ITMI20071083A1 - PROCESS FOR COATING A SURFACE OF A METAL ELEMENT TO INCREASE THE OSTEOINTEGRATION AND PROSTHETIC DEVICE THAT INCLUDES THAT ELEMENT - Google Patents

Description

DESCRIPTION

Attached to a patent application for INDUSTRIAL INVENTION entitled:

"Process for coating a surface of a metal element to increase osseointegration and prosthetic device that includes said element"

The present invention refers to a process for coating at least one metal element of a prosthetic device, in order to obtain a high bone integration between the surface of the metal element and the receiving bone structure, and to the prosthetic device that includes this metal element coated.

Prosthetic devices are for example: implants, means of synthesis, external fixation systems, stabilization systems, fusion cages, dental implants, screws, to be used for clinical / surgical purposes in the orthopedic, maxillofacial and neurosurgical fields.

Human bone is among the most complex examples of biomineralized material existing in nature. It is mainly made up of inorganic components such as hydroxyapatite (HA) and water (70-80%) and of organic components such as type I collagen, proteoglycans and other non-collagenic proteins (20-30%). During bone formation hydroxyapatite nanocrystals accumulate in intimate contact with type I collagen fibrils, generating an ordered composite nano structured hierarchical structure with certain mechanical and elastic characteristics capable of giving the skeletal system structural properties capable of supporting all the organs of the human body. This intimate deposition mechanism of hydroxyapatite nanocrystals attached to collagen fibrils is mediated by competent cells such as fibroblasts and osteoblasts. The loss of bone substance with the consequent need to restore the missing volume or the need for an increase in existing bone volume is one of the major problems in the orthopedic, maxillofacial and neurosurgical fields. Numerous solutions have been proposed to cope with the lack of bone volume, in particular various substances of natural origin, synthetic inorganic or only synthetic with functions of bone substitute have been used. However, the extraordinary mechanical behavior of natural bone made precisely by its nanocomposite hierarchical structure has been shown by numerous authors to be difficult to reach with any other type of biomaterial. Therefore, the ideal bone substitute remains the autologous bone taken from the same patient from the donor site. However, this practice is not free from risks for the patient which very often result in resorption of the bone implant itself and frequent appearance of painful symptoms in the site where the bone graft was removed.

Recent studies have shown that the use of allogeneic bone from a human-derived tissue bank, processed and rendered inert through chemical-physical processes, can represent an alternative to the use of autologous bone. However, even in this practice, there may be risks associated with the contraction of infectious diseases or immune-type reactions.

New biomaterials with the function of bone substitutes have been studied and proposed for clinical use, some have shown positive results following clinical investigations on humans. These materials do not simply have high biocompatibility properties (inert biomaterials), but possess biomimetic characteristics, i.e. chemical and chemical-physical properties similar to human bone capable of activating biological mechanisms (bioactivity) with the receiving bone tissues and cellular components in they contained, promoting the processes of neo-formation and bone consolidation. Once their function of stimulating new bone formation has been completed. In some cases, these materials undergo complete resorption, leaving space exclusively for the newly formed bone.

The kinetics of bone formation and its consolidation require quite prolonged times and in the immediate and intermediate postoperative period, particularly in the reconstruction of some bone structures such as long bones, it is not possible to access immediate loading in the absence of mechanical support.

For this reason, complementary means of stabilization and mechanical fixation of metallic origin are often used which ensure immediate loading. The use of complementary metal structures in bone reconstruction procedures is not limited exclusively to reconstructions in the absence of an immediate mechanical load, but very often they are an integral part of bone regeneration such as in the dental / maxillofacial field where the placement of screws Over time, titanium becomes a single body with the recipient bone, giving rise to an anatomical system capable of housing artificial dental elements to restore the loss of dental elements.

The use of metal devices based on chromium-cobalt alloys or more widely titanium alloys, has allowed to obtain good results in terms of osseointegration, where for osseointegration (concept introduced by Branemark since the 1960s and subsequently deepened in the 1980s with the advent of new histological techniques) means the direct structural and functional conjunction between the receiving vital bone and the surface of a prosthetic device subjected to loading. The realization and maintenance of osseointegration depends on the ability of the bone to heal, repair and remodel.

