DENTAL IMPLANT, COMPONENT FOR DENTAL APPLICATIONS, IMPLANT SYSTEM FOR DENTAL APPLICATIONS, METHOD FOR FORMING A PROTECTIVE LAYER ON THE SURFACE OF AN IMPLANTABLE OR IMPLANT COMPONENT, IMPLANTABLE OR IMPLANT COMPONENT HAVING A PROTECTIVE LAYER, AND USE OF A PROTECTIVE LAYER

Abstract

The present invention provides Dental implant configured to be inserted into a hole in jaw bone and to be at least partially situated in bone tissue when implanted, comprising:

a coronal implant region, the surface of which is at least partly covered by an oxide layer with an average thickness in the range from 60 nm to 170 nm and has an average arithmetical mean height Sa in the range from 0.1 μm to 1.0 μm. Further provided is a component for dental applications, preferably dental abutment, wherein the surface of the component is at least partly covered by an oxide layer with an average thickness in the range from 60 nm to 170 nm and has an average arithmetical mean height Sa in the range from 0.05 μm to 0.5 μm and an implant system comprising the dental implant and the component. Method for forming a protective layer on the surface of an implantable or implant component, the method comprising a) applying a solution on the surface of component, the solution having a pH at 25° C. of 6.8 or less and b) drying the solution applied in step a) to form a protective layer on the surface of the component for dental applications. Finally, part of the present invention is an implantable or implant component having a protective layer obtainable as above and a use of such layer for storage.

Claims

1. Dental implant configured to be inserted into a hole in jaw bone and to be at least partially situated in bone tissue when implanted, comprising: a coronal implant region, the surface of which is at least partly covered by an oxide layer with an average thickness in the range from 60 nm to 170 nm and has an average arithmetical mean height Sa in the range from 0.1 μm to 1.0 μm.

2. Dental implant according to claim 1, wherein the surface of the coronal region is smooth, basically non-porous, nanostructured and/or exhibits an as-machined structure.

3. Dental implant according to claim 1, wherein the surface of the coronal region has an average arithmetical mean height Sa in the range from 0.2 μm.

4. Dental implant according to claim 1, wherein the coronal region exhibits a yellow or pink color when viewed by the human eye.

5. Dental implant according to claim 1, further comprising: a transition implant region; an apical implant region; a longitudinal axis extending from the coronal implant region to the apical implant region; wherein the sequence of regions starting from a coronal end of the dental implant to an apical end of the dental implant along the longitudinal axis is: coronal implant region—transition implant region—apical implant region, and at least one of the following applies with respect to the surface properties of said regions: average arithmetical mean height Sa of the apical implant region>Sa of the transition implant region>Sa of the coronal implant region, average developed interfacial area ratio Sdr of the apical implant region>Sdr of the transition implant region>Sdr of the coronal implant region, average thickness of an oxide layer d.sub.OX on the implant surface of the apical implant region>d.sub.OX of that of the transition implant region>d.sub.OX of that of the coronal implant region, and average phosphorous content C.sub.P of the oxide layer of the apical implant region>C.sub.P of that of the transition implant region>C.sub.P of that of the coronal implant region.

6. Dental implant according to claim 1, wherein the surface properties of the apical implant region, the transition implant region and the coronal implant region change in a stepwise manner or a continuous manner, or combinations thereof between the different regions along the longitudinal axis of the dental implant.

7. Dental implant according to claim 1, wherein, in the apical implant region, the transition implant region and/or the coronal implant region, the oxide layer further comprises calcium, magnesium and/or fluoride; and/or the surface of the apical implant region and the transition implant region are microporous surfaces and/or comprise at least one of a bone-growth-initiating and a bone-growth-stimulating substance.

8. Dental implant according to claim 1, wherein the surface of the apical implant region exhibits at least one of: average Sa: 1.50 μm±0.4 μm, average Sdr: 187%±50%, mean pore diameter: 1.5 μm±0.5 μm, average oxide layer thickness d.sub.OX: 9000 nm±3000 nm, and average phosphorus content C.sub.P: in a range from 4% to 12%, and/or the surface of the transition implant region exhibits at least one of: average Sa: 0.8 μm±0.5 μm, average Sdr: 148%±40%, mean pore diameter: 1.0 μm±0.5 μm average oxide layer thickness d.sub.OX: 7000 nm±3000 nm, and average phosphorus content C.sub.P: in a range from 3% to 11%, and/or the surface of the coronal implant region exhibits at least one of: average Sa: 0.5 μm±0.3 μm, average Sdr: 16.6%±15%, mean Nanostructure size: 80 nm±50 nm, average oxide layer thickness d.sub.OX: 120 nm±40 nm, and average phosphorus content C.sub.P: in a range from 2% to 6%.

9. Dental implant according to claim 1, wherein the surface properties of the apical implant region, the transition implant region and the coronal implant region are at least partially obtainable by performing an anodic oxidation process.

10. Dental implant according to claim 1, wherein the surfaces of the transition implant region and/or the apical implant region are obtainable by performing a spark anodization process.

11. Dental implant according to claim 1, wherein the base material of the dental implant comprises titanium or a titanium alloy.

12. Dental implant according to claim 1, wherein, a) the coronal implant region extends from a coronal end of the dental implant up to 2 mm±0.5 mm along the longitudinal axis towards an apical end of the dental implant, the transition implant region extends from said 2 mm±0.5 mm up to 4 mm±0.5 mm further along the longitudinal axis towards the apical end of the dental implant, and the apical implant region extends from said 4 mm±0.5 mm up to the apical end of the dental implant or b) the coronal implant region has a length measured from a coronal end of the dental implant along the longitudinal axis towards an apical end of the dental implant from 0.5 mm to 6.0 mm.

