SURFACE TREATMENT OF POLY(ARYL ETHER KETONE)S

Abstract

The present invention relates to a process for the surface treatment of poly(aryl ether ketone)s (PAEKs) comprising the following steps: Providing an article comprising one or more poly(aryl ether ketone)s (PAEKs); contacting at least one portion of the surface of the article containing one or more poly(aryl ether ketone)s (PAEKs) with an aldehyde,
wherein the aldehyde reacts with the poly(aryl ether ketone)(s) (PAEKs) on the at least one portion of the surface of the article to form a hydroxyalkyl and/or hydroxyaryl group,
a process for functionalizing surface-treated poly(aryl ether ketone)s (PAEKs) comprising the steps of: a) Treating at least one portion of the surface of an article containing one or more poly(aryl ether ketone)s (PAEKs) with the surface treatment process for poly(aryl ether ketone)s (PAEKs) described herein; b) Coating the treated at least one portion of the surface of the article with a composition comprising a chemical compound having chemical groups capable of forming a covalent bond with hydroxyalkyl and/or hydroxyaryl groups formed on the surface of the article,
an article comprising one or more poly(aryl ether ketone)s (PAEKs) and a coating on at least one surface of the article, wherein on the coated at least one portion of the surface of the article the poly(aryl ether ketone)(s) (PAEKs) contains hydroxyalkyl and/or hydroxyaryl groups; and at least one portion of the hydroxyalkyl and/or hydroxyaryl groups of the poly(aryl ether ketone)(s) (PAEKs) has formed covalent bonds with chemical groups of at least one chemical compound in the coating, and
the use of the article of the invention as described herein as a medical device and/or biotechnological applications, preferably as an implant, scaffold structure for in vitro applications and/or scaffold structure for cell culture applications.

Claims

1. A process for the surface treatment of poly(aryl ether ketone)s (PAEKs) comprising the following steps: Providing an article comprising one or more poly(aryl ether ketone)s (PAEKs); contacting at least one portion of the surface of the article comprising poly(aryl ether ketone) (PAEK) with an aldehyde, wherein the aldehyde reacts with the poly(aryl ether ketone)(s) (PAEKs) on the at least one portion of the surface of the article to form a hydroxyalkyl and/or hydroxyaryl group.

2. The process of claim 1, wherein the poly(aryl ether ketone)s (PAEKs) are selected from poly(ether ketone) (PEK), poly(ether ether ketone) (PEEK), poly(ether ketone ketone) (PEKK), poly(ether ether ether ketone) (PEEEK), poly(ether ether ketone ketone) (PEEKK), poly(ether ketone ether ketone ketone) (PEKEKK), or mixtures thereof.

3. The process according to claim 1, wherein the article comprising one or more poly(aryl ether ketone)s (PAEKs) comprises a blend of the poly(aryl ether ketone)(s) (PAEKs) with an inorganic structural material.

4. The process according to claim 3, wherein the inorganic structural material is selected from glass fibers, carbon fibers, hydroxyapatite, or mixtures thereof.

5. The process according to claim 1, wherein the aldehyde is selected from formaldehyde (methanol), glyoxal (ethanedial), succinaldehyde (butanedial) and glutaraldehyde (pentanedial) or mixtures thereof.

6. The process according to claim 1, wherein the aldehyde is contacted as a liquid, a gas or an aerosol with at least one portion of the surface of the article comprising one or more poly(aryl ether ketone)s (PAEKs).

7. The process according to claim 1, wherein the at least one portion of the surface of the article comprising one or more poly(aryl ether ketone)s (PAEKs) is additionally subjected to at least one further surface treatment, such as a plasma treatment.

8. A process for functionalizing surface-treated poly(aryl ether ketone)s (PAEKs) comprising the steps of: a) Treating at least one portion of the surface of the article comprising one or more poly(aryl ether ketone)s (PAEKs) with the process according to claim 1; b) Coating the treated at least one portion of the surface of the article with a composition comprising a chemical compound having chemical groups capable of forming a covalent bond with the hydroxyalkyl and/or hydroxyaryl groups formed on the surface of the article.

9. The process according to claim 8, wherein the composition comprises biological material or biomolecules.

10. The process according to claim 9, wherein the biological material or biomolecules is/are selected from natural, artificial, chemically modified or biotechnologically produced biological material or biomolecules.

11. The process according to claim 9, wherein the biological material or biomolecules is/are selected from proteins, oligo- or polypeptides, amino acids, mono-, oligo- or polysaccharides, proteoglycans, glycoproteins or glycosaminoglycans, lipids, glycolipids, nucleotides, vitamins and other low molecular weight compounds or mixtures thereof.

12. The process according to claim 9, wherein the biological material or biomolecules is/are selected from collagen or gelatin.

