Assesment of the Biological Activity of Chemically Immobilized rhBMP‐2 on Titanium surfaces in vivo

Previously it has been shown that recombinant human bone morphogenetic protein (rhBMP‐2) can be chemically immobilized by “anchor molecules” on titanium surfaces for serving as a drug delivery device. This opened the question of whether the insoluble immobilized rhBMP‐2 retained its activity in comparison to the same amount of soluble rhBMP‐2 included with the implant samples. Electropolished titanium miniplates (10 × 6 × 0.8 mm) were “surface‐enhanced” by a novel treatment with chromosulfuric acid and then coated with a total amount of 150–200 ng rhBMP‐2 prepared by recombinant technology. Periosteal flaps (7 × 20 mm) were detached and isolated from the anterior surface of the tibiae of adult rabbits and wrapped around the titanium sample plates which were then implanted in the M. gastrocnemius. In the first experimental group various controls without rhBMP‐2 were combined (n = 12). In the second experimental group implants with chemically immobilized rhBMP‐2 (n = 8) were compared with implants to which non‐immobilized soluble rhBMP‐2 was added (n = 8). Animals were sacrificed after 28 days and a quantitative evaluation was carried out by means of serial sections. Untreated control plates showed bone formation in 2/12 implants, rhBMP‐2 coated implants in 6/8 and implants with free rhBMP‐2 administered subperiostally in 8/8 cases. In the case of rhBMP‐2 coated implants the induced bone had direct contact to the implant in all cases while in the group with free administered rhBMP‐2 the bone had no contact to the implant in two cases, but was separated by a fibrous capsule. Bone volume, bone surface area, and trabecular number displayed no difference between the two rhBMP‐2‐groups. However, in the biocoated group a tendency to an increase in the bone‐implant contact area was evident. No differences in osteoid area, osteoid perimeter and eroded perimeter were detected. We conclude that in the case of non‐immobilized rhBMP‐2 there is the danger for formation of fibrous tissue between the implant and the newly formed bone and in addition the generation of ectopic bone at inappropriate places. In contrast chemically immobilized rhBMP‐2 does not have these drawbacks and at the same time displays a biological activity on surfaces similar to that of soluble rhBMP‐2 demonstrating that biomaterial surfaces can be tailored for a selective and specific interaction with the target tissue.     

Bioactive TiOB‐Coating on Titanium Alloy Implants Enhances Osseointegration in a Rat Model

The surface properties of titanium alloy implants for improved osseointegration in orthopaedic and dental surgery have been modified by many technologies. Hydroxyapatite coatings with a facultative integration of growth factors deposited by plasma spraying showed improved osseointegration. Our approach in order to enhance osseointegration was carried out by a surface modification method of titanium alloy implants called plasma chemical oxidation (PCO). PCO is an electrochemical procedure that converts the nm‐thin natural occurring titanium‐oxide layer on an implant to a 5 µm thick ceramic coating (TiOB‐surface). Bioactive TiOB‐surfaces have a porous microstructure and were loaded with calcium and phosphorous, while bioinert TiOB‐surfaces with less calcium and phosphorous loadings are smooth. A rat tibial model with bilateral placement of titanium alloy implants was employed to analyze the bone response to TiOB‐surfaces in vivo. 64 rats were randomly assigned to four groups of implants: (i) pure titanium alloy (control), ii) titanium alloy, type III anodization, (iii) bioinert TiOB‐surface, and (iv) bioactive TiOB‐surface. Mechanical fixation was evaluated by pull out tests at 3 and 8 weeks. The bioactive TiOB‐surface showed significantly increased shear strength at 8 weeks compared to all other groups.     

