Osteoinductive implants and related methods of manufacture

Abstract

An implant device is configured to be at least partially in contact with bone when implanted and has improved osteoinductive characteristics to promote new bone formation. The implant device has one or more bone growth surfaces extending from a solid feature on a structure of the implant device. The one or more bone growth surfaces are configured to simulate adult trabecular bones by having recesses (140) and protrusions (150). The recesses extend from 10 [mu] m to 500 [mu] m in depth and may have an increasing inclination in a direction extending inwardly from the surface and not parallel to the opposing or adjacent walls. The one or more bone growth surfaces form a random and / or non-random network.

Description

Field of the Invention

[0001] Osteoinductive implants having surfaces modified to promote bone growth formation. Methods for making implant devices providing surface features that mimic those of trabecular bone.

[0002] BRIEF DESCRIPTION OF THE DRAWINGS

[0003] Figure 1A is a photograph providing a perspective view of an osteoinductive implant device having a surface that has been etched and treated.

[0004] Figure 1B yes Figure 1A An enlarged perspective view of the osteoinductive implant device depicted in , showing the surfaces that have been etched and treated.

[0005] Figure 1C is an enlarged plan view of the surface of a device that has been laser etched and laser processed.

[0006] Figure 1D is a scanning electron micrograph (SEM) image of a laser-treated surface.

[0007] Figure 1E yes Figure 1D The SEM image of the laser treated surface shown in further magnification.

[0008] Figure 1F is a SEM image of the laser treated surface shown at a scale of 200 nm at 200,000 times magnification.

[0009] Figure 2 is a perspective view of an exemplary laser.

[0010] Figure 3 is a perspective view of an exemplary 3D printer.

[0011] Figure 4A A perspective view of a test disc is depicted.

[0012] Figure 4B is a plan view of a test disc having an etched area and a cut line 4C-4C between point A and point B.

[0013] Figure 4C is an image depicting the measured depths of the concavities and surfaces along the cut line 4C-4C as measured by the profilometer.

[0014] Figure 4D yes Figure 4AA plan image of an enlarged section of a test disc shown in , with a cut line 4E-4E in between and 12 points along the cut line 4E-4E.

[0015] Figure 4E Depicted in Figure 4D A topographic map of the depths of the concavities and surfaces at the 12 points identified.

[0016] Figure 4F Depicted with Figure 4D The same enlarged region depicted in FIG. 1 , wherein several selected recesses are identified as recesses #1-#6 and have horizontal cut lines 4G-4G and vertical cut lines 4H-4H.

[0017] Figure 4G is an image depicting the measured depths of the recesses and surfaces along the cut line 4G-4G as measured by the profilometer.

[0018] Figure 4H is an image depicting the measured depths of the recess and surface along the cutting line 4H-4H as measured by the profilometer.

[0019] Figure 5 The following are photographs of seven disks of samples for comparative analysis observed via scanning electron microscopy (SEM), wherein the samples have different recess groove depths, are etched via laser, use surface texturing, and a control.

[0020] Fig. 6A is a microscopic image of sample #1 having an etched recess having a depth of 100 microns at a 20x magnification level of a section of sample #1 having a length of 2000 μm.

[0021] Figure 6B yes Fig. 6A Microscopic image of a section of sample #1 in FIG. 5 , which is 500 μm in length and further magnified to a level of 120 times magnification.

[0022] Figure 6C yes Fig. 6A Microscopic image of a section of sample #1 in FIG. 5 , which is 500 μm in length and further magnified to a level of 200 times magnification.

[0023] Fig. 7A is a microscopic image of sample #2 having an etched recess of 200 microns in depth at a 20x magnification level of a section of sample #1 of 2000 μm in length.

[0024] Figure 7B yes Fig. 7A Microscopic image of a section of sample #2, which is 500 μm in length and further magnified to a 120x magnification level.

[0025] Figure 7C yes Fig. 7A Microscopic image of a section of sample #2, which is 200 μm in length and further magnified to a 200x magnification level.

[0026] Fig. 8A is a microscopic image of sample #3, another disk similar to sample #1, having etched recesses 100 microns deep at a 20X magnification level of a section of sample #3 2000 μm in length.

[0027] Figure 8B yes Fig. 8A Microscopic image of a section of sample #3, which is 500 μm in length and further magnified to a 120x magnification level.

[0028] Figure 8C yes Fig. 8A Microscopic image of a section of sample #3, which is 200 μm in length and further magnified to a 200x magnification level.

[0029] Fig. 9A is a microscopic image of sample #4, another disk similar to sample #2, having etched recesses 200 microns deep at a 20X magnification level of a section of sample #1 2000 μm in length.

[0030] Fig. 9B yes Fig. 9A Microscopic image of a section of sample #4, which is 500 μm in length and further magnified to a 120x magnification level.

[0031] Fig. 9C yes Fig. 9A Microscopic image of a section of sample #4, which is 200 μm in length and further magnified to a 200x magnification level.

[0032] Fig. 10A is a microscopic image of sample #5, which was treated with a laser that blasted the surface of the disk to produce a nanotextured surface with nano-sized features. Fig. 10A It is a section of the disk of sample #5 at a 20X magnification level of a section having a length of 2000 μm.

[0033] Fig. 10B yes Fig. 10A Microscopic image of a section of sample #5, which is 500 μm in length and further magnified to a 120x magnification level.

[0034] Fig. 10C yes Fig. 10AMicroscopic image of a section of sample #5, which is 200 μm in length and further magnified to a 200x magnification level.

[0035] Fig.11A is a microscopic image of sample #6, which is another disk similar to sample #5 that was treated with a laser that blasted the surface of the disk to produce a nanotextured surface with nanometer-sized features. Fig.11A It is a section of the disk of sample #6 at a 20X magnification level of a section having a length of 2000 μm.

[0036] Fig. 11B yes Fig.11A Microscopic image of a section of sample #6, which is 500 μm in length and further magnified to a 120x magnification level.

[0037] Fig. 11C yes Fig.11A Microscopic image of a section of sample #6, which is 200 μm in length and further magnified to a 200x magnification level.

[0038] Fig.11D yes Fig.11A Microscopic image of a section of sample #6, which has a length of 200 μm and is further magnified to a level of 400 times magnification.

[0039] Fig.12 is a microscopic image of a section of sample #7, which is 500 μm in length and magnified to a 120x magnification level.

[0040] Fig.13 is a photograph focused on the device surface, showing the growth of cellular bone tissue around the grooves and on the treated surface.

[0041] Fig.14 is a SEM image showing bone growth on the laser treated device.

[0042] Fig.15 is a schematic representation of a recess formed by laser etching a solid feature of an implant device to illustrate some of the asymmetry in forming the recess based on the 3D morphology and geometry of trabecular bone.

[0043] Fig.16A are exemplary embodiments of devices, such as spinal implant fusion devices, that are formed at least in part by additive processing.

[0044] Fig. 16B is along Fig.16A The cutting line 16B-16B is intercepted Fig.16A Cross-sectional view of an implanted device.