It is clear how important the complete osseointegration of the metal with the recipient's bone is, as the anatomical and morphofunctional results of many bone reconstruction operations depend on it. For example, in the dental field, if perfect osseointegration with healthy bone is not achieved, there is a risk of mobilization of prosthetic implants.

Titanium alloys (mainly TiéAUV alloys and Ti6Al7Nb alloys) are preferred to other metal alloys not only for their ease of processing, but especially for their high biocompatibility, high mechanical strength, corrosion resistance, the reduced propensity to induce bone resorption and due to the elastic properties which, compared to other metal alloys, are closer to those of human bone (relatively low modulus of elasticity corresponding to 100 GPa compared to over 200 GPa of alternative materials, stainless steels and cobalt alloys). There are numerous factors that are decisive in obtaining a good osseointegration of implantable devices in orthopedic, neurosurgical and maxillofacial surgery: in addition to biomechanical factors related to the geometry and shape of the implant, the topographical and chemical nature of the implant is important. surface of the implant itself that interfaces with healthy bone tissue and its constituent components the connective tissue, first of all the cellular component. The mechanism of bone formation on the implant surface begins with a cellular chemotaxis towards the implant bone interface and migrations of other factors (macromolecules, chemical mediators, proteins, nutrients, etc.) with the formation initially of a clot and subsequently of granulation tissue able to prepare an ideal bed for the transformation of undifferentiated progenitor cells (mesenchymal cells present in the bone marrow) into mature cells capable of synthesizing the mineral bone matrix in the final stage of neossification. Finally, the result of good osseointegration inevitably passes through a perfect quality of the recipient bone. In fact, often failures of metal implants housed in patients suffering from both senile and secondary osteoporosis or other degenerative diseases affecting the skeletal system are noted.

To date, special techniques and treatments are available that are able to implement the properties of osseointegration and therefore of lasting stability of metal implants, through the modification of the surface characteristics (e.g. modification of roughness) thanks to chemical or physical processes that allow deposition , on the surfaces in contact with the bone, of thin ceramic films. These treatments, in addition to conferring greater osseointegration and prolonged stability, can also confer greater biocompatibility of the prosthesis by limiting the phenomenon of the release of metal ions due to mechanical stress and friction. Particular attention was paid to the surface treatment of knee and hip prostheses where the fixation systems must have a macro roughness and particular geometries, while to reduce "stress shielding" the surfaces of the prostheses themselves must be treated with special coatings including coatings of titanium nitride (TiN) or ceramic coated TiNbNi. In the first case, these particular surface treatments are obtained by sandblasting or mechanical processing, or by depositing microparticles of ceramic or metal material thanks to specific coating processes (Ti-plasma spray, deposition of sintered HA microspheres, metal fiber mesh). In the case of external coatings of metal surfaces that interface with other joint surfaces, they are obtained thanks to chemical-physical processes such as CVD (Chemical Vapor Deposition) and PVD (Physical Vapor Deposition) which allow ultra-thin coatings (some order of magnitude). ten nm) and resistant, able to cushion the mechanical stresses due to the rubbing of adjacent joint surfaces, avoiding the release of ions that can induce inflammatory reactions on adjacent tissues.

While these techniques can guarantee primary osseointegration in a shorter time (for example in maxillofacial surgery 3-6 months), in the long term they can be intrinsically subject to risks of "debridement" which can alter the properties mechanical and superficial properties of the metal device, compromising its biocompatibility, stability and osseointegration (inflammation at the connective prosthesis interface, with the formation of superficial gaps and osteolysis).

Other complementary systems, therapies and techniques can be used to promote osseointegration (laser therapy, ultrasound, etc.) through bone stimulation capable of proliferating and differentiating progenitor cells into cells competent for bone matrix synthesis.