Modell zur Analyse des knöchernen Anwachsverhaltens auf bioaktiv beschichteten Implantatoberflächen

Model to analyse the bone on‐growth on bioactive coated implant surfaces Especially on the field of bone regeneration, transient and permanent implants are an important method of therapy in the Orthopaedic Surgery. In this context, bioactive surfaces on metallic implants provide an improved contact to the surrounding bone. The goal of our study was to establish an in‐vitro test system to evaluate the on‐growth of bone‐derived cells on different surface coatings. Therefore, we invented a special kind of clamps made of commercially‐pure (c‐p) titanium and blasted with hydroxyapatite particles followed by electrochemically coating with calcium phosphate (BONIT®‐HA, BONIT®). Definite pieces of human cancellous bone were attached to these clamps, inserted onto tissue culture plates and cultivated in DMEM for ten days. Finally, the contact area between human cancellous bone and the implant surface was analyzed and the spreading of osteoblast‐like cells evaluated by scanning electron microscopy (SEM). A well‐spread morphology of bone cells was observed on the implant surfaces coated with calcium phosphate (CaP). In comparison the clamps without CaP coatings showed only a marginal growth of bone cells on the clamp surface. The presented newly in‐vitro test setup using titanium clamps coated with bioactive layers attached to human cancellous bone represents a well‐functioning model for qualitative evaluation of bone on‐growth.     

Osseointegration of Titanium Implants by Addition of Recombinant Bone Morphogenetic Protein 2 (rhBMP‐2)

The osseointegration of long‐term implants is often incomplete such that gaps remain between the implant surface and the surrounding hard tissue. This study examines the effect of soluble recombinant human bone morphogenic protein 2 (rhBMP‐2) on gap healing and osseous integration. The effect of a single, intraoperative application of soluble rhBMP‐2 on the formation of new bone around titanium implants was studied. A total of 8 titanium‐alloy cylinders (Ti‐6Al‐4V) with a plasma spray coating (TPS; 400 μm thickness) were implanted into femoral condyles of mature sheep: rhBMP‐2 solution (1 μg) was pipetted into the 1 mm wide cleft around 4 implants; 4 further implants served as rhBMP‐2‐free controls. Two of these controls exhibited an additional calciumphosphate‐coating. The cleft around the implants served as testing zone to study the formation of new bone by microradiographical and histological analyses. The follow‐up periods were 4 and 9 weeks, respectively. A significant amount of new bone contacting the implants' surface was detected where rhBMP‐2‐solution had been used: In 50% a circumferential osseoinduction occurred within 4 weeks and a nearly complete osseointegration was observed after 9 weeks. In all cases bone formation was exaggerated and filled the spongiosa with compact bone. Time matched TPS‐controls and controls with calciumphosphate coating showed no notable formation of new bone. The results suggest that a single administration of soluble rhBMP‐2 into a bone cavity can augment bone formation and also osseointegration of titanium implants. Further investigations based on these findings are necessary to develop long‐term implants (e. g. joint replacements) with rhBMP‐2‐biocoating for humans.     

Native MicroRNA Targets Trigger Self‐Assembly of Nanozyme‐Patterned Hollowed Nanocuboids with Optimal Interparticle Gaps for Plasmonic‐Activated Cancer Detection

The modernized use of nucleic acid (NA) sequences to drive nanostructure self‐assembly has given rise to a new class of designed nanomaterials with controllable plasmonic functionalities for broad surface‐enhanced Raman scattering (SERS)‐based bioanalysis applications. Herein, dual usage of microRNAs (miRNAs) as both valuable cancer biomarkers and direct self‐assembly triggers is identified and capitalized upon for custom‐designed plasmonic nanostructures. Through strict NA hybridization of miRNA targets, Au nanospheres selectively self‐assemble onto hollowed Au/Ag alloy nanocuboids with ideal interparticle distances (≈2.3 nm) for optimal SERS signaling. The intrinsic material properties of the self‐assembled nanostructures further elevate miRNA detection performance via nanozyme catalytic SERS signaling cascades. This enables fM‐level miR‐107 detection limit within a clinically‐relevant range without any molecular target amplification. The miRNA‐triggered nanostructure self‐assembly approach is further applied in clinical patient samples, and showcases the potential of miR‐107 as a non‐invasive prostate cancer diagnostic biomarker. The use of miRNA targets to drive nanostructure self‐assembly holds great promise as a practical tool for miRNA detection in disease applications.     

