming parts of the spinal prosthesis as disclosed and described in WO 2006/114646. The prosthesis is an articulating intervertebral disc prosthesis including a first body 301 and a second body 303. Each of the first and second bodies comprises a respective first member 305, 307 and a second member 309, 311. The first body first member 305 has a first vertebra contacting portion 313, and the first body second member 309 has a second vertebra contacting portion 315. Likewise, the second body first member 307 has a first vertebra contacting portion 317, and the second body second member portion 311 has a second vertebra contacting portion 319. Here, the vertebra contacting portions 313, 315, 317, 319 are profiled to be a buttress-thread type ridged surface to prevent translation of the prosthesis when the prosthesis is in place in the spine and in use.

[0087] Each of the first members 305, 307 has a bearing surface 321, 323 (respectively) as shown in FIG. 6. Each of the second members 309, 311 has a bearing surface 325, 327 (respectively) as shown in FIG. 7. Here, each bearing surface 321, 323, 325, 327 is formed to approximate to a portion of an oblate spheroidal surface. In use, the first and second body first member bearing surfaces 321, 323 abut the respective second member bearing surfaces 325, 327.

[0088] Because the prosthesis is an articulating prosthesis having multiple bearing surfaces, it is advantageously made from a material according to Example 2, below. That is, the prosthesis is formed from 98-99 wt % PPSU reinforced composite containing 1-2 wt % reduced graphene oxide/titanium dioxide nanocomposite based on total weight of the composite material, the reduced graphene oxide/titanium dioxide nanocomposite having a TiO.sub.2:rGO ratio of 80:20 by weight. In this way, the prosthesis can provide improved tribological performance in combination with antibacterial capability.

[0089] Porosity Measurement

[0090] Porosity as discussed in the above description refers to bulk porosity defined as 1−V.sub.s, where V.sub.s=solid volume fraction of the material. The solid volume fraction for a sample can be calculated by calculating the ratio between the density of the sample and the theoretical density of a non-porous sample of the same material. However, the skilled person will be well aware of a wide range of suitable methods for measuring bulk porosity of a material.

[0091] Where the above description contains detail of porosities and pore sizes of natural bone, these estimates are calculated from methods including e.g. magnetic resonance imaging (MRI), micro computer tomography (mCT) or microradiography.

[0092] Whilst the above description generally refers to bulk porosity, the skilled person will also understand that it is possible to calculate the interconnected porosity or pore volume of a material using e.g. mercury intrusion porosimetry (MIP). The materials and devices disclosed herein preferably have an interconnected porosity/pore volume which promotes osseointegration.

[0093] Pore Size Measurement

[0094] Pore size as discussed in the above description refers to average diameter of pores within a selected region. The skilled person will be well aware of a wide range of suitable methods for measuring average pore diameter, including e.g. optical microscopy (OM), scanning electron microscopy (SEM), X-Ray scanning, and CT scanning.

EXAMPLES

Example Material 1

[0095] One composite material according to the present invention is as follows:

[0096] 29.5-34.5 wt % PPSU reinforced composite containing 65-70 wt % hydroxyapatite (HAP) nanoparticle and 0.5 wt % reduced graphene oxide/titanium dioxide nanocomposite based on total weight of the composite material, the reduced graphene oxide/titanium dioxide nanocomposite having a TiO.sub.2:rGO ratio of 80:20 by weight.

[0097] Such material may be particularly suitable for promoting osseointegration in combination with antibacterial capability.

Example Material 2

[0098] Another composite material according to the present invention is as follows:

[0099] 98-99 wt % PPSU reinforced composite containing 1-2 wt % reduced graphene oxide/titanium dioxide nanocomposite based on total weight of the composite material, the reduced graphene oxide/titanium dioxide nanocomposite having a TiO.sub.2:rGO ratio of 80:20 by weight.

[0100] Such material may be particularly suitable for providing enhanced tribological performance in combination with antibacterial capability.