13.-44. (canceled)

45. Dental implant according to claim 11, wherein the oxide layer on the surface of the apical implant region and the transition implant region comprises crystalline titanium oxide in the anatase phase, and the remainder comprises rutile and/or amorphous titanium oxide.

46. Dental implant according to claim 45, wherein the oxide layer on the surface of the apical implant region and the transition implant region comprises crystalline titanium oxide in the anatase phase in the range of 70-100%.

47. Dental implant according to claim 11, wherein the oxide layer on the surface of the coronal implant region comprises predominantly or consists of amorphous titanium oxide.

48. Dental implant according to claim 47, wherein the oxide layer on the surface of the coronal implant region is virtually non-crystalline and/or anatase-free.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0117] The drawings presented below are exemplary, non-limiting schematic drawings only.

[0118] FIGS. 1A, 1B, and 1C show a collection of dental implant designs according to the present invention and disclosure.

[0119] FIGS. 2A and 2B show a collection of component designs in the form of dental abutments in line with the present invention and disclosure.

[0120] FIGS. 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, and 3M show an implant system consisting of dental implant and dental abutment according to the present invention and disclosure together with microscopy images illustrating the surface properties and morphologies for each part of the system.

[0121] FIGS. 4A, 4B, 4C, 4D, 4E, and 4F show an illustration of surface properties and functionalities of the implantable or implant component related to using a protective layer according to the present invention. Herein, the implantable or implant component is represented by an implant.

[0122] FIG. 4A shows on the left a state in which the protective layer is formed on an implant surface. Atmospheric molecules, such as water and hydrocarbons, are unable to reach the surface, as the protective layer provides a physical barrier.

[0123] In the middle of FIG. 4A, it is shown how upon contact with body fluid, the protective layer dissolves or disintegrates rapidly. Any molecules that are adsorbed from the air are carried away while the protective layer dissolves or disintegrates.

[0124] On the right side of FIG. 4A, there is illustrated a state of the implant after the protective layer has dissolved or disintegrated to allow interaction of the implantable or implant component with the surrounding tissue. Note that in this exemplary embodiment, the implantable or implant component is made from a material that has hydroxyl groups (OH) on the surface, such as titanium, which indicates a highly hydrophilic surface (water droplet contact angle e.g. in the range of from 0-30°).

[0125] FIG. 4B shows the content of carbon, derived from hydrocarbons that are adsorbed from the surrounding atmosphere, on the surface of implants with and without protective layer (PL) after certain time periods.

[0126] In FIG. 4C, there is illustrated a contact angle measurement on implants having a contact angle of 46.3° (without PL, left) and 0° (with PL, right).

[0127] FIG. 4D illustrates the density of hydroxyl groups on a titanium surface that had not been protected by a PL (left) and on the surface of titanium surface that had been protected by a PL.

[0128] FIGS. 4E and 4F show the metabolic activity after 1, 3 and 7 days on implants that were (with PL) or were not (without PL) provided with a protective layer of the present invention.

DETAILED DESCRIPTION

[0129] The working examples detailed below are meant to be non-limiting. The invention and the above disclosure are not limited to the details of the below working examples, which only describe a preferred way of implementing the present invention.

[0130] FIGS. 1A-1C show a number of different designs of the dental implant according to the present invention and disclosure. As can be seen, the dental implant can be screw-like or a bone screw for insertion into the jaw bone. Various different thread-designs are conceivable, for example, one thread type extending from the apical end to the coronal end of the dental implant. The thread types may also be varied along the longitudinal axis and different threads can be provided in different implant regions. For example, the thread in the apical region is different to the one in the coronal region thereby accommodating different retention needs in the different tissues the dental implant intersects. Other retaining means than threads are also possible, for example, a regular ridge structure with ridges perpendicular to the longitudinal axis. Also the length and longitudinal extent of the different regions of the dental implant can be different. In FIGS. 1A-1C, the length of the coronal region is about 1/7 to ⅛ of the total length of the implant measured from the coronal end of the dental implant. FIGS. 1A-1C indicate via the lighter color that the coronal or collar implant region has a distinctively different appearance than the rest of the dental implant, which is due to the different surface designs. Seen in color, the coronal implant region would exhibit a gold color, i.e., a metallic yellow color, whereas pink is also conceivable. The rest of the implant however would be matt grey. In the present example, the transition to the coronal region is substantially abrupt on a scale visible by the human eye. Exemplarily, FIG. 1B contains reference numerals that also apply to the dental implants in FIGS. 1A and 1C. Indicated in FIG. 1B is the longitudinal axis L of the dental implant, which is the lengthwise spatial extension of the dental implant. The upper end of the dental implant is formed by the coronal end 1. The apex or lower end of the dental implant is formed by the apical end 5. The three different regions: coronal implant region 2, transition implant region 3 and apical implant region 4 are indicated accordingly, but not limited to the ranges indicated therein.

[0131] FIGS. 2A and 2B depict two design options for the component, here in the form of abutments to be used together with dental implants. At the lower ends thereof, one can see geometries provided for combination and connection with a suitable dental implant. When seen in color, the abutments would have a gold color or metallic yellow color depending on the individual part of the abutment glossy or matt.

