WO2007091155A1

WO2007091155A1 - A method for laser treatment of implantable devices, implantable devices obtained using said method, and a laser system for treatment of implantable devices

Info

Publication number: WO2007091155A1
Application number: PCT/IB2007/000295
Authority: WO
Inventors: Enrico Gallus; Francesca Di Narda; Domenico D'antuoni
Original assignee: R.T.M. S.P.A.; Geass S.R.L.
Priority date: 2006-02-08
Filing date: 2007-02-08
Publication date: 2007-08-16
Also published as: EP1991169A1; ITTO20060089A1

Abstract

Method for the laser treatment of implantable devices comprising the step of treating a surface of the implantable device (1) via a diode-pumped solid-state laser (DPSS) in Q-switch regime for creating on the device itself a surface morphology comprising a controlled distribution of pores (5) having a diameter and depth of between 3 and 150 µm and preferably 5-20 µm, and a pitch of between 5 and 300 µm and preferably between 10 and 30 µm.

Description

A METHOD FOR LASER TREATMENT OP IMPLANTABLE DEVICES, IMPLANTABLE DEVICES OBTAINED USING SAID METHOD, AND A LASER SYSTEM FOR TREATMENT OF IMPLANTABLE DEVICES

TECHNICAL FIELD

The present invention relates to a method for laser treatment of implantable devices, to implantable devices obtained using said method, as well as to a laser system for laser treatment of implantable devices.

BACKGROUND ART

In the field ' of implantology, and in particular oral implantology, it is known that the cell response of the host tissue is influenced by the surface roughness of the implant.

It has in fact been demonstrated that the surface microtopography of the implant influences adhesion, proliferation, growth, migration, orientation, and differentiation of the cells of the host tissue.

The studies conducted have demonstrated that micromachined surfaces, characterized by a control of the surface structure that is more precise than what is allowed by currently adopted techniques of surface roughening (sanding, mordanting, plasma spraying) , improve and accelerate integration of a medical device in the surrounding tissue.

DISCLOSURE OF INVENTION

The aim of the present invention is to provide a method of laser treatment that will enable a surface with repeatable and controlled morphological characteristics to be obtained at a micrometric level on the implantable device, said method being able to optimize the response of the surrounding tissue to the device, without introducing at the same time any chemical contamination. A further aim of the present invention is, at the same time, to obtain a high speed of process and hence a high productivity.

The aforesaid aim is achieved by a method of laser treatment of an implantable device comprising the steps of:

- generating a pulsed laser beam by means of a diode-pumped solid-state (DPSS) laser generator in Q-switch regime; - focusing the laser beam on a surface of the implantable device; and

- moving the laser beam with respect to said surface according to a relative motion of scanning for creating a surface morphology comprising a controlled and substantially homogeneous distribution of pores; the power of the laser beam being determined so as to obtain pores having a diameter and depth of between 3 and 150 μm; the motion of scanning and the pulse frequency being controlled so as to obtain pores with a pitch of between 3 and 300 μm.

The present invention likewise regards a laser system for the treatment of an implantable device for creating on said device a surface morphology comprising a controlled distribution of pores, said system being characterized in that it comprises a diode-pumped solid-state (DPSS) generator in Q-switch regime for generating a pulsed laser beam of a power such as to obtain pores having a diameter of between 3 and 150 μm, means for focusing the laser beam on a surface of the device, relative movement means for displacing the laser beam with respect to said surface to create a relative motion of scanning of said surface by means of said laser beam, and means for controlling said relative movement means for creating a scanning motion such as to produce pores with a pitch of between 3 and 300 μm. The present invention moreover regards an implantable device comprising a surface provided with a controlled distribution of pores having a diameter and depth of between 3 and 150 μm and a pitch of between 3 and 300 μm.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the present invention, described in what follows are some preferred embodiments, provided by way of non-limiting examples and with reference to the attached plate of drawings, wherein:

- Figure 1 is a schematic view in elevation of an endosseous implant performed according to the present invention;

- Figure 2 is a schematic illustration of a portion of surface of the implant;

- Figures 3, 4 and 5 are enlarged images, with increasing enlargement, of a detail of a surface of the implant treated by means of the method of the present invention;

- Figures 6 and 7 are two diagrams of laser systems for the treatment of endosseous implants according to the present invention;

- Figure 8 is a graph that presents the results of an in-vitro test of cell proliferation and differentiation on substrates having different surface finishing; - Figures 9 is an enlarged image of an in-vivo implant in the femur of a rabbit, with a machined smooth surface (comparative example) ; and

- Figures 10, 11 and 12 are enlarged images of in-vivo implants in the femur of a rabbit, with laser-treated surface.

