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ispartof: Procedia CIRP vol:113 issue:ISEM 2022 pages:605-610 status: Published online

ispartof: SURFACE ENGINEERING vol:38 issue:4 pages:430-439 status: published

Apart from osseointegration, the stability and long-term survival of percutaneous titanium implants is also strongly dependent on a qualitative soft-tissue integration in the transcutaneous region. A firm connective tissue seal is needed to minimize soft-tissue dehiscence and epithelial downgrowth. It is well-known that the implant surface plays a key role in controlling the biological response of the surrounding keratinized tissue and several coating systems have been suggested to enhance the soft-tissue cell interactions. Although some promising results have been obtained in vitro, their clinical significance can be debated. Therefore, the purpose of this systematic review is to gain more insight into the effect of such coatings on the interface formed with keratinized soft-tissue in vivo. A comprehensive search was undertaken in March 2021. Relevant electronic databases were consulted to identify appropriate studies using a set of search strings. In total, 12 out of 4971 publications were included in this review. The reported coating systems were assigned to several subgroups according to their characteristics: metallic, ceramic and composite. Notwithstanding the differences in study characteristics (animal model, implantation period, reported outcomes), it was noticed that several coatings improve the soft-tissue integration as compared to pristine titanium. Porous titanium coatings having only limited pore sizes (700 μm) allow extensive vascularized soft-tissue infiltration, thereby supporting cell attachment. Nanostructured ceramic coatings are found to reduce the inflammatory response in favor of the formation of cell adhesive structures, that is, hemidesmosomes. Biomolecule coatings seem of particular interest to stimulate the soft-tissue behavior provided that a durable fixation to the implant surface can be ensured. In this respect, fibroblast growth factor-2 entrapped in a biomimetic apatite coating instigates a close to natural soft-tissue attachment with epidermal collagen fibers attaching almost perpendicular to the implant surface. However, several studies had limitations with respect to coating characterization and detailed soft-tissue analysis, small sample size and short implantation periods. To date, robust and long-term in vivo studies are still lacking. Further investigation is required before a clear consensus on the optimal coating system allowing enhancing the soft-tissue seal around percutaneous titanium implants can be reached. ispartof: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS vol:110 issue:7 pages:1713-1723 ispartof: location:United States status: published

Biofilms are an important medical burden, notably for patients with orthopaedic device-related infections. When polymicrobial, these infections are more lethal and recalcitrant. Inter-kingdom biofilm infections are poorly understood and challenging to treat. Here, an in vitro three-species model including Staphylococcus aureus, Escherichia coli and Candida albicans was developed, to represent part of the diversity observed in orthopaedic infections or other clinical contexts. The importance of fungal hyphae for biofilm formation and virulence factor expression was explored. Two protocols were set up, allowing, or not, for hyphal formation. Culturable cells and biomass were characterised in both models, and biofilms were imaged in bright-field, confocal and electron microscopes. The expression of genes related to virulence, adhesion, exopolysaccharide synthesis and stress response was analysed in early-stage and mature biofilms. It was found that biofilms enriched in hyphae had larger biomass and showed higher expression levels of genes related to bacterial virulence or exopolysaccharides synthesis.

The aim of the present study was to fabricate and characterise chitosan scaffolds from animal and fungal sources, with or without gelatine as a co-polymer, and cross-linked to 3-glycidyloxyproply trimethoxysilane (GPTMS) or genipin for application in dental root tissue engineering. Chitosan-based scaffolds were prepared by the emulsion freeze-drying technique. Scanning electron microscopy (SEM) and nano-focus computed tomography (nano-CT) were used to characterise scaffold microstructure. Chemical composition and cross-linking were evaluated by Fourier transform infrared-attenuated total reflectance spectroscopy. Compression tests were performed to evaluate scaffold mechanical properties. Scaffold degradation was evaluated by gravimetric method and SEM. Scaffold bioactivity immersed in simulated body fluid was evaluated by SEM, with associated electron dispersive X-ray spectroscopy, and apatite formation was examined by X-ray diffraction. Finally, human dental pulp stem cells (hDPSCs) viability was evaluated. The fabrication method used was successful in producing scaffolds with organised porosity. Chitosan source (animal vs. fungal), co-polymerisation with gelatine and cross-linking using GPTMS or genipin had a significant effect on scaffold properties and hDPSCs response. Chitosan-genipin (CS-GEN) scaffolds had the largest pore diameter, while the chitosan-gelatine-GPTMS (CS-GEL-GPTMS) scaffolds had the smallest. Animal chitosan-gelatine co-polymerisation increased scaffold compressive strength, while fungal chitosan scaffolds (fCS-GEL-GPTMS) had the fastest degradation rate, losing 80 % of their weight by day 21. Gelatine co-polymerisation and GPTMS cross-linking enhanced chitosan scaffolds bioactivity through the formation of an apatite layer as well as improved hDPSCs attachment and viability. Tailored chitosan scaffolds with tuned properties and favourable hDPSCs response can be obtained for regenerative dentistry applications. ispartof: European Cells & Materials vol:40 pages:485-501 ispartof: location:Switzerland status: published

