Patent Description:
<CIT> discloses a silver nanoparticle coating on a substrate with different size ranges at different heights above the substrate. Particle sizes decrease from larger to smaller farther from the substrate.

<CIT> discloses a surgical implant having a coating formed on the substrate with different size ranges at different heights above the substrate.

<CIT> discloses an implant with layers of different particle materials applied to the implant surface.

<CIT> discloses an implant with graduated pore sizes for osteointegration.

equivalent <CIT>) discloses an implant with zones of different mesh sizes to enhance bone material growth based on different spongiosa of the bone at different locations.

<CIT> discloses a titanium implant with nanotubular hydroxyapatite coating.

<CIT> discloses using silicon nitride on a medical implant to improve the antibacterial properties of the implant.

In the pathogenesis of infection around implants, the initial adhesion of bacteria onto biomaterial surfaces is a critical first step. An important strategy in the reduction of orthopedic infections is to develop implant materials that prevent initial bacteria adhesion and subsequent growth onto implant surfaces. Bacterial localization and biofilm formation may lead to acute and chronic infections. Biofilm formation on implant surfaces protects bacteria from the immune system and antibiotic therapy, thus requiring an aggressive treatment of antibiotics that frequently do not work post biofilm formation. Therefore, to reduce or even prevent implant infections, various strategies have been developed aside from conventional systemic and local antibiotic treatment. Recently, there has been increasing interest for coating implants with other materials to improve osteointegration and prevent infection, chronic inflammation, and unwanted foreign body responses.

It would be beneficial to provide a surface treatment on medical implants and other medical devices that inhibit microbial adhesion and growth and enhance osteointegration of the implant into existing tissue.

The present disclosure relates to a medical device comprising a substrate having an exposed surface and a texture over at least part of the exposed surface. The texture comprises a plurality of nanofeatures that inhibit bacterial adhesion on the surface.

The present invention relates to a medical device comprising a substrate having an exposed surface and a titanium texture over at least part of the exposed surface. The texture comprises a plurality of nanofeatures that inhibit bacterial growth on the surface and have a size range between about <NUM> nanometers and about <NUM>,<NUM> nanometers. The present invention relates to a medical device comprising a substrate having an exposed surface and a texture over at least part of the exposed surface. The texture comprises a plurality of nanofeatures applied thereto. According to the invention, the texture has a first particle size at a first location, a second particle size, different from the first size, at a second location, and, there may be a gradient of particle size from the first particle size to the second particle size between the first location and the second location.

The present invention relates to a device as claimed hereafter. Preferred embodiments of the invention are set forth in the dependent claims.

The embodiments of the invention are primarily illustrated in <FIG>, <FIG> and <FIG>. The exemplary embodiments shown in the other figures do not necessarily form part of the invention but represent background art that is useful for understanding the invention.

Other aspects, features, and advantages of the present invention will become more fully apparent from the following detailed description, the appended claims, and the accompanying drawings in which like reference numerals identify similar or identical elements.

In the drawings, like numerals indicate like elements throughout. Certain terminology is used herein for convenience only and is not to be taken as a limitation on the present invention. For purposes of this description, the terms "anterior", "posterior", "lateral", "medial", "superior" and "inferior" describe the position of surfaces or features relative to the anatomy. The term "anterior" refers to features having a relative position toward the front side of a spine, and "posterior" refers to features having a relative position toward the rear side of the spine. The term "lateral" refers to features having a relative position toward the left or right side of the spine. The term "medial" refers to features having a relative position toward the center of the spine. The term "cranial" refers to features having a relative position above other features, and the term "caudal" refers to features having a relative position below other features. The terminology includes the words specifically mentioned, derivatives thereof and words of similar import.

The embodiments illustrated below are not intended to be exhaustive or to limit the invention to the precise form disclosed. These embodiments are chosen and described to best explain the principle of the invention and its application and practical use and to enable others skilled in the art to best utilize the invention.

Reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the invention.

As used in this application, the word "exemplary" is used herein to mean serving as an example, instance, or illustration. Any aspect or design described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other aspects or designs. Rather, use of the word exemplary is intended to present concepts in a concrete fashion.

