Objectives. The surface of pure titanium (Ti) shows decreased histocompatibility over time; this phenomenon is known as biological ageing. UV irradiation enables the reversal of biological ageing through photofunctionalisation, a physicochemical alteration of the titanium surface. Ti implants are sterilised by UV irradiation in dental surgery. However, orthopaedic biomaterials are usually composed of the alloy Ti6Al4V, for which the antibacterial effects of UV irradiation are unconfirmed. Here we evaluated the bactericidal and antimicrobial effects of treating Ti and Ti6Al4V with UV irradiation of a lower and briefer dose than previously reported, for applications in implant surgery. Materials and Methods. Ti and Ti6Al4V disks were prepared. To evaluate the bactericidal effect of UV irradiation, Staphylococcus aureus 834 suspension was seeded onto the disks, which were then exposed to UV light for 15 minutes at a dose of 9 J/cm. 2. To evaluate the antimicrobial activity of UV irradiation, bacterial suspensions were seeded onto the disks 0, 0.5, one, six, 24 and 48 hours, and three and seven days after UV irradiation as described above. In both experiments, the bacteria were then harvested, cultured, and the number of colonies were counted. Results. No colonies were observed when UV irradiation was performed after the bacteria were added to the disks. When the bacteria were seeded after UV irradiation, the amount of surviving bacteria on the Ti and Ti6Al4V disks decreased at 0 hours and then gradually increased. However, the antimicrobial activity was maintained for seven days after UV irradiation. Conclusion. Antimicrobial activity was induced for seven days after UV irradiation on both types of disk. Irradiated Ti6Al4V and Ti had similar antimicrobial properties. Cite this article: T. Itabashi, K. Narita, A. Ono, K. Wada, T. Tanaka, G. Kumagai, R. Yamauchi, A. Nakane, Y. Ishibashi. Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation. Bone Joint Res 2017;6:108–112. DOI: 10.1302/2046-3758.62.2000619

The Thompson hemiarthroplasty is a common treatment option for acute neck of femur fractures in the elderly population. Our department noted a significant number of patients returning with thigh pain, radiographic loosening and femoral osteolysis following cemented implantation of the titanium alloy version of the Thompson hemiarthroplasty. We are not aware of any previous reports documenting complications specific to the titanium Thompson implant and a retrospective cohort study was therefore initiated following clinical governance approval. 366 titanium alloy Thompson prostheses were implanted for hip fracture treatment between 2017 and 2020. As of February 2023, 6 of these have been revised at our hospital. 5 were revised for symptomatic femoral osteolysis and 1 presented with an acute periprosthetic fracture. All revised cases were determined to be aseptic. 32 living patients were excluded from recall on compassionate grounds due to permanent nursing home residence. 47 living patients were identified of which 33 attended for xray. 28 deceased and/or nursing home resident patients who had pelvis x-rays in the previous 12 months were also included in the analysis. Including the 6 index hips already revised, a total of 61 hip xrays were analysed, of which 19 hips (31.1%) showed radiographic evidence of femoral osteolysis or loosening. We conclude that there is a concerning incidence of femoral osteolysis and implant loosening associated with the titanium Thompson implant. We have discontinued use of the implant and reported our experience to the MHRA. We encourage other Scottish Health-Boards who use this implant to consider enhanced follow-up

