Osteoinductive implant and related manufacturing method

Abstract

An implant device configured to be at least partially in contact with bone during implantation and having improved osteoinductive characteristics for enhancing new bone formation. The implant device has one or more bone growth surfaces extending from a structurally solid feature of the implant device. The one or more bone growth surfaces are configured to mimic adult bone trabeculae by having recesses (140) and protrusions (150). The recesses extend to a depth of 10 to 500 microns and have an increasing slope from a surface that extends inwardly and is not parallel to opposing or adjacent walls. The one or more bone growth surfaces form a random and / or non-random network.

Description

Technical Field

[0001]

[0001] A bone-inductive implant having a surface modified for enhanced bone growth formation. A method for manufacturing an implant device provides surface features that mimic the surface features of trabecular bone.

Brief Description of the Drawings

[0002]

Figure 1AB

[0002] Figure 1A is a view showing a photograph providing a perspective view of a bone-inductive implant device having an etched and processed surface.

[0003] Figure 1B is an enlarged perspective view of the bone-inductive implant device depicted in Figure 1A showing the etched and processed surface.

Figure 1CD

[0004] Figure 1C is a plan view of the surface of the enlarged device that has been laser-etched and laser-processed.

[0005] Figure 1D is a view showing a scanning electron microscope (SEM) image of the laser-processed surface.

Figure 1EF

[0006] Figure 1E is a view showing an SEM image of the laser-processed surface shown in Figure 1D at a further magnification.

[0007] Figure 1F is a view showing an SEM image of the laser-processed surface at a magnification of 200,000x with a scale of 200 nm.

Figure 2

[0008] Perspective view of an exemplary layer.

Figure 3

[0009] Perspective view of an exemplary 3D printer.

Figure 4AB

[0010] Figure 4A is a perspective view of a test disk.

[0011] Figure 4B shows a planar image of the test disk having an etching region and a cut line 4C-4C between points A and B.

Figure 4C

[0012] A view showing an image depicting the recesses and the measured depths of the surface along the cut line 4C-4C as measured by a profilometer.

Figure 4DE

[0013] Figure 4D is a diagram showing a plan view of an enlarged area of the test disk shown in Figure 4A along the cutting line 4E-4E between 12 points and with the cutting line 4E-4E having these points.

[0014] Figure 4E is a diagram depicting a profile topographical mapping of the recesses and surface depths at the 12 points identified in Figure 4D.

Figure 4F

[0015] A diagram depicting the same enlarged area depicted in Figure 4D, with several selected recesses identified as recesses #1-#6, and with horizontal cutting line 4G-4G and vertical cutting line 4H-4H.

Figure 4GH

[0016] Figure 4G is a diagram showing an image depicting the measured depths of the recesses and surface along the cutting line 4G-4G as measured by a profilometer.

[0017] Figure 4H is a diagram showing an image depicting the measured depths of the recesses and surface along the cutting line 4H-4H as measured by a profilometer.

Figure 5

[0018] A photograph of seven disks that were samples subjected to comparative analysis as viewed through a scanning electron microscope (SEM), where the samples had different recess trench depths due to laser etching, use of surface texturing, and control.

Figure 6A-C

[0019] Figure 6A is a diagram showing a microscopic image of sample #1 with a recess having a depth of 100 microns etched in an area of sample #1 at a magnification level of 20x with a length of 2000 μm.

[0020] Figure 6B is a diagram showing a microscopic image of an area of sample #1 within Figure 6A, having a length of 500 μm and further magnified to a level of 120x.

[0021] Figure 6C is a diagram showing a microscopic image of an area of sample #1 within Figure 6A, having a length of 500 μm and further magnified to a level of 200x.

Figure 7A-C

[0022] Figure 7A is a diagram showing a microscopic image of Sample #2 in which a recess having a depth of 200 microns is etched at a magnification level of 20x for a region of Sample #1 having a length of 2000 μm.

[0023] Figure 7B is a diagram showing a microscopic image of a region of Sample #2 in Figure 7A, which has a length of 500 μm and is further magnified to a level of 120x magnification.

[0024] Figure 7C is a diagram showing a microscopic image of a region of Sample #2 in Figure 7A, which has a length of 200 μm and is further magnified to a level of 200x magnification.

Figure 8A-C

[0025] Figure 8A is a diagram showing a microscopic image of Sample #3, which is another disk like Sample #1 having an etched recess with a depth of 100 microns at a magnification level of 20x for a region of Sample #3 having a length of 2000 μm.

[0026] Figure 8B is a diagram showing a microscopic image of a region of Sample #3 in Figure 8A, which has a length of 500 μm and is further magnified to a level of 120x magnification.

[0027] Figure 8C is a diagram showing a microscopic image of a region of Sample #3 in Figure 8A, which has a length of 200 μm and is further magnified to a level of 200x magnification.

Figure 9A-C

[0028] Figure 9A is a diagram showing a microscopic image of Sample #4, which is another disk like Sample #2 having an etched recess with a depth of 200 microns at a magnification level of 20x for a region of Sample #1 having a length of 2000 μm.

[0029] Figure 9B is a diagram showing a microscopic image of a region of Sample #4 in Figure 9A, which has a length of 500 μm and is further magnified to a level of 120x magnification.

[0030] Figure 9C is a diagram showing a microscopic image of a region of Sample #4 in Figure 9A, which has a length of 200 μm and is further magnified to a level of 200x magnification.

Figure 10A-C

[0031] Figure 10A shows a microscopic image of Sample #5 processed with a laser that blasted the surface of the disk to obtain a nanostructured surface having nano-sized features, and is a diagram showing a region of the disk at a magnification level of 20x for a region of Sample #5 having a length of 2000 μm.

[0032] Figure 10B shows a microscopic image of a region of sample #5 within Figure 10A, which has a length of 500 μm and is further magnified to a level of magnification of 120x.

[0033] Figure 10C shows a microscopic image of a region of sample #5 within Figure 10A, which has a length of 200 μm and is further magnified to a level of magnification of 200x.

Figure 11A-C

[0034] Figure 11A shows a microscopic image of sample #6, which is another disk like sample #5 that has been treated with a laser to blast the surface of the disk in order to obtain a nanostructured surface with nano-sized features, showing a region of the disk at a level of magnification of 20x for a region of sample #6 having a length of 2000 μm.

[0035] Figure 11B shows a microscopic image of a region of sample #6 within Figure 11A, which has a length of 500 μm and is further magnified to a level of magnification of 120x.

[0036] Figure 11C shows a microscopic image of a region of sample #6 within Figure 11A, which has a length of 200 μm and is further magnified to a level of magnification of 200x.

Figure 11D

[0037] Figure showing a microscopic image of a region of sample #6 within Figure 11A, which has a length of 200 μm and is further magnified to a level of magnification of 400x.

Figure 12

[0038] Figure showing a microscopic image of a region of sample #7, which has a length of 500 μm and is magnified to a level of magnification of 120x.

Figure 13

[0039] Figure showing a photograph focused on the surface of the device, showing the growth of cancellous bone tissue around the trench and on the treated surface.