[0132] FIGS. 3A-3M show the implant system according to the present invention, where a respective dental implant of a screw-type is combined with a respective component in the form of a dental abutment. FIGS. 3B, 3C, 3E, 3F, 3H, 3I, 3K, and 3L show scanning electron microscopy images at different magnifications. The apical or apex implant region shows a pronounced crater/volcano structure with open pores on the surface reaching opening sizes up to several micrometers. The surface is ragged and comprises a large number of randomly distributed surface structures. The adjacent transition implant region shows a similar crate/volcano and ragged morphology. However, the surface features and pores have become smaller. A significant change occurs in the coronal implant region, where the porous and ragged surface is gone and instead a regular pattern of lines or grooves can be seen, which come from the turning process. Said lines and grooves confer the surface with an oriented line roughness. In higher magnification, one discovers a finely nanostructure surface. Here, the oxide layer basically “decorates” and covers the turning line structure. Finally, turning to the dental abutment, one can see that in the depicted embodiment that the surface morphology of the dental abutment is very similar to that of the coronal implant region, showing an array of turning lines/grooves with a superimposed oxide layer. FIGS. 3D, 3G, 3J, and 3M show 3D reconstructions of surface profiles obtained by white light interferometry that confirm the above observations.

[0133] Regarding the example shown in FIGS. 3A-3M, the following can be detailed. The novel abutment surface was prepared by turning followed by a mild anodization process. The resulting surface is non-porous, smooth with an average surface roughness Sa of 0.13±0.02 μm and a developed surface area ratio Sdr of 3.39% (see: FIGS. 3B and 3D), shows regularly distributed nanostructures of 69±48 nm in size and has an oxide layer thickness of 153±5 nm (see: FIG. 3C). The oxide layer thickness endows the abutment with a yellow color—known as interference color—which has been shown to be beneficial to reduce grey shine-through effects in case of a thin mucosa. Due to the created nanostructures and the approximately 20 times increase in oxide layer thickness compared to unmodified titanium, the created surface should be favorable for epithelial cell and fibroblast attachment. Moreover, the smooth surface is expected to allow for control of plaque retention and facilitate mechanical cleaning. The collar or coronal region of the dental implant (0-2 mm from the coronal end) has a minimal roughness with a Sa of 0.51±0.03 μm and a Sdr of 16.6%. The roughness is obtained by control of the machining parameters resulting in burr-less surfaces with defined turning line dimensions and spacing, as visible in FIGS. 3B and 3D. Additionally, the coronal implant region features similar nanostructures like the abutment 43±21 nm in size and an oxide layer thickness of 142±17 nm (see: FIG. 3F). Minimally rough surfaces with a Sa of 0.5-1.0 μm have shown less marginal bone loss compared to smoother surfaces. The herein created surface roughness for the implant collar/coronal implant region should thus be at a reasonable level to balance the need for osseointegration and the need for maintenance and cleaning. Moreover, the similarity in surface texture, chemical composition, oxide layer thickness and nanostructures between the abutment surface and the coronal implant region allows for a smooth soft tissue transition from the abutment to the implant as mentioned before. The body of the implant is gradually roughened by spark anodization. By varying the density and size of the classical volcano-shape saliencies on the surface, the roughness increases from Sa of 0.92±0.16 μm in the transition implant zone (i.e. 2-4 mm from the coronal end of the dental implant) to a Sa 1.49±0.19 μm in the apex area/apical implant region (4 mm-apex), closely approaching the roughness known to trigger the best bone response in vivo. The increase in roughness from the transition implant region to the apical implant region is also accompanied by an increase in surface area as reflected in the Sdr values of 148% and 187%, respectively. Overall, the increase from coronal end to apical end in Sdr is designed to be contrary to the bone density, which decreases from the implant platform/coronal end to the apex and apical end. This ensures increasing friction towards the apex to allow for proper implant retention. The high currents exceeding the breakdown voltage used for roughening the surface of the transition and/or apex implant region, lead to the formation of oxide layer two orders of magnitude higher, reaching 7.2±0.3 μm and 9.9±1.3 μm for the transition and apical implant region, respectively. These oxide layers are anatase-rich with a high surface energy and many free hydroxyl groups. Compared to sand-blasted and acid-etched commercial implants, anodized surfaces exhibit the most hydroxyl groups. Highly hydroxylated titanium surfaces promote osseointegration and bone formation in vivo, likely through a favorable adsorption of ECM molecules and enhance mineralization and differentiation of osteoblasts. Anatase rich anodized implant regions possess optimized properties for osseointegration resulting in a high treatment predictability of a variety of indications and in lower failure rates than other surface modifications after more than 10 years of function. During the growth, oxygen and phosphorus from the electrolyte are incorporated into the oxide layer. The abutment surface exhibits on average 3.49±0.36% phosphorus, while the surface of the coronal implant region shows 4.00±0.13%, the transition implant region 7.20±0.59% and the apical implant region 8.16±0.31%. The table below summarizes the physiochemical surface properties for the various components and regions of the above implant system.

TABLE-US-00001 TABLE 1 Dental Implant Component Coronal region Transition region Apical region (Abutment) 0-2 mm 2-4 mm 4 mm-Apex Average Sa [μm] 0.13 ± 0.02 0.49 ± 0.03 0.92 ± 0.16 1.49 ± 0.19 Average Sdr [%] 3.39 16.6 148 187 Average pore non-porous non-porous 1.1 ± 0.5 1.7 ± 1.1 diameter [μm] Average 69 ± 48 43 ± 21 Not nano- not nano- Nanostructure size structured structured [nm] Average oxide layer 153 ± 5  142 ± 17  7227 ± 305  9933 ± 1286 thickness on the surface [nm] Average phosphorus .sup. 3.49 ± 0.36% .sup. 4.00 ± 0.13% .sup. 7.20 ± 0.59% .sup. 8.16 ± 0.31% content on the surface

[0134] In the following, the measurement methods used to determine the above physiochemical properties will be explained. Said methods also provide examples for relevant measurement methods generally applicable in order to determine all the parameters mentioned in this description.