[0045] Fig. 16C yes Fig.16A A magnified view of the surface of the device in Figure 2, showing the laser-etched nanogrooves.

[0046] Fig.17 is an enlarged view of a portion of an undulating exterior surface having protruding and recessed features at the surface that simulate trabecular bone.

[0047] Fig.18 is a simplified schematic outline of a portion of the exterior surface of a projection and a recess or groove showing an alternative embodiment.

[0048] Fig.19A is a simplified schematic diagram showing the use of a mobile laser machine to make laser etched grooves.

[0049] Fig.19B is a simplified schematic diagram showing the use of a stationary laser machine and a moving implant to create laser etched grooves.

[0050] Detailed Description

[0051] An implant device is disclosed, which is configured to at least partially contact bone when implanted and has osteoinductive characteristics to promote new bone formation. Also disclosed are related methods for making the device.

[0052] Implanted devices embedded in bone are ideally secured to the bone by new bone growth formation that extends over and into the bone growth surface or conforms to the bone shape, or the new bone growth formation is attached to the implanted device. The understanding of the interaction between biological tissue and material devices has focused on recreating a specific environment, and the surface features and conditions should mechanically mimic the mechanobiological response of cells as closely as possible.

[0053] Such implant device comprises spinal fusion cage (spinal fusion cages), bone screws and other bone fasteners, the plate for fracture (bone fracture) repair, knee and hip repair device, pedicle screw (pedicle) screw, cervical (cervical) plate, non-spinal orthopedic implant, the dental implant of the abutment (abutments) when being implanted in the jawbone at gums and other devices of the bone for stabilizing bone repair process, these devices apply correction (align) and / or amplify the physical effect of normal biological process.Basically, any bone interface device that benefits from bone growth in implant surface and / or bone growth around implant surface can be improved to produce bone growth surface on existing implant device.All these devices are firmly fixed to bone by extending to the bone growth surface of implant device and surrounding the new bone growth of the bone growth surface of implant device.

[0054] For example, one such device is Figure 1A The spinal implant device shown at 100 in the figure. The surgical implantation of interbody cages is generally used to provide support along the spine when a part of the patient's intervertebral anatomical structure has become weak, diseased or damaged, or is damaged in a surgical intervention guided to achieve anatomical stability. Such support systems are also generally used after discectomy, in which the intervertebral disc is surgically removed. Most commonly, existing support systems generally operate by inhibiting the normal movement between adjacent vertebrae, thereby stabilizing these vertebrae relative to each other in a fixed position, wherein the mechanical body of the support structure provides the required support along the patient's spine. Such support systems are generally made of stainless steel, titanium, titanium alloys, polymers (e.g., organic polymer thermoplastics, such as polyether ether ketone (PEEK)), polyether ketone ketone (PEKK), carbon fiber, ceramics, such as metal-ceramic (metal-ceramic) (Cermet) or a combination of ceramics and thermoplastics designed to be permanently maintained in the patient's body. Any bone interface device formed by these materials can be improved to have a bone growth surface.

[0055] In addition to fixation, it is also beneficial to try to stimulate bone growth between adjacent vertebrae. For this reason, in addition to fixation devices, spinal surgeons usually use bone graft materials. Bone grafts do not heal or fuse the spine immediately; on the contrary, bone grafts provide a foundation, a scaffold or a driving force for the patient's body to grow new bone. Bone grafts are not intended to be obstacles to movement, but rather to stimulate the induction of new bone formation. When new bone grows and solidifies, fusion occurs. Although instruments (such as screws, rods) are usually used for initial stabilization (postoperatively), it is the healing of bones that welds vertebrae together to produce long-term stability. There are two general types of bone grafts: actual bone and bone graft substitutes. Real bone can come from the patient (autologous graft) or from donor bone (allograft). Bone substitutes, bone induction agents, stem cell products, bone morphogenetic proteins and bone cement are also used in these types of operations. Bone implant devices as disclosed herein have the characteristics of promoting new bone growth to achieve accelerated attachment and fusion with patient bones.

[0056] The material of the implant device can be any suitable implant material as described above for the support system. Suitable materials include metals, cermets, plastics or bones, where the benefits of enhanced osteoinductivity can be achieved while maintaining appropriate anatomical space.

[0057] The implant device has one or more bone growth surfaces extending from a structurally solid feature of the implant device, because the bone growth surface is not formed as a coating. The one or more bone growth surfaces can be configured to simulate the structure of adult trabecular bone, in which bone tissue is organized into a network of interconnected walls, rods, plates, and arcs called trabeculae.

[0058] The bone growth surface includes primary surface features or structures, and in some embodiments may also include secondary surface structures that are treated surfaces of the primary surface structures. Figure 1A Surface 120 is shown including primary surface features 130 and secondary surface features 160. In one embodiment, the primary surface features and secondary surface features are formed by a laser, such as Figure 2 The laser system depicted at 200 . Figure 1A The spinal implant device depicted in has a length of 35 mm, but is clearly textured so that the surface concavities and convexities can be easily seen by eye without magnification.

[0059] Figure 1B yes Figure 1A 1 is an enlarged view of a portion of a spinal implant device 100 shown in FIG. 1 and depicting a primary surface structure 130 and a secondary surface structure 160. The primary surface structure is formed in a non-random engineered pattern that may appear random on a macroscopic scale, but algorithmically it is not random. The primary surface structures are large enough that they can be seen with the naked eye because they can be measured on a macroscopic scale or a microscopic scale, e.g. Figure 4A The pattern depicted in . Figure 4A Depicted is a test disc 110 having a diameter of 9 mm, an unetched border 112 of 0.5 mm width and a primary surface structure 130 comprising an etched area having a diameter of 8 mm.

[0060] With Figure 1B Compared with the pattern of the primary surface structure shown in 130, as shown in Figure 1B The secondary surface structure shown in 160 is random. The primary surface structure has a size measured in microns or millimeters, and secondary features have significantly smaller sizes because they can be measured in nanometers (e.g., 200 nanometers). Based on the foregoing, the implant device has an ordered or patterned and measured primary surface structure on a macroscale or microscale, and on a nanoscale or nanometer scale, the secondary surface structure is less ordered or patterned than the primary surface structure, making the nanometer scale secondary surface structure look relatively random or at least partially random. More succinctly, when observed from a macroscale or microscale to a nanoscale, the surface tends to be from patterned to random.

[0061] The multiple secondary surface structures respectively produce an improved osteoinductive effect at the surface of the implant device 100. This means that once implanted in the patient, the formation of new bone can be accelerated, and the network 18 of concave and convex portions with secondary surface structures provides features that help provide attachment locations for new bone formation. The macroscopic surface geometry and this continuous and progressive morphology with z-vector changes are important aspects of the embodiments disclosed herein.

[0062] The primary surface structure can be produced by a subtractive laser process, in which the Figure 2 The laser system of laser 212 depicted in and the associated laser computer system laser etches the surface of the device. Etching or ablating a solid body increases the surface area of ​​the device. When the device is laser etched, the resulting surface features or structural recesses can have depth, width, and length dimensions that are typically less than about 1 mm (1,000 μm), and in some cases only a few microns in size, with high repeatability and without causing significant structural damage to the surrounding material. Subtractive processes can also be machining processes.