Figure 14

[0040] Figure showing a SEM image showing bone growth on the laser-treated device.

Figure 15

[0041] Schematic diagram of a recess formed by laser etching the solid features of an implant device in order to show some asymmetry when forming a recess based on trabecular 3D morphology and geometry.

Figure 16A

[0042] FIG. 1 is a diagram showing an exemplary embodiment of an apparatus such as a spinal implant fusion device formed at least in part by an additive process.

Figure 16B

[0043] FIG. 5 is a cross-sectional view of the implant device of FIG. 1A taken along the cut line 1B-1B.

Figure 16C

[0044] FIG. 9 is an enlarged view of the surface of the device within FIG. 1A showing laser-etched nanochannels.

Figure 17

[0045] FIG. 13 is an enlarged view of a portion of the undulating outer surface having protruding and recessed features on a surface mimicking trabecular bone.

Figure 18

[0046] FIG. 17 is a diagram showing a simplified schematic contour of a portion of the outer surface showing protrusions and channels or troughs of an alternative embodiment.

Figure 19AB

[0047] FIG. 19A is a simplified schematic diagram showing the fabrication of laser-etched channels using a moving laser machine.

[0048] FIG. 19B is a simplified schematic diagram showing the fabrication of laser-etched channels using a stationary laser machine with the implant being moved. DETAILED DESCRIPTION OF THE INVENTION

[0003]

[0049] An implant device is disclosed that is configured to be at least partially in contact with bone during implantation and has osteoinductive features to enhance new bone formation. A related method for manufacturing the device is also disclosed.

[0004]

[0050] An implant device implanted in bone is ideally fixed to the bone by new bone growth formation, which extends onto and into the bone growth surface or conforms bone formation to something that adheres to the implant device. A deep understanding of the interaction between biological tissue and a material device has focused on reconstructing a particular environment with surface features and conditions that can best simulate a mechanical approach to the mechanobiological response of cells.

[0005]

[0051] Such implant devices include spinal fixation cages, bone screws and other fixtures, plates used in fracture repair, knee and hip repair devices, pedicle screws, cervical plates, non-spinal orthopedic implants, dental implants including abutments when implanted into the jawbone in the gingiva, and other devices used to stabilize bone for bone repair techniques that exert a physical effect to modulate and / or amplify normal biological processes. In essence, any bone interface device that benefits from bone growth within and / or around the surface of the implant can be modified to create a bone growth surface on an existing implant device. All of these devices are firmly fixed to the bone by new bone growth that extends onto and surrounds the bone growth surface of the implant device.

[0006]

[0052] As an example, one such device is a spinal implant device as shown at 100 in FIG. 1A. When a portion of a patient's intervertebral anatomical structure is weakened, diseased, or destroyed, or impaired in a surgical intervention directed to achieving anatomical stability, surgical implantation of an intervertebral cage is typically used to provide support along the spine. Such support systems are also commonly used after discectomy where the intervertebral disc is surgically removed. Most commonly, existing support systems operate by the mechanical body of the support structure providing the necessary support along the patient's spine, typically inhibiting normal movement between adjacent vertebrae, and thereby stabilizing these vertebrae in fixed positions relative to one another. Such support systems are typically designed to remain permanently within the patient's body and are 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, ceramic, combinations such as metal-ceramic (cermet), or combinations of ceramic and thermoplastic materials. Any bone interface device formed from these materials can be modified to have an osteogenic surface.

[0007]

[0053] In addition to fixation, it is beneficial to attempt to simulate bone growth between adjacent vertebrae. To do so, spinal surgeons often use bone graft material in addition to fixation devices. The bone graft does not immediately heal or fuse the spine; rather, the bone graft provides a substrate, scaffold, or stimulus for the patient's body to grow new bone. The bone graft is not intended to be an impediment to movement and serves an inductive role to simulate new bone formation. When new bone grows and hardens, fusion occurs. Instruments (e.g., screws, rods) are often used for initial (post-operative) stabilization, but it is bone healing that brings the vertebrae together for long-term stability. There are two general types of bone grafts: actual bone and bone graft substitutes. The actual bone can be derived from the patient (autograft) or a donor's bone (allograft). Also used in these types of surgeries are bone substitutes, bone inductive agents, stem cell products, bone morphogenetic proteins, and bone cements. The bone implant device as disclosed herein has the characteristics of promoting new bone growth, achieving rapid attachment, and fusing the patient's bone.

[0008]

[0054] The material from which the implant device is made can be any suitable implant material as described above for the support system. Suitable materials include metals, cermets, plastics, or bone, which can achieve enhanced osteoinductive benefits while maintaining an appropriate anatomical space.

[0009]

[0055] The implant device has one or more bone growth surfaces that extend from the structurally solid features of the implant device, since the bone growth surfaces are not formed as a coating. The one or more bone growth surfaces can be configured to mimic the structure of adult trabecular bone having a network of interconnected walls, rods, plates, and arcs called trabeculae.

[0010]

[0056] The bone growth surface includes primary surface features or structures and, in some embodiments, may also include a secondary surface structure that is a processed surface of the primary surface structure. FIG. 1A shows a surface 120 that includes a primary surface structure 130 and a secondary surface structure 160. In one embodiment, the primary surface features and the secondary surface structure are formed by a laser, such as the laser system depicted at 200 in FIG. 2. The spinal implant device depicted in FIG. 1A has a length of 35 mm, but it is clearly textured such that surface recesses and protrusions can be easily seen with the naked eye without magnification.

[0011]

[0057] FIG. 1B is an enlarged view of a region of the spinal implant device 100 shown in FIG. 1A, depicting the primary surface structure 130 and the secondary surface structure 160. The primary surface structure is formed in a non-random engineered pattern, which may appear random at the macroscale but is not random algorithmically. The primary surface structures are large enough to be visible to the naked eye because they can be measured at the macro or microscale, such as the pattern depicted in FIG. 4A. FIG. 4A depicts a test disk 110 having an etched region with a diameter of 8 mm, an unetched edge 112 that is 9 mm in diameter and 0.5 mm wide, and a primary surface structure 130.

[0012]

[0058] The secondary surface structure, as shown at 160 in FIG. 1B, is random compared to the pattern of the primary surface structure shown at 130 in FIG. 1B. The primary surface structure has dimensions measured in microns or millimeters, while the secondary features have dimensions that can be measured in nanometers, such as 200 nanometers, and are thus significantly smaller. Based on the foregoing, the implant device has a primary surface structure that is regular or patterned and is measured at the macro or micro scale while being at the nanometer scale or nanoscale, and the secondary surface structure is less regular or patterned than the primary surface structure, such that as a result, the nanoscale secondary surface structure appears relatively random or at least partially random. Stated more succinctly, when viewed from the macroscale or microscale to the nanoscale, the surface goes from being patterned to being random.