Dextran‐based coating system for the immobilization of cell adhesion promoting molecules on titanium surfaces

Immobilization of adhesive peptides interacting with cellular integrin receptors onto metallic implant surfaces represents a promising approach to improve osseointegration of implants into the surrounding tissue. In the present study, a functional dextran‐based coating system consisting of an amino titanate adhesion promoter with dendritic structure and a carboxymethyl dextran was established to bind an RGD‐containing adhesive peptide via a selective coupling methodology onto titanium surfaces. The three‐step reaction procedure was characterized by X‐ray photoelectron spectroscopy. In cell adhesion experiments it could be demonstrated that dextran coatings containing immobilized RGD promote attachment and spreading of fibroblast and pre‐osteoblastic cells compared to native as well as CMD‐coated titanium surfaces without RGD. The direct attachment of the RGD sequence to the metal surface via the amino titanate adhesion promoter did not increase pre‐osteoblastic cell spreading, whereas coupling of RGD to the polymeric carboxy­methyl dextran layer slightly enhanced spreading of the cells.     

Nanostructured Titanate with Different Metal Ions on the Surface of Metallic Titanium: A Facile Approach for Regulation of rBMSCs Fate on Titanium Implants

Titanium (Ti) is widely used for load‐bearing bio‐implants, however, it is bio‐inert and exhibits poor osteo‐inductive properties. Calcium and magnesium ions are considered to be involved in bone metabolism and play a physiological role in the angiogenesis, growth, and mineralization of bone tissue. In this study, a facile synthesis approach to the in situ construction of a nanostructure enriched with Ca²⁺ and Mg²⁺ on the surface of titanium foil is proposed by inserting Ca²⁺ and Mg²⁺ into the interlayers of sodium titanate nanostructures through an ion‐substitution process. The characteriz 0.67, and 0.73 nm ation results validate that cations can be inserted into the interlayer regions of the layered nanostructure without any obvious change of morphology. The cation content is positively correlated to the concentration of the solutions employed. The biological assessments indicate that the type and the amount of cations in the titanate nanostructure can alter the bioactivity of titanium implants. Compared with a Na⁺ filled titanate nanostructure, the incorporation of divalent ions (Mg²⁺, Ca²⁺) can effectively enhance protein adsorption, and thus also enhance the adhesion and differentiation ability of rat bone‐marrow stem cells (rBMSCs). The Mg²⁺/Ca²⁺‐titanate nanostructure is a promising implantable material that will be widely applicable in artificial bones, joints, and dental implants.     

Biocoating of Electropolished and Ultra‐Hydrophilic Titanium and Cobalt Chromium Molybdenum Alloy Surfaces with Proteins

Bone morphogenetic proteins (BMPs) play a decisive role in bone development and osteogenesis. In the past they have been the subject of widespread research and clinical trials as stimulants of bone growth. Although recently recombinant human BMP‐2 (rhBMP‐2) has been chemically immobilized on implant surfaces leading to enhanced bone growth and accelerated integration in vivo, the non‐covalent immobilization of proteins on metal surfaces is still poorly understood, since the oxide layers on metals like titanium, stainless steel or cobalt chromium alloys are poor adsorbents of proteins. Protein binding surfaces could either be generated by linking ionic groups (ion‐exchange surface) or by coupling hydrophobic residues (hydrophobic interacting surface, HIS) to the surface. In this paper the preparation of protein adsorbing surfaces on titanium and cobalt chromium molybdenum alloy for the adsorption of rhBMP‐2 and ubiquitin will be described. rhBMP‐2 and ubiquitin are bound extremely tight to surfaces containing propyl or hexyl groups of a certain surface concentration and are slowly released over a range of at least 24–100 days making such surfaces applicable as long‐term drug delivery devices for enhancing bone growth or implant integration.     