Additionally, the term "or" is intended to mean an inclusive "or" rather than an exclusive "or". That is, unless specified otherwise, or clear from context, "X employs A or B" is intended to mean any of the natural inclusive permutations. In addition, the articles "a" and "an" as used in this application and the appended claims should generally be construed to mean "one or more" unless specified otherwise or clear from context to be directed to a singular form.

Referring to <FIG>, a wedge implant <NUM> according to a first exemplary embodiment of the present invention is shown. Wedge implant <NUM> is inserted into a single vertebra <NUM> in a spine <NUM> to readjust the caudal and cranial plans of vertebra <NUM> to alleviate scoliosis in spine <NUM>. While a single wedge implant <NUM> is shown being inserted into a single vertebra <NUM>, those skilled in the art will recognize that additional wedge implants <NUM> can also be inserted into additional vertebrae <NUM> as needed to alleviate scoliosis.

Wedge implant <NUM> includes an outer perimeter <NUM> that defines implant <NUM>. Wedge implant <NUM> also includes a top surface <NUM> extending generally in a first plane P1 and a bottom surface <NUM> extending in a second plane P2. Second plane P2 extends obliquely with respect to first plane P1. As shown in <FIG>, first plane P1 intersects second plane P2 at a location "I" outside outer perimeter <NUM> of implant <NUM>. Top surface <NUM> and bottom surface <NUM> can be planar surfaces. Alternatively, top surface <NUM> and bottom surface <NUM> can have other shapes, such as, for example, domed surfaces.

A medial surface <NUM> extends between top surface <NUM> and bottom surface <NUM> proximate to the intersection of first plane P1 and second plane P2. A lateral surface <NUM> extends between top surface <NUM> and bottom surface <NUM> distal from the intersection of first plane P1 and second plane P2. An anterior surface <NUM> extends a first distance D1 between top surface <NUM> and bottom surface <NUM> between medial surface <NUM> and lateral surface <NUM>. Anterior surface <NUM> extends generally a constant first distance D1 across its length. A posterior surface <NUM> extends a second distance D2 between top surface <NUM> and bottom surface <NUM> between medial surface <NUM> and lateral surface <NUM>. Posterior surface <NUM> extends generally a constant second distance D2 across its length. Second distance D2 is greater than first distance D1.

In an exemplary embodiment, body <NUM> is constructed from a material having a relatively low stiffness, such as, for example, poly-ether-ether ketone ("PEEK"), which has a modulus of elasticity about <NUM> GPa. In an exemplary embodiment, an antimicrobial and/or osteointegration surface <NUM>, shown in detail in <FIG>, can be disposed on each of top surface <NUM> and bottom surface <NUM>. In an exemplary embodiment, the osteointegration portion of surface <NUM> is titanium and the antimicrobial portion of surface <NUM> can be silver (not claimed) or titanium nanotextured or titanium oxide nanostructured.

Osteointegration surface <NUM> extends downwardly from top surface <NUM> along medial surface <NUM>, lateral surface <NUM>, anterior surface114, and posterior surface <NUM> only a portion of the way to bottom surface <NUM>. Similarly, osteointegration surface <NUM> can extend upwardly from bottom surface <NUM> along medial surface <NUM>, lateral surface <NUM>, anterior surface <NUM>, and posterior surface <NUM> only a portion of the way to top surface <NUM>, resulting in a band <NUM> around outer perimeter <NUM> of implant <NUM> that is free from osteointegration surface <NUM>. In an exemplary embodiment, band <NUM> has a cranial-to-caudal dimension of about <NUM>. Alternatively, band <NUM> can have a cranial-to-caudal dimension of greater than about <NUM>. The existence of band <NUM> allows for flexing of implant <NUM>, which is softer with a lower modulus of elasticity than osteointegration surface <NUM>, without loading compressive forces onto osteointegration surface <NUM>.