It is known that direct nucleation in aqueous solution of hydroxyapatite (HA) nanocrystals within collagen fibers allows to obtain a biomimetic composite with characteristics similar to those of human bone. The nucleation of HA within collagen fibers induces the carbonation of HA nanocrystals in position B with replacement of the P04 ion with the C03 ion in a similar way to how it occurs in the deposition process of human apatite, preventing carbonation in position A where the C03 <2-> ion would replace the OH group as occurs in synthetic carbonate apatite. The close analogy in terms of microstructure and chemical composition of the collagen-apatite nanocomposite with human bone can lead to the creation of a bioactive structure which, deposited on a metal surface, is able to modulate the kinetics of bone neoformation and remodeling. Nano-structured calcium-phosphate / collagen composites are suitable for deposition on metal surfaces. However, traditional coating methods such as plasma spray, CVD (Chemical Vapor Deposition) and PVD (Physical Vapor Deposition) are not applicable for this type of material particularly due to the fibrous form of the collagen.

As described in the literature, numerous difficulties have been encountered in making uniform and homogeneous coatings of composite calcium phosphate / collagen on metal surfaces and supports by electrolytic deposition.

For example, in the article by H. Schliephake et al, "Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible" published in J Biomedi. Mater. Res., (2003) 64, p. 225-234., A study on the in vivo effects of titanium implants coated with various materials is reported. In particular, titanium prosthetic implants were used coated with a bioactive calcium-phosphate / collagen multilayer, obtained by electro-crystallization of a calcium phosphate solution on a titanium electrode on the surface of which collagen had previously been deposited through partial integration. of the latter within a layer of oxides obtained by anodic electrodeposition. The integration of the collagen was obtained under galvanostatic conditions using an electrolyte containing collagen in almost physiological conditions (pH 7.4 at 37 ° C), and subsequent immersion in a collagen solution for 10 min, so as to obtain a layer of collagen having a thickness of about 40 nm. As reported by the authors themselves, the overall thickness of the multilayer (about 500 nm) and the degree of mineralization of the collagen were very low.

In the article by Y. Fan et al "A composite coating by electrolysis-induced collagen self-assembly and calcium phosphate mineralization", published in Biomaterials, (2004) 26, pag. 1623-1632, other attempts at electrochemical deposition of multilayer coatings of collagen and calcium phosphate are described. In particular, the electrolytic deposition on a silicon substrate of a first layer with a thickness of about 100 µm of calcium phosphate and a second layer in the form of a gel with a thickness of about 100 µm consisting of a composite of collagen fibrils with octacalcic phosphate (OCP). The electrolytic deposition was carried out in a solution of Ca (N03) 2 and NH4H2P04 added with a 1 M NaOH solution so as to obtain a pH of 4.8-5.3, to which type I collagen in acid solution was subsequently added, followed by by a readjustment of the pH to the values indicated above. The electrolytic deposition was carried out at a constant potential at the cathode of -1, -2 or -3V with respect to the reference cathode (calomel saturated electrode, SCE).

The Applicant has raised the problem of increasing the osseointegration capacity of prosthetic devices that include at least one metal element by means of a process of coating the surface of the latter with at least one layer of a highly biocompatible material, such as to obtain an interface with the bone structure that allows faster bone formation and osseointegration that consolidates over time.

The Applicant has found that this problem can be solved by a process according to the following claims, in which a collagen composite with a calcium phosphate is electrochemically deposited on the surface of the metal element intended to come into contact with the bone structure under conditions process such that the collagen fibers self-assemble with the inorganic calcium-phosphate component near the metal surface, precipitating on the latter in a single HA-based mineral phase, without adding alkaline compounds to the electrolytic bath .

According to a first aspect, the present invention therefore relates to a process for coating a surface of a metal element, which comprises: providing an electrolytic bath comprising at least one collagen, calcium ions and phosphate ions;

immersing in said electrolytic bath at least one cathode and at least one anode, said at least one cathode comprising the metal element to be coated; passing a direct electric current through said electrolytic bath so as to obtain on said surface an electrolytic co-deposition of the collagen with a calcium-phosphate compound comprising hydroxyapatite.