Histomorphometric and histologic evaluation of titanium–zirconium (<Emphasis Type="Italic">a</Emphasis>TiZr) implants with anodized surfaces

The choice of implant surface has a significant influence on osseointegration. Modification of TiZr surface by anodization is reported to have the potential to modulate the osteoblast cell behaviour favouring more rapid bone formation. The aim of this study is to investigate the effect of anodizing the surface of TiZr discs with respect to osseointegration after four weeks implantation in sheep femurs. Titanium (Ti) and TiZr discs were anodized in an electrolyte containing dl-α-glycerophosphate and calcium acetate at 300 V. The surface characteristics were analyzed by scanning electron microscopy, electron dispersive spectroscopy, atomic force microscopy and goniometry. Forty implant discs with thickness of 1.5 and 10 mm diameter (10 of each-titanium, titanium–zirconium, anodized titanium and anodized titanium–zirconium) were placed in the femoral condyles of 10 sheep. Histomorphometric and histologic analysis were performed 4 weeks after implantation. The anodized implants displayed hydrophilic, porous, nano-to-micrometer scale roughened surfaces. Energy dispersive spectroscopy analysis revealed calcium and phosphorous incorporation into the surface of both titanium and titanium–zirconium after anodization. Histologically there was new bone apposition on all implanted discs, slightly more pronounced on anodised discs. The percentage bone-to-implant contact measurements of anodized implants were higher than machined/unmodified implants but there was no significant difference between the two groups with anodized surfaces (P > 0.05, n = 10). The present histomorphometric and histological findings confirm that surface modification of titanium–zirconium by anodization is similar to anodised titanium enhances early osseointegration compared to machined implant surfaces.     

Anodization: a promising nano-modification technique of titanium implants for orthopedic applications

Anodization is a well-established surface modification technique that produces protective oxide layers on valve metals such as titanium. Many studies have used anodization to produce micro-porous titanium oxide films on implant surfaces for orthopedic applications. An additional hydrothermal treatment has also been used in conjunction with anodization to deposit hydroxyapatite on titanium surfaces; this is in contrast to using traditional plasma spray deposition techniques. Recently, the ability to create nanometer surface structures (e.g., nano-tubular) via anodization of titanium implants in fluorine solutions have intrigued investigators to fabricate nano-scale surface features that mimic the natural bone environment. This paper will present an overview of anodization techniques used to produce micro-porous titanium oxide structures and nano-tubular oxide structures, subsequent properties of these anodized titanium surfaces, and ultimately their in vitro as well as in vivo biological responses pertinent for orthopedic applications. Lastly, this review will emphasize why anodized titanium structures that have nanometer surface features enhance bone forming cell functions.     

Rapid Biofilm Eradication on Bone Implants Using Red Phosphorus and Near‐Infrared Light

Bone‐implant‐associated infections are common after orthopedic surgery due to impaired host immune response around the implants. In particular, when a biofilm develops, the immune system and antibiotic treatment find it difficult to eradicate, which sometimes requires a second operation to replace the infected implants. Most strategies have been designed to prevent biofilms from forming on the surface of bone implants, but these strategies cannot eliminate the biofilm when it has been established in vivo. To address this issue, a nonsurgical, noninvasive treatment for biofilm infection must be developed. Herein, a red‐phosphorus–IR780–arginine–glycine–aspartic‐acid–cysteine coating on titanium bone implants is prepared. The red phosphorus has great biocompatibility and exhibits efficient photothermal ability. The temperature sensitivity of Staphylococcus aureus biofilm is enhanced in the presence of singlet oxygen (¹O₂) produced by IR780. Without damaging the normal tissue, the biofilm can be eradicated through a safe near‐infrared (808 nm) photothermal therapy at 50 °C in vitro and in vivo. This approach reaches an antibacterial efficiency of 96.2% in vivo with 10 min of irradiation at 50 °C. Meanwhile, arginine–glycine–aspartic‐acid–cysteine decorated on the surface of the implant can improve the cell adhesion, proliferation, and osteogenic differentiation.     