To correct adult or pediatric scoliosis deformity, implant <NUM> can be inserted into vertebra <NUM> in a lateral-to-medial direction to realign spine <NUM> with the craniocaudal axis <NUM>, as shown in <FIG>. To insert wedge <NUM>, an osteotomy is performed on vertebra <NUM> by making an incision <NUM> in vertebra <NUM>. In an exemplary embodiment, the insertion <NUM> can be made from lateral side <NUM> of vertebra <NUM> inwardly toward the center of vertebra <NUM>, and inserting implant <NUM> into incision <NUM>. Alternatively, incision <NUM> may be made to the contralateral side of vertebra <NUM>, with implant <NUM> being inserted therein. In pediatric patients, the osteotomy is formed in a way not violate the growth plate of vertebra <NUM>. This insertion effectively pivots cranial plane P3 relative to caudal plane P4 of vertebra <NUM> in an effort to make cranial plane P3 and caudal plane P4 closer to match the crainocaudal axis of spine <NUM> and aligned in the sagittal plane.

Similarly, to correct adult or pediatric scoliosis deformity, implant <NUM> can be inserted into vertebra <NUM> in a anterior-to-posterior direction to restore lordosis or kyphosis of the spine, as shown in <FIG>. To insert wedge <NUM>, an osteotomy is performed on vertebra <NUM> by making an incision <NUM> in vertebra <NUM> from posterior side <NUM> of vertebra <NUM> inwardly toward anterior side <NUM> of vertebra <NUM>, and inserting implant <NUM> into incision <NUM>. This insertion effectively pivots cranial plane P3 relative to caudal plane P4 in an effort to make cranial plane P3 and caudal plane P4 closer to normal conditions to restore lordotic or kyphotic angulation the spine <NUM>.

In either of the above two procedures, a retaining plate <NUM> is fixed to vertebra <NUM> to secure implant <NUM> to vertebra <NUM>. <FIG> shows retaining plate <NUM> being used to secure implant <NUM> inserted in the posterior-to-anterior direction in top vertebra <NUM>, and retaining plate <NUM> used to secure implant <NUM> inserted in the lateral-to-medial direction. The retaining plate <NUM> is shown in both anterior-posterior and medial-lateral alignment. However a surgeon will generally only insert retaining plate <NUM> from one direction in vertebra <NUM> or adjacent vertebrae <NUM>.

Retaining plate <NUM> is an elongate member with a first hole <NUM> at a first end <NUM> thereof and a second hole <NUM> at a second end <NUM> thereof. A first screw <NUM> is inserted through first hole <NUM> and into vertebra <NUM> toward or parallel with cranial plane P3, while a second screw <NUM> is inserted through second hole <NUM> and into vertebra <NUM> toward parallel with caudal plane P4. In an exemplary embodiment, retaining plate <NUM> and screws <NUM>, <NUM> can be made from standard biomaterials, such as titanium, or bio-resorbable materials, such as, for example, magnesium-based alloys that will ultimately dissolve by the time implant <NUM> has been fully engaged by vertebra <NUM>.

While an exemplary use of implant <NUM> as described above is used in a single vertebra <NUM>, those skilled in the art will recognize that in some cases, it may be more advantageous to remove a disk <NUM> between two adjacent vertebrae <NUM> and insert implant <NUM> between the two adjacent vertebrae <NUM>, as an interbody implant, as shown in <FIG>. In such a case, screw <NUM> for plate <NUM> can be secured into the upper vertebra <NUM> and screw <NUM> for plate <NUM> can be secured into the lower vertebra <NUM>.

In an exemplary embodiment, it may be necessary to remove at least a lower portion of the upper vertebra <NUM> and an upper portion of the lower vertebra <NUM> in order to properly insert implant <NUM>.

In an alternative embodiment, referring to <FIG>, a bi-planar adjustable implant <NUM> according to an exemplary embodiment of the present invention is shown. Implant <NUM> can be inserted into an osteotomy in vertebra <NUM> as discussed above with respect to implant <NUM>. Alternatively, as also discussed above with respect to implant <NUM>, upon removal of a disk between two adjacent vertebrae <NUM>, implant <NUM> can be inserted into the space between the two vertebrae <NUM>.

Implant <NUM> includes a body <NUM> having a top surface <NUM> and a bottom surface <NUM>, distal from top surface <NUM>. Top surface <NUM> and bottom surface <NUM> can be planar surfaces. Alternatively, top surface <NUM> and bottom surface <NUM> can have other shapes, such as, for example, domed surfaces.