13. The process according to claim 8, wherein the chemical groups capable of forming a covalent bond with the hydroxyalkyl and/or hydroxyaryl groups formed on the surface of the article are selected from amino groups, alcohol groups, aldehyde groups, carboxyl groups, halide groups, or mixtures thereof.

14. The process according to claim 8, wherein the treated at least one portion of the surface is coated with the composition by electrospinning, electrospray, aerosol deposition, doctoring, dip coating or spray coating.

15. The process according to claim 8, wherein after coating the composition is cross-linked.

16. An article comprising one or more poly(aryl ether ketone)s (PAEKs) and a coating on at least one portion of the surface of the article, wherein on the coated at least one portion of the surface of the article, the poly(aryl ether ketone)(s) (PAEKs) contain(s) hydroxyalkyl and/or hydroxyaryl groups; and at least one portion of the hydroxyalkyl and/or hydroxyaryl groups of the poly(aryl ether ketone)(s) (PAEKs) have formed covalent bonds with chemical groups of at least one chemical compound in the coating.

17. The article of claim 16, made by the process of claim 8.

18. The article of claim 16, wherein the article is cytocompatible.

19. The article according to claim 16 being a medical device and/or biotechnological application.

20. The article according to claim 19 being an implant, scaffold structure for in vitro applications and/or scaffold structure for cell culture applications

Description

DESCRIPTION OF THE FIGURE

[0101] FIG. 1 shows a scanning electron microscope image of the boundary phase of a formaldehyde surface-treated molded article of PEEK (FA-etched PEEK) and a gelatin coating formed by electrospinning gelatin nanofibers (intermediate nanofiber layer) on the surface of the surface-treated molded article. The arrows in the FIGURE show the contact area where the fibers of the coating fuse with the formaldehyde treated surface of the molded article by covalent bonding. This fusion provides sufficient structural integrity between the surface of the PEEK molded article and the fibre coating to prevent detachment of the coating, for example by shrinkage.

EXAMPLES

Example 1: Application of a Stable Coating of Non-Oriented Gelatine Nanofibers on CFR-PEEK Samples

[0102] Carbon fiber-reinforced poly(ether ether ketone) (CFR-PEEK) with 30% carbon fibers from POLYTRON Kunststofftechnik (Victrex® PEEK 150CA30, Bergisch Gladbach, Germany) was used for the coating experiments. Test articles with a surface area of 484 mm.sup.2 and a thickness of 1 mm were manufactured from the material. The CFR-PEEK test articles were cleaned with ddH.sub.2O and then immersed in a 37% formaldehyde solution (Carl Roth, Germany) at room temperature. After 30 minutes, the articles were removed from the formaldehyde solution and the excess liquid was removed with a paper towel. The molded articles were coated with protein nanofibers immediately after the formaldehyde activation. For nanofiber coating, the formaldehyde-activated CFR-PEEK molded articles were placed on a plate collector in a custom-built electrospinning experimental setup. 20% (w/v) gelatin was dissolved in 50% (v/v) acetic acid and transferred into a 20 mL syringe (B. Braun Perfusor). The outlet of the syringe was connected to a 21 G blunt cannula via infusion tubing (B. Braun Perfusor). The syringe was placed in a syringe pump (neMESYS, Cetoni GmbH, Germany) with a software controlled feed rate. The syringe was connected to a high voltage DC power source (Heinzinger, Germany) and placed over a grounded copper plate with an area of 10×10 cm.sup.2 at a vertical distance of 12 cm. The voltage was set at 12 kV and the injection rate was set to 5 μL/min. On each formaldehyde activated CFR-PEEK molded article, 0.25 mL of gelatin solution was deposited by electrospinning.

[0103] The CFR-PEEK test articles coated with nanofibers were then dried at 37° C. for 24 hours. The test articles were then placed in a desiccator (total volume approx. 2.4 L) over a reservoir of 37% formaldehyde solution in water. For every 30 mg of gelatin (dry weight), 10 mL of formaldehyde solution was used. The samples were incubated in the desiccator for 105 min to stabilize the gelatin fiber coating applied via electrospinning.

[0104] This process results in an intermediate layer of fibres that adhere firmly to the CFR-PEEK surface. To remove this layer completely, it must be scraped or abraded. The fibers deposited on this interlayer are effectively cross-linked and form a stable coating with an average thickness of 211±49 μm and a dry mass of 3.1±0.3 mg. The average diameter of the deposited fibers was determined by scanning electron microscopy and image analysis to be 143±29 nm for untreated fibers and a slight increase to 155±34 nm after formaldehyde crosslinking.

[0105] This process leads to a less efficient coating of PEEK (without additional material such as glass fibre, carbon fibres or the like), as the homogeneity of the electric field was compromised by direct contact with the collector electrode, which increased the insulating properties of PEEK. The efficiency of the PEEK coating can be significantly improved by modifying the electrospinning system as described in Example 5.