[0013]

[0059] Individually, the secondary surface structures provide an improved osteoinductive effect at the surface of the implant device 100. This means that once implanted into a patient, the formation of new bone can be accelerated, and the network 18 of recesses and protrusions having the secondary surface structure provides features that assist in providing sites for attachment for new bone formation. This continuous and progressive architecture with z - vector variations in addition to the macro surface geometry is an important aspect of the embodiments disclosed herein.

[0014]

[0060] The primary surface structure can be generated by a subtractive laser process in which the surface of the device is laser etched by a laser system, such as laser 212 depicted in FIG. 2, and an associated laser computer system. Etching or ablation of a solid material increases the surface area of the device. When the device is laser etched, the resulting surface features or structural recesses generally have depth, width, and length dimensions of less than about 1 mm (1,000 μm) with high repeatability and without causing significant structural damage to the surrounding material, and in some cases are on the order of just a few microns in size. The subtractive process can also be a machining process.

[0015]

[0061] Alternatively, the primary surface structure of the device can 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 digital 3D model in which material is deposited, joined, or solidified under computer control to create the three-dimensional object, and the material is typically added layer by layer by a 3D printer as shown at 300 in FIG. 3. Whether the implant device and the primary surface structure are formed by an additive process or a subtractive process, the surface can be further modified or processed by a subtractive process to nano-etch the surface of the device to obtain a secondary surface structure or feature. Additional information regarding manufacturing the device by an additive process using 3D printing is disclosed below under the heading “Additional Structures”. Information regarding 3D printing is also disclosed in Application No. 63 / 354,748, filed Jun. 23, 2022, and Application No. 17 / 942,420, filed Sep. 12, 2022. Application No. 63 / 354,748 and Application No. 17 / 942,420 are incorporated herein by reference in their entirety.

[0016]

[0062] As an example, an engineered pattern can be a custom pattern developed using a CAD program based on a 3D image of a region of the structure on the surface of an adult trabecular bone sample, such as a 2×2 cm area that is later used to trace the surface and converted into instructions for a computer-directed laser system. The image of this region can be used to form repeating patterns or to form the same pattern on the same device in the same location. The pattern of the primary surface structure or geometric configuration may appear random at first glance to someone who doesn't know anything, but upon closer observation or by comparing the same device, it should be clear that a pattern has been applied. Such a first impression can be somewhat similar to the experience of first seeing a quick response (QR) code or a digitized pattern for camouflage and then noticing, after more careful investigation, that the pattern is highly applied.

[0017]

[0063] In addition to generating mimicking patterns such as patterns based on trabeculae, the engineered pattern can have any configuration that promotes bone growth. Since the pattern is used to provide instructions for a computer-directed 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. Additional options include the autonomous generation of geometric progressions, where the relative nuances of the continuum are reflected in the emphasis on a historical topographic map and at the same time appear random while being structured and a learned sequence. Such machine learning generation allows for highlighting surfaces that should be distorted or that should retain the sharpness that emphasizes bone healing.

[0018]

[0064] The primary surface structure includes recesses, which are voids or indentations that extend from the outer surface but do not necessarily penetrate the device. The surface around the recesses is herein referred to as protrusions, as the protrusions project relative to the recesses. The recesses extend into the structurally solid features of the implant device as directed by a non - random engineered pattern. The protrusions have surfaces that appear relatively flat at the micro - level and serve as a reference for the depth of adjacent recesses.

[0019]

[0065] Referring to FIG. 1B, each recess 140 has an opening 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 opening 142 of the recess 140 to an end 148. FIG. 1B also depicts an intermediate depth 146 of the sidewall midway between the opening 142 and the end 148. The same features are identified in FIG. 1C, which depicts an area of the device at a greater magnification than that shown in FIG. 1A.

[0020]

[0066] Each recess has a depth, a length, and a width. The depth of each recess, most of the recess, or at least a majority of the recess, as measured from its mouth to its end, is in the range of 100 nm to 2 mm, 500 nm to 2 mm, 1 micron to 2 mm, 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 the recess, or at least a majority of the recess is in the range of 1 micron to 2 mm, 60 to 500 microns, and 80 to 180 microns. The length of each recess is in the range of 10 microns to several millimeters. Additionally, the length is consistent with the meta - morphology of cancellous bone having trabecular width, average trabecular volume, average trabecular void, and trabecular spacing. Predictions of randomness are built in data suggesting that tensile forces not only stabilize the trabeculae but also enable and enhance gene expression that retains the properties of bone - specific proteins, and that the void space is crucial to the major advantages of micro - and nano - elasticity that allow modeling and remodeling according to changing forces that are individual for each bone and region within each bone. When the length of the recess is much larger than the width of the recess, the recess is considered a trench or a trough depending on the configuration of its ends. A recess with a sharply pointed end is a trench while a recess with a flat end is a trough. When the length and width of the recess are approximately the same, the recess is considered a pit.

[0021]

[0067] FIG. 1C depicts two relatively long recesses 140a and 140b. Recess 140a has an end 148a that is relatively flat, and as a result, recess 140a is trough-shaped. In contrast, recess 140b has ends that are trench-shaped because each opposing sidewall or wall abruptly ends at end 148b. However, both wall 144a and wall 144b are tapered inward along the depth of the recess, and as a result, those walls slope from the mouth to the end. Walls or arches that are not in the same plane flare outward from the end of the recess to the mouth. Another way to describe the recess flaring outward as it goes up or tapering inward as it goes down is to consider a horizontal cross-section measured along the depth of the recess from its mouth 142 to its intermediate region 146 and further to its end 148, and this horizontal cross-sectional shape generally decreases in area for at least the majority of the recess. Tests have shown that it is advantageous for the walls to have such an increasing slope from the surface and to extend inwardly because the sloped surface promotes laser treatment and an increased cross-sectional area as a derivative of the sloped laser-treated surface, thereby resulting in robust bone formation after implantation of the device. Some of the recesses within the set may differ from this configuration, but the majority or most of the walls within the set have a tapered configuration. In some embodiments, or in some sets of recesses, the recesses may have walls that are essentially planar such that one wall is parallel to an opposing or adjacent wall and perpendicular to the plane. For example, recesses formed by laser etching have walls that are mostly or all sloped walls, while recesses formed by an additive process may have parallel walls or sloped walls but lack the resolution of a femtosecond laser machining process. Whether the walls are tapered inward from the mouth to the end or are essentially planar, these recesses are not undercut along their depth.

[0022]

[0068] A computer-directed laser system as shown at 200 in FIG. 2 can be used to form the recesses 140. These recesses produced by laser etching can be produced by moving the laser around the surface of the implant device 100 or the implant device 100 can be moved relative to the laser such that the recesses 140 are placed on the outer surface. Alternatively, the process can move both the implant and the laser simultaneously. The same principle applies to the formation of the secondary surface structure 160. It has been found advantageous to apply the laser at an angle other than 90°. For example, it is advantageous to apply the laser shifted from 90° by up to 15°. For example, these angles are useful when forming the recesses. It is useful to avoid re-fixing the device during laser etching or laser treatment so that the device only needs to be inverted once. Limited re-fixing helps ensure that the device has the same pattern at the macro level while maintaining the degree to which it develops a random nano surface.

