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The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 720 - 727
1 Jul 2024
Wu H Wang X Shen J Wei Z Wang S Xu T Luo F Xie Z

Aims

This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

Methods

A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L

Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Methods

The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 58 - 58
1 Oct 2022
Cecotto L van Kessel K Wolfert M Vogely H van der Wal B Weinans H van Strijp J Yavari SA
Full Access

Aim. In the current study we aim to characterize the use of cationic host defense peptides (HDPs) as alternative antibacterial agents to include into novel antibacterial coatings for orthopedic implants. Staphyloccous aureus represent one the most challenging cause of infections to treat by traditional antibacterial therapies. Thanks to their lack of microbial resistance described so far, HDPs represent an attractive therapeutic alternative to antibiotics. Furthermore, HDPs have been showed to control infections via a dual function: direct antimicrobial activity and regulation of immune response. However, HDPs functions characterization and comparison is controversial, as changing test conditions or cell type used might yield different effects from the same peptide. Therefore, before moving towards the development of HDP-based coatings, we need to characterize and compare the immunomodulatory and antibacterial functions under the same conditions in vitro of 3 well-known cathelicidins: human LL-37, chicken CATH-2, and bovine-derived IDR-1018. Method. S. aureus, strain SH1000, was incubated with different concentrations of each HDP and bacterial growth was monitored overnight. Primary human monocytes were isolated from buffy coats using Ficoll-Paque density and CD14 microbeads, and differentiated for 7 days to macrophages. After 24h incubation in presence of LPS and HDPs, macrophages cytokines production was measured by ELISA. Macrophages cultured for 24h in presence of HDPs were infected with serum-opsonized S. aureus. 30 min and 24h after infection, bacterial phagocytosis and intracellular killing by macrophages were measured by flow cytometry and colony forming units (CFU) count respectively. Results. All HDPs efficiently inhibit macrophages LPS-mediated activation, as observed by a reduced production of TNF-α and IL-10. Despite a comparable anti-inflammatory action, only CATH-2 shows direct antibacterial properties at concentrations 10-times lower than those needed to stimulate immune cells. Although stimulation with HDPs fails to improve macrophages ability to kill intracellular S. aureus, IDR-1018 decreases the proportion of cells phagocytosing bacteria. Conclusions. In addition to a strong anti-inflammatory effect provided by all HDPs tested, CATH-2 has direct antibacterial effects while IDR-1018 reduces the proportion of macrophages infected by S. aureus. Use of these HDPs in combination with each other or with other conventional antibacterial agents could lead the way to the design of novel antibacterial coatings for orthopedic implants


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 86 - 86
1 Dec 2021
Kolenda C Medina M Legendre T Blazere L Bergot M Arnaud V Souche A Roussel-Gaillard T Martins-Simoes P Tristan A Ferry T Laurent F
Full Access

Aim. Bacteriophages, viruses specific of bacteria, are receiving substantial attention as alternative antibacterial agents to treat bacteria frequently multi-resistant to antibiotics and/or able to form biofilms, such as staphylococci. The latter are responsible for very difficult to treat bone and joint infections (BJIs). In this context, our consortium aims to develop a production of therapeutic phages in accordance with the will of ANSM (French National Agency for the Safety of Medicines and Health Products) to encourage the development of a national academic platform for phage therapy. We report the isolation and characterization of new anti-Staphylococcus phages as well as the evaluation of their activity on a collection of clinical strains of S. aureus (SA) and coagulase-negative staphylococci (CNS) in order to assess their therapeutic potential. Method. Seventeen phages were isolated from wastewater samples. Their identification was obtained by Illumina whole genome sequencing. To evaluate their spectrum of activity, 30 genetically characterized SA strains representative of the main genetic backgrounds as well as 32 strains belonging to 7 CNS species responsible for BJIs were included. The spot test technique, based on the determination of the Efficiency Of Plating ratio, was used (EOP, ratio between the phage titer obtained on a tested strain/titer on a reference strain, close to 1 if high sensitivity to the phage). Results. All isolated phages belonged to the Myoviridae family: 14/17 and 3/17 to the Kayvirus and Silviavirus genera respectively. Silviavirus phages were more active on SA strains (EOP>0.001 for 73–90% of strains) than Kayvirus phages (EOP>0.001 for 13–70% of strains, except for V1SA21: 80%). In total, 83% of strains were susceptible to the phage with the broadest spectrum in each genus, their combination representing a promising opportunity to prevent the emergence of resistance. Kayvirus phages had polyvalent activity on several CNS species (maximum 47% of tested strains), mainly S. lugdunensis, S. capitis and S. caprae, whereas Silviavirus phages were only active on 6–12% of the tested strains. Conclusions. We report the characterization of a large collection of novel phages with complementary spectra against a collection of SA and CNS strains. Further work is currently focused on i) the isolation of anti-S. epidermidis phages, bacterial species against which the present collection of phages was insufficiently active, while it is a major pathogen in this context, ii) the development of production and purification protocols in order to meet the requirements of ANSM for human use