Structure of the interface between rabbit cortical bone and implants of gold, zirconium and titanium

The role of surface properties (chemical and structural) for the interaction between biomaterials and tissue is not yet understood. In the present study, implants made of titanium, zirconium (transition metals with surface oxides) and gold (metallic surface) were inserted into the rabbit tibia. Light microscopic (LM) morphometry showed that after 1 and 6 mo the gold implants had less amount of bone within the threads and a lower degree of bone-implant contact than the titanium and zirconium implants, which did not differ from each other. These quantitative differences were supported by LM and ultrastructural observations of the interface. The ultrastructural observations in addition demonstrated that the layer of non-collagenous amorphous material located between the implant and the calcified bone was appreciably thicker around zirconium than around titanium implants. The factors potentially responsible for the observed morphological differences in the bone around the different material surfaces are discussed.     

Bioactive Materials for Regenerative Medicine: Zeolite‐Hydroxyapatite Bone Mimetic Coatings

We report the synthesis and characterization of a novel zeolite‐hydroxyapatite composite coating on titanium alloys and stainless steel. The zeolite‐hydroxyapatite coating is superhydrophilic and outperforms the state‐of‐the‐art Ti6Al4V alloys in corrosion resistance tests in aggressive pitting NaCl media, phosphate buffer solution with BSA protein, as well as highly complex DMEM cell culture media. And the composite coating also eliminates the elastic modulus mismatch between coating and bone. In addition, the composite coating has an osteoconductive and osteoinductive effect on hFOBs, indicating that it may enhance osteointegration of implants and speed up post‐surgical recovery, and thus reduce the need for recurring implant replacement surgeries. Replacing titanium with zeolite‐hydroxyapatite coated steel can also significantly reduce implant cost while improving implant lifespan.     

Bimetallic Nanostructures as Active Raman Markers: Gold‐Nanoparticle Assembly on 1D and 2D Silver Nanostructure Surfaces

It is demonstrated that bimetallic silver–gold anisotropic nanostructures can be easily assembled from various nanoparticle building blocks with well‐defined geometries by means of electrostatic interactions. One‐dimensional (1D) silver nanowires, two‐dimensional (2D) silver nanoplates, and spherical gold nanoparticles are used as representative building blocks for bottom‐up assembly. The gold nanoparticles are electrostatically bound onto the 1D silver nanowires and the 2D silver nanoplates to give bimetallic nanostructures. The unique feature of the resulting nanostructures is the particle‐to‐particle interaction that subjects absorbed analytes to an enhanced electromagnetic field with strong polarization dependence. The Raman activity of the bimetallic nanostructures is compared with that of the individual nanoparticle blocks by using rhodamine 6G solution as the model analyte. The Raman intensity of the best‐performing silver–gold nanostructure is comparable with the dense array of silver nanowires and silver nanoplates that were prepared by means of the Langmuir–Blodgett technique. An optimized design of a single‐nanostructure substrate for surface‐enhanced Raman spectroscopy (SERS), based on a wet‐assembly technique proposed here, can serve as a compact and low‐cost alternative to fabricated nanoparticle arrays.     