[0063] Alternatively, the primary surface structure of the device may be manufactured by an additive process using 3D printing. 3D printing is the construction of a three-dimensional object from a computer-aided design (CAD) model or a digital 3D model, in which materials are deposited, connected or solidified under computer control to create a three-dimensional object, wherein the materials are usually deposited, connected or solidified via a process such as Figure 3 The 3D printer shown in 300 in FIG. adds together layer by layer. Regardless of whether the implant device and the primary surface structure are formed by an additive process or a subtractive process, the surface can be further improved or processed by a subtractive process to nano-sculpt the surface of the device to produce secondary surface structures or features. Additional information about manufacturing devices via additive processes using 3D printing is disclosed below under the heading "Additive Structures." In addition, information about 3D printing is also disclosed in applications filed on June 23, 2022 and filed on September 12, 2022. Application No. 63 / 354,748 and Application No. 17 / 942,420 are incorporated herein in their entireties.

[0064] For example, the engineered pattern can be a custom pattern developed using a CAD program based on a three-dimensional image of a portion of the structure at the surface of an adult trabecular bone sample (such as a 2×2 cm portion), which is then used to track the surface and is converted into instructions for a computer-controlled laser system. The image of the portion can be used to form a repeating pattern or to form the same pattern on the same devices at the same position of the same device. The pattern or geometric configuration of the primary surface structure may appear random at first glance to a casual observer, but upon closer inspection or by comparing the same device, it should be obvious that the pattern is engineered. The initial impression may be a bit like the first time you look at a quick response (QR) code or a digitized pattern for camouflage, and then realize that the pattern is highly engineered after a closer study.

[0065] In addition to generating simulated patterns (such as those based on trabecular bone), engineered patterns can have any configuration that promotes bone growth. Because the pattern is used to provide instructions for the computer-controlled laser system, any pattern can be repeatedly used and reproduced to etch the pattern into the surface of the device. For example, complex geometric patterns such as concentric rings or various fractal patterns can be formed. Other options include autonomous generation of geometric series, where the relative subtlety of continuity is reflected in the emphasis on historical topography, and although it looks random, it is a structural and learned development. This machine learning generation allows the tilt of the surface to be emphasized, or the kurtosis that emphasizes bone healing is retained.

[0066] Primary surface structure comprises recess, and it is to extend from outer surface but does not need to pass through the space or the indentation of device.The surface around recess is referred to as convex in this article, because convex is outstanding relative to recess.Recess follows the pattern of non-random engineering approaches to extend into the structural solid feature of implant device.Convex has the surface that seems relatively flat on microscopic level, and is used as the reference of the degree of depth of adjacent recess.

[0067] refer to Figure 1B Each recess 140 has a mouth 142 defined by an adjacent protrusion 150. Each recess 140 has at least one wall or sidewall 144. The sidewall 144 of each recess 140 extends inwardly from the mouth 142 of the recess 140 to an end 148. Figure 1B Also depicted is an intermediate depth 146 of the sidewall midway between the mouth 142 and the end 148. Figure 1C The same features are identified in Figure 1A The magnification shown in FIG. 1 is a section of the device under greater magnification.

[0068] In some embodiments, the depth of each recess is 100nm to 2mm, 500nm to 2mm, 1 micron to 2mm, 10 microns to 1000 microns, 20 microns to 800 microns, 30 microns to 500 microns and 40 microns to 200 microns. For example, the depth can be at least 200 microns or at least 100 microns. The width of each recess, most of recesses or at least most of recesses is in the scope of 1 micron to 2mm, 60 microns to 500 microns and 80 microns to 180 microns. The length of each recess is in the scope of 10 microns to several millimeters. In addition, length is corresponding to the metamorphology (meta-morphology) of cancellous bone, and it has trabecular width, average trabecular volume, average trabecular space and trabecular distance. The expectation of randomness is built in the data, and these data show that tension force not only stabilizes trabecular bone, and can realize and strengthen the gene expression of retaining bone-specific protein markers, and void space is crucial for the key advantage of microelasticity and nanoelasticity (micro and nanoelasticity), which allows modeling and remodeling according to the respective change force of the district in each bone and each bone. When the length of recess is much larger than the width of recess, then according to the configuration of end, recess is considered to groove or flat groove. The recess with sharp tip is groove, and the recess with flat end is flat groove. When the length and width of recess are roughly the same, then this recess is considered to pit.

[0069] Figure 1CTwo relatively long recesses 140a and 140b are depicted. Recess 140a has a relatively flat end 148a, so that it is shaped like a flat groove. In contrast, recess 140b has an end shaped like a groove because each opposing side wall or wall ends abruptly at end 148b. However, both wall 144a and wall 144b taper inwardly along the depth of the recess so that their walls slope from the mouth to the end. The non-coplanar walls or arches flare outwardly from the end of the recess to the mouth. Another way to illustrate that the recess flares outwardly upward or tapers inwardly downward is to consider a horizontal cross-section measured along the depth of the recess from its mouth 142 to its middle section 146 and further to its end 148, and for at least most recesses, the area of ​​the horizontal cross-sectional shape is generally reduced. Tests have shown that it is advantageous for the wall to have such an increased inclination from the surface and to extend inwardly, because the inclined surface facilitates laser processing compared to those perpendicular to the surface protrusions, and the inclined laser-treated surface can increase the cross-sectional area and thereby provide solid bone formation after the implantation of the device. Some recesses in a group may be different from this configuration, but most or most of the walls in a group have a tapered configuration. In some embodiments or in some recess groups, the recess may have a substantially planar wall so that the wall is parallel to the relative or adjacent wall and perpendicular to the surface. For example, most or all of the walls of the recess formed by laser etching are inclined walls, while the recess formed by the additive process may have parallel walls, or inclined walls but lack the precision (resolution) of the femtosecond laser process. Whether the wall is tapered inward from the mouth to the end or is substantially planar, these recesses will not be undercut along their depth.

[0070] like Figure 2 A computer-controlled laser system shown at 200 can be used to form the recesses 140. These recesses produced by laser etching can be made by moving the laser relative to the surface of the implant device 100; or the implant device 100 can be moved relative to the laser so that the recesses 140 are formed on the external surface. Alternatively, the process can move the implant and the laser simultaneously. The same principles apply to the formation of the secondary surface structure 160. It has been found that it is advantageous to apply the laser at an angle other than 90°. For example, it is advantageous to apply the laser at a maximum of 15° away from 90°. For example, these angles are helpful in forming recesses. It is helpful to avoid re-fixing the device during laser etching or laser processing of the device so that the device only needs to be flipped once. Limited re-fixing helps ensure that the device has the same pattern at the macroscopic level while advancing the degree of evolution of the random nanosurface.