A medial side <NUM> connects top surface <NUM> and bottom surface <NUM>. A lateral side <NUM> is located distal from medial side <NUM>. An anterior side <NUM> extends between medial side <NUM> and lateral side <NUM> such that anterior side <NUM> connects top surface <NUM> and bottom surface <NUM> to each other. A posterior side <NUM> extends between lateral side <NUM> and medial side <NUM>, distal from anterior side <NUM>.

Implant <NUM> has a first slot <NUM> extending from lateral side <NUM> toward medial side <NUM> and a second slot <NUM> extending from posterior side <NUM> toward anterior side <NUM>. Slots <NUM>, <NUM> allow for the insertion of wedges to alter the angle of the plane of top surface <NUM> with respect to bottom surface <NUM>. The location of slot <NUM> relative to slot <NUM> allows for the adjustment of top surface <NUM> relative to bottom surface <NUM> about two axes, namely, the x and z axes as shown in <FIG>.

A first wedge assembly <NUM> is inserted into first slot <NUM>. As used herein, the term "wedge assembly" means any device, inserted in an implant, that can be manipulated to change the angle of at least one face of the implant. First wedge assembly <NUM> has a first member <NUM> translatable in a lateral-to-medial direction. In an exemplary embodiment, first member <NUM> is a wedge having a tapered profile from the lateral direction to the medial direction as shown in <FIG>. A second member <NUM> is operatively connected to first member <NUM> such that operation of second member <NUM> translates first member <NUM> in the lateral-to-medial direction. In an exemplary embodiment, second member <NUM> can be a screw threadedly inserted through first member <NUM>, such that rotation of second member <NUM> about the "Z" axis translates first member <NUM> in the "Z" direction. Second member <NUM> can include an adjusting mechanism <NUM>, such as, for example, a screw head, extending from anterior side <NUM>.

Similarly, a second wedge assembly <NUM> is inserted into second slot <NUM>. Second wedge assembly <NUM> has a first member <NUM> translatable in a posterior-to-anterior direction. Similar to first wedge assembly <NUM>, first member <NUM> is a wedge having a tapered profile from the lateral direction to the medial direction as shown in <FIG>. A second member <NUM> is operatively connected to first member <NUM> such that operation of second member <NUM> translates first member <NUM> in the posterior-to-anterior direction. In an exemplary embodiment, second member <NUM> can also be a screw threadedly inserted through first member <NUM>, such that rotation of second member <NUM> about the "X" axis translates second member <NUM> in the "X" direction. Second member <NUM> can include an adjusting mechanism <NUM>, such as, for example, a screw head, extending from anterior side <NUM>.

Translation of first member <NUM> of first wedge assembly <NUM> pivots top surface <NUM> with respect to bottom surface <NUM> about medial side <NUM> and translation of first member <NUM> of second wedge assembly <NUM> pivots top surface <NUM> with respect to bottom surface <NUM> about anterior side <NUM>.

In an alternative exemplary embodiment of a wedge assembly <NUM>, shown in <FIG> and <FIG>, instead of the wedge provided as first member <NUM> and <NUM>, wedge assemblies <NUM>, <NUM> utilize a cylinder <NUM>, <NUM>. Second member <NUM>, <NUM> from wedge assembly <NUM> can be used to activate cylinder <NUM>, <NUM>, respectively. It is noted, however, that, for either wedge assembly <NUM> or wedge assembly <NUM>, first wedge assembly <NUM> is actuated from lateral side <NUM> while second wedge assembly <NUM> is actuated from posterior side <NUM>. It is desired to be able to actuate both first wedge assembly <NUM> and second wedge assembly <NUM> from the same side in order to minimize incisions made into the patient. Therefore, if wedge assembly <NUM>, <NUM> is inserted from the lateral side of vertebra <NUM>, it is desired to be able to actuate first wedge assembly <NUM> and second wedge assembly <NUM> from the lateral side of vertebra <NUM>. Therefore, to actuate second wedge assembly, it may be desired to use a driver (not shown) having a right angle drive.