[0023]

[0069] Figures 1D and 1E are images of the secondary surface structure 160 on the surface. The secondary surface structure 160 is also referred to herein as surface deformation, nano-sized features, and nanostructures. Surface deformation is a modification to the surface resulting from laser treatment of the surface of the sidewalls of the recesses and the surface around the mouth of each recess. The display in FIG. 1D is enlarged and has a scale indicating a length of 100 μm. FIG. 1E is a further enlarged view of the surface with a scale indicating a length of 1.00 μm. Both show surface deformations 160 in a random configuration.

[0024]

[0070] Figure 1F is an image of the laser-treated surface at a magnification of 200,000x with a scale indicating a length of 200 nm, and each tic is 20 nm. The surface has been previously laser-etched and the etched recesses have a maximum depth of about 100 um.

[0025]

[0071] The surface deformation is particularly random compared to the pattern of the recesses and is significantly smaller than the width of the recesses. The surface deformation includes nano-features that are distinguishable at magnifications such as 5,000x and 50,000x and also includes nano-sized uneven structures that can have a width or diameter of less than about 200 nanometers. These surface deformations can also have a height of less than about 200 nm. The surface deformation can be regarded as blasting, pitching, or surface peening over a substantially entire wide range of the surface where the laser is directed. The area of the implant device being laser-treated has an increased surface area after laser treatment. In some embodiments, the laser-treated area has a surface area that is about 100 times or more larger than the area of the same size of the surface of a structurally solid feature that has not been laser-treated and has surface deformation.

[0026]

[0072] The surface deformation can only be seen through a powerful magnification that provides sub-micron resolution. As shown, these surface deformations exhibit a very high surface area relative to their size. This large surface area induces new bone growth and creates a favorable area for receiving it. Osteoblasts attach to these nano-sized surface deformations much more easily and closely than to the solid untreated surface of the implant. Osteoblasts are "activated" to form and remodel new bone through their biological changes in morphology and biochemistry resulting from their interaction with this unique surface structure. The activation progresses through cell-to-cell communication and nurtures a tissue-based mechanism that evolves from cell-based induction.

[0027]

[0073] The surface deformation is only a few nanometers (1 nm = 10 -9It may have dimensions of (m). The device can be modified to have larger surface deformations, including those having dimensions of about 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 nm or more, at least about 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 nm or more, or not exceeding about 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 nm or more, or ranges including any two of the foregoing values. Most of the surface deformations are about 5 times, 10 times, 50 times, 100 times, 150 times, 200 times, 250 times, 300 times, 350 times, 400 times, 450 times, 500 times, 550 times, 600 times, 650 times, 700 times, 750 times, 800 times, 850 times, 900 times, 950 times, 1000 times, 5000 times, 10000 times, or more, or ranges including any two of the foregoing values, smaller than the width or depth of most of the recesses.

[0028]

[0074] The surface deformations roughen the surface and provide a structure to support the bone processes. The bone processes function like numerous outgrowths or tentacles. Considering that typical osteoblasts have a diameter of about 25 - 50 microns and are morphologically diverse, the size and random configuration of the surface deformations are ideal for bone growth. The same principle applies to the short protrusions on the surfaces and processes of osteoblasts that connect to adjacent cells to form a network structure.

[0029]

[0075] The laser etching or texturing processes used to form the pattern or random surface deformations vary depending on the device material and structure to be fabricated. For example, a laser beam having a power intensity wavelength in the range of about 470 - 570 nanometers can be used to form both primary and secondary surface structures, and the exposure duration is varied to be longer for the primary surface structure than for the secondary structure.

[0030]

[0076] Laser etching can be carried out by exposure to a "green laser", which refers to a laser having a wavelength that varies between 470 and 570 nm, and more particularly between 515 and 532 nm, and having an appropriate power required for industrial applications as used herein. Many common green lasers are actually infrared lasers, which originally emit light at 1064 nm, but use a second crystal to double the frequency and halve the wavelength down to 532 nm, thereby providing green light. In such frequency-doubled IR lasers, the infrared light is then filtered to obtain only the green output. Lasers having higher wavelengths, such as infrared lasers having a wavelength of 1030 nm, can also be used. However, green lasers are relatively cooler, which results in less thermal damage, and as a result, green lasers are typically superior because the nanostructures are finer. Other lasers, such as those using a 300-nm wavelength, those having parametrically adjustable potentials to achieve other wavelengths, and those having a range of 0.15 nm or 10 keV, can also be utilized.

[0031]

[0077] The laser may be a "femtosecond laser" that emits ultrashort light pulses with a duration much less than 1 ps (10 -12 s), i.e., within the femtosecond (1 fs = 10 -15 s) range. Femtosecond (FS) lasers thus belong to the category of ultrafast or ultrashort pulse lasers (including picosecond lasers) having a pulse duration within the femtosecond range or one quadrillionth of a second. The duration of exposure to such FS lasers affects the depth of the structure being fabricated. The ultrashort (FS) pulse duration features outstanding precision in machining and insignificant edges or burrs around the laser irradiation zone. As a result, no additional mechanical or chemical post-processing steps are required.

[0032]

[0078] The depth of the recess can be determined by the dwell time of the laser etching. A longer dwell time results in a deeper etching. The recesses can have the same or different depths. Those with different depths can essentially have several sets of the same depth. For example, one-third of the recess can have the same depth A, the second one-third portion can have the same depth B, and the third portion can have depth C. By allowing for various depths, the recesses can result in different bone growths, and as a result, the diversity enhances the overall success.

[0033]

[0079] As shown above, the implant can be made of a metallic material. When the metallic material is exposed to a laser, this material exhibits an increase in oxidation on the surface and chemically changes the material to enhance its osteoinductivity for new bone growth formation when implanted. Thus, there is a metallurgical change in the material and the metal is no longer chemically pure. For example, the metal can be a titanium alloy, and when exposed to a laser, the surface is strengthened with an oxide. An example of a preferred titanium alloy includes 90 percent titanium, 6 percent aluminum, and 4 percent vanadium. When such a titanium alloy is exposed to a laser, the laser changes the chemical structure on the surface by forming an oxide which can be titanium oxide, aluminum oxide, or vanadium oxide. The oxide is configured to mimic trabeculae and change the basic valence and dictate charge fluctuations across the surface, strengthening the new bone growth features on the surface. Laser exposure can also introduce electrical conductivity, and as a result, there is charge present on the surface. Such a surface facilitates the bone process to adhere to and be fixed to the surface to promote bone growth.

[0034]

[0080] As shown above, the implant may also incorporate ceramic as part of its construction. Cermets can combine attractive properties of both ceramics, such as high temperature resistance and hardness, and the hardening characteristics of metals, such as the ability to undergo plastic deformation. Depending on the physical structure of the material, cermets may also be considered metal matrix composites, although cermets typically contain less than 20% metal by volume. Exemplary cermets include zirconia-titanium sintered constructs. Cermets have been used in the manufacture of resistors (particularly potentiometers), capacitors, and other electronic components. It is not surprising that it has long been known that zirconia-titanium sintered constructs enhance osteocyte response in the context of biological systems based on membrane polarization and nanovoltages.