BEST MODE FOR CARRYING OUT THE INVENTION

With reference to Figure 1, designated as a whole by 1 is an endosseous implant, in particular a dental implant.

The implant 1, illustrated purely by way of example, comprises a threaded stem 2 and a substantially cylindrical or slightly conical head 3 and is provided with a threaded axial internal seat 4, axially open on the side of the head 3, for connection of a prosthetic element. The implant 1 is designed to be inserted in an implantation site obtained by surgery in a mandibular or maxillar bone of the patient, and is made of commercially pure titanium or else a biocompatible metal alloy, for example a titanium alloy.

According to the present invention, the side surface 4 of the implant 1 has surface microholes or pores 5 obtained by means of laser treatment.

The pores 5 are arranged in a plurality of rows 6 set alongside^' one another and at equal distances apart from one another. The rows can present a rectilinear or preferably helical pattern, as is described in greater detail in what follows. The pores can present a square-matrix arrangement, a honeycomb arrangement, or some other configuration.

The diameter and depth of the pores are between 3 and 150 μm, preferably between 3 and 30 μm, and even more preferably between 5 and 20 μm. The average pitch between adjacent pores is 3-300 μm, preferably 5-150 μm, and even more preferably 10- 30 μm.

Tests carried out in vitro on specimens of laser-treated titanium with pores having a diameters and depths of 5, 10 and 20 μm have revealed a tendency towards cell proliferation increasing with the dimensions of the pores.

Smaller dimensions of the pores are, on the other hand, considered more "biomimetic"; i.e., they are able to simulate better the morphology of the bone tissue and consequently stimulate cell differentiation to the advantage of characteristics of an osteoblastic type.

It is consequently deemed that the best compromise between cell proliferation and cell differentiation is obtainable in the range of pore dimensions of between 5 and 20 μm.

In-vitro and in-vivo tests were conducted in order to evaluate cell adhesion, proliferation and differentiation of the cells of an osteoblastic type on laser-treated surfaces according to the present invention.

As regards the in-vitro tests, the experimental materials were constituted by sterile cylinders made of commercially pure titanium of the same degree as that of the implants, having a diameter of 4 mm and a length of 13 mm.

The specimens were characterized by different surface finishes :

- surface obtained by means of machining using a machine tool, i.e., substantially smooth and without any induced porosities

(MAC) ;

- sanded surface (SAB) ;

- laser-treated surface with holes having a diameter of 5 μm, a pitch of 15 μm, and a depth of 5 μm (L5) ; - laser-treated surface with holes having a diameter of 10 μm, a pitch of 20 μm, and a depth of 10 μm (LlO) ; and

- laser-treated surface with holes having a diameter of 20 μm, a pitch of 30 μm, and a depth of 10 μm (L20) .

The cells used for the adhesion test were of an osteoblastic type of the cell line SaOS-2.

The SaOS-2 cells are of a continuous tumoural cell line, phenotypically stable and homogeneous human osteosarcoma, which are easy to cultivate and propagate and are able in any case to express many of the properties of non-transformed osteoblasts.

The tests of cell adhesion, proliferation and differentiation were conducted according to the protocols listed in the international bibliography.

CELL-ADHESION TESTS

A suspension of 1.25 x 10⁴ SaOS-2 cells in 2.5 ml of McCoy's culture medium with the addition of 15% of bovine foetal serum, L-glutamin, penicillin, streptomycin and amphotericin B was introduced into sterile containers made of polystyrene with twelve compartments. Simultaneously also the cylinders to be tested were introduced, after being extracted from the sterile pack under the laminar-flow hood. The containers were then put to incubate at 37⁰C, 5% CO₂ and relative humidity of 98% for β hours and 24 hours.

