Abstract
An implant for the replacement and regeneration of biological tissue in the shape of a plug, comprising a base section (2) configured for anchoring in bone tissue, a middle section (3) configured for replacing cartilage tissue, and a top section (4) configured for growing cartilage tissue onto and into, wherein the middle and top sections comprise the same thermoplastic elastomeric material, which is porous in the top section, and non-porous in the middle section, and wherein the base section comprises a substantially non-porous polyaryletherketone polymer with a porosity of less than 20%, relative to the total volume of the polyaryletherketone polymer.
Claims
1. An implant for the replacement and regeneration of biological tissue in the shape of a plug, comprising a base section configured for anchoring in bone tissue, a middle section configured for replacing cartilage tissue, and a top section configured for growing cartilage tissue onto and into, wherein the middle and top section comprise the same thermoplastic elastomeric material, which is porous in the top section, and non-porous in the middle section, and wherein the base section comprises a substantially non-porous polyaryletherketone polymer with a porosity of less than 20%, relative to the total volume of the polyaryletherketone polymer.
2. The implant according to claim 1, wherein the base section comprises a core of non-porous polyaryletherketone polymer and a circumferential shell of porous polyaryletherketone polymer, wherein the shell has a thickness that is less than 10% of a largest diameter of the base section.
3. The implant according to claim 1, wherein the base section extends between a top surface and a bottom surface, and comprises a layer of porous polyaryletherketone polymer, wherein the layer is adjacent to the top surface and has a thickness that is less than 10% of a largest height of the base section, and wherein the pores of the polyaryletherketone polymer in the layer comprise the biocompatible elastomeric material.
4. The implant according to claim 1, wherein the top surface of the base section comprises irregularities or undulations.
5. The implant according to claim 1, wherein the base section comprises a centrally located cavity that comprises the biocompatible elastomeric material.
6. The implant according to claim 1, wherein the base section comprises a non-porous polyaryletherketone polymer.
7. The implant according to claim 1, wherein the base section further comprises a phosphate mineral comprising an apatite.
8. The implant according to claim 1, wherein the base section comprises an outer surface having irregularities or undulations.
9. The implant according to claim 1, wherein the elastomeric material of the middle section has an elastic modulus at room temperature of less than 10 MPa.
10. The implant according to claim 1, wherein the porous elastomeric material of the top section has an elastic modulus at room temperature of less than 80% of the elastic modulus of the elastomeric material of the middle section.
11. The implant according to claim 1, wherein a height of the base section, a height of the non-porous middle section, and a height of the porous top section are selected such that a top surface of the implant comes to lie below a top surface of cartilage present on an osteochondral structure when implanted, preferably over a distance of between 0.1-1 mm.
12. The implant according to claim 1, wherein a height of the base section, a height of the non-porous middle section, and a height of the porous top section are selected such that a bottom surface of the middle section comes to lie about level with a bottom surface of cartilage present on an osteochondral structure when implanted.
13. The implant according to claim 1, comprising a top section with a slightly curved top surface, having a radius of curvature in a sagittal and/or a medial-lateral plane ranging from 15 mm to 150 mm.
14. The implant according to claim 1, wherein the polyaryletherketone polymer of the base section comprises a reinforcing material selected from the group consisting of fibrous or particulate polymers and/or metals.
15. The implant according to claim 1, wherein the thermoplastic elastomeric material comprises a linear block copolymer comprising urethane and urea groups, and is substantially free of an added peptide compound having cartilage regenerative properties.
16. The implant according to claim 15, wherein the thermoplastic elastomeric material further comprises carbonate groups.
17. The implant according to claim 16, wherein the thermoplastic elastomeric material comprises a poly-urethane-bisurea-alkylenecarbonate.
18. The implant according to claim 1, wherein the thermoplastic elastomeric material is aliphatic.
19. The implant according to claim 1, wherein the middle section comprises a core of non-porous elastomeric material and a circumferential shell of porous elastomeric material, wherein the shell has a thickness that is less than 10% of a largest diameter of the middle section.