[0035]

[0081] Examples of structures formed by subtractive processes

[0082] The following are examples of osteoconductive surfaces that can be used to fabricate devices having osteoconductive surfaces by subtractive (non-additive) processes. Exemplary configurations and conditions are given by way of example and not limitation.

[0036]

[0083] Example 1

[0084] The test disk, such as test disk 110 in FIG. 4A, was analyzed. The test disk had a primary surface structure including an unetched edge that was 9 mm in diameter, 0.5 mm wide, and an etched area having a diameter of 8 mm. FIG. 4B depicts the test disk in a plan view with a cutting 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 recesses and the surface along the line are depicted in the graph in FIG. 4C. The recess with the maximum depth has a recess of about 0.18 mm, and the one 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 points A and B, but only four different depths. Of course, an infinite width can be associated with differences in depth along the surface for different lines drawn either perpendicular or oblique to the structure. For example, the same variation applies to the ground line connecting the radial potential at one point to any other point on the opposite side of the trench, like the topography of the Grand Canyon in North America that varies according to the track between the northern elevation and the southern elevation.

[0037]

[0085] An enlarged area of the test disk is shown in FIG. 4D with two points identified as C and D and a cutting line 4E-4E connecting these two points at points 1-12 between points C and D. The length of the line between points C and D is 7500 μm (7.5 mm). FIG. 4E depicts the depth of the recesses and the surface at points 1-12 as measured by a profilometer. The depth of the recesses and the surface at points 1-12 are summarized in the following table.

[0038]

[0086]

Table 1

[0039]

[0087] Figure 4F depicts the same enlarged area depicted in Figure 4D and several selected recesses identified as recesses #1 - #6. Recesses #1 - #4 are examples of indentations. Recesses #5 - #6 are long trenches. The following table lists the average depth, maximum depth, and outer perimeter of each recess.

[0040]

[0088]

Table 2

[0041]

[0089] The average depth has a maximum of 160.15 μm, a minimum of 172.61 μm, an overall average of 164.58 μm, a standard deviation of 4.19 μm, and a 3 - sigma of 12.58 μm. The maximum depth has a maximum of 195.26 μm, a minimum of 212.11 μm, an overall average of 204.80 μm, a standard deviation of 6.83 μm, and a 3 - sigma of 20.50 μm.

[0042]

[0090] Figure 4F also features horizontal line EF and vertical line GH taken between points E and F and points G and H respectively. The depths of these lines are also depicted in Figures 4G and 4H.

[0043]

[0091] Example 2

[0092] This example depicts seven discs that were samples subjected to comparative analysis as viewed through a scanning electron microscope (SEM), and provides comparative information about different configurations on several discs as shown in FIG. 5, where the samples have different recess trench depths due to laser etching, use of surface texturing, and control. The sample, sometimes referred to as T5, was formed from a medical titanium alloy that is generally formed as an empirical composition of 90% titanium, 4% aluminum, and 6% vanadium. Sample #1 and Sample #3 were discs etched to form recesses with a depth of 100 microns. Sample #2 and Sample #4 were etched deeper to have recesses with a depth of 200 microns. Samples #1 - #4 were also surfaces treated with a laser that blasted the surface of the discs to obtain a nanotextured surface with nano-sized features. The laser etching and laser treatment for Samples #1 - #4 were performed under an atmosphere. Samples #5 and #6 were not laser etched to form macro-sized recesses or surface recesses and were only treated with a laser that blasted the surface of the discs to obtain a nanotextured surface with nano-sized features. Sample #7 was a control group as it was smooth and not laser etched or laser blasted to obtain nano-sized features. Images of the discs were taken at different levels of magnification on a 3D digital microscope made by Hirox.

[0044]

[0093] Sample #1 is shown in FIGS. 6A - 6C. The deepest recess in Sample #1 is shown with the darkest shading and has a depth of 100 microns. FIG. 6A shows a section of Sample #1 having a length of 2000 μm at a magnification of 20x. FIG. 6B shows a section of Sample #1 within FIG. 6A having a length of 500 μm and further magnified to a level of 120x. FIG. 6C shows a section of Sample #1 within FIG. 6A having a length of 500 μm and further magnified to a level of 200x.

[0045]

[0094] Sample #2 is shown in FIGS. 7A - 7C. The deepest recess in Sample #1 is shown with the darkest shading and has a depth of 200 microns. FIG. 7A shows a section of Sample #2 with a length of 2000 μm at a magnification of 20x. FIG. 7B shows a section of Sample #2 within FIG. 7A with a length of 500 μm and further magnified to a level of 120x. FIG. 7C shows a section of Sample #2 within FIG. 7A with a length of 500 μm and further magnified to a level of 200x. As is apparent by comparing FIGS. 7A - 7C with FIGS. 6A - 6C, the recesses are darker in FIGS. 7A - 7C because the recesses are deeper.

[0046]

[0095] Sample #3 is shown in FIGS. 8A - 8C. The deepest recess in Sample #3 is shown with the darkest shading and has a depth of 100 microns. FIG. 8A shows a section of Sample #3 with a length of 2000 μm at a magnification of 20x. FIG. 8B shows a section of Sample #3 within FIG. 8A with a length of 500 μm and further magnified to a level of 120x. FIG. 8C shows a section of Sample #3 within FIG. 8A with a length of 500 μm and further magnified to a level of 200x. Since Sample #3 repeats the pattern from Sample #1 with a greater recess depth, as expected, they appear the same with respect to their trench patterns, but the trenches in Sample #3 are depicted darker. However, as is best shown by comparing FIGS. 6B and 6C with FIGS. 8A and 8C, the surface treatments are different. This is an expected result since the surface treatment is random.

[0047]

[0096] Sample #4 is shown in FIGS. 9A - 9C. The deepest recess within Sample #4 is indicated by the darkest shading and has a depth of 200 microns. FIG. 9A shows a section of Sample #4 having a length of 2000 μm at a magnification of 20x. FIG. 9B shows a section of Sample #4 within FIG. 9A having a length of 500 μm and further magnified to a level of 120x. FIG. 9C shows a section of Sample #4 within FIG. 9A having a length of 500 μm and further magnified to a level of 200x. Since Sample #4 repeats the pattern from Sample #2 with a greater recess depth, as expected, they appear the same with respect to their trench patterns, although the trenches within Sample #2 are depicted darker. However, as best shown by comparing FIGS. 7B and 7C with FIGS. 9A and 9C, the surface treatments are different. This is an expected result since the surface treatments are random.