Objectives. Laser-engineered net shaping (LENS) of coated surfaces can overcome the limitations of conventional coating technologies. We compared the in vitro biological response with a titanium plasma spray (TPS)-coated titanium alloy (Ti6Al4V) surface with that of a Ti6Al4V surface coated with titanium using direct metal fabrication (DMF) with 3D printing technologies. Methods. The in vitro ability of human osteoblasts to adhere to TPS-coated Ti6Al4V was compared with DMF-coating. Scanning electron microscopy (SEM) was used to assess the structure and morphology of the surfaces. Biological and morphological responses to human osteoblast cell lines were then examined by measuring cell proliferation, alkaline phosphatase activity, actin filaments, and RUNX2 gene expression. Results. Morphological assessment of the cells after six hours of incubation using SEM showed that the TPS- and DMF-coated surfaces were largely covered with lamellipodia from the osteoblasts. Cell adhesion appeared similar in both groups. The differences in the rates of cell proliferation and alkaline phosphatase activities were not statistically significant. Conclusions. The DMF coating applied using metal 3D printing is similar to the TPS coating, which is the most common coating process used for bone ingrowth. The DMF method provided an acceptable surface structure and a viable biological surface. Moreover, this method is automatable and less complex than plasma spraying. Cite this article: T. Shin, D. Lim, Y. S. Kim, S. C. Kim, W. L. Jo, Y. W. Lim. The biological response to laser-aided direct metal-coated Titanium alloy (Ti6Al4V). Bone Joint Res 2018;7:357–361. DOI: 10.1302/2046-3758.75.BJR-2017-0222.R1

Introduction. Hydroxyapatite and poly-L-lactide (HA/PLLA) composites are osteoconductive and biodegradable. They have already been used clinically to treat fractured bones by inducing osteosynthesis and serving as the bone filling material. During revision of total hip arthroplasty, we have grafted bone onto the bone defect and covered it with an HA/PLLA mesh instead of using a metal mesh on the non-load bearing portion of the cup (Figure 1). However, whether the interface between the HA/PLLA and the titanium alloy cup was stable remains unclear. Objectives. The purpose of this study was to determine and compare the histological osteoconductivity and osteoinductivity of HA/PLLA and titanium alloy. Methods. Semicylindrical samples (diameter: 3 mm; height: 5 mm) were fabricated from a composite unsintered-HA/PLLA containing 40% fine HA particles and from titanium alloy (Ti-6AL-4V). These two samples were combined to form one cylinder (Figure 2). Defects 3 mm in diameter were drilled into both femoral condyles of nine Japanese white rabbits, and the samples were implanted by press fitting. The rabbits were euthanized at 2, 4, 8, and 25 weeks after implantation, and undecalcified ground samples were prepared. New bone formation was examined histologically using Toluidine blue and Villanueva Goldner stains. Results. New bone formation was observed around the sample at 4 weeks, and the amount increased by 8 weeks. In addition, partial remodeling of the trabecular bones and absorption of the HA/PLLA were found at 25 weeks. Small amounts of new bone formation were found at 4 weeks between the HA/PLLA and titanium alloy materials (Figure 3: Toluidine blue stain), and the amount increased at 8 and 25 weeks. The HA/PLLA had been slightly absorbed and new bone was formed in the gap, which was close to the border between the materials, at 25 weeks. However, the amount of absorption was limited, and no new bone was found in samples where the materials were firmly in contact. Conclusions. HA/PLLA was only slight absorbed at 25 weeks, suggesting that it was stable in vivo and has good osteoconductive and osteoinductive properties. No new bone was found in the regions where the sample was stable and had no gaps between the HA/PLLA and titanium alloy, probably because there was no space for new bone to form in those regions. In contrast, new bone formation was found in gaps of more than 20 μm. Clinically, many gaps likely exist, allowing new bone formation to occur even in a stable implant. This may stabilize the HA/PLLA and titanium alloy materials for longer times. As expected, the HA/PLLA and titanium alloy were mostly stablein vivo

Aims. The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) may improve quality of life for amputees by avoiding soft-tissue complications associated with socket prostheses and by improving sensory feedback and function. It relies on the formation of a seal between the soft tissues and the implant and currently has a flange with drilled holes to promote dermal attachment. Despite this, infection remains a significant risk. This study explored alternative strategies to enhance soft-tissue integration. Materials and Methods. The effect of ITAP pins with a fully porous titanium alloy flange with interconnected pores on soft-tissue integration was investigated. The flanges were coated with fibronectin-functionalised hydroxyapatite and silver coatings, which have been shown to have an antibacterial effect, while also promoting viable fibroblast growth in vitro. The ITAP pins were implanted along the length of ovine tibias, and histological assessment was undertaken four weeks post-operatively. Results. The porous titanium alloy flange reduced epithelial downgrowth and increased soft-tissue integration compared with the current drilled flange. The addition of coatings did not enhance these effects. Conclusion. These results indicate that a fully porous titanium alloy flange has the potential to increase the soft-tissue seal around ITAP and reduce susceptibility to infection compared with the current design. Cite this article: Bone Joint J 2017;99-B:393–400