A hybrid coating was fabricated on ZK60 magnesium (Mg) alloy using alternating current electrophoretic deposition (AC-EPD). The hybrid coating comprised chitosan, gelatin (Type-B), bioactive glasses (BG(a,b)) and nanoparticles of ZnO/CeO2. Fourier-transform infrared (FTIR) spectra confirmed the presence of the above-mentioned materials on coated samples. Scanning electron microscopy (SEM) images showed that coating morphology was homogeneous and covered the maximum surface area. Potentiodynamic polarization measurements (PDP) of coated samples were investigated in Ringer’s solution at 25°C. PDP results showed that lowest corrosion current density values of 1.39 and 1.84 µA cm−2 were observed for suspensions CS0.8–G0.8–BG(b)1.0–ZnO0.6 and CS0.8–G0.8–G(a)1–CeO2(0.6), respectively. SEM analysis and PDP results confirmed that best AC-EPD parameters for ZK60 are (Voltage = 35 V, Frequency = 300 Hz, DC off-set = 2 V, Time = 480 s, Distance = 10 mm). DC off-set with the same direction to high amplitude peak was a promising addition in AC-EPD parameters.

Objectives: New strategies for implant surface functionalization in the prevention of peri-implantitis while not compromising osseointegration are currently explored. The aim of this in vivo study was to assess the osseointegration of a titanium-silica composite implant, previously shown to enable controlled release of therapeutic concentrations of chlorhexidine, in the Göttingen mini-pig oral model. Material and methods: Three implant groups were designed: macroporous titanium implants (Ti-Porous); macroporous titanium implants infiltrated with mesoporous silica (Ti-Porous + SiO2 ); and conventional titanium implants (Ti-control). Mandibular last premolar and first molar teeth were extracted bilaterally and implants were installed. After 1 month healing, the bone in contact with the implant and the bone regeneration in the peri-implant gap was evaluated histomorphometrically. Results: Bone-to-implant contact and peri-implant bone volume for Ti-Porous versus Ti-Porous + SiO2 implants did not differ significantly, but were significantly higher in the Ti-Control group compared with Ti-Porous + SiO2 implants. Functionalization of titanium implants via infiltration of a SiO2 phase into the titanium macropores does not seem to inhibit implant osseointegration. Yet, the importance of the implant macro-design, in particular the screw thread design in a marginal gap implant surgery set-up, was emphasized by the outstanding results of the Ti-Control implant. Conclusions: Next-generation implants made of macroporous Ti infiltrated with mesoporous SiO2 do not seem to compromise the osseointegration process. Such implant functionalization may be promising for the prevention and treatment of peri-implantitis given the evidenced potential of mesoporous SiO2 for controlled drug release. ispartof: Clinical and Experimental Dental Research vol:7 issue:4 ispartof: location:United States status: published

The aim of this study was to examine the potential influence of antithrombotics on leukocyte- and platelet-rich fibrin (L-PRF) membranes.Tensile tests and cell counts were performed with L-PRF membranes originating from patients on anticoagulants and antiplatelets versus patients not taking antithrombotics.For the tensile tests, 13 control patients, 12 on anticoagulants, and 10 on antiplatelets donated blood. Compared to controls, membranes from anticoagulated donors were weaker (strength 0.57 ± 0.24 MPa vs. 0.80 ± 0.27 MPa, p = .03) and could not be stretched as far (1.8 ± 0.3 vs. 2.1 ± 0.3 times the initial length, p = .01). For the cell counting, 23 control patients, 16 on anticoagulants, and 16 on antiplatelets donated blood. The percentage of platelets was ±50% in the three groups. The percentage of leukocytes was lower in the anticoagulant group compared with controls (69 ± 10% vs. 78 ± 8%, p = .04). However, because of the unknown error of method, it is questionable whether the statistical significance is meaningful. There was no difference between membranes from the control group and the group on antiplatelets.Our results indicate that L-PRF membranes originating from patients on anticoagulants are weaker, stretch less far, and contain less leukocytes than L-PRF membranes of patients not taking these drugs.

Objectives: Cemented polished tapered stems have demonstrated excellent long-term outcomes. Based on this concept, many generic tapered stems have been released into the market. The aim of this study was to evaluate implant-related complications of 1 specific stem design. Methods: Between 2010 and 2017, 315 total hip replacements were performed using a Fortress stem (Biotechni, La Ciotat, France). Patient records and radiology were retrospectively reviewed for implant-related complications. A failure analysis was performed on the failed Fortress stems in order to determine the cause of premature failure. Results: 7 (2.2%) patients sustained a fracture of the neck of the implant after a mean of 5 years (range 50–81 months). All fractures were atraumatic, originating at the introducer inlet of the stem. All fractured occurred in obese patients (BMI >33 kg/m2) with a small sized prosthesis. Of these, there were 5 135° and 2 125° stems. Fracture risk was 23% (7/30) for patients with a small sized stem and a BMI >30 kg/m2. All cases were revised using a cement-in-cement technique or a cementless modular revision stem. Failure analysis on the retrieved stems revealed a stress riser at the bottom of the introducer inlet. Conclusions: An alarmingly high rate of early implant fractures was seen using this specific type of cemented stem, particularly when using smaller implant sizes in obese patients. Although based on a proven design, a specific modification led to a stress riser in the neck area, which resulted in a high incidence of implant failure. This series underlines the importance of a stepwise introduction into the market of new orthopaedic devices even when based on established concepts. Generic stems may not behave as the original stem upon which it was designed.