20. A method for the preparation of an implant, comprising: a) providing in a mold at room temperature a base section that comprises a substantially non-porous polyaryletherketone polymer with a porosity of less than 20% relative to the total volume of the polyaryletherketone polymer; and granules of a thermoplastic elastomeric material on top of the base section; b) closing the mold and heating the above assembly to a temperature of between 100° C. and 250° C. under a pressure of between 1 and 2 GPa, such that the thermoplastic elastomeric material melts and fuses with the base section; and c) cooling the assembly to room temperature to consolidate the thermoplastic elastomeric material and opening the mold; d) providing a top section of the thermoplastic elastomeric material with pores either before or after opening the mold.
21. The method according to claim 20, wherein after step b) the mold is opened and additional granules of the thermoplastic elastomeric material are added to the mold, and step b) is repeated.
22. Osteochondral structure comprising an implant according to claim 1, wherein a top surface of the implant lies below a top surface of the cartilage layer on the osteochondral structure.
Description
BRIEF DESCRIPTION OF THE FIGURES
[0045] The invention will now be further elucidated by the following figures and examples, without however being limited thereto. In the figures:
[0046] FIGS. 1A to 1D show a schematic side view of four embodiments of an exemplary implant according to the present invention;
[0047] FIG. 2A shows a schematic perspective view of a base section according to an embodiment of the invention;
[0048] FIG. 2B shows a schematic cross-section of the embodiment of FIG. 2A;
[0049] FIGS. 2C and 2D show a schematic detailed view of parts B and C of the embodiment of FIG. 2B;
[0050] FIG. 3 shows a schematic representation of a possible synthetic route to the thermoplastic polycarbonate material according to an embodiment of the invention;
[0051] FIG. 4 shows a .sup.1H-NMR spectrum of the thermoplastic polycarbonate material according to an embodiment of the invention;
[0052] FIGS. 5A to 5C show DSC thermograms of the thermoplastic polycarbonate material according to an embodiment of the invention at different heating rates;
[0053] FIGS. 6A to 6C show a schematic representation of a defect in an osteochondral structure (6A), the osteochondral structure comprising an implant according to an embodiment of the invention (6B) and the same osteochondral structure after on-/ingrowth of cartilage (6C);
[0054] FIGS. 7A to 7D show a schematic side view of four embodiments of an implant according to yet another embodiment of the present invention; and finally
[0055] FIGS. 8A to 8C show a schematic representation of a defect in an osteochondral structure (8A), the osteochondral structure comprising an implant according to another embodiment of the invention (8B) and the same osteochondral structure after on-/ingrowth of cartilage (8C).
[0056] Referring to FIG. 1A, a side view of an embodiment of an exemplary implant according to the present invention is shown. The implant 1 in the shape of a plug comprises a base section 2, configured for anchoring in bone tissue, a middle section 3 configured for replacing cartilage tissue, and a top section 4 configured for growing cartilage tissue onto and into. The middle section 3 and top section 4 comprise the same thermoplastic elastomeric material. The thermoplastic elastomeric material in this embodiment comprises a poly-urethane-bisurea-hexylenecarbonate, the preparation and properties whereof will be elucidated further below. The top section 4 however comprises poly-urethane-bisurea-hexylenecarbonate in porous from, whereas the middle section 3 comprises the same poly-urethane-bisurea-hexylenecarbonate without any pores. The base section 2 comprises a non-porous polyaryletherketone polymer, which, in the embodiment shown is a non-porous PEKK polymer. The implant 1 is cylindrical and has a diameter 10 of 6 mm. The height 20 of the base section 2, the height 30 of the middle section 3, and the height 40 of the top section 4 add up to a total height of 6 mm.