[0071] Figure 1D and Figure 1Eis an image of a secondary surface structure 160 on the surface. The secondary surface structure 160 is also referred to herein as surface deformations, nano-sized features, and nanostructures. The surface deformation is a modification of the surface produced by the laser treatment surface of the device, including the surface of the side walls of the recesses and the surface around the mouth of each recess. Figure 1D The view in is magnified and has a range showing a length of 100 μm. Figure 1E is a further magnified view of the surface, where the range shows a length of 1.00 μm. Both show the surface deformation 160 in a random configuration.

[0072] Figure 1F is an image of a laser treated surface at 200,000 times magnification, showing a range of 200 nm in length, so each scale is 20 nm. The surface was previously laser etched, wherein the etched recesses have a maximum depth of about 100 μm.

[0073] Compared with the pattern of the recess, the surface deformation is particularly random, and is significantly smaller than the width of the recess. The surface deformation is included in the nano features discernible under magnification (e.g., 5,000 times and 50,000 times magnification), and includes convex and concave structures of nanometer size that width or diameter can be less than about 200 nanometers. These surface deformations can also have a height less than about 200nm. The surface deformation can be considered as a comprehensive impact (blasting), ablation (pitting) or surface strengthening (surface peening) of the substantially entire surface pointed by the laser. The region of the implant device treated by laser has an increase in surface area after being treated by laser. In certain embodiments, the surface area of ​​the region treated by laser is about 100 times or more of the same size area of ​​the surface of the solid feature on the structure that is not treated by laser to have the surface deformation.

[0074] The surface deformations can only be seen through powerful magnification that provides submicron resolution. As shown in the figure, these surface deformations show a very high surface area relative to their size. This large surface area creates a favorable zone for inducing and accepting new bone growth. Bone-forming cells attach to these nano-sized surface deformations with greater ease and affinity than the solid, untreated surface of the implant. Due to the interaction with this unique surface structure, bone-forming cells are "activated" to form and remodel new bone through biological changes in their morphology and biochemistry. Intercellular communication promotes activation, cultivating tissues based on an organizational approach that evolved from cell-based induction.

[0075] The surface deformation can be only a few nanometers (1nm = 10 -9m). The device can be modified to have a larger surface deformation, including about, at least about, or no more than about 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 nm or more, or a range including any two of the foregoing values. Most of the surface deformation is less than the amount of the width or depth of most of the recesses multiplied by about 5, 10, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 5000, 10000 or more, or a range including any two of the foregoing values.

[0076] Surface deformations roughen the surface and provide structure for bone processes to be anchored. Bone processes function like multiple extensions or tentacles. Considering that a typical osteoblast has a diameter of about 25 microns to 50 microns and has a variety of morphologies, the size and random configuration of surface deformations are ideal for bone growth. The same principle applies to the short protrusions, synapses, on the surface of osteoblasts that connect to neighboring cells and form a network structure.

[0077] The laser etching or texturing process used to form the pattern or random surface deformation varies depending on the device material and the structure to be produced. For example, a laser beam having a power intensity wavelength in the range of about 470 nanometers to 570 nanometers can be used to form both the primary surface structure and the secondary surface structure, the two having different exposure times, wherein the exposure time of the primary surface structure is longer than the exposure duration of the secondary structure.

[0078] Laser etching can be performed by exposure to a "green laser", where the green laser mentioned herein refers to a laser with the appropriate power required for industrial applications, wherein the wavelength varies between 470nm and 570nm, and more specifically between 515nm and 532nm. Many common green lasers are actually infrared lasers that naturally emit 1064nm light, but use a second crystal to double the frequency and halve the wavelength to 532nm, thereby providing green light. In this frequency-doubled IR laser, the infrared light is then filtered out to produce only green output. Lasers with higher wavelengths, such as infrared lasers with a wavelength of 1030nm, can also be used. However, green lasers are generally better because green lasers are relatively cool, which produces less thermal damage, making the nanostructure finer. Other lasers can also be used, for example, lasers using a 300nm wavelength, lasers with parameter-adjustable potentials to achieve other wavelengths, and lasers with a range of 0.15nm or 10kEv.

[0079] The laser may be a "femtosecond laser", which is a laser with an emission duration much less than 1 ps (10 -12 s) (i.e. in the femtosecond range (1fs = 10 -15 Femtosecond (FS) lasers are lasers that produce ultrashort light pulses of 100 s). Therefore, femtosecond (FS) lasers belong to the category of ultrafast lasers or ultrashort pulse lasers (which also includes picosecond lasers) with pulse durations in the femtosecond range or quadrillionths of a second. The duration of exposure to the laser light of such FS lasers influences the depth of the produced structures. The ultrashort (FS) pulse durations are characterized by excellent machining accuracy and virtually no edges or burrs around the laser irradiation area. Therefore, no additional mechanical or chemical post-processing steps are required.

[0080] The depth of the recesses can be determined by the dwell time of the laser etching. Longer dwell times provide deeper etchings. The recesses can have the same or different depths. Those recesses with different depths can have several sets of substantially the same depth. For example, one third of the recesses can have the same depth A, a second third have the same depth B, and a third third have a depth C. By allowing different depths, the recesses can provide different bone growth, so that the variety increases the overall success rate.

[0081] As described above, the implant can be made of a metallic material. When the metallic material is exposed to a laser, the material exhibits increased oxidation on the surface and chemically modifies the material to enhance the osteoinductivity of new bone growth formation during implantation. Therefore, the material undergoes metallurgical changes and the metal is no longer chemically pure. For example, the metal may be a titanium alloy, and when exposed to a laser, the surface is enhanced by oxides. Examples of preferred titanium alloys include 90% titanium, 6% aluminum, and 4% vanadium. When this titanium alloy is exposed to a laser, the laser changes the chemical structure at the surface by forming an oxide, which may be titanium oxide, aluminum oxide, or vanadium oxide. The oxide enhances the new bone growth characteristics at the surface (which are configured to simulate trabecular bone) and changes the element valence and charge arrangement changes on the surface. Laser exposure can also introduce conductivity so that there is an electric charge at the surface. This surface makes it easier for bone protrusions to attach and be anchored to the surface to promote bone growth.

[0082] As also described above, the implant may also include ceramics as part of its composition. Metal ceramics can combine the beneficial properties of ceramics, such as high temperature resistance and hardness, with the hardening characteristics of metals, such as the ability to undergo plastic deformation. Depending on the physical structure of the material, metal ceramics can also be considered metal matrix composites, but metal ceramics generally have less than 20% metal by volume. Exemplary metal ceramics include zirconium oxide-titanium sintered structures. Metal ceramics have been used to make resistors (especially potentiometers), capacitors, and other electronic components. In the context of biological systems based on membrane polarization and nanovoltage, it is not surprising that zirconium oxide-titanium sintered structures have long been known to enhance bone cell responses.

[0083] Examples of structures formed by subtractive processes

[0084] The following are examples of osteoinductive surfaces that can be used to manufacture devices having osteoinductive surfaces via subtractive (non-additive) processes. The exemplary configurations and conditions are given by way of example and not limitation.