OBJECTIVE AND BACKGROUND: Little is known about structural and mechanical properties of leukocyte- and platelet-rich fibrin (L-PRF) membranes and even less about the influence of antithrombotic drugs on L-PRF. The aim of this in vitro study is therefore to investigate mechanical properties, fibrin structure and cell content of L-PRF membranes and the impact of anticoagulant therapy on L-PRF. METHODS: Blood samples were obtained from 12 volunteers and supplemented with either no, 1.25 IU, 2.5 IU, 5 IU, or 10 IU enoxaparin. L-PRF membranes were characterized with tensile testing, scanning electron microscopy, and measurement of platelets and leukocytes. Control and enoxaparin-supplemented L-PRF membranes were compared. RESULTS: At 10 IU enoxaparin, no L-PRF membranes could be generated, whereas the low doses of 1.25 and 2.5 IU had no influence on L-PRF properties. The mechanical properties, fibrin networks, and number of platelets and leukocytes of 5 IU supplemented membranes were unlike the control membranes, but were not found to be significantly different because of limited sampling and inter- and intra-variability. CONCLUSION: Low doses of the anticoagulant enoxaparin do not affect mechanical properties, fibrin network, nor cellular content of L-PRF, whereas high doses impair L-PRF generation. ispartof: JOURNAL OF PERIODONTAL RESEARCH vol:55 issue:5 pages:686-693 ispartof: location:United States status: published

Magnesium alloys have gained significant attention as degradable implant materials, but the fast and localized corrosion behavior leading to hydrogen gas evolution and alkaline poisoning limits their clinical application. In this research, the possibility of controlling the fast degradation rate of an experimental Mg-Si-Sr alloy by applying hybrid biopolymer chitosan (CS)-gelatin (G)-bioactive glass (BG) coatings was investigated. Electrophoretic deposition using alternating current fields (AC-EPD) was employed for surface coating and the influence of suspension parameters (biopolymer type and concentration, BG particle size), and key AC-EPD parameters (voltage amplitude, frequency, and time) on the coating quality were investigated. Stable suspensions of positively charged biopolymer/BG particles deposited on the Mg alloy coupled as a cathode during the high-amplitude peak. Furthermore, coating homogeneity improved with increasing peak-to-peak-voltage and the hybrid nature of the coatings was confirmed by scanning electron microscopy and Fourier transform infrared spectroscopy. Corrosion studies revealed a significantly decreased corrosion rate down to 0.08 mm/year for the Mg-Si-Sr alloy incorporating CS-G-BG b AC-EPD coating.

The wear of a novel temporomandibular joint (TMJ) prosthesis was evaluated in an animal model. The prosthesis consisted of an additively manufactured titanium alloy (Ti6 Al4 V) mandibular condyle and glenoid fossa created through selective laser melting, with a machined vitamin E-enriched ultra-high molecular weight polyethylene (UHMWPE) surface attached to the fossa. Thirteen TMJ prosthesis were implanted in sheep, six of which had condylar heads coated with HadSat® diamond-like carbon (H-DLC). Euthanasia took place after 288 days, equaling 22 years of human mastication. Linear and volumetric wear analysis of the fossa was performed by optical scanning. The condylar head surfaces were assessed by scanning electron and confocal laser microscopy. The average linear UHMWPE wear, when combined with the coated condyle, was 0.67 ± 0.28 mm (range: 0.34-1.15 mm), not significantly differing (p = .3765, t-test) from the non-coated combination average (0.88 ± 0.41 mm; range: 0.28-1.48 mm). The respective mean volumetric wear volumes were 25.29 ± 11.43 mm3 and 45.85 ± 22.01 mm3 , not significantly differing (p = .1448, t-test). Analysis of the coated condylar surface produced a mean Ra of 0.12 ± 0.04 μm and Sa of 0.69 ± 0.07 μm. The non-coated condylar surface measured a mean Ra of 0.28 ± 0.17 μm and Sa of 2.40 ± 2.08 μm. Both Sa (p = .0083, Mann-Whitney U test) and Ra (p = .0182, Mann-Whitney U test), differed significantly. The prosthesis exhibits acceptable wear resistance and addition of the H-DLC-coating significantly improved long-term condylar surface smoothness. ispartof: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS vol:110 issue:6 pages:1425-1438 ispartof: location:United States status: published

