Biomedical Implant Having Conical-Tipped Titania Nanorods

Abstract

A method of making a biomedical implant comprising the steps of contacting a biomedical implant having a surface comprising titanium with an acidic solution comprising a titanium precursor capable of hydrolysis to titanium for a time sufficient to epitaxially grow titania nanorods on the surface. Preferably, the titanium precursor is selected from the group consisting of titanium butoxide, TTIP and titanium tetrachloride. Carrying out the method provides a biomedical implant having a surface having nanorods comprising at least 50% titania extending therefrom, wherein the nanorods terminate in a substantially conical tip, wherein the nanorods have a density on the implant of at least 10 nanorods/um.sup.2.

Claims

1. A biomedical implant having a surface having nanorods comprising at least 50% titania extending therefrom, wherein the nanorods terminate in a substantially conical tip, wherein the nanorods have a density on the implant surface of at least 10 nanorods/um.sup.2.

2. The implant of claim 1 wherein the tip forms an angle of no more than 90 degrees.

3. The implant of claim 1 wherein the tip forms an angle of no more than 60 degrees.

4. The implant of claim 1 wherein the tip forms an angle of no more than 45 degrees.

5. The implant of claim 1 wherein the implant is a spinal implant.

6. The implant of claim 1 wherein the implant is a pedicle screw.

7. The implant of claim 1 wherein the nanorods have an average mid-height diameter of between about 50 nm and 300 nm.

8. The implant of claim 1 wherein the nanorods have an average length of between about 500 nm and about 3000 nm.

9. The implant of claim 1 wherein the nanorods extend substantially in the same direction.

10. A biomedical implant having a surface having nanorods comprising at least 50% titania extending therefrom, wherein the nanorods terminate in a substantially jagged tip having step edges.

11. The implant of claim 10 wherein the nanorods consist essentially of titania.

12. The implant of claim 11 wherein the implant is a spinal implant.

13. The implant of claim 11 wherein the implant is a pedicle screw.

14. The implant of claim 11 wherein the nanorods have an average mid-height diameter of between about 50 nm and 300 nm.

15. The implant of claim 11 wherein the nanorods have an average length of between about 500 nm and about 3000 nm.

16. The implant of claim 11 wherein the nanorods extend substantially in the same direction.

17. A method of making a biomedical implant comprising the steps of: a) contacting a biomedical implant having a surface comprising titanium with an acidic solution comprising a titania precursor capable of hydrolysis to titania for a time sufficient to epitaxially grow titania nanorods on the surface, wherein the nanorods terminate in conical tips.

18. The method of claim 17 wherein the titanium precursor is selected from the group consisting of titanium butoxide, TTIP and titanium tetrachloride.

19. The method of claim 17 wherein the titanium precursor is titanium butoxide.

20. A biomedical implant having titania nanorods extending therefrom, wherein the nanorods having a spacing therebetween, and wherein the spacing is filled with a coating.

21. The implant of claim 20 wherein the coating is a resorbable polymeric coating.

22. The implant of claim 20 wherein the coating is polyglycolic acid.

23. The implant of claim 20 wherein the coating comprises calcium phosphate.

24. The implant of claim 20 wherein the coating comprises hydroxyapatite.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0022] For the purposes of the present invention, nanorods with pyramidal-shaped tips are considered to have conical tips, as that is their appearance in an SEM side-view photo thereof.

[0023] Preferably, the bulk material of the implant comprises at least 50% titanium, and is more preferably Ti6Al4V, which comprises about 90% titanium. However, it may also be commercially pure titanium.

[0024] In some embodiments, there is provided a biomedical implant having a surface having nanorods consisting essentially of titania extending therefrom, wherein the nanorods terminate in a substantially conical tip.

[0025] Preferably, the conical tip forms a cone angle of no more than 90 degrees, more preferably no more than 60 degrees, most preferably no more than 45 degrees.

[0026] In some embodiments, the implant is a spinal implant, preferably a pedicle screw or an interbody fusion cage. In other embodiments, the implant is selected from the group consisting of a hip implant (such as an acetabular cup or a femoral insert); a knee implant (such as a tibial tray or a femoral stem), a shoulder implant and a trauma implant (such as a plate or a nail).

[0027] In some embodiments, the nanorods have an average mid-height diameter of between about 50 nm and 300 nm.