According to a further aspect, the present invention relates to a prosthetic device comprising at least one metal element, said metal element having at least one surface coated with at least one layer obtainable by electrolytic co-deposition of a collagen with a calcium-phosphate compound comprising hydroxyapatite.

According to a preferred embodiment, at the beginning of the co-deposition the electrolytic bath has a pH between 3.0 and 4.5, preferably between 3.5 and 4.0, said pH rising near the cathode to a value higher than 8, generally between 10 and 12, during the co-deposition process without adding alkaline compounds. At the end of the electrolytic co-deposition process, the electrolytic bath has a pH generally comprised between 4.0 and 6.0, preferably between 4.5 and 5.5.

According to a preferred embodiment, the electrolytic co-deposition is carried out with a substantially constant direct current. Preferably the direct current is kept at relatively low values in order to avoid detachments of the deposited material caused by an excessive development of gaseous hydrogen at the cathode. Generally the direct current has a value comprised between 10 and 60 mA, more preferably between 30 and 40 mA.

Preferably, the collagen is of type I. Preferably, the collagen is previously subjected to an enzymatic digestion step in order to remove the telopeptides present on the collagen molecules which can hinder the self-assembly of the protein on the metal surface.

Preferably, the collagen in the electrolytic bath is present in the form of a suspension and generally has an initial concentration of between 0.005 and 0.05% weight / volume, preferably between 0.01 and 0.02% weight / volume.

Preferably, the calcium ions are added to the electrolytic bath in the form of a salt that is soluble under the reaction conditions, for example calcium nitrate. The initial concentration of the calcium ions in the electrolytic bath is generally comprised between 0.01 and 0.1 moles / liter, preferably between 0.02 and 0.06 moles / liter.

Preferably, the phosphate ions are added to the electrolytic bath in the form of a salt that is soluble under the reaction conditions, for example ammonium dihydrogen phosphate.

The initial concentration of the phosphate ions in the electrolytic bath is generally comprised between 0.01 and 0.10 mol / liter, preferably between 0.02 and 0.04 mol / liter. Within the scope of the present invention, the term "phosphate ions" includes both the phosphate ions P04 <3->, and the hydrogen- and dihydrogen-phosphate ions HP04 and H2P04 possibly present in equilibrium with the P04 ions in varying quantities according to the pH.

Preferably, the metal element comprises titanium or an alloy thereof, for example Ti6Al4V alloys or Ti6Al7Nb alloys.

By carrying out the process according to the present invention it is possible to vary the thickness of the collagen and hydroxyapatite layer within wide margins, passing from a thickness of a few nm, for example from 10 nm to 500 nm, up to more consistent thicknesses, generally comprised between 50 pm and 500 pm, preferably between 100 pm and 200 pm. The thickness of the collagen and hydroxyapatite layer is preferably not greater than 500 pm, as higher thicknesses can cause delamination phenomena that would cause surface irregularities, affecting the osseointegration capacity of the treated surface. Preferably, the calcium-phosphate compound comprises at least 90 % by weight, more preferably at least 95% by weight, of hydroxyapatite. Preferably, the hydroxyapatite is present in the form of crystals having a flattened lanceolate morphology (biomimetic morphology), having average dimensions of the longest side of less than 300 nm, more preferably between 100 and 200 nm.

The layer obtained by electrolytic co-deposition according to the present invention generally comprises: from 10 to 90% by weight of hydroxyapatite and from 10 to 90% by weight of collagen. More preferably, said layer comprises: from 60 to 70% by weight of hydroxyapatite and from 30 to 40% by weight of collagen.

The present invention will now be illustrated by means of some embodiment examples, which are provided purely by way of example but not limitative of the scope of the invention itself.