[0101] Example Material Specifications

[0102] The initial materials used in manufacture of the above composite materials above are standard, commercially-available materials such as the following:

[0103] PPSU: Solvay Specialty Polymers VERIVA™ VR-500 Polyphenylsulfone having the following typical properties:

TABLE-US-00001 TABLE 1 VERIVA ™ VR-500 material specification Property Value Test Method Specific Gravity 1.27 to 1.31 g/cc ASTM D792 Melt Mass-Flow Rate (MFR) 13 to 20 g/10 min ASTM D1238 (365° C./5.0 kg) Tensile Modulus >275000 psi ASTM D638 Tensile Strength (Yield)  >10000 psi ASTM D638 Tensile Elongation (Break) >6.5% ASTM D638 Notched Izod Impact >10 ft .Math. lb/in ASTM D256 Cytotoxocity Pass ISO 10993:5 Physiochemical Testing Pass ISO 10993:18

[0104] TiO2: 99.9% purity, anastase phase, 18 nm (US Research Nanomaterials) having the following typical properties:

TABLE-US-00002 TABLE 2 99.9% purity pure anastase 18 nm (US Research Nanomaterials) material specification Property Value Purity 99.9% Average particle diameter 18 nm Specific surface area 200-240 m.sup.2/g Color white Bulk Density 0.24 g/cm.sup.3 True Density 3.9 g/cm.sup.3 PH 6-6.5

[0105] Graphene oxide: Research Grade Single Layer Graphene Oxide Dry Nanopowder (US Research Nanomaterials) having the following typical properties:

TABLE-US-00003 TABLE 3 Research Grade Single Layer Graphene Oxide Dry Nanopowder (US Research Nanomaterials) material specification Property Value Purity >99.3% Single layer graphene Oxide Trace elements C: 68.44%, O: 30.92, Free C: 0.4%, S: 0.13% Diameter 1.5-5.5 μm Thickness 0.43-1.23 nm Colour Amber

[0106] Hydroxyapatite: nanoXIM HAp200 (Fluidinova) having the following typical properties:

TABLE-US-00004 TABLE 4 nanoXIM HAp200 (Fluidinova) material specification Property Value Phase purity, Ca.sub.10(PO.sub.4).sub.6(OH).sub.2 100% Specific surface area BET, ≥100 m2/g Heavy metals, as Pb, ≤20 ppm Particle size, d.sub.50 5.0 ± 1 μm, 10.0 ± 2 μm

[0107] The composite materials of Example 1 and Example 2 may be made from these initial materials using any suitable method known in the state of the art, including but not limited to acoustic mixing, acoustic milling ultrasonification, mechanical paddle mixing, melt flow mixing, static melt blending or spiral flow jet milling to disperse or distribute the filler material components throughout the polymeric matrix material in a known manner. The filler material or filler material components may initially be provided as a suspension or dispersion in a suitable aqueous or polar solvent e.g. ethanol.

[0108] In some cases it may be advantageous to first dissolve the polymeric matrix material in a suitable solvent before addition of the filler material, however this may not be necessary where the polymeric matrix material is hot melt processable e.g. in powder, or granule form.

[0109] In some cases it may be preferred to first form a TiO.sub.2-Graphene nanocomposite from the initial materials before combining this nanocomposite filler material with the matrix material. One method for preparation of TiO.sub.2-reduced graphene oxide (rGO) nanocomposites using UV-assisted photocatalytic reduction is described in a paper by Williams et al: “TiO.sub.2-Graphene Nanocomposites. UV-Assisted Photocatalytic Reduction of Graphene Oxide,” ACS Nano, (2008), 2 (7), 1487-1491. Another method is described in Yang et al. “Synthesis of r-GO/TiO2composites via the UV-assisted photocatalytic reduction of graphene oxide” (2016). In this method, irradiation is performed for 5 hours using a low pressure mercury lamp having a narrow band UV emission at a wavelength of 254 nm and a power of 18 W.

[0110] An alternative method for preparation of TiO.sub.2-reduced graphene oxide (rGO) nanocomposites is via a hydrothermal method, such as that described in a paper by Fan et al.: “Nanocomposites of TiO.sub.2 and Reduced Graphene Oxide as Efficient Photocatalysts for Hydrogen Evolution”: J. Phys. Chem. C 2011, 115, 10694-10701.

[0111] The photoactive nanocomposite may then be dispersed through the polymeric matrix material using one of the methods discussed above.

[0112] Photoactivation (or top-up photoactivation) of the nanocomposite material may be performed, before or after dispersion of the nanocomposite in the polymeric matrix material.

[0113] The resulting powder/polymer aggregate may then be pelletised, extruded, compression or injection moulded, thermoformed or 3D printed. E.g., the powder/polymer aggregate may be extruded via a hot melt process to form filament for use in fusion deposition modelling.