Oxide Layer Thickness d.SUB.OX

[0135] Said thickness is measured on cross-sections of the dental implant or the component. For that, the dental implant or component can be cold mounted in an acrylic resin, ground and polished to achieve cross sections along its centerline or its longitudinal axis (which will be defined below). The flank of the dental implant or component can be imaged by scanning electron microscopy (SEM) and the oxide layer thickness measured software-aided in said SEM images at various positions, which is a procedure well familiar to the skilled person. For the measurements made here, a Zeiss Leo 1530 scanning electron microscope, a secondary electron detector and 5 kV acceleration voltage at various magnifications were used. Pore diameter and nanostructures were determined using the ImageJ software and SEM images with a magnification of 1 k and 10 k respectively. 6 images were used for each condition. Preferably, the above thickness of the oxide layer is an average thickness, meaning that it was measured at various position of the coronal implant region or any implant region of relevance and then the mathematical average calculated from all of the measurements.

Roughness Parameters Sa and Sdr

[0136] Were measured using white light interferometry. Image stacks of the implant surface were acquired with an Optical 3D Profilometer, gbs, smart WLI extended (Gesellschaft für Bild and Signalverarbeitung mbH, Ilmenau, Germany) using a 50× objective. The data obtained was subsequently processed with the MountainsMap® software for determination of the surface roughness. Parameters Sa and Sdr were determined after applying a polynomial 3 removal form and a Gaussian filter (FALG, ISO 16610-61) with a 50 μm cut-off. The measuring area was 350×220 μm for all measurements. Four components and 4 dental implants were measured, the dental implants were measured on 9 areas each for each region depicted in FIGS. 3A-3M, i.e., coronal, transition and apical regions. The abutments were measured on 9 areas each.

Phosphorus Content CP and Surface Chemistry

[0137] For determining the elemental composition of the surfaces X-ray photoelectron spectroscopy (XPS) measurements were performed with the following procedure. Samples were rinsed two times 120 s in 10 mL ultrapure water (type 1, 18.2 MΩ.Math.cm resistivity). The samples were then dried with a stream of nitrogen gas and mounted on a XPS sample holder. Care was taken to expose the cleaned implants for the minimal amount of time to the laboratory atmosphere. XPS measurements were performed with a Kratos Axis Ultra spectrometer using monochromatic Al Kα X-rays (1486.6 eV). Binding energy calibration of the Kratos Axis Ultra DLD XPS instrument, S/N C332549/01 was carried out on 18th July 2018, according to BS ISO 15472:2010. For each sample, a survey spectrum was acquired from an area of ˜2 mmט1 mm (pass energy=160 eV), from which the surface elemental composition was determined. Charge compensation was achieved using a beam of magnetically focused electrons as a flood current. The standard photoelectron take-off angle used for analysis is 90° giving a sampling depth in the range 5-8 nm.

Pore Diameter and Nanostructure Size

[0138] Were determined based on SEM images of the respective surfaces. Conventional image software was used to measure pore sizes and nanostructure sizes.

[0139] Method for forming a protective layer, Use and Implant or implantable component having a protective layer.

[0140] The present inventors have surprisingly found that the surface of an implantable or implant component can be protected during storage e.g. against contamination by providing a protective layer formed from a solution having a relatively low pH as described below. Such a protective layer can be more quickly and more completely be removed as compared to layers formed in the prior art, and/or can provide or maintain a surface state of the implantable or implant component that is preferable for biointegration.

[0141] In one aspect, the present invention relates to a method for forming a protective layer on the surface of an implantable or implant component, the method comprising [0142] a) applying a solution on the surface of component, the solution having a pH at 25° C. of 6.8 or less; [0143] b) drying the solution applied in step a) to form a protective layer on the surface of the implantable or implant component.

[0144] Herein and throughout the present invention, the term “solution” denotes a composition that is in a liquid state at 20° C. and 1 atm pressure.

[0145] In one embodiment, the solution comprises inorganic cations and inorganic anions in a solvated (dissolved) state. In the present invention, the terms “inorganic cation” and “inorganic anion”, respectively, denote charged species of an element or an element group that together form a salt. Examples of inorganic cations are cations of the alkaline metals, the earth alkaline metals, and any other metal. The term however also includes ammonium and cations of e.g. Boron, Arsenic, Tellurium, etc., Put differently, an “inorganic cation” can be described as including any positively charged species not containing carbon.

[0146] The term “inorganic anion” includes any negatively charged species not containing a carbon atom. In one embodiment, the term “inorganic anion” includes the anions of the halogens (in particular F, Cl, Br, I), anions containing nitrogen and oxygen atoms, such as nitrate or nitrite, anions containing nitrogen and oxygen atoms, such as sulfate or sulfite, and anions containing phosphorous and oxygen atoms, such as phosphate, pyrophosphate, or phosphite. Incidentally, in the present invention ions that are formed by dissociation of water (i.e. H.sup.+/H.sub.3O.sup.+ and OH.sup.−) are not included in the terms “inorganic cation” and “inorganic anion”, respectively.