This work focused on the influence of TiC reinforcing particles on the tribological properties of titanium matrix composites (TMCs) with open porosity, processed by spark plasma sintering (SPS). Materials composed of an equimolar mixture of Ti and TiH2 with 0, 3, 10 and 30 vol.% of TiC were sintered at 850 °C. Nanoindentation and wear tests were carried out to assess the nanohardness and the wear resistance in a tribometer with a reciprocating sliding ball-on-flat configuration. Results showed a nanohardness increment from 5 to 14 GPa with increasing TiC content. The coefficient of friction (CoF) showed a minimum of 0.2 for 10% TiC grade, which also showed the lowest wear rate. For the low TiC content sample, adhesive wear with severe plastic deformation was identified. Meanwhile, medium content TiC sample showed a mechanical mixed layer (MML), whereas high TiC content composite showed abrasive as the main wear mechanism. In conclusion, the wear mechanisms, CoFs and wear volume changed with TiC content.

Study Design Descriptive study (/review containing supporting case studies). Objective The temporomandibular joint has some distinctive features that were not taken into account during the initial development of temporomandibular joint prostheses, such as laterotrusive movements that are necessary for the proper grinding of food as well as synchronous and congruent movements made in conjunction with the healthy, contralateral joint. The aim of this article is to describe the development of a novel type of TMJ prosthesis that optimizes temporomandibular joint replacement. Methods The development was initiated by using contemporary technologies like computer-aided design customization, additive manufacturing, and surface treatments. Biocompatibility, proper fixation, and wear resistance, being prerequisites for the longevity of prostheses, were investigated next. Individual variables (condylar path, condylar axis angle, Bennet shift) were introduced as the main basis for physiological movements with the restoration of all functions. Early post-operative results ranging from 1 month to 4.5 years (11 patients, average follow-up period was 23.3 months) were assessed. Results The experience with 16 individualized total joint replacements in 11 patients is presented. The 3-year follow-up results of two-patient detailed studies are discussed, which show evidence of the promising restoration of all mandibular movements, when preoperatively present. Conclusions By incorporating various innovative and novel features (scaffold for re-attachment of lateral pterygoid, patient-specific functional parametrization, saddle-like design for retention, …) into a novel TMJ prosthesis concept, a major advance in function-reconstructive temporomandibular joint replacement was achieved. Early in vivo results (1 year after surgery) showed promising outcomes, involving both high increases in mandibular movements and decreases in pain scores.

Biofilms, especially those formed by Staphylococcus aureus, play a key role in the development of orthopedic implant infections. Eradication of these infections is challenging due to the elevated tolerance of biofilm cells against antimicrobial agents. In this study, we developed an antibiofilm coating consisting of 5-(4-bromophenyl)-N-cyclopentyl-1-octyl-1H-imidazol-2-amine, designated as LC0024, covalently bound to a titanium implant surface (LC0024-Ti). We showed in vitro that the LC0024-Ti surface reduces biofilm formation of S. aureus in a specific manner without reducing the planktonic cells above the biofilm, as evaluated by plate counting and fluorescence microscopy. The advantage of compounds that only inhibit biofilm formation without affecting the viability of the planktonic cells, is that reduced development of bacterial resistance is expected. To determine the antibiofilm activity of LC0024-Ti surfaces in vivo, a biomaterial-associated murine infection model was used. The results indicated a significant reduction in S. aureus biofilm formation (up to 96%) on the LC0024-Ti substrates compared to pristine titanium controls. Additionally, we found that the LC0024-Ti substrates did not affect the attachment and proliferation of human cells involved in osseointegration and bone repair. In summary, our results emphasize the clinical potential of covalent coatings of LC0024 on titanium implant surfaces to reduce the risk of orthopedic implant infections. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1908-1919, 2019. ispartof: Journal of Biomedical Materials Research Part B - Applied Biomaterials vol:107 issue:6 pages:1908-1919 ispartof: location:United States status: published

Laser surface texturing is widely explored for modifying the surface topography of various materials and thereby tuning their optical, tribological, biological, and other surface properties. In dentistry, improved osseointegration has been observed with laser textured titanium dental implants in clinical trials. Due to several limitations of titanium materials, dental implants made of zirconia-based ceramics are now considered as one of the best alternatives. Laser surface texturing of zirconia dental implants is therefore attracting increasing attention. However, due to the brittle nature of zirconia, as well as the metastable tetragonal ZrO2 phase, laser texturing in the case of zirconia is more challenging than in the case of titanium. Understanding these challenges requires different fields of expertise, including laser engineering, materials science, and dentistry. Even though much progress was made within each field of expertise, a comprehensive analysis of all the related factors is still missing. This review paper provides thus an overview of the common challenges and current status on the use of lasers for surface texturing of zirconia-based ceramics for dental applications, including texturing of zirconia implants for improving osseointegration, texturing of zirconia abutments for reducing peri-implant inflammation, and texturing of zirconia restorations for improving restoration retention by bonding. ispartof: Materials Science & Engineering C-Materials For Biological Applications vol:123 ispartof: location:Netherlands status: Published online