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 13 - 13
1 Nov 2021
Dubus M Rammal H Scomazzon L Baldit A Braux J Mauprivez C Kerdjoudj H
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Introduction and Objective. Alveolar bone resorption following tooth extraction or periodontal disease compromises the bone volume required to ensure the stability of an implant. Guided bone regeneration (GBR) is one of the most attractive technique for restoring oral bone defects, where an occlusive membrane is positioned over the bone graft material, providing space maintenance required to seclude soft tissue infiltration and to promote bone regeneration. However, bone regeneration is in many cases impeded by a lack of an adequate tissue vascularization and/or by bacterial contamination. Using simultaneous spray coating of interacting species (SSCIS) process, a bone inspired coating made of calcium phosphate-chitosan-hyaluronic acid was built on one side of a nanofibrous GBR collagen membrane in order to improve its biological properties. Materials and Methods. First, the physicochemical characterizations of the resulting hybrid coating were performed by scanning electron microscopy, X-ray photoelectron, infrared spectroscopies and high-resolution transmission electron microscopy. Then human mesenchymal stem cells (MSCs) and human monocytes were cultured on those membranes. Biocompatibility and bioactivity of the hybrid coated membrane were respectively evaluated through MSCs proliferation (WST-1 and DNA quantification) and visualization; and cytokine release by MSCs and monocytes (ELISA and endothelial cells recruitment). Antibacterial properties of the hybrid coating were then tested against S. aureus and P. aeruginosa, and through MSCs/bacteria interactions. Finally, a preclinical in vivo study was conducted on rat calvaria bone defect. The newly formed bone was characterized 8 weeks post implantation through μCT reconstructions, histological characterizations (Masson's Trichrome and Von Kossa stain), immunohistochemistry analysis and second harmonic generation. Biomechanical features of newly formed bone were determined. Results. The resulting hybrid coating of about 1 μm in thickness is composed of amorphous calcium phosphate and carbonated poorly crystalline hydroxyapatite, wrapped within chitosan/hyaluronic acid polysaccharide complex. Hybrid coated membrane possesses excellent bioactivity and capability of inducing an overwhelmingly positive response of MSCs and monocytes in favor of bone regeneration. Furthermore, the antibacterial experiments showed that the hybrid coating provides contact-killing properties by disturbing the cell wall integrity of Gram-positive and Gram-negative bacteria. Its combination with MSCs, able to release antibacterial agents and mediators of the innate immune response, constitutes an excellent strategy for fighting bacteria. A preclinical in vivo study was therefore conducted in rat calvaria bone defect. μCT reconstructions showed that hybrid coated membrane favored bone regeneration, as we observed a two-fold increase in bone volume / total volume ratios vs. uncoated membrane. The histological characterizations revealed the presence of mineralized collagen (Masson's Trichrome and Von Kossa stain), and immunohistochemistry analysis highlighted a bone vascularization at 8 weeks post-implantation. However, second harmonic generation analysis showed that the newly formed collagen was not fully organized. Despite a significant increase in the elastic modulus of the newly formed bone with hybrid coated membrane (vs. uncoated membrane), the obtained values were lower than those for native bone (approximately 3 times less). Conclusions. These significant data shed light on the regenerative potential of such bioinspired hybrid coating, providing a suitable environment for bone regeneration and vascularization, as well as an ideal strategy to prevent bone implant-associated infections