[0028] In some embodiments, the nanorods have an average length of between about 500 nm and about 3000 nm.

[0029] In some embodiments, the nanorods extend substantially in the same direction. That is, at least 85% of the nanorods extends extend at an angle of between 45 degree and 135 degrees from the implant surface.

[0030] Wang I discloses nanorod densities on the substrate of about 100 nanorods/um.sup.2, respectively. Therefore, assuming the nanorods of Wang I can be replicated on titanium-based substrates, in some embodiments, the titania nanorods have a density on the implant of at least 10 nanorods/um.sup.2, preferably at least 25 nanorods/um.sup.2, more preferably at least 50 nanorods/um.sup.2, most preferably at least 75 nanorods/um.sup.2. It is believed that these greater densities will produce more effective bacterial killing rates than the lower pyramid-tipped densities of Sjostrom.

[0031] Although the implants having the conical tips are preferred, it is nonetheless believed that the jagged tips having step edges are also useful for killing bacteria. Therefore, in some embodiments, there is provided a biomedical implant having a surface having nanorods comprising titania extending therefrom, wherein the nanorods terminate in a substantially jagged tip having step edges. Preferably, the nanorods consist essentially of titania.

[0032] In some embodiments, there is provided a method of making a biomedical implant comprising the steps of: [0033] a) contacting a biomedical implant having a surface comprising titanium with an acidic solution comprising a titania precursor capable of hydrolysis to titania for a time sufficient to epitaxially grow titania nanorods on the surface; [0034] b) optionally, annealing the implant.

[0035] In some embodiments, the titania precursor is selected from the group consisting of titanium butoxide, titanium tetraisopropoxide (TTIP) and titanium tetrachloride, and is preferably titanium butoxide.

[0036] In one article involving the hydrothermal synthesis of titania with TTIP as the titania precursor, Yamazaki discloses alpha-hydroxy acids such as lactic acid and glycolic acid as structure-directing agents. Yamazaki, ACS Omega, 2021, 6, 31557-65. Therefore, in some embodiments, an alpha-hydroxy acid is added to the aqueous acidic solution comprising the titanium precursor as a way of directing formation of the conical tips.

[0037] It is noted that there are some commercial pedicle screws (e.g., Nanovis) having titania nanotubes, thereby demonstrating that titania nanostructures have the strength to withstand screw insertion. It is further noted that the literature on titania nanotubes generally reports SEM pictures showing the nanotubes closely packed together. Because the technology disclosed in Table I generally produces nanorods with a fair amount of spacing therebetween, the question is raised as to whether the nanorods of the present invention will have sufficient strength to withstand screw insertion. Therefore, in accordance with the present invention, there is provided a biomedical implant having titania nanorods extending therefrom, wherein the nanorods having a spacing therebetween, and wherein the spacing is filled with a coating. It is believed the coating will provide mechanical strength to the implant and protect the nanorods it envelops during screw insertion. Preferably, the coating is a resorbable polymeric coating, such as polyglycolic acid. In other embodiments, the coating comprises calcium phosphate such as hydroxyapatite.

PROPHETIC EXAMPLE I

[0038] This prophetic example reports a recipe for making the inventive biomedical implant and essentially adopts the technology disclosed in Wang I for making titania nanorods, but with a titanium alloy replacing FTO.

[0039] In particular, 12 mL of deionized water was mixed with 12 mL of concentrated hydrochloric acid (mass fraction 36.5-38%). The mixture wa stirred under ambient conditions for 5 minutes before adding 0.4 mL of titanium butoxide (Beijing Chemical Co.). After stirring for another 5 minutes, the mixture was placed in a Teflon-lined stainless steel autoclave of 45 mL volume. Then, a Ti6Al4V spinal pedicle screw, ultrasonically cleaned for 60 minutes in a mixed solution of deionized water, acetone and 2-propanol (volume rations 1:1:1) was placed at an angle against the wall of the Teflon liner. The hydrothermal synthesis was conducted at 150 C. for 20 hours in an electric oven. After the synthesis, the screw as taken out, rinsed extensively in deionized water and dried in ambient air.

PROPHETIC EXAMPLE II

[0040] This prophetic example essentially follows Prophetic Example I above, but then further anneals the resulting nanorod-laden pedicle screw at 450 C. for 30 minutes.