DNase coatings show great potential to prevent biofilm formation in various applications of the medical implant, food and marine industry. However, straightforward and quantitative methods to characterize the enzymatic activity of these coatings are currently not available. We here introduce the qDNase assay, a quantitative, real-time method to characterize the activity of DNase coatings. The assay combines (1) the use of an oligonucleotide probe, which fluoresces upon cleavage by coated DNases, and (2) the continuous read-out of the fluorescent signal within a microplate fluorometer format. The combination of these two properties results in a real-time fluorescent signal that is used to directly quantify the activity of DNase coatings. As a proof of concept, bovine DNase I coatings were immobilized on titanium by means of chemical grafting and their activity was estimated at 3.87 × 10−4 U. To our knowledge, the qDNase assay provides the first approach to report the activity of a DNase coating in absolute DNase activity units. This assay will not only serve to compare existing DNase coating methods more accurately, but will also enable the rational design of new DNase coating methods in the future.

Electrophoretic deposition (EPD) is a powerful technique to assemble carbon nanotube (CNT) coatings and composite films with controlled architectures. This comprehensive review of the EPD of CNTs and CNT-containing composites focuses on achievements within the last 15 years and ongoing challenges. Stable CNT suspensions are a pre-requisite for successful EPD and have been prepared by a variety of strategies, discussed here. The resulting film microstructure is determined by the initial feedstock, the suspension, and the EPD approach applied, as well as a variety of EPD processing parameters. Nanocomposites can be prepared via co-deposition, sequential deposition, or post-deposition treatments, to introduce metallic, ceramic or polymeric phases. There are numerous potential applications for both homogeneous and patterned CNT films, including as structural reinforcements for composites, as field emission, energy storage and conversion devices, as well as in biomedical applications. The advantages and disadvantages of EPD processing in these contexts are discussed.

Laser texturing of zirconia-alumina ceramics is a promising surface modification method for many applications, such as enhancing osseointegration of alumina toughened zirconia (ATZ) dental implants or improving friction behavior of zirconia toughened alumina (ZTA) hip replacement bearing components. The common problems in laser texturing of ATZ/ZTA ceramics are thermal cracking, low material removal rate (MRR), and laser-induced phase transformation (LIPT). Furthermore, the compositional variation of those ceramics will complicate these problems. In order to improve the manufacturing processability, ultrashort pulsed laser ablation behavior of ATZ/ZTA composites was investigated in this research. Single phase zirconia and alumina were found to have smaller MRRs than their composites, and this behavior was negatively correlated to the materials single-pulse laser ablation threshold. However, under multi-pulse laser irradiation, the ablation thresholds of all materials saturated to the same level, indicating that single phase materials were more sensitive to the incubation effect than their composites. This led to the MRRs of the single phase materials being reduced at larger scan speeds, while the MRRs of their composites remained independent of scan speed. It was also shown that single phase materials were less susceptible to thermal cracking than their composites under excessive heat accumulation. These results suggest that a lower scan speed is preferred for single phase materials in order to achieve a larger MRR, while a higher scan speed is beneficial for the composites for suppressing thermal cracking without compromising ablation efficiency. In addition, no LIPT was detected for zirconia dominated materials after laser ablation.

Although Ti alloys are generally regarded to be highly corrosion resistant, inflammatory conditions following surgery can instigate breakdown of the TiO2 passivation layer leading to an increased metal ion release. Furthermore proteins present in the surrounding tissue will readily adsorb on a titanium surface after implantation. In this paper alternating current electrophoretic deposition (AC-EPD) of bovine serum albumin (BSA) on Ti6Al4V was investigated in order to increase the corrosion resistance and control the protein adsorption capability of the implant surface. The Ti6Al4V surface was characterized with SEM, XPS and ToF-SIMS after long-term immersion tests under physiological conditions and simulated inflammatory conditions either in Dulbecco´s Modified Eagle Medium (DMEM) or DMEM supplemented with fetal calf serum (FCS). The analysis showed an increased adsorption of amino acids and proteins from the different immersion solutions. The BSA coating was shown to prevent selective dissolution of the vanadium (V) rich β-phase, thus effectively limiting metal ion release to the environment. Electrochemical impedance spectroscopy measurements confirmed an increase of the corrosion resistance for BSA coated surfaces as a function of immersion time due to the time-dependent adsorption of the different amino acids (from DMEM) and proteins (from FCS) as observed by ToF-SIMS analysis. publisher: Elsevier articletitle: Albumin coatings by alternating current electrophoretic deposition for improving corrosion resistance and bioactivity of titanium implants journaltitle: Materials Science and Engineering: C articlelink: http://dx.doi.org/10.1016/j.msec.2016.12.129 content_type: article copyright: © 2017 Elsevier B.V. All rights reserved. ispartof: Materials Science and Engineering C, Materials for Biological Applications vol:73 pages:798-807 ispartof: location:Netherlands status: published