An alternative embodiment of an implant assembly <NUM> according to the present invention is shown in <FIG>. Implant assembly <NUM> is similar to implant assembly <NUM>, with the exception of, instead of second wedge assembly <NUM>, a second wedge assembly <NUM> is provided. Second wedge assembly <NUM> includes a first member <NUM>, which is a cylinder having a plurality of gear teeth <NUM> formed around an exterior perimeter thereof. Second wedge assembly <NUM> includes a second member fixedly <NUM> connected to body <NUM> of implant assembly <NUM>. In an exemplary embodiment, second member <NUM> is a toothed rack engageable with gear teeth <NUM> of first member <NUM> such that, when first member <NUM> is rotated, gear teeth <NUM> translates first member <NUM> along second member <NUM>. An exemplary embodiment, as shown <FIG>, two sets of gear teeth <NUM> are formed on first member <NUM> and two sets of toothed racks of second member <NUM> are connected to body <NUM>, although those skilled in the art will recognize that more or less than two sets can be used.

An advantage of implant assembly <NUM> is that first member <NUM>. A first wedge assembly <NUM>, and first member <NUM> of second wedge assembly <NUM> can both be actuated from the same side of the patient, such as, for example, the lateral side.

Also, similar to wedge implant <NUM>, wedge implant assembly <NUM>, <NUM>, <NUM> can include an antimicrobial and/or osteointegration surface disposed on top and bottom surfaces thereof, with only a portion of each of the medial side, the lateral side, the anterior side, and the posterior side, including the osteointegration surface disposed thereon. An alternative embodiment of an implant assembly <NUM> according to the present invention is shown in <FIG>. Implant assembly <NUM> is a non-adjustable bi-planar wedge. Wedge <NUM> is similar to wedge <NUM>, but, instead of anterior surface <NUM> extending generally a constant first distance D1 across its length and posterior surface <NUM> extending generally a constant second distance D2 across its length, as shown in <FIG>, at least two adjacent surfaces taper from larger to smaller, forming a bi-planar top surface <NUM>.

By way of example only, posterior surface <NUM> tapers from larger to smaller in a left-to-right direction and lateral surface <NUM> tapers from larger to smaller in a posterior-to-anterior direction, resulting in wedge assembly <NUM> that can be implanted into vertebra <NUM>, as shown in <FIG>. An advantage of wedge assembly <NUM> is that wedge assembly <NUM> can be used to simultaneously correct a spinal column <NUM> that has abnormal curvature into the lateral-to-medial direction as well as in the posterior-to-anterior direction. Optionally, although not shown, a retaining plate <NUM> can be used to secure wedge assembly <NUM> in vertebra <NUM>.

<FIG> shows wedge assembly <NUM> inserted between two adjacent vertebrae <NUM> with a disk, similar to disc <NUM> previously disposed between the adjacent vertebrae <NUM>, having been removed and wedge assembly <NUM> inserted therein. Optionally, plate <NUM> can be used to secure wedge assembly <NUM> between the adjacent vertebrae <NUM> using screw <NUM> to secured plate <NUM> to the upper vertebra <NUM> and screw <NUM> to secure plate <NUM> to the lower vertebra <NUM>. As shown <FIG>, plate <NUM> is attached to a lateral side of spine <NUM>. Those skilled in the art, however, will recognize that plate <NUM> can also be attached to spine <NUM> along the posterior side of spine <NUM>.

As used herein, the term "medical device" means a medical implant, an insertion or other type of tool, or any other item that contacts or is inserted into a patient, including, but not limited to, the devices and structures described above.

The medical device can be treated with a surface treatment that performs and/or achieves one or more of the following purposes: inhibition of microbial, bacterial, and other types of unwanted adhesion on the surface; inhibition of microbial, bacterial, and other types of unwanted growth on the surface; and enhanced osteointegration with bone and other types of living matter. Osteointegration can be defined as a "direct structural and functional connection between ordered living material, such as bone, and the surface of a load-carrying or other type of implant.

<FIG> are confocal images showing S. aureus colony forming units on (a) untreated Ti and (b) treated TiO<NUM> after <NUM> hours of incubation. SEM images show the (c) untreated Ti surface and the (d) treated TiO<NUM> surface. While TiOz was used to show the effectiveness of a treated surface with respect to bacteria, such as S. aureus, those skilled in the art will recognize that other bacteria, microbes, and other unwanted growths can be inhibited and even killed using other nanofeatures such as non-TiOz or non-oxides on an exposed surface. Examples of non-titanium base oxides can be AgOz, while examples of non-oxides can by hydroxyapatite (HA) or CaPO<NUM>. As used herein, the term "nanofeatures" is used to mean nanoparticles, nanotexturing, or other application to or modification of a surface that results in nano-sized fetaures or irregularties being present on the surface.