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 423 - 429
1 Mar 2021
Diez-Escudero A Hailer NP

Periprosthetic joint infection (PJI) is one of the most dreaded complications after arthroplasty surgery; thus numerous approaches have been undertaken to equip metal surfaces with antibacterial properties. Due to its antimicrobial effects, silver is a promising coating for metallic surfaces, and several types of silver-coated arthroplasty implants are in clinical use today. However, silver can also exert toxic effects on eukaryotic cells both in the immediate vicinity of the coated implants and systemically. In most clinically-used implants, silver coatings are applied on bulk components that are not in direct contact with bone, such as in partial or total long bone arthroplasties used in tumour or complex revision surgery. These implants differ considerably in the coating method, total silver content, and silver release rates. Safety issues, such as the occurrence of argyria, have been a cause for concern, and the efficacy of silver coatings in terms of preventing PJI is also controversial. The application of silver coatings is uncommon on parts of implants intended for cementless fixation in host bone, but this option might be highly desirable since the modification of implant surfaces in order to improve osteoconductivity can also increase bacterial adhesion. Therefore, an optimal silver content that inhibits bacterial colonization while maintaining osteoconductivity is crucial if silver were to be applied as a coating on parts intended for bone contact. This review summarizes the different methods used to apply silver coatings to arthroplasty components, with a focus on the amount and duration of silver release from the different coatings; the available experience with silver-coated implants that are in clinical use today; and future strategies to balance the effects of silver on bacteria and eukaryotic cells, and to develop silver-coated titanium components suitable for bone ingrowth.

Cite this article: Bone Joint J 2021;103-B(3):423–429.


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 234 - 244
1 Feb 2021
Gibb BP Hadjiargyrou M

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics.

Cite this article: Bone Joint J 2021;103-B(2):234–244.


Aims

In wound irrigation, 1 mM ethylenediaminetetraacetic acid (EDTA) is more efficacious than normal saline (NS) in removing bacteria from a contaminated wound. However, the optimal EDTA concentration remains unknown for different animal wound models.

Methods

The cell toxicity of different concentrations of EDTA dissolved in NS (EDTA-NS) was assessed by Cell Counting Kit-8 (CCK-8). Various concentrations of EDTA-NS irrigation solution were compared in three female Sprague-Dawley rat models: 1) a skin defect; 2) a bone exposed; and 3) a wound with an intra-articular implant. All three models were contaminated with Staphylococcus aureus or Escherichia coli. EDTA was dissolved at a concentration of 0 (as control), 0.1, 0.5, 1, 2, 5, 10, 50, and 100 mM in sterile NS. Samples were collected from the wounds and cultured. The bacterial culture-positive rate (colony formation) and infection rate (pus formation) of each treatment group were compared after irrigation and debridement.


The Bone & Joint Journal
Vol. 102-B, Issue 6 Supple A | Pages 158 - 162
1 Jun 2020
Griseti Q Jacquet C Sautet P Abdel MP Parratte S Ollivier M Argenson J

Aims

The aim of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement, and smooth titanium alloy to inhibit staphylococci in an in vitro environment, based on the evaluation of the zone of inhibition (ZOI). The hypothesis was that there would be no significant difference in the inhibition of methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA/MRSA) between the two groups.

Methods

A total of 30 beads made of three different materials (tantalum/3D porous titanium and smooth titanium alloy) were bathed for one hour in a solution of 1 g vancomycin in 20 ml of sterile water for injection (bath concentration: 50 mg/mL). Ten 1 cm3 cylinders of antibiotic-loaded cement were also created by mixing standard surgical cement with 1 g of vancomycin in standardized sterile moulds. The cylinders were then placed on agar plates inoculated with MSSA and MRSA. The ZOIs were measured each day and the cylinders were transferred onto a new inoculated plate.