[0057] FIG. 1B schematically represents a side view of another embodiment of an implant according to the present invention. The embodied implant 1 in the shape of a plug again comprises a base section 2, configured for anchoring in bone tissue, a middle section 3 configured for replacing cartilage tissue, and a top section 4 configured for growing cartilage tissue onto and into. The middle section 3 and top section 4 comprise the same poly-urethane-bisurea-hexylenecarbonate material, which is porous in the top section 4, and non-porous in the middle section 3. The base section 2 comprises a substantially non-porous PEKK polymer with a porosity of less than 20%, relative to the total volume of the PEKK polymer. The base section 2 of this embodiment in particular comprises a core 21 of non-porous PEKK polymer and a circumferential shell 22 of porous PEKK polymer. The shell 22 has a thickness 23 of about 8% of the diameter 10 of the base section 2 (and implant 1). The base section 2 further extends between a top surface 24 and a bottom surface 25, and comprises a layer 26 of porous PEKK polymer, which layer 26 is adjacent to the top surface 24 and has a thickness 27 of about 8% of the height 20 of the base section 2. The pores of the PEKK polymer in the layer 26 comprise the biocompatible poly-urethane-bisurea-hexylenecarbonate which originates from the middle section 3 and has infiltrated the pores of the PEKK polymer in the layer 26 during manufacturing. A method for manufacturing the implant will be elucidated further below. As with the embodiment of FIG. 1A, the implant 1 is cylindrical and has a diameter 10 of 6 mm. The height 20 of the base section 2, the height 30 of the middle section 3, and the height 40 of the top section 4 add up to a total height of 6 mm.
[0058] FIG. 1C schematically represents a side view of yet another embodiment of an implant according to the present invention. The embodied implant 1 in the shape of a plug again comprises a base section 2, configured for anchoring in bone tissue, a middle section 3 configured for replacing cartilage tissue, and a top section 4 configured for growing cartilage tissue onto and into. The middle section 3 and top section 4 comprise the same poly-urethane-bisurea-hexylenecarbonate material, which is porous in the top section 4, and substantially non-porous in the middle section 3. The base section 2 comprises a substantially non-porous PEKK polymer with a porosity of less than 20%, relative to the total volume of the PEKK polymer. The base section 2 of this embodiment in particular extends between a top surface 24 and a bottom surface 25, and comprises a layer 26 of porous PEKK polymer, which layer 26 is adjacent to the top surface 24 and has a thickness 27 of about 8% of the height 20 of the base section 2. The pores of the PEKK polymer in the layer 26 comprise the biocompatible poly-urethane-bisurea-hexylenecarbonate which originates from the middle section 3 and has infiltrated the pores of the PEKK polymer in the layer 26 during manufacturing. The middle section 3 of this embodiment in particular comprises a core 31 of non-porous poly-urethane-bisurea-hexylenecarbonate polymer and a circumferential shell 32 of porous poly-urethane-bisurea-hexylenecarbonate polymer. The shell 32 has a thickness 33 of about 8% of the diameter 10 of the middle section 3 (and implant 1). The base section 2 further extends between a top surface 24 and a bottom surface 25, and comprises a layer 26 of porous PEKK polymer, which layer 26 is adjacent to the top surface 24 and has a thickness 27 of about 8% of the height 20 of the base section 2. The dimensions and shape are the same as in the embodiments of FIGS. 1A and 1B.
[0059] FIG. 1D schematically represents a side view of yet another embodiment of an implant according to the present invention. The embodied implant 1 in the shape of a plug corresponds to the one shown in FIG. 1C. In addition, the middle section 3 of this embodiment now has a circumferential shell 32 of porous poly-urethane-bisurea-hexylenecarbonate polymer having a thickness 33 of about 10% of the diameter 10 of the middle section 3 (and implant 1). Further, the base section 2 comprises a layer 26 of porous PEKK polymer, which layer 26 is adjacent to the top surface 24 and has a thickness 27 of about 5% of the height 20 of the base section 2. The pores of the PEKK polymer in the layer 26 comprise the biocompatible poly-urethane-bisurea-hexylenecarbonate which originates from the middle section 3 and has infiltrated the pores of the PEKK polymer in the layer 26 during manufacturing. The base section 2 further comprises a core 21 of non-porous PEKK polymer and a circumferential shell 22 of porous PEKK polymer. The shell 22 has a thickness 23 of about 5% of the diameter 10 of the base section 2 (and implant 1). Finally, the base section 2 also comprises a layer 28 of porous PEKK polymer, which layer 28 is adjacent to the bottom surface 25 and has a thickness 29 of about 5% of the height 20 of the base section 2. The dimensions and shape are the same as in the embodiments of FIGS. 1A to 1C.
[0060] Please note that in FIGS. 1B, 1C, and 1D the circumferential shells (22, 32) are shown in cross-section to show their respective thicknesses (23, 33). In a side view, they would extend over the complete diameter 10 of the implant 1.