Referring to <FIG>, a medical device <NUM> includes a substrate <NUM> having an exposed surface <NUM>. Substrate <NUM> can be constructed from a metallic material such as, for example, titanium or some other biocompatible material. Alternatively, substrate <NUM> can be constructed from a non-metallic material such as, for example, polyether ether ketone (PEEK) or some other biocompatible material. Still alternatively, substrate <NUM> can be constructed from a mix/combination of metallic and non-metallic materials.

A texture <NUM> is formed over at least part of exposed surface <NUM>. Texture <NUM> comprises a plurality of nanofeatures <NUM> that can inhibit bacterial adhesion and/or growth on surface <NUM>. Additionally, nanofeatures <NUM> can promote osteointegration with adjoining tissue <NUM>.

In an exemplary embodiment, nanofeatures <NUM> have a size range between about <NUM> nanometers and about <NUM>,<NUM> nanometers. In another exemplary embodiment, nanofeatures <NUM> have a size range between about <NUM> nanometers and about <NUM> nanometers and in yet another exemplary embodiment, nanofeatures <NUM> have a size range between about <NUM> nanometers and about <NUM> nanometers.

In an exemplary embodiment, texture <NUM> comprises an oxide, such as, for example, a titanium oxide or a titanium dioxide, although those skilled in the art will recognize that other types of oxides or even non-oxides can be provided as texture <NUM>.

In a further exemplary embodiment, texture <NUM> comprises the deposition of a coating of an oxide (or other nanofeatured material) onto substrate <NUM>. In an exemplary embodiment of a deposition method, nanophase titanium dioxide was synthesized using a wet chemical synthesis and was deposited on Ti-6AI-4V titanium screws (equivalent to substrate <NUM>) using a cathodic arc deposition plasma system. Bacterial assays were conducted using Staphylococcus aureus (ATCC® <NUM>™), Pseudomonas aeruginosa (ATCC® <NUM>™) and an ampicillin resistant strain of E. coli (BIO-RAD Strain HB101 K-<NUM> #<NUM>-<NUM> and pGLO Plasmid #<NUM>-<NUM>). <NUM>% tryptic soy broth (TSB) (Sigma Aldrich, Cat # <NUM>) and agar (Sigma-Aldrich, Cat # A1296) were used as the media and colony forming assays were performed to determine bacterial adhesion.

Nanophase titanium dioxide was successfully synthesized and applied onto the desired exposed surface of a substrate. A statistically significant decrease in bacterial adhesion was observed across all <NUM> strains of bacteria; an example of confocal images for S. Aureus is given in <FIG>. In addition, decreased macrophage functions and increase osteoblast functions were also observed in the nano TiO2 treated Ti6Al4V screws. It is noted that this was all achieved without the use of drugs and/or antibiotics, decreasing the chance for the spread of antibiotic resistant bacteria and drug side effects.

An alternative method or nanotexturing surface <NUM> is by surface etching or otherwise treating surface <NUM> according to known methods. For example, a titanium surface can be bombarded with oxygen to simultaneously texturize and oxidize surface <NUM> such that the nanofeatures are formed from substrate <NUM> itself.

Referring to <FIG>, nanoparticles having a first particle size range <NUM> and a second particle size range <NUM> can by mixed together and randomly applied to substrate <NUM>. Alternatively, referring to <FIG>, nanoparticles having a first size range <NUM> (such as, for example, about <NUM> nanometers) can be applied to substrate <NUM> and then nanoparticles having a second size range <NUM> (such as, for example, about <NUM> nanometers) can be applied on top of the nanoparticles having the first size range <NUM>.

As shown in <FIG>, nanoparticles <NUM>, <NUM> can be different shapes. Although spherical nanoparticles <NUM> and elongated nanoparticles <NUM> are shown, those skilled in the art will recognize that the nanoparticles can be other shapes, such as, for example, irregularly shaped, nanotubular, or other shapes.