Bone & Joint Research
Vol. 8, Issue 5 | Pages 199 - 206
1 May 2019
Romanò CL Tsuchiya H Morelli I Battaglia AG Drago L

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma.

Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199–206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 294 - 295
1 Mar 2018
Sprowson† AP Jensen C Ahmed I Parsons N Partington P Emmerson K Carluke I Asaad S Pratt R Muller S Reed MR


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 296 - 302
1 Mar 2018
Sprowson† AP Jensen C Parsons N Partington P Emmerson K Carluke I Asaad S Pratt R Muller S Ahmed I Reed MR

Aims

Surgical site infection (SSI) is a common complication of surgery with an incidence of about 1% in the United Kingdom. Sutures can lead to the development of a SSI, as micro-organisms can colonize the suture as it is implanted. Triclosan-coated sutures, being antimicrobical, were developed to reduce the rate of SSI. Our aim was to assess whether triclosan-coated sutures cause a reduction in SSIs following arthroplasty of the hip and knee.

Patients and Methods

This two-arm, parallel, double-blinded study involved 2546 patients undergoing elective total hip (THA) and total knee arthroplasty (TKA) at three hospitals. A total of 1323 were quasi-randomized to a standard suture group, and 1223 being quasi-randomized to the triclosan-coated suture group. The primary endpoint was the rate of SSI at 30 days postoperatively.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_7 | Pages 108 - 108
1 May 2016
De Villiers D Banfield S Housden J Shelton J
Full Access

Introduction. Revision of total hip replacements (THRS) is predominantly due to aseptic loosening, pain and infection [1]. The current method used to address the risk of infection is to administer antibiotics and to include antibacterial agents into bone cement (if used) and on implant coatings [2–4]. Currently, silver (Ag) coatings have only been applied to titanium hip stems [3]. Cobalt chromium alloy (CoCr) is a widely used orthopaedic alloy which is commonly used as a bearing surface; revisions of joints using this material often describe adverse reactions to the particulate wear debris [1]. This study considers an Ag containing CrN based coating on a CoCr substrate with the aim to reduce cobalt (Co) release and promote antibacterial silver release. Methods. Silver Chromium Nitride (CrNAg) coatings were developed and applied onto the bearing surfaces of 48 mm diameter metal-on-metal THRs. Three coatings were evaluated: high Ag at the surface (CrNAg+), low Ag at surface (CrNAg-) and uniform Ag (CrNAg=). All bearings were tested under ISO 14242-3 conditions for 0.17 million cycles (mc) representing approximately 2 months use in vivo. Wear was determined gravimetrically; Ag and Co levels in the lubricant were measured using graphite furnace atomic absorption spectroscopy. Testing of the CrNAg= bearings were continued to 2mc under standard conditions; CrNAg- bearings to 5mc incorporating lateralisation, which created separation at swing phase and rim contact at heel strike. Wear volume and Ag/Co release were monitored at 0.33, 0.67, 1mc and every mc thereafter. Results. All bearings produced low levels of wear and released silver into the lubricating fluid. An increase in silver concentration at the surface of the bearings was found to increase both the silver released and wear, Figure 1. Negligible cobalt was released. Testing of the CrNAg= coating to 2mc showed the wear rate to decrease after 0.17mc, Figure 2. Ag release continued up to 2mc but at a decreased rate. The CrNAg- coating tested under lateralisation conditions to 5mc showed no coating failure and negligible cobalt release. Wear and silver release showed similar patterns and reached a steady state after 1mc, Figure 3. Discussion. The AgCrN coatings on bearing surfaces of a hip joint are capable of releasing Ag at concentrations within the ‘No Observable Adverse Effect Limit’ [5]. These coatings also prevented Co release while maintaining a low wear rate. All coatings remained intact and did not delaminate, even under adverse conditions. These coatings have been tested in a metal-on-metal hip bearing surface, the most controversial and challenging condition for a coating, wearing against itself. CoCr is used as a bearing surface against polyethylene in hips and knees, in stems and tapers, as tibial trays in knee replacement and as shells for acetabular cups. This coating may be applied to a wide range of applications, removing some of the challenges over the use of CoCr while reducing infections