At the end of each period of growth the SaOS-2 cells in contact with the specimens were observed at the inverse optical microscope to verify the absence of cytotoxic effects that would invalidate the result. After this step, the specimens were washed with Dulbecco' s phosphate buffered saline (DPBS) in order to remove the non-adherent cells, and subjected to fixation and to all the procedures necessary for subsequent observation at the electronic microscope.

Observation at the electronic microscope had the purpose of providing an evaluation of the number of the cells present on the various surfaces and of the regularity with which the surface had been colonized. Another important datum obtainable by means of SEM observation was the one linked to the morphology assumed by the cells of the osteoblastic lines in the course of colonization of the surface: the structural details of the body of the cells are simply a response to the stimuli coming from the surface morphology and can provide a clear indication of the type of cell differentiation.

Results Specimens with machined surface (MAC)

After six hours of contact the surface presented numerous cells already with flattened shape tending to reproduce the underlying surface, together with cells with a more rounded morphology typical of the cells in suspension. The body of the cells during flattening frequently showed numerous vesicles indicating high metabolic activity and numerous filopodia and pseudopodia. This revealed that the chemico-physical characteristics of the starting surface are such as not to hamper colonization of the substrate.

After 24 hours of contact, the SEM images revealed considerable cell proliferation, but above all the marked process of flattening of the cell body. There were in fact no longer visible cells with globose morphology or vesicles of cell activity.

Specimens with sanded surface (SAB)

In this case, the SEM images showed a coexistence on the surface of cells with more flattened morphology alongside other more globose cells with intermediate morphology. After 24 hours, the cell density was visibly increased, but there were also present areas not yet colonized.

This would seem to indicate that, as compared to the machined specimen, the process of adhesion is followed by a slower process of colonization and proliferation.

Specimens with laser-treated surface

All the laser-treated specimens (L5, LlO, L20) enabled adhesion and colonization by the SaOS-2 cells. This means that the laser treatment undergone by the surface of the titanium is not such as to induce onset of cytotoxic phenomena.

The specimens L20 were the ones with the largest number of cells both after 6 and after 24 hours. The SEM images revealed that the bodies of the cells were strictly adherent both to the bottoms of the holes and to the portions of surface between the holes.

Conclusions

In conclusion, the results of the evaluation of cell adhesion are certainly favourable in so far as they highlight that the complex of the chemico-physical and morphological characteristics of all the laser-treated surfaces tested does not hamper the normal events of adhesion, colonization and proliferation by cells of an osteoblastic type.

As regards the specimens with a surface subjected to laser treatments, the specimens L20 supported the highest cell proliferation. Whereas the cells grown on the specimens MAC always exhibit a flattened morphology of a fibroblastic type, on all the laser-treated surfaces the cell body is frequently forced to assume shapes imposed by the structural irregularities, with characteristics more of an osteoblastic type. This datum suggests that the surfaces with holes obtained by means of laser treatment can present an effective improvement as compared to machined surfaces or to irregularly rough surfaces (such as sanded surfaces) , where cells coexist with a very different (flattened and polygonal) morphology.

CELL-PROLIFERATION AND CELL-DIFFERENTIATION TESTS Once the morphological data and the data regarding the influence of the different surfaces on adhesion and proliferation, at different times, of cells of a SaOS-2 osteoblastic type were acquired, the purpose of this experimentation phase was to evaluate the production by said cells, at different times, of the alkaline-phosphatase (ALP) enzyme, which is an early indicator of osteoblastic differentiation.

The experimental materials were constituted by cylinders made of commercially pure titanium having the same characteristics and the same surface finish as the ones described previously and designated by SAB, L5, LlO and L20.

The cells used for the test were always of an osteoblastic type (SaOS-2) , as in the previous experiment.