[0147] The term “monovalent”, “bivalent” and “trivalent” denote the charge of a cation or anion. Examples of monovalent cations are those of the alkali metals such as Na.sup.+ or K.sup.+ and ammonium, and examples of monovalent anions include Cl.sup.− and H.sub.2PO.sub.4.sup.−. Examples of bivalent cations include those of the earth alkaline metals, such as Ca.sup.2+ and Mg.sup.2+, and examples of bivalent anions include e.g. SO.sub.4.sup.2− and HPO.sub.4.sup.2−. Examples of trivalent anions include e.g. PO.sub.4.sup.3−.

[0148] The solution may be an aqueous solution. Herein, the term “aqueous” denotes that the solution comprises 50% by weight of the total composition or more of water, such as 70% by weight or more or 80% or more, such as 90% by weight or more. Other co-solvents that may optionally be present in addition to water include water-miscible solvents, in particular alcohols and ketones such as methanol, ethanol, isopropanol, 1-butanol, 2-butanol, or acetone. These co-solvents are typically present in an amount of less than 50% by weight of the total weight of the composition, such as 30% by weight or less or 20% by weight or less.

[0149] The solution may also be a non-aqueous solution. This denotes a solution that does not comprise water or comprises it in an amount of less than 50% by weight of the total composition. In this case, the solvent may be selected from the group consisting of water-miscible solvents, in particular alcohols and ketones such as methanol, ethanol, isopropanol, 1-butanol, 2-butanol, or acetone. These can be used singly or in combination. The choice of solvent is mainly determined by the ease of handling and the ability to dissolve the components of the protective layer, but may also be influenced by other factors, such as flammability or toxicity.

[0150] In one embodiment, the co-solvent is absent, water being the only solvent. In a preferred aspect thereof, the solution consists of water and inorganic salts that are in a dissolved state to form solvated cations and anions. Herein, the salts preferably include monovalent cations, such as salts of the alkali metals, preferably sodium. In one embodiment, the cations in the solution are selected from sodium and magnesium, other cations being absent or being present in an amount of 10 mol % or less, such as 5 mol % or less, of all cations in the solution. Incidentally, throughout the invention, ions that are formed by dissociation of water (i.e. H.sup.+/H.sub.3O.sup.+ and OH.sup.−) are disregarded for the calculation of relative and total amounts of cations and anions in the solution, as their concentration determines the pH. Put differently, in the present invention the concentrations and amounts of anions and cations is expressed independently of the pH of the solution, and H.sup.+/H.sub.3O.sup.+ and OH.sup.− are disregarded for the calculation of absolute and relative amounts of inorganic and organic cations and anions.

[0151] In one embodiment, the solution may or may not contain organic components and additives. These may in one embodiment be selected from the group consisting sugars, water-soluble polymers such as polyvinyl pyrrolidone (e.g. with number-average molecular weight of 15,000 or less or 10,000 or less), collagen, antioxidants or antifoulants, such as BHT, pharmaceutically active components, such as vitamins, antibacterial or disinfecting agents or antiobiotics.

[0152] The solution may or may not comprise organic salts. The term “organic salt” denotes a material which upon dissolution and dissociation in water forms cations and anions, and wherein either the cation or the anion is an organic compound containing carbon. Examples of such organic salt include sodium acetate, sodium acetyl acetonate, sodium formiate, etc., as well as pyridinium chloride, quaternary ammonium salts such as tetramethylammonium chloride, etc.

[0153] In one embodiment, the amount of organic components and additives is 10% by weight or less of the total weight of the composition, such as 5% by weight or less, e.g. 2% by weight or less. In one embodiment, such organic components and additives are absent.

[0154] In one embodiment, the aqueous solution does not contain an organic salt, nor any other organic compound or additive. In a preferred aspect of this embodiment, the salts are formed by sodium and magnesium salts only, and more preferably are formed from sodium and magnesium phosphates, hydrogen phosphates, dihydrogen phosphates, and chlorides.

[0155] In one embodiment, the solution comprises monovalent inorganic cations other than H.sup.+ and H.sub.3O.sup.+ and monovalent, bivalent or trivalent inorganic anions. In one aspect of this embodiment, the monovalent inorganic cations are selected from the group consisting of Na.sup.+, K.sup.+, and NH.sub.4.sup.+, preferably Na.sup.+ and K.sup.+, more preferably Na.sup.+. Herein, the amount of monovalent inorganic cations is preferably such that 50 mol % or more of all inorganic cations are selected from monovalent inorganic cations, preferably 60 mol % or more, such as 65 mol % or more or 70 mol % or more.

[0156] In one embodiment, the amount of monovalent inorganic cations is thus 50 mol % or more of all inorganic cations, preferably 60 mol % or more, such as 65 mol % or more or 70 mol % or more, and the monovalent inorganic cations are then selected from the group consisting of Na.sup.+ and K.sup.+. In one embodiment, the monovalent inorganic cation is Na.sup.+, which is present in an amount of 50 mol % or more of all inorganic cations, preferably 60 mol % or more, such as 65 mol % or more or 70 mol % or more.

[0157] In one embodiment, Na.sup.+ is present, K.sup.+ is absent, and the remaining inorganic cations are preferably selected from the group consisting of bivalent inorganic cations, more preferably Mg.sup.2+ and Ca.sup.2+, further more preferably Mg.sup.2+. In a preferred aspect, the inorganic cations are formed by only Na.sup.+ and Mg.sup.2+, i.e. the solution does not contain any cations other than Na.sup.+ and Mg.sup.2+. Herein, again, the amount of Na.sup.+ is preferably 50 mol % or more of all inorganic cations, preferably 60 mol % or more, such as 65 mol % or more or 70 mol % or more.