Interfacial Capillary‐Force‐Driven Self‐Assembly of Monolayer Colloidal Crystals for Supersensitive Plasmonic Sensors

Colloidal lithography technology based on monolayer colloidal crystals (MCCs) is considered as an outstanding candidate for fabricating large‐area patterned functional nanostructures and devices. Although many efforts have been devoted to achieve various novel applicatons, the quality of MCCs, a key factor for the controllability and reproducibility of the patterned nanostructures, is often overlooked. In this work, an interfacial capillary‐force‐driven self‐assembly strategy (ICFDS) is designed to realize a high‐quality and highly‐ordered hexagonal monolayer MCCs array by resorting the capillary effect of the interfacial water film at substrate surface as well as controlling the zeta potential of the polystyrene particles. Compared with the conventional self‐assembly method, this approach can realize the reself‐assembly process on the substrate surface with few colloidal aggregates, vacancy, and crystal boundary defects. Furthermore, various typical large‐scale nanostructure arrays are achieved by combining reactive ion etching, metal‐assisted chemical etching, and so forth. Specifically, benefiting from the as‐fabricated high‐quality 2D hexagonal colloidal crystals, the surface plasmon resonance (SPR) sensors achieve an excellent refractive index sensitivity value of 3497 nm RIU^?1, which is competent for detecting bovine serum albumin with an ultralow concentration of 10^?8 m . This work opens a window to prepare high‐quality MCCs for more potential applications.     

Light-induced bone cement-philic titanium surface

The survival of cemented endosseous implants can be improved by enhancing the bond between the implant and the cement. We hypothesized that the light-inducible generation of super-hydrophilicity of titanium positively affects its bone cement-philicity and bone cement–titanium bonding. Commercially pure titanium disks with machined surface and acid-etched micro roughened surfaces were prepared. Ultra-violet (UV) light treatment (0.1 mW/cm² UVA and 0.03 mW/cm² UVB for 48 h) created a super-hydrophilic surface for both surface types. The area of poly-methyl methacrylate (PMMA)-based bone cement spread increased by 30% and 20% on the light-treated machined titanium and acid-etched titanium surfaces, respectively, compared to the matched untreated ones. The contact angle of the bone cement decreased significantly after the light treatment, confirming the enhanced wettability of bone cement by the light treatment. Interfacial tensile stress between the bone cement material and titanium was increased 100% for the machined surface and 50% for the acid-etched surface by light treatment. Interfacial shear stress measured by a push-out test of titanium rods also revealed a 40% increase for the machined surface and 25% increase for the acid-etched surface. In conclusion, the pre-UV light treatment of titanium enhances the wettability and bonding strength of poly-methyl-methacrylate-based bone cement.     

Variation of roughness and adhesion strength of deposited apatite layers on titanium dental implants

It is known that surface roughness and chemical composition of the titanium surface influence the osseointegration of titanium implants. Most commercial dental implants offer a shot-blasted rough surface. It is also known that apatite layers coating the surface of titanium implants improve bone response, but the adhesion of the layer to the substrate poses some problems.In this study the roughness and adhesion strength to a titanium dental implant surface of an apatite layer deposited via wet chemistry after a thermochemical treatment were compared with those of plasma-sprayed apatite layers and machined titanium surfaces. Different surface conditions have been studied: (a) as-received machined dental implant surface; (b) grit-blasted titanium surface; (c) grit-blasted and thermochemically-treated titanium surface; (d) titanium surfaces coated with plasma-sprayed apatite. The morphology and roughness of the samples were measured and compared. The adhesion of the apatite layers to the titanium was compared by means of a scratch test.Measured roughness showed that the deposition of an apatite layer did not affect roughness but plasma-sprayed apatite produced a decrease on roughness values when compared to control samples. Both roughness and adhesion strength of the deposited apatite layer to the titanium substrate were higher than those of the plasma-sprayed apatite.     