A suspension of 1.53 x 10⁵ SaOS-2 cells in 2 ml of McCoy's culture medium with the addition of 15% of bovine foetal serum, L-glutamin, penicillin, streptomycin, and amphotericin B was introduced into sterile containers made of polystyrene with twelve compartments. Each well containing a cylinder hence received approximately 3 x 10⁶ SaOS-2 cells. Simultaneously, after extraction from the sterile pack under the laminar-flow hood, all the cylinders available were also introduced. The containers were then put to incubate (5% CO₂, 37°C, R. H. 98%), some for 3 days, others for 7 days, and others for 10 days. At the end of each period of growth, 2 specimens for each type were removed from the well and, after 3 delicate washings with sterile phosphate buffer, were covered for 10 min with trypsin/EDTA solution so as to proceed to detachment and subsequent count of the adherent cells. Finally, the trypsin was neutralized with bovine foetal serum, and the cells in suspension were counted using a Burker counting chamber. The count was carried out 3 times on each specimen.

Simultaneously, another four specimens for each type of treatment surface were removed from the wells of polystyrene, washed as described above with phosphate buffer and then immersed in a solution of 0.1% Triton X-IOO¹, and incubated for 30 min in an incubator at 37⁰C so as to enable lysis of the cells grown on the surface. Subsequently, to 1 ml of each lysed cell 1 ml of reactive mixture was added made up in equal parts of MgCl₂-7H₂θ 2mM, p-nitrophenylphosphate 2 mM and 2- amino-2 methyl-1-propanol 2 mM. After 2 min of incubation at 37⁰C, the reaction was blocked with NaOH IM. The absorbance was read at 405 nm via spectrophotometer.

The alkaline-phosphatase enzyme catalyses conversion of p- nitrophenylphosphate into p-nitrophenol, which has an intense yellow colour and can thus be read spectrophotometrically at the corresponding wavelength.

The value of the activity of the enzyme that is quantified by the absorbance was normalized by the total number of cells (specific activity) and then expressed as absorbance/cell.

Results

As emerges clearly from the graph appearing in Figure 8, all the laser-treated surfaces promoted a significantly higher specific activity than the sanded surface.

The surface L20 emerged clearly, however, as being the most stimulating one as compared to the SaOS-2 cells, followed by

LlO. At 7 days of growth, the highest specific activity belonged to L5.

After 10 days, there is a general levelling, and the differences between the various pairs are no longer significant: this probably depends upon the fact that the cells have densely colonized the entire implant surface and undergo phenomena of metabolic inhibition and slowing that have an adverse effect on their possibility of differentiation in response to the stimuli deriving from the underlying surfaces.

Conclusions On the basis of the above results, it may be concluded that the laser treatment of the surface significantly influences the proliferation and differentiation of osteoblastic cells. In particular, it clearly emerged that the specific activity of the alkaline-phosphatase enzyme, which is an indication of osteoblastic differentiation, at the two experimental times most significant for the test (3 and 7 days) was significantly higher for all the laser-treated surfaces as compared to the control sanded surface. In particular, the datum that the surface L20 in short times provides the best stimulus to differentiation seems to be confirmed.

IN-VIVO TESTS

There were moreover conducted 2 in-vivo tests for explorative purposes .

Both tests were conducted on New Zealand rabbits of both sexes with an average weight of approximately 3.8 kg.

The first of these tests basically had the purpose of verifying whether the numerous extroversions present around the pores obtained with the laser (particularly evident on the surfaces with smaller pores) could release into the surrounding tissues micrometric particles of titanium, which are sometimes indicated in the literature as cause of inhibition of the mineralizing activity of the cells of bone tissue, of localized inflammatory processes, and also of diffusion of particles of titanium through the blood circulation to other organs.

For this purpose, it was necessary to compare the behaviour of specimens with a smooth surface that cannot release any type of particles with that of specimens having a laser-treated surface, on which these extroversions have greater incidence: a surface with pores having a diameter of 5 μm, a pitch of 15 μm, and a depth of 5 μm was chosen for the purpose.

The tests were conducted by implanting in the femur of the rabbit, on three different subjects, a cylinder machined to a smooth surface with a diameter of 2.5 mm and a length of 6 mm, and a laser-treated cylinder of similar dimensions presenting a porous surface with the characteristics recalled above.

The results are summed up in the following table, in which BIC% indicates the percentage of bone-to-implant contact.

Results

Smooth implants

The BIC is decidedly low, and osteoconductivity is not present on this implant surface.