[0158] The inorganic anions in the solution are not particularly limited, and any anion can be present as long as it forms a salt with the cations that is readily soluble in the body fluids. As a general guideline, a salt that dissolves in water in an amount of 50 g/l or more at 20° C., such as 100 g/l or more, 150 g/l or more, or even 200 g/l or more can be used in the solution of the present invention, with highly soluble salts being preferred. The combination of anions and cations should hence be chosen such that no salt with low solubility is formed, so that e.g. carbonates and hydrogen carbonates should be avoided, in particular if bivalent cations such as Mg.sup.2+ and Ca.sup.2+ are present, as this will lead to the formation of precipitation of only sparely soluble carbonate salts typically having a solubility of about 0.1 g/l at 20° C. Hence, in one embodiment the anions are selected from the group consisting of nitrate (NO.sub.3.sup.−), sulfate (SO.sub.4.sup.2−), halogens, in particular chloride (Cl.sup.−), phosphate (PO.sub.4.sup.3−), hydrogen phosphate (HPO.sub.4.sup.2−) and dihydrogen phosphate (H.sub.2PO.sup.4−).

[0159] In one embodiment, the solution does not contain any other salts but those selected from the chlorides, phosphates, hydrogen phosphates and dihydrogen phosphates of sodium and magnesium.

[0160] In one embodiment, the solution comprises sodium cations, and the sodium cations form 30-100 mol %, such as 50-99 mol % of the total of all alkaline and earth alkaline metal cations in the solution, and the solution comprises phosphate, hydrogen phosphate and/or dihydrogen phosphate anions, and the phosphate, hydrogen phosphate and/or dihydrogen phosphate anions form 30 mol % or more, such as 50 mol % or more, of the total of all inorganic anions. Herein, the alkali metal cations include all cations of metals in group 1 of the periodic table except hydrogen (i.e. Li, Na, K, Rb, Cs and Fr), and the earth alkali metal cations include all cations of group 2 of the periodic table (i.e. Be, Mg, Ca, Sr, Ba, and Ra).

[0161] In one embodiment, the solution comprises magnesium ions, and preferably the magnesium ions form 0.1-50 mol % of the total of all alkaline and earth alkaline metal cations in the solution. The remainder may then be formed by sodium and potassium cations, and preferably the remainder is formed by sodium cations.

[0162] In one embodiment, the solution does not contain calcium ions, and preferably also does not contain ammonium ions.

[0163] It has surprisingly been found that the pH of the solution has a great influence on the properties of the protective layer, and that a protective layer that has been formed from solution having a pH of 6.8 or less (at 25° C.) is superior in terms of removability and in providing, after dissolution of the protective layer, a surface that is highly hydrophilic (has a high surface energy). It is believed that both of these effects facilitate the incorporation of the implant or implantable component, as after dissolution of the protective layer, a highly hydrophilic and pure implant or implantable component surface can be provided. For instance, when the implant or implantable component is made from a metal or metal alloy, in particular titanium or a titanium alloy, the surface of the implant or implantable component after dissolution of the protective layer can exhibit a high density of hydroxyl groups, which is considered to facilitate the integration with the surrounding tissue.

[0164] While the effect is not yet fully understood, and without wishing to be bound by theory, it is believed that the charge of a surface (e.g. of a titanium or titanium alloy implant or implantable component) strongly depends on the pH of the solution it is immersed in. At low pH, the surface of the implant or implantable component surface (e.g. made from a metal or metal alloy, or also from a metal oxide, such as titanium oxide) is believed to be positively charged, and the surface charge gradually decreases in solution with increased pH. This is expressed by the isoelectric point, i.e. the pH at which there is a balance between positive and negative charges on the surface. For materials made from titanium, titanium alloys and titanium oxides, the isoelectric point is generally comprised between pH 4.0-6.8.

[0165] When the surface is negatively charged, cations in solution strongly interact with the surface, and are difficult to be rinsed off. Conversely, a positive charge may facilitate removal of cations, as these are less attracted to the surface.

[0166] By using a protective layer solution with a pH of 6.8 or lower, the interaction between the cations and the surface are weak, which may explain an easier removal of cations when rinsed in water or when contacting body fluids. Preferably, the pH of the solution is thus also lower than the isoelectric point of the surface on which the protective layer is to be formed.

[0167] It might further possibly be assumed that a low pH of 6.8 or lower might prevent or reduce the uptake of carbon dioxide and possibly other species from the atmosphere during preparation of the protective layer and/or during storage of the implant or implantable component having the protective layer. If carbon dioxide is absorbed, it forms carbonate and hydrogen carbonate ions in solution, which in turn form salts having relatively low solubility, in particular in combination with earth alkaline metal cations. Also, carbonates are a less hydrophilic material, and might thus facilitate the adsorption of organic contaminants to the protective layer surface. As the formation of carbonates is reduced or prevented with the solution for forming a protective layer of the present invention, the protective layer may dissolve more rapidly due to the absence or reduced amount of carbonates having low solubility, and contamination with organic substances might be prevented or reduced. This is a further reason why pH of the solution at 25° C. is thus 6.8 or less, such as 6.5 or less, 6.0 or less, 5.5 or less or 5.0 or less.

[0168] In one embodiment, the pH of the solution at 25° C. is thus below the isoelectric point of the surface of the implant or implantable component, which depending on the metal or alloy used, may be 6.8 or less such as 6.5 or less, 6.0 or less, 5.5 or less or 5.0 or less.