[0085] Example 1

[0086] The test disks were analyzed, e.g. Figure 4A The test disc 110 in FIG. 1 has a diameter of 9 mm, a non-etched border 0.5 mm wide and a primary surface structure consisting of an etched area with a diameter of 8 mm. Figure 4B The test disc is depicted in a plan view with a cut line 4C-4C taken from two points identified as A and B. The length of the line between points A and B is 11 mm. The depth of the concave and surface along the line is Figure 4C The recess with the greatest depth has a recess of about 0.18 mm, and the recess with the shallowest depth has a depth of about 0.02 mm. The other recesses have depths of about 0.04 mm and 0.12 mm. There are 18 different recesses along the line between point A and point B, but only four different depths. Of course, various different widths can be associated with differences in depth for different lines drawn along the surface relative to perpendicular or oblique to the conformation. For example, just as the topography of the Grand Canyon in North America may vary depending on the trajectory between the north and south facades, the same variations apply to the site lines connecting the radial position of one point to any other point on the opposite side of the trench.

[0087] Figure 4D An enlarged section of a test disc is shown in , where two points are identified as C and D, and a cut line 4E-4E connects these two points, with points 1-12 between points C and D. The length of the line between points C and D is 7500 μm (7.5 mm). Figure 4EDepths of the valleys and surfaces at points 1-12 as measured by the profilometer are depicted. The following table summarizes the depths of the valleys and surfaces at points 1-12.

[0088]

[0089] Figure 4F Depicted with Figure 4D 1 and several selected recesses identified as recesses #1-#6. Recesses #1-#4 are examples of pits. Recesses #5-#6 are long grooves. The table below lists the average depth, maximum depth, and perimeter of each recess.

[0090]

[0091] The average depth maximum is 160.15 μm, the minimum is 172.61 μm, the overall average is 164.58 μm, the standard deviation is 4.19 μm, and 3 Sigma is 12.58 μm. The maximum depth maximum is 195.26 μm, the minimum is 212.11 μm, the overall average is 204.80 μm, the standard deviation is 6.83 μm, and three Sigma is 20.50 μm.

[0092] Figure 4F Also shown are the horizontal line EF and the vertical line GH taken between points E and F and between points G and H, respectively. The depths of these lines are also shown at Figure 4G and Figure 4H Depicted in.

[0093] Example 2

[0094] This example provides Figure 5Comparative information of different configurations on several disks shown, which depict seven disks as samples subjected to comparative analysis when viewed via a scanning electron microscope (SEM), these samples have different recess groove depths, are respectively laser etched, surface texturing is used, and controls. The samples are formed of medical grade titanium alloy, sometimes referred to as T5, but are usually formed as empirical alloys of 90% titanium, 4% aluminum, and 6% vanadium. Samples #1 and #3 are disks etched to form recesses with a depth of 100 microns. Samples #2 and #4 are etched more deeply to have recesses with a depth of 200 microns. Samples #1-#4 are also surface treated with a laser, which impacts the surface of the disk to produce a nanotextured surface with nanometer-sized features. The laser etching and laser treatment of samples #1-#4 are performed under atmosphere. Samples #5 and #6 were not laser etched to form macro-scale or surface depressions and were treated only with a laser that blasted the surface of the disk to produce a nanotextured surface with nano-sized features. Sample #7 was a control that was polished but not laser etched or laser blasted to produce nano-sized features. Images of the disks were taken at different magnification levels on a 3D digital microscope manufactured by Hirox.

[0095] Sample #1 is shown in Figure 6A-6C The deepest recess in sample #1 is shown as the darkest shade and has a depth of 100 microns. Fig. 6A A section of sample #1 2000 μm in length is shown at 20x magnification. Figure 6B Shows Fig. 6A A section of sample #1, 500 μm in length, was further magnified to a level of 120X magnification. Figure 6C Shows Fig. 6A A section of sample #1 with a length of 500 μm is further magnified to a level of 200 times magnification.

[0096] Sample #2 is shown in Figure 7A-7C The deepest recess in sample #1 is shown as the darkest shade and has a depth of 200 microns. Fig. 7A A section of sample #2 with a length of 2000 μm is shown at 20X magnification. Figure 7B Shows Fig. 7A A section of sample #2, 500 μm in length, was further magnified to a level of 120 times magnification. Figure 7C Shows Fig. 7A A section of sample #2 in the middle, with a length of 500 μm, is further magnified to a level of 200 times magnification. Figure 7A-7C and Figure 6A-6C It can be clearly seen that Figure 7A-7C The concave areas in the are darker because they are deeper.

[0097] Sample #3 is shown in Figure 8A-8C The deepest depression in sample #3 is shown as the darkest shade and has a depth of 100 microns. Fig. 8A A section of sample #3 with a length of 2000 μm is shown at 20X magnification. Figure 8B Shows Fig. 8A A section of sample #3, which is 500 μm in length, is further magnified to a level of 120 times magnification. Figure 8C Shows Fig. 8A A section of sample #3 in FIG. 5 is taken at 500 μm in length and further magnified to a level of 200 times magnification. Sample #3 repeats the pattern of sample #1 but with a greater valley depth, so as expected they appear identical in terms of their groove pattern, but the grooves in sample #3 are depicted darker. However, the surface treatments are different, as shown by Figure 6B and Figure 6C and Fig. 8A and Figure 8C This is best shown by comparison. Since the surface treatment is random, this is an expected result.

[0098] Sample #4 is shown in Figure 9A-9C The deepest recess in sample #4 is shown as the darkest shade and has a depth of 200 microns. Fig. 9A A section of sample #4 with a length of 2000 μm is shown at 20X magnification. Fig. 9B Shows Fig. 9A A section of sample #4, which is 500 μm in length, is further magnified to a level of 120 times magnification. Fig. 9C Shows Fig. 9A A section of sample #4 in Figure 5 is 500 μm in length and further magnified to a level of 200x magnification. Sample #4 repeats the pattern of sample #2 but with a greater valley depth, so as expected they appear identical in terms of their groove pattern, but the grooves in sample #2 are depicted darker. However, the surface treatments are different, as shown by Figure 7B and Figure 7C and Fig. 9A and Fig. 9C This is best shown by comparison. Since the surface treatment is random, this is an expected result.

[0099] Sample #5 is shown in Figure 10A-10C Sample #5 was treated with a laser that impinged upon the surface of the disk to produce a nanotextured surface having nano-sized features, also referred to as surface modifications or secondary surface structures or features. Fig. 10A It is a section of the disk of sample #5 at a 20X magnification level of a section having a length of 2000 μm. Fig. 10B yes Fig. 10A SEM image of a section of sample #5, which has a length of 500 μm and is further magnified to a 120x magnification level. Fig. 10C yes Fig. 10A SEM image of a section of sample #5, which has a length of 200 μm and is further magnified to a 200-fold magnification level.