[0061] Referring to FIG. 7A, a side view of another embodiment of the implant according to the present invention is shown. The implant 1 in the shape of a plug comprises the same materials and sections as shown in FIG. 1A. The dimensions of the implant of FIG. 7A are the same as those of the implant of FIG. 1A with one exception. Instead of having a flat top surface 41 of the top section 4 (and the implant 1), as in FIG. 1A, the top surface 41a of the top section 4 is spherical with a radius of curvature R of about 28 mm (not drawn to scale).
[0062] Referring to FIG. 7B, a side view of another embodiment of the implant according to the present invention is shown. The implant 1 in the shape of a plug comprises the same materials and sections as shown in FIG. 1B. The dimensions of the implant of FIG. 7B are the same as those of the implant of FIG. 1B with one exception. Instead of having a flat top surface 41 of the top section 4, as in FIG. 1B, the top surface 41a of the top section 4 is spherical with a radius of curvature R of about 28 mm (not drawn to scale). Referring to FIG. 7C, a side view of another embodiment of the implant according to the present invention is shown. The implant 1 in the shape of a plug comprises the same materials and sections as shown in FIG. 1C. The dimensions of the implant of FIG. 7C are the same as those of the implant of FIG. 1C with one exception. Instead of having a flat top surface 41 of the top section 4, as in FIG. 1C, the top surface 41a of the top section 4 is spherical with a radius of curvature R of about 28 mm (not drawn to scale).
[0063] Referring to FIG. 7D, a side view of another embodiment of the implant according to the present invention is shown. The implant 1 in the shape of a plug comprises the same materials and sections as shown in FIG. 1D. The dimensions of the implant of FIG. 7D are the same as those of the implant of FIG. 1D with one exception. Instead of having a flat top surface 41 of the top section 4, as in FIG. 1D, the top surface 41a of the top section 4 is spherical with a radius of curvature R of about 28 mm (not drawn to scale).
[0064] Again note that in FIGS. 7B, 7C, and 7D the circumferential shells (22, 32) are shown in cross-section to show their respective thicknesses (23, 33). In a side view, they would extend over the complete diameter 10 of the implant 1 (not drawn to scale).
[0065] Referring to FIGS. 2A to 2D, an embodiment of a base section 2 of the invented implant 1 is schematically shown. The base section 2 shown is essentially cylindrical-shaped with a diameter 10, and a height 20. The top surface 24 of the base section has a circumferential flat rim part 240 that gradually extends into a centrally located cavity 241. The cavity 241 is provided with locking parts 242 that have a larger diameter than the diameter of the cavity 241. A shown in detail in FIG. 2C, the locking parts 242 of the cavity 241 are disk-shaped whereby the outer rim of the disk makes an angle 246 with the longitudinal direction 247 of the base section 2 of between 1° and 20°, more preferably between 5° and 15°. The cavity 241 (and parts 242) during manufacturing of the implant fills with part of the biocompatible elastomeric material to provide an adequate locking of the middle section 3 to the base section 2. As discussed above, the base section 2 comprises a PEKK polymer which may be non-porous or substantially non-porous, the latter embodiment including the examples disclosed above. The base section 2 is further seen to comprise an outer surface having irregularities or undulations. In the present embodiment, these comprise circumferential ridges 243 which, in cross-section, are saw-tooth-shaped, as shown in detail in FIG. 2D. The angle 244 under which the saw-tooth flanks extend with respect to the transverse direction 245 of the base section 2, is preferably between 70° and 85°, more preferably between 75° and 80°.