One prominent cause of implant failure is infection; therefore, research is focusing on developing surface coatings that render the surface resistant to colonization by micro-organisms. Permanently attached coatings of antimicrobial molecules are of particular interest because of the reduced cytoxicity and lower risk of developing resistance compared to controlled release coatings. In this study, we focus on the chemical grafting of bioactive molecules on titanium. To concentrate the molecules at the metallic implant surface, we propose electrophoretic deposition (EPD) applying alternating current (AC) signals with an asymmetrical wave shape. We show that for the model molecule bovine serum albumin (BSA), as well as for the clinically relevant antifungal lipopeptide caspofungin (CASP), the deposition yield is drastically improved by superimposing a DC offset in the direction of the high-amplitude peak of the AC signal. Additionally, in order to produce immobilized CASP coatings, this experimental AC/DC-EPD method is combined with an established surface activation protocol. Principle component analysis (PCA) of time-of-flight secondary ion mass spectrometry (ToF-SIMS) data confirm the immobilization of CASP with higher yield as compared to a diffusion-controlled process, and higher purity than the clinical CASP starting suspensions. Scratch testing data indicate good coating adhesion. Importantly, the coatings remain active against the fungal pathogen C. albicans as shown by in vitro biofilm experiments. In summary, this paper delivers a proof-of-concept for the application of AC-EPD as a fast grafting tool for antimicrobial molecules without compromising their activities.

Roughened surfaces are increasingly being used for dental implant applications as the enlarged contact area improves bone cell anchorage, thereby facilitating osseointegration. However, the additional surface area also entails a higher risk for the development of biofilm associated infections, an etiologic factor for many dental ailments, including peri-implantitis. To overcome this problem, we designed a dental implant composed of a porous titaniumsilica (Ti/SiO2 ) composite material and containing an internal reservoir that can be loaded with antimicrobial compounds. The composite material consists of a sol-gel derived mesoporous SiO2 diffusion barrier integrated in a macroporous Ti load-bearing structure obtained by powder metallurgical processing. The antimicrobial compounds can diffuse through the porous implant walls, thereby reducing microbial biofilm formation on the implant surface. A continuous release of µM concentrations of chlorhexidine through the Ti/SiO2 composite material was measured, without initial burst effect, over at least 10 days and using a 5 mM chlorhexidine solution in the implant reservoir. Metabolic staining, CFU counting and visualisation by scanning electron microscopy confirmed that Streptococcus mutans biofilm formation on the implant surface was almost completely prevented due to chlorhexidine release (preventive setup). Moreover, we demonstrated efficacy of released chlorhexidine against mature Streptococcus mutans biofilms (curative setup). In conclusion, we provide a proof of concept of the sustained release of chlorhexidine, one of the most widely used oral antiseptics, through the Ti/SiO2 material thereby preventing and eradicating biofilm formation on the surface of the dental implant. In principle, our flexible design allows for the use of any bioactive compound, as discussed. ispartof: European Cells & Materials vol:33 pages:13-27 ispartof: location:Switzerland status: published

The radish defensin RsAFP2 was previously characterized as a peptide with potent antifungal activity against several plant pathogenic fungi and human pathogens, including Candida albicans. RsAFP2 induces apoptosis and impairs the yeast-to-hypha transition in C. albicans. As the yeast-to-hypha transition is considered important for progression to mature biofilms, we analyzed the potential antibiofilm activity of recombinant (r)RsAFP2, heterologously expressed in Pichia pastoris, against C. albicans biofilms. We found that rRsAFP2 prevents C. albicans biofilm formation with a BIC-2 (i.e., the minimal rRsAFP2 concentration that inhibits biofilm formation by 50% as compared to control treatment) of 1.65 ± 0.40 mg/mL. Moreover, biofilm-specific synergistic effects were observed between rRsAFP2 doses as low as 2.5 μg/mL to 10 μg/mL and the antimycotics caspofungin and amphotericin B, pointing to the potential of RsAFP2 as a novel antibiofilm compound. In addition, we characterized the solution structure of rRsAFP2 and compared it to that of RsAFP1, another defensin present in radish seeds. These peptides have similar amino acid sequences, except for two amino acids, but rRsAFP2 is more potent than RsAFP1 against planktonic and biofilm cultures. Interestingly, as in case of rRsAFP2, also RsAFP1 acts synergistically with caspofungin against C. albicans biofilms in a comparable low dose range as rRsAFP2. A structural comparison of both defensins via NMR analysis revealed that also rRsAFP2 adopts the typical cysteine-stabilized αβ-motif of plant defensins, however, no structural differences were found between these peptides that might result in their differential antifungal/antibiofilm potency. This further suggests that the conserved structure of RsAFP1 and rRsAFP2 bears the potential to synergize with antimycotics against C. albicans biofilms.