It may in fact be noted in Figure 9, which refers to one of these tests, how the bone, even though it attempts to encapsulate the implant apex, fails to form direct relationships with the smooth titanium. There are in fact noted small points of bone contact (dark areas) alternating with large medullar lacunae (light areas) . Laser implants

The laser-treated implants have a higher degree of bone contact (BIC 29.39%). There is noted a good level of osteoconductivity (Figures 10 and 11) . The bone tends to encapsulate the implant, creating a perfect bone contact in the areas of adjacency, far more regular and continuous than in smooth titanium.

Also observable are small islands of bone contact detached from the cortical walls, clearly conducted along the surface by the good conductive properties of the surface to the laser (Figure 12) .

The process of osteo-integration is not yet completed, given that the implants were removed after 2 months from positioning, and osteoid islands still being formed on the laser-treated surface may be noted.

Conclusions The data gathered have enabled certain exclusion of effects of toxicity on the cells of the bone tissue due to the release of micrometric particles.

The second in-vivo test was conducted once again on New Zealand rabbits, using, however, implants made of threaded titanium (diameter 2.5 mm; length 5 mm) specifically designed for use in rabbits.

The purpose was to compare the degree of osteo-integration expressed as BIC% of laser-treated implants with pores of a diameter of between 5 and 40 μm and sanded implants.

Considering the high number of surfaces to be compared, this preliminary study was conducted using just two implants per type of surface. Albeit not having a high statistical significance, this study had, however, the very important aim of confirming the data provided by the in-vitro tests and thus restricting the number of laser-treated surfaces to be compared in vivo in an experiment that was conducted with statistically significant numbers.

The results obtained appear in the table below.

1: laser-treated surface with holes having a diameter of 5 μm, and a pitch of 15 μm; 2: laser-treated surface with holes having a diameter of

10 μm, and a pitch of 20 μm;

3: laser-treated surface with holes having a diameter of

20 μm, and a pitch of 30 μm;

4: laser-treated surface with holes having a diameter of 20 μm, and a pitch of 20 μm;

5: laser-treated surface with holes having a diameter of 25 μm, and a pitch of 30 μm;

6: laser-treated surface with holes having a diameter of

30 μm, and a pitch of 40 μm; 7 : laser-treated surface with holes having a diameter of

40 μm, and a pitch 50 μm.

From the above data it emerges clearly that almost all the laser-treated surfaces yield better results than do the sanded surface and in particular that the laser-treated surface with holes having a diameter of 20 μm and a pitch of 30 μm is the one that guarantees the highest degree of osteo-integration.

The above preliminary finding is substantially in agreement with the indications deriving from the tests conducted in vitro described previously.

Figures 3 to 5 are photographs taken at the microscope, with increasing levels of enlargement, of an example of laser- treated implant according to the present invention.

Figures β and 7 illustrate two possible laser systems 10, 11 for the treatment of the implants.

Figure 6 illustrates a simplified system 10 that is able to create a distribution of pores on the surface of the implant that is substantially homogeneous; even though the distribution is not perfect, it is obtained with a very high productivity.

The system 10 comprises a laser generator 12, a scanning head 13, and a piece-holder assembly 14 for support, positioning and movement of the implants 1 during the process.

The piece-holder assembly 14 basically comprises a horizontal table 15, which moves along two mutually perpendicular horizontal axes (X, Y) , and a spindle 16 for gripping the piece, which can turn about an axis α of its own coinciding in use with the axis of the implant being machined. The spindle is carried by a head 17, which is in turn carried by the table 15 and is orientable about a horizontal axis β perpendicular to the axis α so as to enable variation of the inclination of the axis α of the implant and compensate for the possible conicity of the implant to be machined. The laser generator 12 is of a DPSS (diode-pumped solid-state) type in Q-switch regime. The laser beam L generated is sent along an optical path P to the scanning head 13 set above the table. The scanning head 13 is designed to cause the laser beam to oscillate in a vertical plane containing the axis α of the spindle 16, with an alternating to-and-fro motion between two limit positions forming a pre-set angle between them so as to direct the beam on the implant substantially along a generatrix of the implant itself.

The scanning head 13 is conveniently provided with an 18 f- theta lens that is able to focus correctly the beam L as its position varies during the movement of scanning.