Bone & Joint 360
Vol. 4, Issue 5 | Pages 31 - 31
1 Oct 2015
McNamara I


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 284 - 284
1 Jul 2014
Meani E Fini M Giavaresi G Drago L Romanò C
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Summary Statement. An Implant Disposable Antibacterial Coating (i-DAC®) is described, consisting of a fully resorbable, biocompatible hydrogel, able to release antibacterial and antibiofilm agents. Direct application of the hydrogel on implants prevented infection occurrence in an in vitro model of peri-prosthetic infection. Introduction. Biofilm-related infections are among the main reasons for failure of joint prosthesis with high associated social and economical costs. Bacterial adhesion and subsequent biofilm formation have been shown to develop early after biomaterials implant into the human body, when a “race to the surface” takes place between the host's cells and the colonizing bacteria eventually present at the surgical site. Providing an antibacterial/antibiofilm coating of the implant may then play a strategic role in preventing biofilm related infections. Here we report the results of a series of in vitro and in vivo studies, partially performed under the European 7th Framework Programme (Implant Disposable Antibiotic Coating, IDAC, collaborative research project # 277988), concerning a fully resorbable, biocompatible antibacterial hydrogel coating (DAC®, Novagenit, Italy). The patented hydrogel, a co-polimer comprising of hyaluronic acid and a polylactic acid, has been designed to be mixed with various antibacterial agents and applied directly on the implant at the time of surgery, being fully resorbed within few days. Patients & Methods. The tested hydrogel (DAC®, Novagenit, Italy) is a derivative of a low molecular weight hyaluronan, grafted with poly-D, L-lactic acid and provided in powder form. At the point of care, the powder is hydrated with the antibiotic or antibiofilm solution, thus generating the final compound to be applied onto the implant surface. In vitro studies were conducted using DAC® coating on different biomaterials, including titanium, chrome-cobalt and polyethylene discs. The release of different antibacterial agents, including vancomycin, ciprofloxacin, meropenem, gentamycin, amikacin, tobramycin, clindamycin, doxycyclin, linezolid, NAsalycilate and N-acetylcisteine, adequately mixed with the hydrogel, has been tested by means of gas chromatography and microbiological methods. In vivo studies were then performed on 35 rabbits divided in 7 groups. Animals were implanted with an intramedullary titanium rod in their femur, with a known inoculum of methicillin-resistant Staph. aureus and vancomycin-loaded DAC® at different concentrations (2% and 5%) and compared with controls. Results. Regardless of the tested material, in vitro studies showed the ability of the hydrogel to be loaded and to sustain the release of the following antibacterial/antibiofilm compounds for up to 96 hours: vancomycin, ciprofloxacin, meropenem, gentamycin, amikacin, tobramycin, clindamycin, doxycyclin, linezolid, NAsalycilate, N-acetylcisteine. In vivo studies showed a bacterial load reduction ranging from 94% to 99.9% using vancomycin-loaded DAC®, compared to controls. Discussion/Conclusion. DAC®, a fast-resorbable antibacterial coating, showed the ability to be loaded with various antibacterial compounds and the ability to provide a highly significant reduction of bacterial colonization of implanted biomaterials in an animal model, opening a new pathway to local prevention and treatment of biofilm-/implant-related infections


Bone & Joint Research
Vol. 3, Issue 7 | Pages 223 - 229
1 Jul 2014
Fleiter N Walter G Bösebeck H Vogt S Büchner H Hirschberger W Hoffmann R

Objective

A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation.