[0100] Sample #6 is shown in Figures 11A-11D Like sample #5, sample #6 was treated with a laser that impinged on the surface of the disk to produce a nanotextured surface with nanometer-sized features. Fig.11A It is a section of the disk of sample #6 at a 20X magnification level of a section having a length of 2000 μm. Fig. 11B yes Fig.11A SEM image of a section of sample #6, which has a length of 500 μm and is further magnified to a 120x magnification level. Fig. 11C yes Fig.11A SEM image of a section of sample #6 in FIG. 5 , which is 200 μm in length and further magnified to a 200x magnification level. As expected, Figure 11A-11C The image looks similar to Figure 10A-10C However, because the laser treatment is random, no pattern can be discerned when samples are compared at the same magnification level. Fig.11D The texture of concave and convex structures is best seen in Fig.11A SEM image of a section of sample #6 in FIG. 5 , which has a length of 200 μm and is further magnified to a level of 400 times magnification.

[0101] Sample 7 was the control plate and was Fig.12 Shown in. Fig.12 is a control SEM image of sample #7, 500 μm in length and magnified to a 120X magnification level. As expected, its surface topography is essentially flat, very smooth, and featureless - not roughened like the sample with random rough topography due to laser treatment.

[0102] Example 3

[0103] Fig.13 is a composite image of photographs taken while focusing on a surface that is laser etched to form grooves 140 and has a laser processed surface 160 . Fig.13A few non-viable cells 170 and many healthy bone cells 180 are identified. Healthy bone cells 180 are shown growing around the grooves 170, particularly at the mouth 142 of the grooves 140. Healthy bone cells 180 are not shown growing in the grooves 140 simply because the photograph was focused on the surface and out of focus in the grooves 140 due to the depth of the grooves 140. The determination of viability is independent of the expression of genes known to define the osteoblastic lineage. By using transgenic insertions that respond to fluorescence at a specified wavelength, it can be shown that cells determined to be viable on the surface are consistent with markers that identify them as osteocytes.

[0104] Fig.14 is a SEM image showing in vitro bone growth on a laser treated device. Healthy bone cells 180 are shown growing robustly through the white portion, which includes many bone protrusions or extensions. The test also showed proliferation, gene expression and robust production of the bone specific proteins bone sialoprotein and tooth matrix protein. Fig.14 The images provided in were taken only 14 days after cell exposure and show robust cell attachment and bone growth. Such bone formation rates are unprecedented and indicate that healthy in vivo regeneration should be expected after implantation. More specifically, the test shows that the improved surface as disclosed herein provides rapid bone growth and may promote and improve the rate of fusion of bone with the implant surface. Therefore, these purposes can be achieved without bone grafts or bone graft substitute products.

[0105] Example 4

[0106] After etching and impacting the surface of a disk formed from a titanium alloy containing 90% titanium, 6% aluminum, and 4% vanadium, a clear oxidation change was observed in electron dispersive spectroscopy (EDS). Oxidation can produce titanium oxide, aluminum oxide, or vanadium oxide.

[0107] Vanadium increases the hardness of titanium and has a bonding pattern similar to that of phosphorus, which has been suggested as a property that underscores its role as an insulin mimetic and positively influences osteoblast proliferation. As a core principle of surface modification, incorporation of a positive effect on osteoblastogenesis is an important part of the bone healing process. Insulin has been shown to improve bone healing in both normal and diabetic bone healing models, and insulin mimetic compounds such as zinc chloride (ZnCl 2 ) and vanadyl acetylacetonate (VAC) have also been shown to improve bone healing. Vanadium may act in a similar way to zinc.

[0108] Example 5

[0109] Fig.15 A schematic representation of a recess formed by laser etching a solid feature of an implant device. The recess has relatively pointed ends and is approximately the same width and length, so that the recess is shaped like a pit. The sidewalls taper inwardly along the depth of the recess, or flare outwardly upwardly from the ends or taper inwardly downwardly.

[0110] The shape of the concave portion is based on the x, y and z axes derived from the trabecular structure, so the shape of the pit is asymmetric in nature. Fig.15 The dimple pair shown is divided into two parts 144a and 144b, showing some symmetric areas and some asymmetric areas. The dimple is essentially a dimple, but not completely conical. Therefore, using trabecular bone as a model does introduce some asymmetry.

[0111] Structures mainly formed by additive processes

[0112] According to one embodiment, a method for manufacturing a device (such as a spinal implant fusion device) via an additive process includes the following steps: using 3D printing to manufacture an implant body structure to produce an implant body structure; additively constructing a body structure having an upper load-bearing surface and a lower load-bearing surface and a wall structure; and wherein at least a portion of the body structure has a plurality of interconnected columns that form a porous wall having openings or channels that extend inward from an outer surface to a depth of 1.0 mm or greater, thereby forming a porous portion, and the ratio of the void volume to the solid block volume simulates trabecular bone. Alternatively, the 3D printed structure can be completely or substantially solid, with a surface structure consisting of interconnected arcs that are raised or produce grooves or flat grooves that appear to be cut into the surface but are actually produced by 3D printing.

[0113] The average or nominal ratio of the void volume to the block volume in the porous portion can vary depending on the purpose, such as replicating the trabecular bone of an adult male or female. For example, the density can be in the range of 65% or greater, such as 75%. A density of about 75% replicates the density of trabecular bone in an adult male.

[0114] The columns of porous walls are curved or arched with openings communicating with adjacent walls. The porous portion of the implant body structure extends at least partially through the outer surface of the implant body structure, forming a conduit for fluid to pass through the entire device. The curved or arched columns of these walls create a load-bearing capacity to withstand vertical loads without collapsing. The implant fusion device has an upper load-bearing surface and a lower load-bearing surface having nano-grooves etched on the exposed surface. The etching is produced by a subtractive laser process.

[0115] In another embodiment, a method of manufacturing a device such as a spinal implant fusion device includes the steps of providing a 3D printed implant body structure; and subsequent subtractive laser etching, which produces nanoscale structures on at least a portion of one or more surfaces of the implant body structure, the nanostructures producing new bone growth attachment features to enhance the osteoinductivity of the spinal implant or orthopedic fusion device. The 3D printed structure can be solid or relatively solid before using the laser etching subtractive process, the laser etching subtractive process obtaining a nanotechnology level of the surface for inducing bone formation and growth.

[0116] The laser etched nanostructure features are formed into a random pattern or a network of features in an organized pattern. The laser etching is formed by emitting an unobstructed laser beam to the surface of the implant. The method of manufacturing a device such as a spinal implant fusion device or other orthopedic or bone implant also has the step of moving the laser relative to the implant body structure to produce the network of features, or the method has the step of moving the implant body structure relative to the laser to produce the network of features.

[0117] In another embodiment, combining 3D printing and laser etching for the manufacture of a device such as a spinal implant fusion device or an orthopedic or bone device includes the following steps: using 3D printing to manufacture an implant main structure to produce an implant main structure; additively constructing a main structure having an upper supporting surface and a lower supporting surface and a wall structure; wherein at least a portion of the main structure has a plurality of interconnected columns, the plurality of interconnected columns forming a porous wall, the porous wall having openings extending inward from an outer surface to a depth of 1.0 mm or greater to form a porous portion having a ratio of void volume to solid block volume that simulates trabecular bone; and laser etching to produce nano-sized features on at least a portion of one or more external surfaces of the implant main structure, the nano-sized features such as grooves producing new bone growth attachment features to enhance the osteoinductivity of the spinal implant fusion device.