[0048]

[0097] Sample #5 is shown in FIGS. 10A - 10C. Sample #5 was treated with a laser that blasted the surface of the disk to obtain a nanostructured surface having nano - sized features also referred to as surface modification or secondary surface structures or features. FIG. 10A is a view of a section of the disk at a level of 20x magnification of a section of Sample #5 having a length of 2000 μm. FIG. 10B is a SEM image of a section of Sample #5 within FIG. 10A having a length of 500 μm and further magnified to a level of 120x. FIG. 10C is a SEM image of a section of Sample #5 within FIG. 10A having a length of 200 μm and further magnified to a level of 200x.

[0049]

[0098] Sample #6 is shown in FIGS. 11A - 11C. Like sample #5, sample #6 was treated with a laser that blasted the surface of the disk to obtain a nanotextured surface with nanoscale features. FIG. 11A is an area of the disk at a 20x magnification level of a section of sample #6 having a length of 2000 μm. FIG. 11B is an SEM image of a section of sample #6 within FIG. 11A having a length of 500 μm and further magnified to a level of 120x magnification. FIG. 11C is an SEM image of a section of sample #6 within FIG. 11A having a length of 200 μm and further magnified to a level of 200x magnification. As expected, the images in FIGS. 11A - 11C appear similar to the images in FIGS. 10A - 10C. However, the pattern cannot be identified when comparing samples at the same level of magnification because the laser treatment is random. The texture of the uneven structure is best seen in FIG. 11D, which is an SEM image of a section of sample #6 within FIG. 11A having a length of 200 μm and further magnified to a level of 400x magnification.

[0050]

[0099] Sample 7 is a control disk and is shown in FIG. 12. FIG. 12 is an SEM image of a section of sample #7 having a length of 500 μm and magnified to a level of 120x magnification. As expected, its surface topography is essentially flat, very smooth, and featureless, and is not roughened like the samples having a topography randomly roughened due to laser treatment.

[0051]

[0100] Example 3

[0101] Figure 13 is a composite image of photographs taken when focused on a surface that has been laser-etched to form the trench 140 and has a laser-treated surface 160. Figure 13 identifies some non-viable cells 170 and a large number of healthy bone cells 180. Healthy bone cells 180 growing around the trench 170, particularly at the mouth 142 of the trench 140, are shown. Since the photograph was focused on the surface and healthy bone cells 180 growing within the trench 140 are not shown only because the focus was not achieved within the trench 140 due to the depth of the trench 140. Viability was assayed separately from the expression of genes known to define the osteoblast lineage. By using a gene recombination insertion that reacts to a fluorescent lamp of a given wavelength, it was possible to interpret that the cells on the surface determined to be viable coincided with a marker that identifies them as bone cells.

[0052]

[0102] Figure 14 is a SEM image showing in vitro bone growth in a laser-treated device. Robustly growing healthy bone cells 180, including a large number of bone processes or protrusions, are indicated by the white portions. The test also showed the growth, gene expression, and robust production of bone-specific proteins, osteopontin, and dental matrix proteins. The image provided in Figure 14 was taken only 14 days after cell exposure and shows robust cell attachment and bone growth. Such a rate of bone formation is unprecedented and indicates that healthy in vivo regeneration should be predicted after transplantation. More specifically, this test indicates that the surface modified as disclosed herein is likely to result in rapid bone growth and accelerate and improve the rate of bone fusion to the implant surface. Thus, it may be possible to achieve these objectives without bone grafts or bone graft substitutes.

[0053]

[0103] Example 4

[0104] After etching and blasting the surface of a disk formed from a titanium alloy containing 90 percent titanium, 6 percent aluminum, and 4 percent vanadium, there were distinct variations in oxidation observed by electron dispersive spectroscopy (EDS). Oxidation can result in titanium oxide, aluminum oxide, or vanadium oxide.

[0054]

[0105] Vanadium imparts rigidity to titanium and has an adhesion pattern similar to that of phosphorus, which is suggested to have characteristics that accentuate its role as an insulin mimetic and have a beneficial effect on bone cell growth. As a central tenet of surface modification, incorporating beneficial effects on osteoblast formation is an essential part of the bone healing process. Insulin has been shown to improve bone healing in both normal and diabetic bone healing models, and insulin-like compounds such as zinc chloride (ZnCl2) and vanadyl acetylacetonate (VAC) have also been shown to improve bone healing. Vanadium may act in a manner similar to zinc.

[0055]

[0106] Example 5

[0107] Figure 15 is a schematic view of a recess formed by laser etching the solid features of an implant device. The recess has a relatively pointed end, and the width and length are approximately the same such that the recess has a dimpled-like shape. The side walls are tapered inward along the depth of the recess, or put another way, flare outward as going up or taper inward as going down.

[0056]

[0108] The shape of the recess is based on the x, y, and z axes derived from the trabecular structure, and thus the shape of the dimple was essentially asymmetric. For example, the two-part division of the dimple into 144a and 144b as shown in Figure 15 shows some symmetric regions and some asymmetric regions. The recess is essentially dimpled but not perfectly conical. Thus, the use of trabecular bone as a model introduces some asymmetry.

[0057]

[0109] Structure formed by a single additive process

[0110] According to one embodiment, a method of fabricating a device such as a spinal implant fusion device by an additive process includes fabricating an implant body structure using 3D printing to fabricate the implant body structure, and additionally constructing a body structure having a superior load-bearing surface and an inferior load-bearing surface and a wall structure, the body structure having at least a portion of a body structure having a plurality of interconnected struts forming a porous wall having an opening or passage extending inwardly from the outer surface to a depth of 1.0 mm or more, to form a porous portion having a void volume relative to a solid mass volume that mimics trabecular bone. Alternatively, the 3D printed structure can be completely or substantially solid with a surface structure consisting of raised interconnected arcs, or can be made to appear as a cut into the surface, but made like a trench or trough made by 3D printing.

[0058]

[0111] The average or nominal ratio of void volume to mass volume in the porous portion can vary depending on the purpose, such as reproducing trabecular bone in an adult male or female. For example, the density can be in the range of 65 percent or more, such as 75 percent. A density of about 75 percent reproduces that of adult male trabecular bone.

[0059]

[0112] The struts of the porous wall are curved or arch-shaped with openings that communicate with adjacent walls. The porous portion of the implant body structure extends at least partially across the outer surface of the implant body structure to form conduits for fluid passage throughout the device. The curved or arch-shaped struts of the wall create a load-bearing capacity to withstand vertical loads without collapsing. The implant fusion device has a superior load-bearing surface and an inferior load-bearing surface having nanochannels etched on the exposed surface. The etching is created through a subtractive laser process.

[0060]

[0113] In another embodiment, a method of fabricating a device such as a spinal implant fusion device includes providing a 3D printed implant body structure and a subsequent subtractive laser etching step that results in nanostructured features on at least a portion of the surface(s) of the implant body structure, the nanostructure creating a new bone growth attachment feature to enhance the osteoinductivity of the spinal implant or orthopedic fusion device. The 3D printed structure can be solid or relatively solid prior to the use of the subtractive process of laser etching that results in a nanoscale surface for induction of bone formation and growth.