Method

A total of 20 patients with post-traumatic/post-operative bone infections were enrolled in this open-label, prospective study. After radical surgical debridement, the bone cavity was filled with this material. The 21-day hospitalisation phase included determination of gentamicin concentrations in plasma, urine and wound exudate, assessment of wound healing, infection parameters, implant resorption, laboratory parameters, and adverse event monitoring. The follow-up period was six months.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 86 - 86
1 Jul 2014
Spriano S Ferraris S Miola M
Full Access

Summary Statement. The problem facing this research is to promote rapid osteointegration of titanium implants and to minimise the risks of infections by the functionalization with different agents, each designed for a specific action. A patented process gives a multifunctional titanium surface. Introduction. A patented process of surface modification is described. It gives a multifunctional surface with a multiscale roughness (micro and nano topography), that is excellent for osteoblast adhesion and differentiation. It has a high degree of hydroxylation, that is relevant for inorganic bioactivity (apatite-HA precipitation) and it is ready for a functionalization with biological factors. A direct grafting of ALP has been obtained. Moreover, the growth of an antibacterial agent within the surface oxide layer can be useful in order to combine the osteoinduction ability to antimicrobial effects. The selection of an inorganic agent (metal nanoparticles) has the advantage to avoid an eventual development of antibiotic resistance by bacteria. Experimental Methods. Ti-cp and Ti6Al4V samples were polished or blasted, etched in diluted hydrofluoric acid (step 1a), oxidised in hydrogen peroxide (step 1b), incubated in Tresyl chloride (step 2a) and Alkaline phosphatase (ALP) enzyme (step 2b) [1, 2]. A water solution, containing a salt of the metal to be added to the surface as an inorganic antibacterial agent, can be introduced during the oxidation in hydrogen peroxide. Surface morphology and chemical composition were investigated by Scanning Electron Microscopy (SEM) and Field Emission Scanning Electron Microscopy (FESEM) equipped with Energy Dispersive Spectroscopy (EDS). The composition of the outermost surface layer and the chemical state of elements were analyzed by X-Ray Photoelectron Spectroscopy (XPS). The activity of grafted enzyme was studied by an enzymatic activity test. In vitro bioactivity was evaluated by soaking the samples in simulated body fluid and SEM observation to verify hydroxyapatite (HA) precipitation. Antibacterial activity has been determined by inhibition halo test against S aureus. Results and Discussion. A peculiar multi-scale topography, with spongy-like nanometric features, was obtained after the inorganic treatment (step 1a-1b). This morphology can be superimposed on the micro-or macro roughness deriving from acid etching or blasting, by properly optimizing the process parameters. Moreover, the treated surfaces present a high density of hydroxyl groups (XPS data) and they are bioactive (HA precipitation after soaking in SBF for 15 days). Metal (Ag, Cu, Zn) nanoparticles can be grown within the surface oxide layer and they are effective as antimicrobial inorganic agents. The amount of the metal nanoparticles can be tailored in order to have an antibacterial or a bacteriostatic surface. The effective grafting of ALP (step 2a-2b) has been shown by XPS because of the appearance of characteristic peaks in the carbon region. Moreover, it has been observed that ALP maintains its activity after grafting by an enzymatic activity test. ALP grafting improves HA precipitation kinetics. Conclusions. An innovative process was applied to titanium surfaces in order to obtain a better bone integration ability and antibacterial activity. A multi scale surface topography (micro and nano features) was successfully obtained together with an high hydroxylation degree. Modified surfaces are able to induce hydroxyapatite precipitation in vitro and to graft ALP, maintaining its activity and improving bioactivity. Metal nanoparticles embedded in the surface oxide layer have an antibacterial effect