The figures attached to this description illustrate:

Fig. 1: a schematic representation of a device for carrying out the electrolytic codeposition according to the invention;

Fig. 2: SEM image of the coating obtained by co-deposition of collagen and hydroxyapatite according to the invention after 5 min. of electrodeposition;

Fig. 3: TEM images of the coating obtained by co-deposition of collagen and hydroxyapatite according to the invention: (a) and (b) after 5 min. of electrodeposition, (c) and (d) after 30 min. of electrodeposition;

Fig. 4: FTIR spectrum of the coating obtained by co-deposition of collagen and hydroxyapatite according to the invention after 30 min. of electrodeposition (spectrum A), compared with the FTIR spectrum of a bone tissue (spectrum B); Fig. 5: X-ray diffractogram of the coating obtained by co-deposition of collagen and hydroxyapatite according to the invention after 30 min. of electrodeposition; in the insert a portion of an X-ray diffractogram of a bone tissue is reported for comparison;

Fig. 6: SEM images of the self-assembled collagen fibers according to the invention, after decalcification with EDTA / glutaric aldehyde.

EXAMPLE 1.

Materials used.

All reagents were Chemical grade.

The type I collagen used in the experiments was extracted from equine tendon using a standard production method where animal tissues and derived raw tissue were subjected to rigorous veterinary medical controls. After having completely removed the synovial membrane, the tissue was finely chopped and suspended in aqueous solution of HCl at pH 2.5 and then digested with pepsin for 24h. After enzymatic digestion, the collagen was precipitated by raising the pH to 5.5 by adding a NaOH solution and subsequently washed with distilled water and subsequently treated with 1M NaOH for 1h in order to remove any glycosidic residue and ensure complete viral inactivation. At the end of the procedure it was treated in an environment at pH 5.5 by adding HCl. Shortly before the deposition process, the collagen fibers were homogeneously resuspended (1% w / w) in 0.3% (w / v) acetic acid.

The 99.7% titanium sheets were obtained by Sigma (code 267503-25.2G) and subsequently cut into strips of dimensions 15 mm x 25 mm.

Process conditions.

The electrolytic deposition processes described below were carried out with a two-electrode electrochemical system illustrated schematically in Figure 1, which comprises an electrolytic bath (1) in which calcium ions, phosphate ions and collagen are present in the form of a suspension in the aqueous medium; a cathode (2) and an anode (3) are immersed in the electrolytic bath (1), between which direct electric current passes through a potentiostat (4), used as a galvanostat (Amel model 552-Potenziostat / Amel model 721-Integrator ). The cathode consisted of a titanium sheet measuring 15mm x 25mm. Before the electrolytic deposition, the titanium sheet was cleaned by ultrasonic treatment in an acetone bath and subsequently in distilled water in order to remove any residue.

The electrolytic bath was prepared by dissolving Ca (N03) 2 and NH4H2P04 in distilled water until obtaining a concentration of 42 mM of [Ca] and 25 mM of P04 <3->. A type I collagen suspension prepared as described above was added to the electrolytic bath at a concentration of 0.012% w / v. The initial pH of the electrolytic bath was about 4.0. At the end of the codeposition the pH of the electrolytic bath was about 5.0-5.5.

During the electrolytic deposition, the electrochemical cell with the electrolytic bath inside was kept at room temperature by applying a substantially constant current of 34 mA. The duration tests of the deposition process of the collagen / ΉΑ composite coating were established in 5 seconds, 30 seconds, 5 minutes, 30 minutes.

In consideration of the electrolytes present in solution, the main reactions that are generated at the titanium cathode when the current passes through the electrodes are the following:

1)

2)

3)

4)

5)

It is believed that these reactions are able to increase the pH value in the cathode zone so as to create the conditions suitable for the co-deposition of collagen with hydroxyapatite without the addition of alkaline compounds. It can therefore be assumed that the collagen begins to self-assemble only in the vicinity of the cathode, where a local increase in pH is obtained due to the electrochemical process, and not in the whole mass of the bath due to the effect of added OH <-> ions.

The initial pH of the electrolytic bath is adjusted to a value below the isoelectric point of the collagen in order to allow the positively charged molecule to migrate to the cathode. The reactions at the cathode illustrated above, producing OH- ions, lead to the overcoming of the isoelectric point of the collagen and at the same time generate the conditions suitable for the deposition of calcium phosphate, with consequent simultaneous self-assembly of the collagen and association of the same with the mineral phase , so as to deposit the desired composite on the cathode surface.