[0169] A highly acidic solution will also solve the problems of the present invention, but may possibly have a detrimental biological effect upon dissolution in the patient's body. Hence, the pH of the solution is preferably 0.0 or higher, 0.5 or higher or 1.0 or higher, such as 1.5 or higher or 2.0 or higher. The pH can thus e.g. be in the range from 2.8-to 3.4, from 3.6 to 4.9, or from 3.5 to 5.5.

[0170] Further, due its low pH, the protective layer preserves the amount of available functional groups (e.g. OH groups) on the surface of the implantable or implant component made from e.g. titanium during storage. This means that the protective layer is configured to reduce carbon deposition and preserve hydrophilicity and/or the density of free/unbound hydroxyl groups on the surface of the implantable or implant component during dry storage as compared to storage without said protective layer.

[0171] The protective layer of the present invention thus allows dry storage of an implant or implantable component. The present invention also encompasses the use of the protective layer obtainable by drying the solution as described herein for protecting an implantable or implant component during storage against contamination, wherein preferably the implantable or implant component is in a dry state during storage.

[0172] The salt concentration of the solution is not particularly limited, but can be adjusted by a skilled person in order to obtain the desired thickness of the protective layer. In one embodiment, the solution has a total concentration of inorganic salts of 1 to 200 mM, 2 to 50 mM or 5 to 20 mM, such as 7-10 mM, expressed as the total of all salts formed by the inorganic cations and the inorganic anions described above.

[0173] The salt concentration can be as high as 2, 4, 5, 7, 10, 20, 40, or 50 mM or higher, but can be as low as 180, 150 or 125 mM or lower. Within these ranges, a sufficiently thick salt layer can be formed by wetting or immersing the implant, followed by drying.

[0174] The protective layer formed from the solution described above protects the implantable or implant component during storage against contamination. This means that the amount of contaminants is reduced as compared to an implantable or implant component not having the protective layer.

[0175] The protective layer also preserves the hydrophilicity of the implantable or implant component during storage. Accordingly, a highly hydrophilic surface of the implantable or implant component can be maintained and revealed again after the protective layer is removed/dissolved. To achieve this, the surface must either by hydrophilic (i.e. must have an increased free surface energy) prior to application of the solution, or is must be rendered hydrophilic at the same time when the solution is applied. In one embodiment, hence the implantable or implant component exhibits a water contact angle of 0-30 both prior to application of the solution in step a) and after removal of the protective layer, assessed by rinsing the implant or component with water at 25° C. for 2 minutes, followed by drying.

[0176] It follows that in one embodiment of the method for forming a protective layer of the present invention, the method further comprises a step for increasing the free surface energy of the implantable or implant component prior to or simultaneous with the application of the solution in step a). This can be effected by a number of ways known to a skilled person, such as acid etching with an inorganic acid, such as HF, HCl, H.sub.2SO.sub.4 or mixtures thereof, UV irradiation, oxidation with oxygen peroxide, plasma treatment, etc. Also, the method described in EP 0 388 576 may be employed.

[0177] The protective layer formed from the solution as described above can be easily removed when implanted. This can be assessed by testing the removal of the elements of the protective layer in a rinsing test. In one embodiment, after rinsing the implant or component with water at 25° C. for 2 minutes (e.g. by putting it under a flow of gently flowing water), 30 atom % or less, such as 20 atom % or less, preferably less than 10 atom % of the protective layer remain on the surface. This can be assessed by any suitable surface analysis technique, such as XPS or Auger.

[0178] After the solution is applied in step a), it is dried in step b). The application can be performed by any suitable technique, such as coating, spraying or dipping/immersing the implantable or implant component into the solution.

[0179] The following process parameters may be adhered to:

[0180] Process parameters during application: [0181] Temperature: generally 0-100° C., preferably 20-90° C. [0182] Pressure: usually atmospheric pressure; [0183] Time: sufficient to ensure complete wetting, such as 5 seconds or longer, but typically 5 minutes or less;

[0184] Process parameters during drying: [0185] Temperature: sufficient to enable drying, preferably 30-95° C., more preferably 50-90° C. [0186] Time: sufficient to achieve dry state, preferably 15-120 minutes, more preferably 30-100 minutes [0187] Pressure: atmospheric pressure (1 atm) or less, such as 50-770 mm Hg.

[0188] Generally, a drying at moderate temperatures for longer duration and under relatively high pressure may be preferred in order to avoid the formation of a highly porous layer that may not completely cover the implant surface.

[0189] The implantable or implant component is not particularly limited, but is preferably an implantable or implant component that is made from metal, a metal alloy, a plastic material and a ceramic material. Preferably, the implantable or implant component is made from a metal or metal alloy, with titanium and a titanium alloy being particularly preferable.

[0190] The implantable or implant component is also not limited with respect to its form and shape, and any implantable or implant component may be subject to the method and use of the present invention. This includes e.g. hip implants, knee implants, implants designed as replacement of parts of the arms or legs, and dental implant and dental implant components, such abutments, crowns and bridges. The implantable or implant component is preferably a dental implantable or implant component, more preferably a dental implant or a dental implant abutment. In one embodiment, the implantable or implant component may be the implant, the implant system or the component also disclosed in the present disclosure.

[0191] The present invention not only includes the method for forming a protective layer and the use of the layer for protecting an implant or implantable component during storage as described above, but also envisages that the solution per se is an inventive contribution to the art. The solution that has been described above with respect to the method and the use is thus considered to be claimable aspect of the present invention, and this includes all embodiments and preferred aspects of the solution that has been described above for the method and the use.