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 7 - 7
1 Jul 2014
Brockett C Carbone S Jennings L Fisher J
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Summary Statement. Wear of total knee replacement (TKR) is a clinical concern. This study demonstrated low-conformity moderately cross-linked-polyethylene fixed bearing TKRs showed lower volumetric wear than conventional-polyethylene curved fixed bearing TKRs highlighting potential improvement in TKR performance through design and material selection. Introduction. Wear of total knee replacement (TKR) continues to be a significant factor in the clinical performance of the implants. Historically, failure due to delamination and fatigue directed implant design towards more conforming implants to reduce contact stress. However, the new generations of more oxidatively-stable polyethylene have improved the long-term mechanical properties of the material, and therefore allowed more flexibility in the bearing design. The purpose of this study was to investigate the effect of insert conformity and material on the wear performance of a fixed bearing total knee replacement through experimental simulation. Methods. The wear of TKR bearings were investigated using a physiological six station Prosim knee wear simulator (Simulator Solutions, UK). Six samples of each test configuration (Sigma CR fixed bearing knees (DePuy Synthes, UK) were studied, and compared with previously reported data, tested under identical conditions (1, 2). The central axis of the implant was offset from the aligned axes of applied load and tibial rotation to replicate a right knee. High kinematics, under anterior-posterior displacement control was used for this study (3). The lubricant was 25% (v/v) calf serum supplemented with 0.03% (v/v) sodium azide solution in deionised water, as an antibacterial agent, and was changed approximately every 0.33Mc. Wear was assessed gravimetrically and moisture uptake accounted for using unloaded soak controls. Results. The wear rates for the moderately cross-linked inserts (XLK) were significantly lower than the conventional polyethylene (GVF) for all geometries (ANOVA, p<0.05). There was a significant reduction in wear rate as the insert geometry became less conforming for both materials (ANOVA, p<0.05). The wear scars areas were comparable in size and shape between materials, within a geometry group. The size of the wear scar changed with conformity, with the curved inserts showing the largest scars in both anterior-posterior and medial-lateral dimensions, and the flat inserts showing the smallest wear scars. Discussion/Conclusion. The introduction of a moderately cross-linked polyethylene insert was shown to significantly reduce the wear of a fixed bearing total knee replacement compared with a conventional material. There was a trend for reducing wear rate with reducing conformity for both materials, suggesting that reduced conformity results in higher contact pressures and reduced contact area, leading to a reduced surface for wear to occur. Both material and conformity were shown to have a significant impact on the wear of a fixed bearing TKR, and therefore provide opportunity for enhancing wear performance through material and design selection