<FIG> shows nanoparticles of differing size ranges being applied to different locations on substrate <NUM>. Nanofeatures <NUM> at a first location <NUM> have a first size range and nanofeatures <NUM> at a second location <NUM> have a second size range, different from the first size range. Optionally, as shown in <FIG>, nanofeatures <NUM> at first location <NUM> have a first shape, and nanofeatures <NUM> at second location <NUM> have a second shape, different from the first shape.

The features shown in <FIG> can be formed by masking second location <NUM> of substrate <NUM> with a mask so that nanofeatures cannot be applied to second location <NUM>. Nanofeatures <NUM> are then applied to the exposed (first location <NUM>) portion of substrate <NUM>.

Then, the mask is removed from second location <NUM> and a second mask is applied over first location <NUM> and nanofeatures <NUM> are then applied to the exposed (second location <NUM>) portion of substrate <NUM>.

The material used for the mask can be bees wax, fish glue, coconut oil, sequential dipping, tape, plastic caps, metallic feature, or any other material or method can be used to cover substrate <NUM>. Alternatively, if the nanotexturing is applied by electrochemical deposition, only the portion of substrate <NUM> to which the nanofeatures are to be applied is dipped in a chemical bath so that only that part of substrate <NUM> is coated.

Additionally, nanoparticles having different size ranges can be provided at surface <NUM> to perform different functions. For example, a first particle size range is sized to enhance osteoconductivity and a second particle size range is sized to enhance anti-bacterial properties.

By way of example only, and referring back to <FIG>, a texture extends over at least part of the exposed surface <NUM>. The texture comprises a plurality of nanofeatures, such as, for example, differing sizes and differing shapes, as described above. The nanofeatures inhibit bacterial growth on surface <NUM> and can have a size range between about <NUM> nanometers and about <NUM>,<NUM> nanometers.

In an exemplary embodiment, a first range within the size range produces a first property and a second range within the size range produces a second property, different from the first property. For example, the first property can inhibit bacterial adhesion on the surface <NUM> while the second property enhances osteointegration of the texture <NUM>. Further, the first size range can be between about <NUM> nanometers and about <NUM>,<NUM> nanometers, while the second size range can be between about <NUM> nanometers and about <NUM> millimeters.

Referring to <FIG>, a substrate <NUM> has an exposed surface <NUM> and has a texture <NUM> over at least part of exposed surface <NUM>. Texture <NUM> has a plurality of nanofeatures applied thereto. Texture <NUM> has a first particle size <NUM> at a first location <NUM>, a second particle size <NUM> at a second location <NUM>, and a gradient <NUM> of particle size from first particle size <NUM> to second particle size <NUM> between first location <NUM> and second location <NUM>.

<FIG> shows a graph of anti-bacterial properties of different sized nanofeatures and how they kill S. aureus bacteria. As seen on the graph, smaller sized nanofeatures (in the range of about <NUM> nanometers and smaller) are more effective at killing S. aureus than larger size nanofeatures (in the range of greater than about <NUM> nanometers).

By comparison, <FIG> shows a graph of osteointegration of nanofeatures on a substrate after <NUM> days (left column of each pair) and <NUM> days (right column of each pair). As can be seen, nanofeatures in the <NUM> nanometer range demonstrate the largest amount of osteoblasts, indicating better osteointegration capability.

Therefore, by providing nanofeatures of differing size ranges, such as about <NUM> nanometers and smaller and about <NUM> nanometers, a nanotextured surface has both antimicrobial and osteo integration properties.

Claim 1:
A medical device comprising:
a substrate (<NUM> ) having an exposed surface (<NUM>); and
a titanium texture (<NUM>) over at least part of the exposed surface (<NUM>), the texture (<NUM>) comprising a plurality of nanofeatures applied thereto, the texture having a first particle size (<NUM>)at a first location (<NUM>) on the exposed surface (<NUM>), a second particle size (<NUM>), different from the first size, at a second location (<NUM>) on the exposed surface (<NUM>),
characterized in that the second particle size (<NUM>) is selected to inhibit bacterial adhesion and/or growth on the surface (<NUM>) and has a size range is between <NUM> nanometers and <NUM>,<NUM> nanometers.