[0118] Fig.16Ais an exemplary embodiment of a device 210, such as a spinal implant fusion device, formed at least in part by an additive process. The configuration of the implant device 210 as shown has a first or upper surface 214, a second or lower surface 216, and a side surface 215, which surround an implant body structure 212 and form an outer surface of the implant body structure 212. When used as a spinal implant fusion device, the first surface 214 and the second surface 216 provide the device 210 with surfaces that will support the bone structure of the adjacent vertebral bodies when implanted between two adjacent vertebral bodies. These first surfaces 212 and second surfaces 216 can be in direct contact with the bone structure of the adjacent vertebral bodies of the patient when the device 10 is implanted through a surgery in which the implant fusion device is implanted to correct a degenerative condition or other condition of the patient. As shown, the exemplary embodiments are merely examples having simple shapes. In addition to Fig.16A In addition to the cubic shape depicted in the figure, any number of shapes can be used, and any number of polygonal shapes of various shapes and sizes can be used. For example, the device can be rectangular, oblong, or elongated. A cylindrical device with rounded sides can be used. Similarly, the device can have sides that are not round but are pentagonal or hexagonal in shape. When designed for use as a spinal implant fusion device, the only limitation on the shape is that it has a size sufficient to support the load between adjacent vertebrae to serve as a suitable implant fusion device.

[0119] refer to Fig. 16B ,along Fig.16A The cutting line 16B-16B from Fig.16A Take a cross-sectional view. The cross-sectional view shows the internal structure of the device 210. As shown, the main structure 212 of the device 210 can have a solid central area or zone and an outer area with a relatively high ratio of void volume to block volume and replicating trabecular bone (more specifically, cancellous trabecular bone), wherein the high porosity creates an open path for fluid to move in and out, similar to what occurs in natural bone. The main structure 212 of the implant device 210 is formed by 3D or additive printing, thereby producing an outer portion made of a plurality of interconnected posts 226. The posts 226 are curved or arched and spaced apart between the connecting portions, and the openings 228 form a porous wall having a porosity that replicates the porosity of an adult male or female depending on the implant produced.

[0120] The area with a high porosity ratio extends inwardly toward the central area of ​​the device 210. The ratio of the void volume to the bulk volume can be significantly reduced when the device extends from the periphery to the outer surface 214, 215, 216 of the device 210, which occurs when performing the 3D construction of the device. Therefore, the outer surface 214, 215, 216 of the porous wall can extend about 1 mm or more from the outer surface to the inside, wherein the central portion of the main structure has a greatly reduced ratio of the void volume to the bulk volume. This reduced ratio is more tightly compacted, thereby producing a core inside the device and a porous structure surrounding the entire device 210. This enhances the structural strength of the device 210 and provides such an excellent bone: it generates an outer surface with one or more more open porosities, and the inner core of the main structure 212 provides high strength.

[0121] Optionally, if desired, the porous structure of the interconnecting posts 226 can be made to extend through the implant main structure. In practice, it has been found that the depth of the surface of the simulated trabecular bone of at least 1mm depth is ideal for new bone formation, and therefore by limiting the depth to 1mm or more, the 3D manufacturing of the implant can be made simpler and cheaper. In addition, the upper surface 214 and the lower surface 216 should have porous trabecular features, but the sidewalls can be solid, as an optional way to manufacture the device.

[0122] refer to Fig. 16C and Fig.17 , showing a portion of the exterior surfaces 214, 215, 216. The porous exterior surface can be along the surface of the first surface 214, the second surface 216, or the side surface 215, or all of these surfaces.

[0123] like Fig. 16C and Figure 19A-19B As shown, nanostructures such as nano grooves 230 can be formed by a laser etching machine, for example, by Figure 2 The laser etcher depicted in the laser system 200 in FIG. These nano-grooves 230 can be arranged in a network 218 in an organized uniform pattern or a random non-uniform pattern throughout the external surfaces 214, 215, 216. Ideally, these nano-grooves 230 are produced along at least the first surface 214 and the second surface 216 of the implant device 10. The nano-grooves 30 are small laser etched cuts that can be arranged along the entire external surface in a subtractive laser etching process. These nano-grooves 230 produced by laser etching can be as shown in FIG. Fig.19A As shown, the nanogrooves 30 are formed by moving the laser 200 around the outer surfaces 214, 215, 216 of the implant device; or the device 210 can be moved relative to the laser so that the nanogrooves 230 are arranged on the outer surfaces 214, 215, 216, as shown. Fig.19BAs shown. These nano groove features produce improved osteoinductive effects at the surface of the implant device 210, respectively. This means that once implanted in the patient, the formation of new bone can be accelerated, and the network 218 of the nano groove 230 provides features that help provide attachment locations for new bone formation. This is an important feature provided in the present invention and is ideal because it does not require a smooth or flat external surface to form grooves that are effectively etched or burned into the external surface. As long as the path of the laser beam is unobstructed, grooves can be produced. As a result, even if the porous wall of the external surface has slight undulations 220, 222 and openings, the network 218 of the nano groove 230 can be formed unaffected and is not limited to the morphology of the external surface that is usually found in the implant device molded or otherwise having a smooth external surface. In fact, it can be found that the nano groove 230 is formed at different depths where the opening allows the laser beam to pass. The nano groove preferably has a width and depth of 10 nanometers or more, up to 1000 nanometers. These features are very small, and unlike micro channel laser etching, the nano groove can be etched very quickly due to its small size.

[0124] Fig.18 2 is a simplified schematic outline of a portion of an alternative embodiment of an outer surface 214, 215, 216. The outer surfaces 214, 215, 216 have an undulating feature such that the outer surface has slightly outwardly protruding protrusions 220 and slightly concave grooves or flat grooves 222. These features form an undulating surface, and when formed on an implanted fusion device, they enhance the ability of the device 210 to form a space between adjacent vertebrae after the device 10 is implanted. Additionally, the entire surface is then processed using laser etching to produce Fig. 16C Nano-grooves 230 are best shown in FIG.

[0125] The above embodiments detail methods for making a device (e.g., an orthopedic device) having a surface pattern that simulates trabecular bone. The body of the device can be made by any conventional process or by 3D printing. The surface can be formed by a subtractive or additive process. The surface can be treated to form a nanostructure, regardless of whether the body is formed by a subtractive or additive process. Such a surface structure is nanoscale and is bioactive in inducing bone growth.

[0126] Although structures, devices, methods and systems have been described according to specific embodiments, those skilled in the art will readily recognize that many variations of the specific embodiments are possible, and therefore any variation should be considered within the spirit and scope of the disclosure herein. Therefore, those skilled in the art may make many modifications without departing from the spirit and scope of the appended claims.