Preparation of the Elastomeric Material of the Top and Middle Section
[0066] The aliphatic poly-urethane-urea-hexylene carbonate biomaterial of the middle section 3 and the top section 4 was manufactured as follows (with reference to FIG. 3). Poly(hexylene carbonate) diol (23.9 g, 11.9 mmol) was weighed in a 500 mL 3-necked flask and dried by heating to 75° C. overnight under vacuum, after which it was allowed to cool to room temperature. Under an argon atmosphere, 1,6-diisocyanatohexane (4.1 g, 23.9 mmol), DMAc (20 mL) and a drop of Sn(II)bis(2-ethylhexanoate) were added, after which the mixture was heated and stirred for 3 hours upon which the viscosity increased. The mixture was allowed to cool to room temperature, was diluted with DMAc (100 mL) and a solution of 1,6-diaminohexane (1.4 g, 11.9 mmol) in DMAc (50 mL) was added at once under thorough mixing. A gel was immediately formed upon addition and mixing. The mixture was further diluted with DMAc (150 mL) and was heated in an oil bath of 130° C. to acquire a homogeneous viscous slurry. After cooling to room temperature, the mixture was precipitated in a water/brine mixture (2.75 L water+0.25 L saturated brine) to yield a soft white material. This material was cut into smaller pieces and was stirred in a 1:5 mixture of methanol and water (3 L) for 64 hours. After decanting the supernatant, the resulting solid was stirred in a 2:1 mixture of methanol and water (0.75 L) for 6 hours. Decanting of supernatant, stirring in a 2:1 mixture of methanol and water (0.75 L) for 16 hours, decanting of the supernatant, and drying of the solid at 70° C. in vacuo yielded a flexible, tough elastomeric polymer.
[0067] .sup.1H NMR spectroscopy was performed on the resulting polymer, using a Varian 200, a Varian 400 MHz, or a 400 MHz Bruker spectrometer at 298K. DSC was performed using a Q2000 machine (TA Instruments). Heating scan rates of 10° C./min and 40° C./min were used for the assessment of the melting temperature (Tm) and the glass transition temperature (Tg), respectively. The Tm was determined by the peak melting temperature and the Tg was determined from the inflection point.
[0068] All reagents, chemicals, materials, and solvents were obtained from commercial sources and were used without further purification. The used poly(hexylene carbonate) diol had an average molecular weight of approximately 2 kg/mol. FIGS. 4 and 5 show the .sup.1H NMR spectrum and DSC thermograms of the obtained polymer, respectively. The .sup.1H NMR spectrum results may be summarized as follows: .sup.1H NMR (400 MHz, HFIP-d2): δ=4.23 (m, n*4H, n ˜14.3), 4.10 (m, 4H), 3.17 (m, 12H), 1.87-1.32 (multiple signals for aliphatic CH2 methylenes) ppm. The average molecular weight of the repeating hard/soft block sections is about 2.5 kDa. The DSC results may be summarized as follows: DSC (10° C./min, FIG. 5A): Tm (top)=20.9° C. (soft block melt); DSC (40° C./min, FIG. 5B): Tg=−38.0° C. No second melting point for the hard block was observed up to 200° C. However, in a final heating run up to 250° C. at 10° C./min (FIG. 5C), a small and broad melting transition was observed at ca. 227° C. In the DSC-diagrams, the endothermic melting peaks are plotted downwards, whereas the exothermic crystallizations are plotted upwards.
[0069] The non-porous aliphatic poly-urethane-urea-hexylene carbonate biomaterial had an elastic modulus according to ASTM D638 of 3.6±0.03 MPa.
Preparation of Biomaterial-Capped PEKK Bone Anchors
[0070] The implant 1 was manufactured by attaching the top and middle sections (4, 3) to a PEKK base section 2 which serves as bone anchor. In a method according to an embodiment of the invention, PEKK bone anchors were capped with the poly-urethane-urea-hexylene carbonate biomaterial by pressing small granules of the aliphatic polycarbonate polymer on top of and into the PEKK anchors. For this purpose, a custom press setup was used. Various temperatures (100° C. to about 150° C.), compressive forces (2 kN to about 4 kN) and methods have been tested. The best results were obtained using a two-step procedure, employing a temperature of 150° C. and using a compressive force of 40 kN (4 tons, or 4000 kg; corresponding to a pressure of 1.4 GPa). Lower temperatures than 150° C. seemed to give less homogenously pressed poly-urethane-urea-hexylene carbonate biomaterial layers (sections 3 and 4), while higher temperatures are less desired as the urea groups in the poly-urethane-urea-hexylene carbonate biomaterial may then degrade to some extent. In the first step, ca. 50 mg of the polymer 12 was pressed onto and into the PEKK bone anchor for 15 minutes, while in the second step, ca. 2 mg of polymer 12 was added to the setup and the sample was pressed for another 15 minutes under the same conditions (150° C. and 40 kN). The samples were subsequently removed from the compression setup and were then allowed to cool. After the second pressing step, the surface of the poly-urethane-urea-hexylene carbonate biomaterial layer (sections 3 and 4) on top of the base section 2 seemed to be substantially flat. The biomaterial was almost transparent and colorless. The edges of the biomaterial showed some fringes or frays, and these were removed using a scalpel.