Characterization of coatings.

Various samples obtained according to Example 1 were characterized as follows. The infrared microscopy (FTIR) spectra were obtained by means of an infrared spectrophotometer Perkin-Elmer mod. Spectrum One FT-IR with attached Perkin-Elmer microscope (Perkin-Elmer Autoimage microscope). The resolution of the spectra was 4 cm <"1>, the spatial resolution was 100x100 pm while the spectrum was the result of 32 scans. The baseline of the spectrum was obtained from a region in the absence of a sample. The specific areas to be subjected to during analysis they were identified by viewing with a camera positioned on the microscope.

The scanning microscope (SEM) images were obtained using a Philips 515 microscope. The titanium sheet subjected to the electrochemical coating was suitably positioned and treated with colloidal gold coating in a time range between 30 and 180 seconds at a voltage of 30 mV.

Transmission electron microscope (TEM) analysis was performed with a Philips 420T microscope. A sample of the pulverized coating was suspended in bi-distilled water and a drop of suspension thus obtained was deposited on a perforated carbon foil supported by a copper micro-grid.

X-ray diffractometry was used to determine the degree of crystallinity using an Analytical X'Pert Pro difractometer using a CuK radiation generated at 40 kV and 40 mA. The instrument was configured 1 ° divergence and 0.2 mm receiving slot. The degree of crystallinity was evaluated by applying the formula:

The size of the single crystal was determined by applying Scherrer's formula:

where 0 represents the diffraction angle, ΔΓ and Δ0 the amplitude in radians of the reflection angle at half height respectively for the reference peak of the final product and hydroxyapatite, at λ = 1.5405 À.

Comments on the results obtained.

The SEM observation of the coating obtained after an electrodeposition lasting 5 minutes (see Fig. 2) shows the presence of a mineral phase intimately associated with the collagen fibrils. From the image it is possible to understand the important role of consolidation of the inorganic component by the collagenic fibrous network.

By increasing the electrodeposition time to 30 minutes, in the SEM image the collagen fibers appear as completely immersed in the nano-crystalline inorganic phase.

Analysis of the FTIR spectrum of the same coating (see Fig. 4) shows the maximum absorption peaks of collagen and hydroxyapatite. Note the presence in the A spectrum of a peak at 1422 cm <_1> quite similar to that present in the bone tissue (spectrum B), typically present in the hydroxyapatite of mineralized tissues as a consequence of a type B carbonation.

The deposition of collagen fibrils with different degrees of mineralization found in the TEM images (see Fig. 3), highlights how there are hydroxyapatite nanocrystals associated with the collagen fibrillar structure, the dimensions of which change as a function of the deposition time. The nanocrystals in the initial deposition phase (deposition time 5 sec., Images (a) and (b)) are 40 ± 10 nm in size and have an irregular shape. After a deposition time of 30 minutes, the hydroxyapatite crystals take on a needle-like appearance with a length of 160 ± 20 nm and a width of 60 ± 10 nm (images (c) and (d)). During the first deposition phase of the coating, the crystals appear to be located within the collagen fibrils in the less mineralized area of the sample while the reverse phenomenon occurs in the more mineralized area, i.e. mineralization occurs outside the collagen fibrils. This phenomenon suggests that the self-assembly phase of the collagen I molecules deprived of telopeptides, to then precipitate in fibrillar form occurs simultaneously with the nano-crystallization phase of the carbonate-hydroxyapatite. During this process, the nucleation of hydroxyapatite nanocrystals and their deposition inside the collagen fibrils (calcification process) occurs only during the first phase, while the nucleation of the apatite on the surface of the fibrils occurs in a subsequent phase. These two different mineralization processes of collagen fibers substantially reproduce the process observed during the preparation of self-assembled collagen fibers / hydroxyapatite nanocrystals in aqueous solution. However, by employing the electrodeposition process it is possible not only to control the process but also to modulate and localize the deposition on the substrate surface.