The scanning head 13 is conveniently mounted on a vertical guide 20 (axis Z) that enables regulation of the vertical position of the scanning head 13.

A control unit 24 controls, in a co-ordinated way, the laser generator 12, the scanning head 13, and the piece-holder assembly 14.

From the foregoing description, it emerges clearly that the axes X, Y, Z and β are only axes of preliminary positioning, which are not involved in the movements of machining.

Machining is carried out by scanning the implant 1 with the laser beam L moved by the scanning head 13 and by simultaneous rotation of the implant about the axis a.

The laser in Q-switch regime (nanosecond pulses) enables formation, during the scanning motion, of a succession of pores, by synchronizing appropriately the scanning speed and pulse frequency. Thanks to the high pulse frequency (e.g., 10 kHz) , it is possible to operate at very high scanning speeds (e.g., 300 mm/s) .

The rotation of the piece can be intermittent or else, preferably, continuous. In the first case, each sweep of the motion of the scanning laser describes a generatrix of the implant, which remains stationary during machining; the implant is then rotated by a pitch at the end of each scanning sweep.

In the second case, the scanning laser, in combination with the continuous rotation of the implant, describes a succession of helical lines on the latter.

In this way, it is possible to simplify to the maximum the controls and optimize the production rate.

Since the laser beam L is always directed on the implant 1 in a direction substantially perpendicular to the generatrix scanned (but for the inclination due to the scanning motion) , the incidence of the laser beam is in actual fact normal to the surface of the implant only in the bottom lands and top lands of the thread, but is necessarily inclined in the area of the flanks of the threads. This can produce both a dimensional alteration of the pores and a local variation in the distribution thereof. In this case, the dimensions and the pitch of the pores described and claimed are to be understood as average values.

In general, the above lack of uniformity is tolerable and does not alter significantly the biomimetic characteristics of the surface finish 1.

The system 11 of Figure 7 differs from that of Figure 6 in so far as it is able to control the angle of incidence of the laser beam on the implant. In this case, the laser beam L is directed on the implant by a focusing head 24, which is able to move along two axes Y and Z, by means of which it is possible to control the position of the beam L along the axis of the implant 1 and the distance of the focusing head with respect to the surface of the implant. The implant is mounted on a piece-holder head 26 having two degrees of freedom of rotation (about the axes α and β) .

The control unit 24 controls the four axes in a co-ordinated way during machining so as to keep the direction of incidence of the laser beam on the implant 1 instant by instant substantially perpendicular to the surface of the implant itself.

To make pores with dimensions comprised between 3 and 15 μm, DPSS lasers in Q-switch regime are conveniently used in the UV (third and fourth harmonic, wavelength of 355 and 266 nm, respectively) in TEMOO single-mode operation. To make pores with dimensions comprised between 15 and 30 μm, the second harmonic (532 nm) in the green is conveniently used, once again in single-mode operation, and for pores with dimensions comprised between 30 and 50 μm the fundamental wavelength (1064 nm) in the IR is conveniently used, once again in single-mode operation.

For holes with larger dimensions, the same laser sources can be used, but functioning in multimode (higher power) .

Laser machining can be carried out in a controlled atmosphere, for example using argon or neon as covering gas, or in vacuum conditions, in order to prevent any chemical alteration of the surface of the implant.

From an examination of the characteristics of the invention, the advantages that it makes possible are evident.

The use of a laser source of a DPSS type in Q-switch regime enables implants presenting an optimized surface topography, suitable for favouring proliferation and differentiation of cells of an osteoblastic type, to be obtained rapidly and economically.

Finally, it is clear that modifications and variations can be made to the method and to the laser system described herein, without thereby departing from the sphere of protection defined by the annexed claims.

In particular, the method and the laser systems can be used for the treatment of implantable devices of another type, not necessarily for oral surgery.