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 278 - 278
1 Jul 2014
Della Valle C Candiani G Pezzoli D Visai L Rimondini L Cochis A De Giglio E Cometa S Bucciotti F Chiesa R
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The aim of the work is to develop innovative antibacterial surface modification treatments for titanium capable to limit the bacterial adhesion and proliferation as weel as the biofilm formation while maintaining an high osteointegrative potential. The goal is to contrast the infections which represent a serius complication related to the use of implantable devices. Introduction. Titanium and titanium alloy are considered the golden standard materials for the applications in contact with bone especially for dental and orthopaedic applications. To extend the implantable component lifetime and increase their clinical performance some surface modifications are required, to promote and speed up the osteointegration process increasing the rate of bone bonding. Unfortunately, among the different complications related to the use of titanium implantable devices the infections represent the most serious, often leading to implant failure and revision. The use of surface modification with specific metal ions represents a promising approach to fight implant-related infections. In particular gallium has recently shown efficacy in the treatment of infections: exploiting the chemical similarity of Ga. 3+. with Fe. 3+. , it can interfere in the iron metabolism for a wide range of bacteria. The aim of this work is to develop and characterise new biocompatible biomimetic treatments with anodic spark deposition (ASD) technique on titanium characterised by antibacterial properties maintaining high osteointegrative potential. Experimental Methods. Three surfaces were developed using titanium grade 2 samples (12 mm diam., 0.5 mm thick): i) SiB-Na: ASD treatment performed in an electrolytic solution containing Ca, P, Si and Na. 1. used as control; ii) GaOss: ASD treatment performed in the SiB-Na solution enriched with gallium nitrate and oxalic acid; iii) GaCis: ASD treatment performed in the SiB-Na solution enriched with with gallium nitrate and L-cysteine. The ASD was carried out in galvano-static condition with a current density of 10 mA/cm. 2. reaching 295V (for SiB-Na, GaCis) and 310V for GaOss. Untreated Ti was used as control. The surface morphology and chemistry were analysed using SEM, EDS and XPS. Ga release in D-PBS was studied up to 21 days using ICP/OES analysis. The structure of the titanium oxide was investigated using XRD while the surface wettability was studied using OCA measurements. The coating mechanical stability was evaluated using scratch test and three-point bending test. Human osteoblastic cells (Saos2) indirect citotoxicity was asessed using Alamar Blue assay. Saos2 morphology and adhesion to the treated surfaces were evaluated using SEM and actin staining. Saos2 viability was assessed up to 21 of cell cultured in direct contact with antibacterial surfaces while the Saos2 alkaline phosphatase activity (ALP) was evaluated up to 21 day as a marker of new bone formation. The antibacterial properties were assessed with S. mutans, S. epidermidis and E. coli bacterial strains even after 21 days of the antibacterial agents release to test the long lasting antibacterial activity. Also the effectiveness in limiting biofilm formation was evaluated against S. epidermidis and A. baumanni biofilm producers. Results and discussion. The developed surfaces showed a microporous morphology without the presence of any delamination. The EDS showed the presence of Ga, Si, P and Ca for GaCis and GaOss. Ga-based treatments revealed a similar concentration of the antimicrobial agent although the Ga released from GaOss was extremely higher than on GaCis. XRD analysis revealed the presence of the anatase cristallographic form which is associated with an higher surface wettability than Ti. The coatings showed a good mechanical stability both after three point bending test and scratch test. The antibacterial surfaces did not show any indirect citotoxicity for Saos2. Also the cell morphology and viability were not negatively affected by the presence of the antibacterial agent: GaOss treatment displayed a stimulating effect on ALP activity of osteoblastic cells than controls. A strong reduction of bacterial adhesion and proliferation for both of the Ga-based treatments especially for GaOss (≈ 40% vs Ti) was observed as well as a long-lasting antibaterial activity. Finally, a significative reduction of S. epidermidis and A. baumanni biofilm production than Ti was observed for GaOss and GaCis treatments. Conclusion. The treatments developed in the present study represent a promising class of antibacterial and osteointegrative coatings for titanium in particular for dental and orthopaedic applications


The Bone & Joint Journal
Vol. 96-B, Issue 5 | Pages 569 - 573
1 May 2014
Sullivan MP McHale KJ Parvizi J Mehta S

Nanotechnology is the study, production and controlled manipulation of materials with a grain size < 100 nm. At this level, the laws of classical mechanics fall away and those of quantum mechanics take over, resulting in unique behaviour of matter in terms of melting point, conductivity and reactivity. Additionally, and likely more significant, as grain size decreases, the ratio of surface area to volume drastically increases, allowing for greater interaction between implants and the surrounding cellular environment. This favourable increase in surface area plays an important role in mesenchymal cell differentiation and ultimately bone–implant interactions.

Basic science and translational research have revealed important potential applications for nanotechnology in orthopaedic surgery, particularly with regard to improving the interaction between implants and host bone. Nanophase materials more closely match the architecture of native trabecular bone, thereby greatly improving the osseo-integration of orthopaedic implants. Nanophase-coated prostheses can also reduce bacterial adhesion more than conventionally surfaced prostheses. Nanophase selenium has shown great promise when used for tumour reconstructions, as has nanophase silver in the management of traumatic wounds. Nanophase silver may significantly improve healing of peripheral nerve injuries, and nanophase gold has powerful anti-inflammatory effects on tendon inflammation.

Considerable advances must be made in our understanding of the potential health risks of production, implantation and wear patterns of nanophase devices before they are approved for clinical use. Their potential, however, is considerable, and is likely to benefit us all in the future.

Cite this article: Bone Joint J 2014; 96-B: 569–73.