[0192] The thickness of the protective layer is not particularly limited, and a low thickness may be sufficient to obtain the desired protection. The thickness is determined by the concentration of the protective layer components in the solution and the application amount of the solution. The thickness may be between 0.1-20 μm, such as 0.2-5 μm. or 0.3-3.1 μm.

[0193] The present invention also encompasses a package containing an implant or implantable component having the protective layer as described above. The package may be filled with the dry implantable or implant component having the protective layer in an atmosphere that is selected from air, nitrogen or other inert gases. As the implant is protected by the protective layer, air may be used, and the package does not need to be airtight. Optionally, a sterilization with e.g. ethylene oxide gas may be applied, which may be effected prior to packaging or even after packaging has taken place, due to the ethylene oxide gas permeating into the packaging.

Example 1—Effect of the Salt Composition

[0194] The effects of the salt composition were assessed by preparing aqueous solutions containing only water as the solvent with the following compositions:

38.5 mM Na.sub.2HPO.sub.4+7.15 mM NaH.sub.2PO.sub.4+2.5 mM MgCl.sub.2  Solution 1

38.5 mM K.sub.2HPO.sub.4+7.15 mM KH.sub.2PO.sub.4+2.5 mM MgCl.sub.2  Solution 2

[0195] Titanium implants were wetted with Solution 1 or 2, respectively, and dried to obtain a salt layer on the implant.

[0196] In order to assess whether the salt layer could be removed by a simple washing process, each implant was rinsed 3 times in 10 ml water. Thereafter, the remaining salt layer elements were assessed by Auger spectroscopy. It was found that for the salt layer obtained from Solution 1, 15% of the elements remained on the surface of the implant, while for the salt layer obtained from Solution 2, 26% of the elements remained on the surface. This shows that the sodium-based solution can be more easily removed than a potassium-based solution.

Example 2—Influence of pH and Surface Energy

[0197] In order to assess the influence of pH, Example 1 was performed with two modifications of Solution 1 having the same salt concentration, but a pH of 7.1 or 4.0, respectively. It was found that, again after rinsing 3 times with 10 ml water, the salt layer obtained from the solution having a pH of 7.1 led to 15 atom % of remaining elements on the surface, while for the solution having a pH of 4.0, only 3 atom % of the elements stayed on the surface.

[0198] This shows that adjusting the pH of the solution to acidic values allows obtaining a layer that can more easily and completely be removed.

[0199] In a further test, it was evaluated whether the surface energy of the implant substrate influences the removability of the salt layer. Two tests were performed with Solution 1, one on an implant having a high surface energy (water contact angle=0°) and one on an implant having a low surface energy (water contact angle=47°). It was found that after rinsing the implant 3 times with 10 ml water, for the implant with high surface area 15 atom % of the elements of the salt layer remained on the surface, while for the implant with low surface energy only 2% of the elements remained on the surface. This shows that the removal is facilitated by a lower surface energy of the underlying implant surface.

Example 3—Protective Effect Against Contamination

[0200] To test the efficacy of the protective layer in protecting the surface from adsorbing atmospheric elements molecules, the carbon content was measured on abutment surfaces stored in an environmental chamber (set at 25° C. and 50% humidity) with or without protective layer.

[0201] Abutment surfaces were UV-ozone treated for 15 min, if applicable an protective layer formed from the above Solution 1 was applied and dried, and the resulting abutment was handled in a protective environment of a nitrogen filled glove-box (these samples are referred as time 0). The samples with or without protective layer were exposed to air for 2 minutes, 1 hour or 3 days. Other samples, not initially UV cleaned, were used as the final time point (t inf.). For each time point, samples were rinsed in ultra-pure water and blow dried with a nitrogen stream. The carbon content at the surface was determined as atomic percentage by XPS or Auger spectroscopy (see also FIG. 4B).

[0202] During storage, hydrocarbons and other atmospheric elements deposit on the surface. Carbon accumulation was confirmed by assessing the carbon content on UV-ozone cleaned abutment 7.2 at %. When exposed to atmospheric conditions, the carbon content rapidly increases to 13.4 at % after 2 min, 14.3 at % after 1 hour and 20.4 at % after 72 h. Interestingly, when the abutment featured the protective salt layer obtained from Solution 1, the carbon content was consistently lower, reaching 12.4 at % after 72 h. The carbon content on abutments that were not UV cleaned and stored in standard packaging (Inf) remained also significantly lower when the salt layer was applied compared to abutments without salt layer (14.6 at % versus 34.9 at %, respectively). See also FIG. 4B.

[0203] Beside the carbon content, the ratio of other elements composing the surface were not significantly different after rinsing off the device, showing the full dissolution of the protective layer. This data suggests that the layer indeed fully dissolved, revealing a pristine surface as indicated by the low carbon levels after rinsing.

[0204] It is further known that the surface energy, correlated to the hydrophilicity, decreases with atmospheric contaminants depositing on the surface. The assessment of the hydrophilicity of stored samples confirmed the preservation of high surface energy and hydroxyl groups as indicated by a contact angle of 0°, compared to samples stored without protective salt layer (contact angle: 46.3±5.6°), confirming a lower carbon content and higher surface energy of samples stored with the protective layer obtained from the solution of the present invention (see also FIG. 4C).

[0205] Lastly, no difference in cell proliferation was observed in response to the protective layer, whether for keratinocytes seeded on abutments nor for MSC seeded on implants (see FIGS. 4E and 4F, respectively), confirming the cell-friendliness of the protective layer.