A new powder metallurgical processing route for porous Ti coatings on Ti-6Al-4V substrates based on the electrophoretic deposition (EPD) of TiH2 suspensions is presented. After dehydrogenation and sintering in vacuum, coatings with a fully interconnected porosity (up to 51%, interconnective pore channels (IPC) of 2-50 µm) and high adhesion strength (up to 47 MPa) are obtained. Further evaluation of these coatings for potential use in biomedical implants shows that EPD Ti coatings are significantly less prone to bacterial adhesion compared to state-of-the-art vacuum plasma sprayed (VPS) coatings, while still allowing substantial bone ingrowth. Using EPD, the coating process can easily be transferred to complex-shaped implant components.

Magnesium and magnesium alloys are gaining considerable attention for use in biomedical applications due to their capability to completely resorb in the human body without noticeable side effects. For structural biomedical applications however, the resorption rate is too large. In order to decrease this rate researchers are investigating magnesium alloys with an increased corrosion resistance and/or biodegradable coatings, such as dense protein layers, which retard the resorption.In this work, we demonstrate the electrophoretic deposition of Bovine Serum Albumin (BSA) directly onto pure magnesium substrates using unbalanced alternating fields (AC-EPD). The effect of the obtained coatings on the corrosion behavior of the substrates was evaluated by potentiodynamic polarization. The results show that an albumin layer deposited by AC-EPD from a 50/50 ethanol/H2O medium significantly reduces the corrosion rate.

In the past, biofilm-related research has focused mainly on axenic biofilms. However, in nature, biofilms are often composed of multiple species, and the resulting polymicrobial interactions influence industrially and clinically relevant outcomes such as performance and drug resistance. In this study, we show that Escherichia coli does not affect Candida albicans tolerance to amphotericin or caspofungin in an E. coli/C. albicans biofilm. In contrast, ofloxacin tolerance of E. coli is significantly increased in a polymicrobial E. coli / C. albicans biofilm compared to its tolerance in an axenic E. coli biofilm. The increased ofloxacin tolerance of E. coli is mainly biofilm specific, as ofloxacin tolerance of E. coli is less pronounced in polymicrobial E. coli/C. albicans planktonic cultures. Moreover, we found that ofloxacin tolerance of E. coli decreased significantly when E. coli/C. albicans biofilms were treated with matrix-degrading enzymes such as the β-1,3-glucan-degrading enzyme lyticase. In line with a role for β-1,3-glucan in mediating ofloxacin tolerance of E. coli in a biofilm, we found that ofloxacin tolerance of E. coli increased even more in E. coli/C. albicans biofilms consisting of a high-β-1,3-glucan-producing C. albicans mutant. In addition, exogenous addition of laminarin, a polysaccharide composed mainly of poly-β-1,3-glucan, to an E. coli biofilm also resulted in increased ofloxacin tolerance. All these data indicate that β-1,3-glucan from C. albicans increases ofloxacin tolerance of E. coli in an E. coli/C. albicans biofilm.

Titanium-based implants are widely used in modern clinical practice, but their “optimal” properties in terms of porosity and topology, roughness and hydrophilic parameters are being a subject of intensive discussions. Recent in vitro results have shown a possibility to optimize the surface of an implant with maximal repelling of bacteria (Staphylococcus aureus, Staphylococcus epidermidis) and improvement in human osteogenic and endothelial cell adhesion, proliferation and differentiation. In this work, these different grades titanium implants were tested in vivo using the same analytical methodology. In addition to material parameters, key histomorphometrical parameters such a regeneration area, bone adaptation area and bone-to-implant contact were determined after 2 and 4 weeks of implantation in rabbit animal model. Porous implants have more clear differences than non-porous ones, with the best optimum values obtained on hydrothermally treated electrophoretically deposited titanium. These in vivo data correlate well with the optimal prediction made by in vitro tests. publisher: Elsevier articletitle: Titanium implants with modified surfaces: Meta-analysis of in vivo osteointegration journaltitle: Materials Science and Engineering: C articlelink: http://dx.doi.org/10.1016/j.msec.2014.12.074 content_type: article copyright: Copyright © 2014 Elsevier B.V. All rights reserved. ispartof: Materials Science and Engineering C, Materials for Biological Applications vol:49 pages:152-158 ispartof: location:Netherlands status: published

The alloplastic total temporomandibular joint (TMJ) prosthesis has a long history, with many different materials and designs used. While several of these materials have proven valuable over time, many others have not been suitable for implantation, resulting in failure and the need for explantation of the implant. Because of the failure of several of these systems, the use of alloplastic prostheses has reduced dramatically, despite their advantages over autogenous restoration. The aim of this narrative review is to discuss the criteria that must be met by a biomaterial in order for it to be considered suitable for implantation, as well as the common complications that can occur. Currently used materials are highlighted, as well as potential future materials that might prove better suitable for implantation. Several surface modification techniques are proposed as an alternative to the materials used in current TMJ prosthesis systems.