A S‐Layer Protein of Bacillus anthracis as a Building Block for Functional Protein Arrays by In Vitro Self‐Assembly

S‐layer proteins create a cell‐surface layer architecture in both bacteria and archaea. Because S‐layer proteins self‐assemble into a native‐like S‐layer crystalline structure in vitro, they are attractive building blocks in nanotechnology. Here, the potential use of the S‐layer protein EA1 from Bacillus anthracis in constructing a functional nanostructure is investigated, and apply this nanostructure in a proof‐of‐principle study for serological diagnosis of anthrax. EA1 is genetically fused with methyl parathion hydrolase (MPH), to degrade methyl parathion and provide a label for signal amplification. EA1 not only serves as a nanocarrier, but also as a specific antigen to capture anthrax‐specific antibodies. As results, purified EA1–MPH forms a single layer of crystalline nanostructure through self‐assembly. Our chimeric nanocatalyst greatly improves enzymatic stability of MPH. When applied to the detection of anthrax‐specific antibodies in serum samples, the detection of our EA1–MPH nanostructure is nearly 300 times more sensitive than that of the unassembled complex. Together, it is shown that it is possible to build a functional and highly sensitive nanosensor based on S‐layer protein. In conclusion, our present study should serve as a model for the development of other multifunctional nanomaterials using S‐layer proteins.     

Surface functionalization of materials to initiate auto‐biocompatibilization in vivo

Cellular growth and differentiation in contact with artificial materials is controlled by exchange of information between solid and components of the extracellular matrix. Usually cells are connected with the extracellular matrix via adhesive proteins, f. i. fibronectin or laminin. Fibronectin is a large glycoprotein consisting of a dimer of two subunits which are connected via two disulfide‐bonds at their carboxy terminal ends. Each subunit contains binding sites for heparin, collagen and the cell itself. Fibronectin is bound via sequences of type III to cellular integrins. The cell‐specifity of the implant‐surface can be realized by physical, chemical or biological functionalization. The RGD type III‐sequence arg‐gly‐asp of fibronectin can be connected to the implant surface via metal organic spacers. Already experimentally performed was the reaction between short‐chain III sequences with titanium alcoxides. The metal‐organic compound carries the sequence as a functional group. The coupling to the metal(oxide)‐surface takes place with a sol‐gel‐process via hydrolysis and condensation of the alkoxide groups. In appropriate preparatory work mono amino acids, polycarbocylic acids and other short chain biological effective molecules have already been bound to titanium. The free functionalities: ‐NH₂, ‐COOH, ‐SO₃ were prooved by FT‐IR‐ or surface enhanced raman spectroscopy (SERS). The provided surfaces show differently strong mineralization after incubation in simulated body fluids containing calcium phosphates; a sterilization in an autoclave does not modify the chemical composition and the morphology of the surface modification. The goal for implants with contact to hard tissue is to prepare a surface with free functionalities which adsorb preferently adhesive proteins from the host extracellular matrix as an auto‐biocompatibilization.     

Antimicrobial Potential of Copper‐Containing Titanium Surfaces Generated by Ion Implantation and Dual High Power Impulse Magnetron Sputtering

The application of antimicrobial surfaces to titanium alloy (Ti) implants would be beneficial to prevent implant‐associated infections of joint endoprostheses and osteosyntheses. Copper (Cu) could be advantageously applied for this purpose, since it exhibits a well‐known antimicrobial activity and is a trace element in the human body, i.e., it is non‐toxic in small concentrations. This approach was evaluated with two plasma‐based surface modification procedures:

• 1) Implantation of Cu ions into Ti by means of plasma immersion ion implantation (PIII) and
• 2) Coating of Ti surfaces with Cu? Ti films by means of dual high power impulse magnetron sputtering (dual HiPIMS).

In this manner, the surfaces could be equipped with various amounts of Cu, as it was analyzed by X‐ray photoelectron spectroscopy (XPS). The surfaces released up to 8 mmol · L^?1 of Cu within 24 h, measured with atomic absorption spectroscopy (AAS). Hence, the surfaces possessed an antimicrobial potential against typical infect‐associated bacteria (Staphylococcus aureus). Surfaces with a higher Cu release prepared by HiPIMS technique revealed a higher antimicrobial effect, while surfaces implanted by PIII were less cytotoxic to osteoblasts (MG‐63 cells). These results show that Cu doped and coated implants could be useful for prevention and therapy of implant‐associated infections.