Example 2: Application of a Stable Coating of Oriented Gelatine Nanofibres on CFR-PEEK Test Specimens

[0106] CFR-PEEK test articles were prepared and pre-activated as described in Example 1. After formaldehyde pretreatment, the test articles were placed in an electrospinning device between two grounded copper collector plates, each having an area of 2×1 cm.sup.2. Subsequently, the test articles were coated with gelatin nanofibers by electrospinning as described in Example 1. The modified collector setup resulted in a coating with oriented fibers.

Example 3: Improved Cytocompatibility and Cell Proliferation

[0107] CFR-PEEK test articles were cut to 10×10×1 mm.sup.3 dimensions and then sanded with 500 grit sandpaper to achieve a surface roughness of 0.37 μm. The test articles were pre-activated by incubation in 37% formaldehyde solution as described in Example 1. The samples were then coated with gelatin nanofibers by electrospinning as described in Example 1. For this procedure, 0.1 mL of gelatin solution was electrospun and applied to six test articles. After electrospinning, the test articles were dried at 37° C. for 24 hours before the fibers were cross-linked by formaldehyde fumigation as described in Example 1. To optimize the test articles for cell culture experiments, the test articles were stored at 50° C. and 80 mbar for 48 h and placed in a 24-hole plate. Each article was disinfected by immersing it in 1 mL of 70% ethanol for 2 h at room temperature under a biological workbench. The ethanol was rinsed from the articles with sterile phosphate buffered saline (PBS). The articles were stored in 1 mL of Delbecco's Modified Eagle Medium F-12 (DMEM/F-12) at 37° C. for 24 h before cell seeding.

[0108] Human chondrosarcoma cells (SW1353) were cultured to confluence in a culture medium consisting of DMEM/F-12, 10% fetal bovine serum (FBS), 1% L-glutamine, and 1% penicillin/streptomycin at 37° C. in a humid atmosphere at 5% CO.sub.2. The Cells were seeded in polystyrene perforated plates (control), on untreated and on gelatin-coated CFR-PEEK samples (n=6) at a density of 5000 cells/cm.sup.2. Cell viability assays (CellTiter-Blue, Promega) were performed on days 0, 1, 2, 3, 4, 7 and 8, respectively. Cell viability in the control groups was ≥97.8%. The cell count on the gelatin-coated CFR-PEEK test articles was approximately 33% higher after 192 hours compared to the cell count on the untreated CFR-PEEK test articles. Compared to Example 1, the modified coating procedure described herein resulted in a large increase in cytocompatibility.

Example 4: Alternative Cross-Linking Strategy

[0109] CFR-PEEK test articles (22×22×1 mm.sup.3) were prepared as described in Example 1, cleaned, and immersed in 37% formaldehyde solution for 30 minutes at room temperature. The test articles were then removed from the liquid. The test articles were then dried and coated with gelatin fibers by electrospinning as described in Example 1. After electrospinning, the fiber coated CFR-PEEK samples were dried at 37° C. for 24 hours. The fibers were stabilized by chemical cross-linking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, Merck, Germany). 100 mM EDC-HCl was dissolved in isopropanol. 3 mL of EDC solution per mg of gelatin fibers (dry weight) was added to a small container. The CFR-PEEK test articles coated with fibers were then immersed in the EDC solution in the container for 2 hours at room temperature.

[0110] The average fiber diameter of the deposited and EDC-crosslinked fibers was 450±34 nm (determined by scanning electron microscopy and image analysis). An interlayer formed, which strongly adhered to the CFR-PEEK surface and had to be scraped or abraded for complete removal. However, the cross-linking of the fibers deposited on this interlayer was less effective than in Example 1.

Example 5: Application of Devices on a Production Scale

[0111] PEEK and CFR-PEEK test articles were prepared as described in Example 1 and inserted into a Nanospider NS 1WS 500 U electrospinning device (Elmarco, Czech Republic). For this purpose, the test articles were fixed to the polypropylene substrate with double-sided adhesive tape. A protein/polymer solution containing native collagen, poly(ethylene oxide) and hydroxyapatite (SpinPlant GmbH, Germany) was electrospun at 80 kV for 30 minutes and applied to the CFR-PEEK test articles. Since the articles were not in direct contact with the collector electrode, the nanofibers were deposited equally efficiently on PEEK and CFR-PEEK specimens.

Example 6: 3D Coating of CFR-PEEK Implants

[0112] A block of CFR-PEEK was fabricated and pre-activated by immersion in a 37% formaldehyde solution as described in Example 1. The block was then mounted on a custom-made spinning device and this was placed in the electrospinning apparatus described in Example 1 between the grounded copper collector plate and the needle connected to the high voltage DC power source. The electrospinning was performed as described in Example 1. In this case, the spinning device with the CFR-PEEK block was rotated at a speed of about 10 rpm. This resulted in a homogeneous coating of all sides of the CFR-PEEK block. Subsequent cross-linking by formaldehyde fumigation as described in Example 1 resulted in a stable coating.