Claims

1. A method for laser treatment of an implantable device (1) comprising the steps of: - generating a pulsed laser beam (L) by means of a diode- pumped solid-state (DPSS) generator (12) in Q-switch regime;

- focusing the laser beam (L) on a surface (4) of the device; and

- moving the laser beam (L) with respect to said surface (4) according to a relative scanning motion for creating a surface morphology comprising a controlled distribution of pores (5) ; the power of the laser beam (L) being determined so as to obtain pores (5) having a diameter and depth of between 3 and 150 μm; the motion of scanning and the pulse frequency being controlled so as to obtain pores (5) with a pitch of between 3 and 300 μm.

2. The method according to Claim 1, characterized in that it comprises the step of making pores (5) having a diameter and depth of between 3 and 30 μm.

3. The method according to Claim 1 or Claim 2, characterized in that it comprises the step of making pores (5) having a diameter and depth of between 5 and 20 μm.

4. The method according to Claim 1, characterized in that the pitch between the pores (5) is equal to 5-150 μm.

5. The method according to Claim 1 or Claim 4, characterized in that the pitch between the pores (5) is equal to 10-30 μm.

6. The method according to Claim 1 for making pores (5) with a diameter of between 3 and 15 μm, characterized in that a DPSS generator (12) in the UV in TEMOO single-mode operation is used .

7. The method according to Claim 1 for making pores (5) with a diameter of between 15 and 30 μm, characterized in that a DPSS generator (12) in the green in TEMOO single-mode operation is used.

8. The method according to Claim 1 for making pores (5) with a diameter of between 30 and 50 μm, characterized in that a DPSS generator (12) operating in the IR in TEMOO single-mode operation is used.

9. The method according to Claim 1 for making pores (5) with a diameter of between 50 and 150 μm, characterized in that a DPSS generator (12) in multi-mode is used.

10. A laser system (10, 11) for the treatment of an implantable device (1) for creating on said device a surface morphology comprising a controlled distribution of pores (5) , characterized in that it comprises a diode-pumped solid-state

(DPSS) generator (12) in Q-switch regime for generating a pulsed laser beam (L) of a power such as to obtain pores (5) having a diameter of between 3 and 150 μm, focusing means (18,

25) for focusing the laser beam (L) on a surface (4) of the device (1), relative movement means (13, 14, 15) for displacing the laser beam (L) with respect to said surface (4) for creating a relative motion of scanning of said surface (4) by means of said laser beam (L), and control means (24) for controlling said relative movement means (13, 14, 15) for creating a scanning motion such as to produce pores (5) with a pitch of between 3 and 300 μm.

11. The laser system according to Claim 10, characterized in that said generator (12) operates in the UV.

12. The laser system according to Claim 10, characterized in that said generator (12) operates in the green.

13. The laser system according to Claim 10, characterized in that said generator (12) operates in the IR.

14. The laser system according to Claim 10, characterized in that said generator (12) operates in TEMOO single-mode operation.

15. The laser system according to Claim 10, characterized in that said generator (12) operates in multi-mode.

16. The laser system according to Claim 10, characterized in that said relative movement means comprise supporting means

(16, 26) for supporting said device (1) so that it can turn about a first axis (α) coinciding with an axis of the device (1) itself.

17. The system according to Claim 16, characterized in that said supporting means (16, 26) for supporting said device (1) can turn about a second axis (β) orthogonal with respect to said first axis (α) .

18. The system according to Claim 16 or Claim 17, characterized in that said relative movement means comprise means (13, 25) for moving said laser beam (L) with reciprocating motion substantially along a generatrix of said device (1) .

19. The system according to Claim 18, characterized in that said relative movement means comprise a scanning head (13) .

20. The system according to Claim 19, characterized in that said focusing means comprise an f-theta lens (18) carried by said scanning head (13) .

21. An implantable device comprising a surface provided with a controlled distribution of pores (5) having a diameter and depth of between 3 and 150 μm and a pitch of between 3 and 300 μm.

22. The implantable device according to Claim 21, characterized in that said pores (5) have a diameter and depth of between 3 and 30 μm.

23. The implantable device according to Claim 21 or Claim 22, characterized in that said pores (5) have a diameter and depth of between 5 and 20 μm.

24. The implantable device according to Claim 23, characterized in that the pitch between the pores (5) is equal to 5-150 μm.

25. The implantable device according to Claim 21 or Claim 24, characterized in that the pitch between the pores (5) is equal to 10-30 μm.