[0061]

[0114] The laser etched nanostructured features form a network of features in either a random or regular pattern. Laser etching is formed by emitting an unobstructed laser beam onto the surface of the implant. The method of fabricating a device such as a spinal implant fusion device or other orthopedic or bone implant further includes moving the laser around the implant body structure to create a network of features, or the method includes moving the implant body structure around the laser to create a network of features.

[0062]

[0115] In an additional embodiment, a combination of 3D printing and laser etching for manufacturing a device such as a spinal implant fusion device or an orthopedic or bone device includes the steps of fabricating an implant body structure using 3D printing to create the implant body structure, and additionally constructing a body structure having a superior load-bearing surface and an inferior load-bearing surface and a wall structure, wherein the body structure has at least a portion of a body structure having a plurality of interconnected struts forming a porous wall having openings extending inwardly from an outer surface to a depth of at least 1.0 mm to form a porous portion having a void volume relative to a solid mass volume mimicking trabecular bone, and laser etching at least a portion of an outer surface or surface of the implant body structure to obtain nano-sized features, wherein the nano-sized features such as channels create new bone growth attachment features to enhance the osteoinductivity of the spinal implant fusion device.

[0063]

[0116] FIG. 16A is an exemplary embodiment of an apparatus 210 such as a spinal implant fusion device that is at least partially formed by an additive process. The configuration of the implant device 210 as illustrated has a first or upper surface 214, a second or lower surface 216, and side surfaces 215 that surround and form the 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 support the bone structure of adjacent vertebral bodies during implantation between two adjacent vertebral bodies. These first and second surfaces 212, 216 may be in direct contact with the bone structure of the patient's adjacent vertebral bodies during implantation of the device 10 for a procedure in which the implant fusion device is implanted to correct degenerative or other conditions in the patient. As shown, the exemplary embodiment is merely an example of a simple shape. In addition to the cube shape depicted in FIG. 16A, any number of shapes may be used and may be any number of polygons of various shapes and sizes. For example, the device may be rectangular, oval, or elongated. A cylindrical device having circular side surfaces may be used. Similarly, the device may have a pentagonal or hexagonal shape with non-circular side surfaces. 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 vertebral bodies to function as an appropriate implant fusion device.

[0064]

[0117] Referring to FIG. 16B, a cross-sectional view is taken from FIG. 16A along the cutting line 16B-16B of FIG. 16A. This cross-sectional view shows the internal structure of the device 210. As shown, the body structure 212 of the device 210 may have a solid central region (area or region), and an outer region having a relatively high ratio of void volume to mass volume that reproduces trabeculae, more specifically, cancellous bone-like trabeculae. The high porosity creates open passages for fluid to move in and out, similar to what occurs in natural bone. The body structure 212 of the implant device 210 is formed by 3D or additive printing that results in an outer portion made of a plurality of interconnected struts 226. The struts 226 are curved or arched and are spaced apart at the connections with the openings 228 that form a porous wall having a porosity that reproduces that of an adult male or female depending on the implant being generated.

[0065]

[0118] The region having a high ratio of porosity extends inwardly towards the central region of the device 210. Since the device extends from the outer periphery to the outer surfaces 214, 215, 216 of the device 210, this ratio of void volume to mass volume can be dramatically reduced, which occurs when the 3D construction of the device is being carried out. As such, the outer surfaces 214, 215, 216, the porous wall can extend inwardly from the outer surface by approximately 1 mm or more with the central portion of the body structure having a much reduced ratio of void volume to mass volume. This reduced ratio is more densely compressed to create a core inside the device with a porous structure around the entire device 210. This increases the structural strength of the device 210, with the internal core of the body structure 212 providing high strength and the superior bone providing a more open porous outer surface or surfaces.

[0066]

[0119] Optionally, the porous structure of the interconnected struts 226 can be made to extend across the entire implant body structure, if desired. In fact, a surface depth that mimics trabeculae at least 1 mm in depth has been found to be ideal for new bone formation, and thus 3D manufacturing of the implant can be made simpler and less expensive by limiting the depth to 1 mm or more. Additionally, the upper surface 214 and the lower surface 216 should have a porous strut feature, but the side walls can be solid as an optional way to manufacture the device.

[0067]

[0120] Referring to FIGS. 16C and 17, a portion of the outer surfaces 214, 215, 216 is shown. This porous outer surface may be along the surface of the first surface 214, the second surface 216, or the side surface 215, or all of these surfaces.

[0068]

[0121] As shown in FIGS. 16C and 19-19B, nanostructures such as the nanochannels 230 can be formed by a laser etching machine such as that depicted by the laser system at 200 in FIG. 2. These nanochannels 230 can be arranged within the network 218 in either a regular uniform pattern or a random non-uniform pattern across the entire outer surfaces 214, 215, 216. Ideally, these nanochannels 230 are fabricated at least along the first and second surfaces 214, 216 of the implant device 10. The nanochannels 30 are small laser-etched incisions that can be arranged along the entire outer surface in a subtractive laser-etching process. These nanochannels 230 fabricated by laser etching can be fabricated by moving the laser 200 around the outer surfaces 214, 215, 216 of the implant device to form the nanochannels 30 as shown in FIG. 19A, or the device 210 can be moved relative to the laser such that the nanochannels 230 are arranged on the outer surfaces 214, 215, 216 as shown in FIG. 19B. The nanochannel features individually provide an improved osteoinductive effect at the surface of the implant device 210. This means that once implanted into a patient, the formation of new bone can be accelerated, and the network 218 of nanochannels 230 provides features that assist in providing an attachment site for new bone formation. This is an important feature provided in the present invention and is ideal in that it does not require a smooth or flat outer surface to form channels that are effectively etched or implanted into the outer surface. The channels can be fabricated as long as the path of the laser beam is not obstructed. As a result, even if the porous walls of the outer surface have slight undulations 220, 222 and openings, the network 218 of nanochannels 230 can be formed regardless, is not limited to the topography of the outer surface commonly seen in implant devices having a separately smooth outer surface, and can be modeled. In fact, nanochannels 230 formed at various depths can be seen, with the openings allowing the laser beam to pass through. The nanochannels preferably have a width and depth of 10 nanometers or more, up to 1000 nanometers.These features are very small and, unlike microchannel laser etching, the nanochannels can be etched very quickly due to their small size.

[0069]

[0122] Figure 18 is a simplified schematic contour of a portion of the outer surfaces 214, 215, 216 of an alternative embodiment. The outer surfaces 214, 215, 216 have undulating features such that the outer surface has protrusions 220 that protrude slightly outward and slightly recessed channels or troughs 222. These features create an undulating surface and, when formed on the implant fusion device, enhance the ability of the device 210 to create a space between adjacent vertebrae after the device 10 has been implanted. Additionally, the entire surface is then processed using laser etching to create nanochannels 230, which are best shown in FIG. 16C.

[0070]

[0123] The embodiments described above detail a method of making a device, such as an orthopedic device, having a surface pattern that mimics trabecular bone. The body of the device can be made by any conventional process or by 3D printing. The surface can be formed by either a subtractive or an additive process. The surface can be processed to form nanostructures whether the body is formed by a subtractive process or an additive process. Such surface structures are on the nanometer scale and are biologically active in inducing bone growth.