[0071] A central hole (241, 242) of the base section 2 was about 4.5 mm deep and about 2 mm in diameter. The hole was substantially filled with the poly-urethane-urea-hexylene carbonate biomaterial, and the attachment of the biomaterial to the PEKK base section 2 seemed quite strong and robust. Removing the biomaterial from the PEKK base section by force, or loosening the connection at the PEKK-biomaterial interfaces, proved practically impossible. All used equipment and accessories that were intended to come into contact with the PEKK base section 2 and/or with the elastomeric biomaterial were rinsed with ethanol or isopropanol and were thereafter dried. After pressing, and cutting the frays, the PEKK-biomaterial plug implant was rinsed with isopropanol and dried. The plugs may also be produced in a sterilized environment, if needed.
[0072] As assessed by measuring, the PEKK base section was 6 mm in diameter and 6 mm tall (a height of 6 mm). The central cavity in the base section was about 2 mm in diameter and about 4.5 mm deep. The elastomeric biomaterial (the aliphatic polycarbonate) positioned onto the PEKK base section was about 6 mm in diameter and about 1 mm high. Accordingly, the total PEKK-biomaterial plug implant was about 7 mm tall.
[0073] The top section 4 was provided with pores by drilling holes in it with an average diameter of 300 micron, to a final porosity of 50 vol. %. The porous aliphatic poly-urethane-urea-hexylene carbonate biomaterial of the top section 4 had an elastic modulus according to ASTM D638 of 0.9±0.2 MPa.
[0074] The implant 1 may be implanted into an osteochondral defect 8 as shown in FIGS. 6A to 6C. In a typical method, a cartilage defect extending into the subchondral bone (FIG. 6 A) is drilled out and a plug-shaped implant 1 is implanted into the drilled hole under some pressure (‘press fit’), as shown in FIG. 6B. Bone then grows onto, and in some embodiments into, the PEKK base section 2, anchoring the implant 1. Surrounding native cartilage 5 grows onto a top side 41 of the top section 4 and new cartilage 5a is generated on top of the implant 1, as shown in FIG. 6C. As is also shown in FIG. 6C, the height 20 of the base section 2, the height 30 of the non-porous middle section 3, and the height 40 of the porous top section 4 are selected such that a top surface 41 of the implant 1 comes to lie below a top surface 50 of cartilage 5 present on an osteochondral structure (5, 6) when implanted, preferably over a distance 51 of between 0.1-1 mm. In the present case, this distance was about 0.5 mm. The osteochondral structure (5, 6) comprises subchondral bone 6 and a cartilage layer 5 on top of it. A synovial cavity 7 is generally also present.
[0075] As also shown in FIGS. 6B and 6C, the height 20 of the base section 2, the height 30 of the non-porous middle section 3, and the height 40 of the porous top section 4 are selected such that a bottom surface 24 of the middle section 3 (or top surface 24 of the base section 2) comes to lie about level with a bottom surface 51 of the cartilage layer 5 of the osteochondral structure (5, 6) when implanted.
[0076] Finally, the implant according to the embodiment shown in FIGS. 7A to 7D may also be implanted into an osteochondral defect 8 as shown in FIGS. 8A to 8C. Due to a spherical top surface 41a of the top layer 4, this embodiment may regenerate a new cartilage layer 5a on the top surface 41a of the top section 4 of the implant 1 of about equal thickness across the top surface 41a. The result may be a radius of a top surface 50 of the regenerated cartilage 5a that is about the same as the radius of the surrounding native cartilage layer 5 next to the implant, thereby showing a continuity in radius.
[0077] It will be apparent that many variations and applications are possible for a skilled person in the field within the scope of the appended claims of the invention.