Current orthopaedic implant technology focuses on fixation by osseointegration to maximise the implant longevity and reduce the need for burdensome and expensive revision surgery. In this respect, porous Ti coated implants, which enable bone ingrowth into the porous structure and the establishment of biological anchoring of the implant, are of interest. In previous work a new powder metallurgical processing route was reported for the application of porous Ti coatings on Ti alloy substrates by electrophoretic deposition (EPD) of TiH2 powder suspensions. To validate the function of these coatings for potential clinical applications, the early peri-implant bone response was evaluated in vivo in a rabbit model. The results clearly demonstrate bone ingrowth in porous coatings with pore channels down to 10 μm, as opposed to the minimum pore size of 50–100 μm commonly claimed in the literature. Moreover, the observed inter-connectivity with surrounding cortical bone confirmed the envisaged mechanical interlockin...

Bone growth on and into implants exhibiting substantial surface porosity is a promising strategy in order to improve the long-term stable fixation of bone implants. However, the reliability in clinical applications remains a point of discussion. Most attention has been dedicated to the role of macroporosity, leading to the general consensus of a minimal pore size of 50–100 μm in order to allow bone ingrowth. In this in vivo study, we assessed the feasibility of early bone ingrowth into a predominantly microporous Ti coating with an average thickness of 150 μm and the hypothesis of improving the bone response through surface modification of the porous coating. Implants were placed in the cortical bone of rabbit tibiae for periods of 2 and 4 weeks and evaluated histologically and histomorphometrically using light microscopy and scanning electron microscopy. Bone with osteocytes encased in the mineralized matrix was found throughout the porous Ti coating up to the coating/substrate interface, highlighting that osseointegration of microporosities (

Biofilm-associated infections, particularly those caused by Staphylococcus aureus, are a major cause of implant failure. Covalent coupling of broad-spectrum antimicrobials to implants is a promising approach to reduce the risk of infections. In this study, we developed titanium substrates on which the recently discovered antibacterial agent SPI031, a N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol, was covalently linked (SPI031-Ti). We found that SPI031-Ti substrates prevent biofilm formation of S. aureus and Pseudomonas aeruginosa in vitro, as quantified by plate counting and fluorescence microscopy. To test the effectiveness of SPI031-Ti substrates in vivo, we used an adapted in vivo biomaterial-associated infection model in mice in which SPI031-Ti substrates were implanted subcutaneously and subsequently inoculated with S. aureus. Using this model, we found a significant reduction in biofilm formation (up to 98%) on SPI031-Ti substrates compared to control substrates. Finally, we demonstrated that the functionalization of the titanium surfaces with SPI031 did not influence the adhesion and proliferation of human cells important for osseointegration and bone repair. In conclusion, these data demonstrate the clinical potential of SPI031 to be used as an antibacterial coating for implants, thereby reducing the incidence of implant-associated infections. ispartof: Journal of Orthopaedic Research vol:34 issue:12 pages:2191-2198 ispartof: location:United States status: published

In this systematic review, the authors explored the surface aspects of various titanium (Ti) or Ti alloy medical implants, examining the interface formed between the implant and surrounding nonkeratinized soft tissues (periosteum, muscles, tendons, fat, cicatrix, or dura mater). A comprehensive search undertaken in July 2019 used strict keywords in relevant electronic databases to identify relevant studies. Based on the authors’ inclusion criteria (restricted to in vivo studies), 19 of 651 publications qualified, all pertaining to animal models. The syrcle's risk of bias tool for animal studies was applied at study level. Given the broad nature of the reported results and the many different parameters measured, the articles under scrutiny were assigned to five research subgroups according to their surface modification types: mechanical surface modifications, oxidative processes (e.g., acid etching, anodization, microarc oxidation), sol-gel derived titania (TiO2) coatings, biofunctionalized surfaces, and a subgroup for other modifications. The primary outcome was a liquid space at the interface (e.g., seroma formation) that was reported in six studies. Machining Ti implants to a roughness between Ra = 0.5 and 1.0 μm was shown to induce soft-tissue adhesion. Smoother surfaces, with the exception of acid polished and anodized Ti (Ra = 0.2 μm), prevented soft-tissue adhesion. A fibroblast growth factor 2 apatite composite coating promoted soft-tissue attachment via Sharpey-like fibers. In theory, this implant-soft tissue interface could be nearly perfect.In this systematic review, the authors explored the surface aspects of various titanium (Ti) or Ti alloy medical implants, examining the interface formed between the implant and surrounding nonkeratinized soft tissues (periosteum, muscles, tendons, fat, cicatrix, or dura mater). A comprehensive search undertaken in July 2019 used strict keywords in relevant electronic databases to identify relevant studies. Based on the authors’ inclusion criteria (restricted to in vivo studies), 19 of 651 publications qualified, all pertaining to animal models. The syrcle's risk of bias tool for animal studies was applied at study level. Given the broad nature of the reported results and the many different parameters measured, the articles under scrutiny were assigned to five research subgroups according to their surface modification types: mechanical surface modifications, oxidative processes (e.g., acid etching, anodization, microarc oxidation), sol-gel derived titania (TiO2) coatings, biofunctionalized surfaces, and a...