[0071]

[0124] Structures, devices, methods, and systems are described in accordance with specific embodiments, but one of ordinary skill in the art will readily recognize that many variations to the specific embodiments are possible, and thus any variations should be considered to be within the spirit and scope disclosed herein. Accordingly, many modifications can be made by one of ordinary skill in the art without departing from the spirit and scope of the appended claims.

[0072]

[0125] Various combinations or sub - combinations of the specific features and aspects of the embodiments disclosed above can be made, and it is contemplated that these still fall within one or more of the present invention. Further, the disclosure herein of any specific feature, aspect, method, property, characteristic, quality, attribute, element, or the like related to one embodiment can be used in all other embodiments specified herein. Thus, it should be understood that the various features and aspects of the disclosed embodiments can be combined with each other to form various modes of the disclosed invention or can be substituted for each other. Therefore, it is intended that the scope of the present invention within the present disclosure should not be limited by the specific disclosed embodiments described above. Furthermore, the present invention is susceptible to various modifications and alternative forms, and specific examples thereof are shown in the drawings and described in detail herein. However, the present invention should not be limited to the specific forms or methods disclosed, but rather, the present invention should cover all modifications, equivalents, and alternative forms that fall within the spirit and scope of the various embodiments described and the appended claims. Any method disclosed herein need not be performed in the order recited.

[0073]

[0126] Any range disclosed herein also encompasses all overlaps, sub - ranges, and combinations thereof. Words such as "at most", "at least", "greater than", "less than", "between", and the like include the recited numbers. Numbers preceded by terms such as "approximately", "about", "substantially" include, when used herein, the recited numbers (e.g., about 10% = 10%) and also represent an amount close to the recited amount that still performs the desired function or achieves the desired result. For example, the terms "approximately", "about", "substantially" can refer to an amount within less than 10%, less than 5%, less than 1%, less than 0.1%, less than 0.01% of the recited amount.

[0074]

[0127] The claims following the disclosure in this document are hereby expressly incorporated into the disclosure in this document, and each claim stands alone as a separate embodiment. The present disclosure includes all permutations of the independent claims, along with their dependent claims. Further, additional embodiments that are derivable from the independent and dependent claims that follow are also expressly incorporated into the description in this document. These additional embodiments are determined by replacing the dependency of a given dependent claim with the expression "any of the claims starting with claim [x] and ending with the claim immediately preceding this claim", where the item [x] within the parentheses is replaced with the number of the most recently recited independent claim. For example, for a first set of claims starting with independent claim 1, claim 3 may be dependent on either claim 1 or 2, and these separate dependencies result in two different embodiments; claim 4 may be dependent on any one of claims 1, 2, or 3, and these separate dependencies result in three different embodiments; claim 5 may be dependent on any one of claims 1, 2, 3, or 4, and these separate dependencies result in four different embodiments, and so on.

[0075]

[0128] The recitation of the term "first" in a claim with respect to a feature or element does not necessarily imply the existence of a second or additional such feature or element. If there are any elements specifically recited in means-plus-function form, this is intended to be construed as covering the corresponding structures, materials, or acts, and their equivalents, described herein, in accordance with paragraph 6 of section 112(f) of the United States Patent Code. The embodiments of the invention that are claimed in an exclusive nature or privilege are defined as follows.

Claims

1. A method of manufacturing an implant device configured to have at least one osteoinductive feature to enhance new bone formation after implantation, comprising: providing an implant device; 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 side walls extending between the mouth and the end and into the implant device; wherein the recesses are shaped as defined by a non-random engineering pattern; laser etching the surface such that the mouth of each recess has a width, and most of the mouth has a width in the range of about 100 nm to about 2 mm; laser treating the surface of the implant device including the surface of the side walls of the recesses and the surface around the mouth of each recess to create surface deformations that are random compared to the pattern of the recesses and significantly smaller than the width of the recesses.

2. The method of 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 mm.

3. The method of claim 1, wherein most of the surface deformations have a length or width of less than about 200 nanometers.

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

5. The method of claim 1, wherein the one or more surfaces of the implant device are chemically changed by oxidation resulting from laser etching or laser treating the one or more surfaces.

6. The method of claim 1, wherein the implant device is a titanium alloy and titanium oxide is formed on the surface by the laser etching.

7. The method of claim 1, wherein the side walls of each recess have an intermediate depth in the middle between the mouth and the end, and at least most of the recesses are structured to gradually narrow because the side walls are inclined from the mouth of the recess to the end of the recess or at least to its intermediate depth.

8. The method of claim 1, wherein most of the surface deformations are at least five times smaller than the width of most of the recesses.

9. ​ A method of manufacturing an implant device configured to have at least one osteoinductive feature to enhance new bone formation after implantation, providing one or more surfaces to the implant device, wherein the one or more surfaces have a plurality of recesses extending into the implant device, each recess having a mouth, an end opposite the mouth, and side walls extending between the mouth and the end and into the implant device, the recesses being arranged in a non-random engineering pattern, each recess having a depth, and providing one or more surfaces, most of the recesses having a width in the range of about 1 micron to about 2 mm, laser treating the surface of the implant device including the surface of the side walls of the recesses and the surface around the mouth of each recess to create surface deformations that are random compared to the pattern of the recesses and significantly smaller than the width of the recesses, most of the surface deformations having a length or width of less than 200 nanometers when viewed at high magnification, the method comprising laser treating the surface.

10. The method according to claim 8, wherein the recesses are formed by laser treating the one or more surfaces of the implant device.

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

12. The method according to claim 9, wherein the one or more surfaces of the implant device are chemically changed by oxidation resulting from laser etching or laser treating the one or more surfaces.

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

14. An implant device configured to have at least one osteoinductive feature to enhance new bone formation after implantation, the implant device comprising one or more surfaces of the implant device having a plurality of recesses extending into the implant device, each recess having a mouth, an end opposite the mouth, and side walls extending between the mouth and the end, the side walls extending inwardly from the mouth to the end and having an intermediate depth in the middle between the mouth and the end, Each recess has a depth measured from its mouth to its end, and at least a majority of said recesses have a depth within the range of about 10 to about 500 microns. At least a majority of said recesses are structured to become gradually narrower inwardly because the side walls of said recesses, which are structured to become gradually narrower inwardly, are inclined from the mouth of the recess to the end of the recess, or at least to an intermediate depth thereof. The implant device is structured to become gradually narrower inwardly.

15. The implant device according to claim 14, wherein the implant device 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 percent titanium, 6 percent aluminum, and 4 percent vanadium.

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

19. The recesses are arranged in a non - random engineering pattern. The one or more surfaces of the implant device are random compared to the pattern of the recesses and include surface deformations that are significantly smaller than the depth of the recesses. The implant device according to claim 14.

20. The implant device according to claim 14, wherein the recesses have various depths such that not all of the recesses have essentially the same depth.

Images