[0114] Example Method for Production of Composite Material Filament

[0115] One suitable method for production of a TiO.sub.2/rGO PPSU nanocomposite filament having a composition of e.g. Example Material 1 is as follows. The quantities of each material are not specified below as this method may be used to manufacture TiO.sub.2/rGO PPSU nanocomposite filaments having a range of compositions. Accordingly, the quantities of each material may be selected as appropriate for the desired composition of the composite material. [0116] A. Ultrasonication of a graphene oxide (GO) dispersion in water or ethanol for 60 mins whilst adding TiO.sub.2 to form a colloidal suspension of TiO.sub.2 and GO. [0117] B. Transfer of said suspension to a suitable immersion well photoreactor, where the suspension undergoes UV-assisted photocatalytic reduction for at least 5 hrs but more preferably 24-48 hrs under nitrogen purge & continuous stirring to maximise yield of photoactivated reduced graphene oxide/titanium dioxide nanocomposite powder (rGO)/TiO2) [0118] C. Separation of the TiO.sub.2/rGO nanocomposite powder by centrifuging at 5000 rpm for 30 mins. [0119] D. Washing and filtration of the separated TiO.sub.2/rGO nanocomposite powder (washing and filtration may be performed multiple times), followed by vacuum drying for 4 hrs at 60° C. [0120] E. Addition of the dried powder to a coarse mixture of pre-dried HAP nanopowder and PPSU granules or powder. [0121] F. Acoustic mixing/milling of the TiO.sub.2/rGO/HAP/PPSU mixture for 1-2 hrs to produce the final polymer/powder aggregate. [0122] G. Vacuum drying of the powder/polymer aggregate for 4 hrs at 60° C. prior to hot-melt flow mixing and/or static melt blending and hot melt extrusion to form filament. [0123] H. Air drying of the filament at 80° C. for 12 hrs prior to FDM printing.

[0124] Fusion Deposition Modelling

[0125] As mentioned above, materials and devices according to the present invention may be processed or manufactured using fusion deposition modelling techniques. The skilled person will be aware of commercially available fusion deposition modelling machines having resolutions as low as 50 μm or less, which would be suitable for use in processing and/or manufacturing materials and devices as discussed above.

[0126] To generate a prosthesis by fusion deposition modelling, an STL or OBJ file of the desired product should first be generated (e.g. for a cranial plate by converting patient specific high resolution 3D CT, MRI or surface scan data to an STL or OBJ file using software in a manner well known to the skilled person). The model can then be imported into software associated with the FDM machine, which computes the required tool paths for the extrusion nozzle of the FDM machine. The extrusion nozzle then draws cross-sectional layers one at a time in the X, Y, Z coordinates using a heated material extrusion process to form the FDM printed prosthesis.

[0127] Example FDM processing parameters for production of an orthopaedic, spinal or craniomaxillofacial implant from the material of the first aspect including PPSU as the polymeric matrix material are as follows:

[0128] A) Filament air drying prior to printing at about 80° C. for 12 hrs

[0129] B) Extruder nozzle diameter: 0.2 mm [0130] Layer height: 0.05-0.1 mm [0131] Print speed: 10-80 mm/s (preferably around 10 mm/s)

[0132] C) Printer extruder nozzle temperature: [0133] 260-400° C. [0134] Heated build platform: 150° C. [0135] Heated build chamber: 70° C.

[0136] D) Post-print surface finishing followed by annealing

[0137] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0138] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0139] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations.

[0140] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0141] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0142] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” or “around” one particular value, and/or to “about” or “around” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedents “about” or “around”, it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example+/−10%.

REFERENCES

[0143] A number of publications are cited above in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below. The entirety of each of these references is incorporated herein. [0144] The Williams' Dictionary of Biomaterials, D. F. Williams, Liverpool University Press, 1999 [0145] Visai et al.: Titanium oxide antibacterial surfaces in biomedical devices; Int J Artif Organs (2011); 34 (9); 929-946 [0146] Diez-Pascual et al.: Effect of TiO2 nanoparticles on the performance of polyphenylsulfone biomaterial for orthopaedic implants; J Materials Chemistry B; (2014); 2; 7502-7514 [0147] Williams et al.: TiO.sub.2-Graphene Nanocomposites. UV-Assisted Photocatalytic Reduction of Graphene Oxide; ACS Nano, (2008), 2 (7), 1487-1491 [0148] Kralchevska et al: Influence of gamma-irradiation on the photocatalytic activity of Degussa P25 TiO.sub.2; J Mater Sci; (2012); 47; 4936-4945 [0149] Fan et al.: Nanocomposites of TiO.sub.2 and Reduced Graphene Oxide as Efficient Photocatalysts for Hydrogen Evolution’: J. Phys. Chem. C 2011, 115, 10694-10701 [0150] Yang et al: ‘Synthesis of r-GO/TiO2composites via the UV-assisted photocatalytic reduction of graphene oxide’: Applied Surface Science 380 (2016) 249-256