X-ray diffractometric analysis (see Fig. 5) of the coating obtained according to the present invention after 30 min. of electrodeposition shows the characteristic peaks of the mineral phase HA at the 2 Theta = 32 and 26 values. the invention.

In order to verify the morphology of the collagen fibrils deposited on the titanium electrode after 30 minutes, some samples were decalcified in 10% EDTA solution for 24 hours. This process allows the complete removal of the mineral phase that surrounds the fibers allowing a better characterization and quantification of the same. The SEM images relating to the coating on the titanium sheet subjected to the decalcification process are shown in Figure 6. The collagen fibers are homogeneously deposited on the titanium surface without any preferential orientation; this suggests that the mineralization process does not substantially modify the typical morphology of this molecule.

Claims (18)

CLAIMS 1. Process of coating a surface of a metal element, which includes: providing an electrolytic bath comprising at least one collagen, calcium ions and phosphate ions; immersing in said electrolytic bath at least one cathode and at least one anode, said at least one cathode comprising the metal element to be coated; passing a direct electric current through said electrolytic bath so as to obtain on said surface an electrolytic co-deposition of the collagen with a calcium-phosphate compound comprising hydroxyapatite. 2. Process according to claim 1, in which at the beginning of the codeposition the electrolytic bath has a pH between 3.0 and 4.5, preferably between 3.5 and 4.0, said pH rising in proximity of the cathode to a value higher than 8, preferably between 10 and 12 during the co-deposition process without adding alkaline compounds. Process according to claim 2, wherein at the end of the co-deposition process the electrolytic bath has a pH between 4.0 and 6.0, preferably between 4.5 and 5.5. Process according to any one of the preceding claims, in which the electrolytic co-deposition is carried out with a substantially constant direct current. Process according to claim 4, wherein the direct current has a value comprised between 10 and 60 mA, preferably between 30 and 40 mA. Process according to any one of the preceding claims, wherein said at least one collagen is a type I collagen. 7. Process according to any one of the preceding claims, in which said at least one collagen is previously subjected to an enzymatic digestion step. Process according to any one of the preceding claims, wherein said at least one collagen is present in the electrolytic bath with an initial concentration comprised between 0.005 and 0.05% weight / volume, preferably between 0.01 and 0.02% weight / volume . Process according to any one of the preceding claims, wherein the calcium ions are present in the electrolytic bath with an initial concentration comprised between 0.01 and 0.1 mol / liter, preferably between 0.02 and 0.06 mol / liter . Process according to any one of the preceding claims, in which the phosphate ions are present in the electrolytic bath with an initial concentration of between 0.01 and 0.10 mol / liter, preferably between 0.02 and 0.04 mol / liter. 11. Process according to any one of the preceding claims, wherein the metallic element comprises titanium or an alloy thereof. Process according to any one of the preceding claims, in which a layer having a thickness between 10 nm and 500 nm is obtained from the co-deposition of the collagen and the calcium-phosphate compound. Process according to any one of claims 1 to 11, wherein a layer having a thickness of between 50 µm and 500 µm, preferably between 100 µm and 200 µm, is obtained from the co-deposition of the collagen and the calcium-phosphate compound. Process according to any one of the preceding claims, wherein the calcium-phosphate compound comprises at least 90% by weight, preferably at least 95% by weight, of hydroxyapatite. Process according to any one of the preceding claims, in which the hydroxyapatite is present in the form of crystals having a flattened lanceolate morphology, having average dimensions of the longest side of less than 300 nm, preferably between 100 and 200 nm. Process according to any one of the preceding claims, wherein the layer obtained by electrolytic co-deposition comprises: from 10 to 90% by weight, preferably from 60 to 70% by weight, of hydroxyapatite, and from 10 to 90% by weight , preferably from 30 to 40% by weight, of collagen. 17. Prosthetic device comprising at least one metal element, said metal element having at least one surface coated with at least one layer obtainable by electrolytic co-deposition of a collagen with a calcium-phosphate compound comprising hydroxyapatite. Device according to claim 17, wherein the electrolytic co-deposition is defined according to any one of claims 1 to 16.