[0127] It is conceivable that various combinations or sub-combinations of the specific features and aspects of the above-disclosed embodiments can be made and still fall within one or more of the present invention. In addition, any specific features, aspects, methods, performances, characteristics, qualities, attributes, elements, etc. disclosed herein in conjunction with the embodiments can be used in all other embodiments set forth herein. Therefore, it should be understood that the various features and aspects of the disclosed embodiments can be combined or replaced with each other to form different modes of the disclosed invention. Therefore, it is expected that the scope of the present invention disclosed herein should not be limited by the above-mentioned specific disclosed embodiments. In addition, although the present invention is susceptible to various improvements and alternative forms, its specific examples have been shown in the drawings and described in detail herein. However, it should be understood that the present invention is not limited to the specific forms or methods disclosed, on the contrary, the present invention covers all improvements, equivalents and alternatives that fall within the spirit and scope of the various embodiments described and the appended claims. Any method disclosed herein does not need to be performed in the described order.

[0128] Any range disclosed herein also encompasses any and all overlaps, sub-ranges, and combinations thereof. Languages ​​such as "at most," "at least," "greater than," "less than," "between," etc. include the numbers listed. As used herein, numbers preceded by terms such as "approximately," "about," and "roughly" include the numbers (e.g., about 10%=10%), and also represent an amount that is close to the amount and still performs the desired function or achieves the desired result. For example, the terms "approximately," "about," and "roughly" may refer to an amount within less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the amount.

[0129] The claims following this written disclosure are hereby expressly incorporated into this written disclosure, with each claim standing on its own as a separate embodiment. This disclosure includes all permutations of independent claims and their dependent claims. In addition, additional embodiments that can be derived from the following independent and dependent claims are also expressly incorporated into this written description. These additional embodiments are identified by replacing the dependencies of a given dependent claim with the phrase "any claim that begins with claim [x] and ends with the claim immediately preceding that claim", where the term "[x]" in parentheses is replaced with the number of the most recently cited independent claim. For example, for a first claim set that begins with independent claim 1, claim 3 can depend on any one of claims 1 and 2, with these independent dependencies yielding two different embodiments; claim 4 can depend on any one of claims 1, 2, or 3, with these independent dependencies yielding three different embodiments; claim 5 can depend on any one of claims 1, 2, 3, or 4, with these independent dependencies yielding four different embodiments; and so on.

[0130] The recitation of the term "first" with respect to a feature or element in the claims does not necessarily imply the presence of second or additional such features or elements. Elements specifically recited in means-plus-function format, if any, are intended to be interpreted to cover the corresponding structures, materials, or acts described herein and their equivalents. Embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows.

Claims

1. A method of manufacturing an implant device, the implant device being configured to have at least one osteoinductive feature to promote new bone formation after implantation, the method comprising: providing implantable devices; laser etching one or more surfaces of the implant device to create a plurality of recesses extending into the implant device; - wherein each recess has a mouth, an end opposite the mouth and a side wall extending between the mouth and the end and extending into the implant device; - wherein said recesses are shaped following a non-random engineered pattern; and - wherein the mouth of each recess has a width, and a majority of said mouths have a width in the range of about 100 nm to about 2 mm; and The surface of the implant device is laser treated to produce surface deformation, and the surface treated to produce surface deformation includes the surface of the side wall of the recess and the surface of the mouth surrounding each recess, and the surface deformation is random compared to the pattern of the recess, and the surface deformation is significantly smaller than the width of the recess.

2. The method according to claim 1, wherein: Each recess has a depth measured from its mouth to its end, and most of the recesses have a depth in the range of about 1 micron to about 2 millimeters.

3. The method according to claim 1, wherein: A majority of the surface deformations have a length or width of less than about 200 nanometers.

4. The method according to claim 1, wherein: The laser treated region of the implant device has an increase in surface area after being laser treated.

5. The method according to claim 1, wherein: The one or more surfaces of the implant device are oxidized to be chemically modified as a result of laser etching or laser treatment of the one or more surfaces.

6. The method according to claim 1, wherein: The implant device is a titanium alloy, and wherein titanium oxide is formed at the surface by the laser etching.

7. The method according to claim 1, wherein: The sidewalls of each recess have an intermediate depth midway between the mouth and the ends, and wherein at least most of the recesses are configured such that they taper as the sidewalls slope from their mouths to their ends or at least to their intermediate depths.

8. The method according to claim 1, wherein: A majority of the surface deformations are at least 5 times smaller than the width of a majority of the recesses.

9. A method of manufacturing an implant device configured to have at least one osteoinductive feature to promote new bone formation after implantation, the method comprising: providing an implant device having one or more surfaces with a plurality of recesses extending into the implant device; - wherein each recess has a mouth, an end opposite the mouth and a side wall extending between the mouth and the end and extending into the implant device; - wherein the recesses are arranged in a non-random engineered pattern; and - wherein each recess has a depth and a majority of the recesses have a width in the range of about 1 micron to about 2 mm; and Laser-treating the surface of the implant device to generate surface deformation, the surface subjected to laser treatment to generate surface deformation includes the surface of the side wall of the recess and the surface of the mouth surrounding each recess, the surface deformation is random compared to the pattern of the recess, and the surface deformation is significantly smaller than the width of the recess; Among them, when observed under high magnification, most of the surface deformations have a length or width of less than 200 nanometers.

10. The method according to claim 8, wherein: The recess is formed by laser processing the one or more surfaces of the implant device.

11. The method according to claim 9, wherein: The laser treated region of the implant device has an increase in surface area after being laser treated.

12. The method according to claim 9, wherein: The one or more surfaces in the implant device are oxidized to be chemically modified as a result of laser etching or laser treatment of the one or more surfaces.

13. The method according to claim 9, wherein: The implant device is a titanium alloy, and wherein titanium oxide is formed at the surface by the laser etching.

14. An implant device configured to have at least one osteoinductive feature to promote new bone formation after implantation, the implant device comprising: one or more surfaces of the implant device, the one or more surfaces having a plurality of recesses extending into the implant device; wherein each recess has a mouth, an end opposite to the mouth, and a side wall extending between the mouth and the end; wherein the sidewall extends inwardly from the mouth to the end and has an intermediate depth midway from the mouth to the end; wherein each recess has a depth measured from its mouth to its end, and at least a majority of said recesses have a depth in the range of about 10 microns to about 500 microns; and Therein, at least most of the recesses are configured to gradually narrow inwardly, because the side walls of the recesses configured to gradually narrow inwardly are inclined from their mouths to their ends or at least to their middle depths.

15. The implant device according to claim 14, wherein: The implant is made of metal.

16. The implant device according to claim 15, wherein: The metal is a titanium alloy.

17. The implant device according to claim 16, wherein: The titanium alloy is 90% titanium, 6% aluminum and 4% vanadium.

18. The implant device according to claim 16, wherein: The implant device has at least one surface comprising titanium oxide.

19. The implant device according to claim 14, wherein: The recesses are arranged in a non-random engineered pattern; as well as Wherein the one or more surfaces of the implant device include surface deformations that are random compared to the pattern of the recesses and are significantly smaller than the depth of the recesses.

20. The implant device of claim 14, wherein: The recesses have varying depths such that not all of the recesses have substantially the same depth.

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