Introduction. We have investigated the long-term (minimum follow-up period; 10 years) clinical results of the total hip arthroplasty (THA) using K-MAX HS-3 tapered stem. Materials and Methods. In K-MAX HS-3 THA (Kyocera Medical, Kyoto, Japan), cemented titanium alloy stem and all polyethylene cemented socket are used. This stem has the double tapered symmetrical stem design, allowing the rotational stability and uniform stress distribution. The features of this stem are; 1. Vanadium-free high-strength titanium alloy (Ti-15Mo-5Zr-3Al), 2. Double-tapered design, 3. Smooth surface (Ra 0.4µm), 4. Broad proximal profile, 5. Small collar. Previous type stem, which was made of the same smooth-surface titanium alloy, has the design with cylindrical stem tip, allowing the maximum filling of the femoral canal. Osteolysis at the distal end of the stem had been reported in a few cases in previous type with cylindrical stem tip, probably due to the local stress concentration. Therefore the tapered stem was designed, expecting better clinical results. 157 THAs using HS-3 taper type stem were performed at Kitano Hospital between March 2004 and March 2008. And 101 THAs, followed for more than 10 years, were investigated (follow-up rate; 64.3%). The average age of the patients followed at the operation was 61.7 years and the average follow-up period was 10.9 years. The all-polyethylene socket was fixed by bone cement, and the femoral head material was CoCr (22mm; 5 hips, 26 mm; 96 hips). Results. Two hips were revised, one was due to late infection, and the other due to breakage of the implant in trauma. Japanese orthopaedic association (JOA) score improved from 40 to 86 points. Postoperative complication was three periprosthetic fractures (one femoral shaft fracture and two greater trochanteric fractures) and femoral shaft fracture case was operated. Dislocation was not observed. Socket loosening (Hodgkinson, Type 3, 4) and stem loosening (Harris, definite and probable) were not observed radiographically. Cortical hypertrophy was observed in 7.9%. The survival rate of HS-3 tapered stem was 98% for revision due to any reason and 100% for revision due to aseptic loosening. Discussion. The long-term clinical results of K-MAX HS-3 tapered stem were excellent. The osteolysis at the stem tip was not observed in this type, which was observed in a few cases in previous type. From the X-ray finding, it was suggested that this taperd stem had more uniform stress distribution to the femoral bone than previous type. Moreover, the problems associated with titanium alloy usage were not observed. From the present investigation, good farther long-term results of the tapered titanium stem were expected

Introduction. We have compared the middle-term (average follow-up period; 10 years) clinical results of the K-MAX HS-3 tapered stem with those of the previous type having cylindrical tip. Materials and Methods. In K-MAX HS-3 THA (Kyocera Medical, Kyoto, Japan), cemented titanium alloy stem and all polyethylene cemented socket are used. This stem has the double tapered symmetrical stem design, allowing the rotational stability and uniform stress distribution (Type T) (Fig. 1). The features of this stem are; 1. Vanadium-free high-strength titanium alloy (Ti-15Mo-5Zr-3Al), 2. Double-tapered design, 3. Smooth surface (Ra 0.4μm), 4. Broad proximal profile, 5. Small collar. In contrast, previous type stem, which was made of the same smooth-surface titanium alloy, has the design with cylindrical stem tip, allowing the maximum filling of the femoral canal (Type C) (Fig. 2). Osteolysis at the distal end of the stem had been reported in a few cases in Type C, probably due to the local stress concentration. Therefore the tapered stem was designed, expecting better clinical results. All surgery was performed at Kitano Hospital between September 2003 and June 2006. 72 THA were performed (Type T; 52 hips, Type C; 20 hips). The average age of the patients at the operation was 61 and 69 years and the average follow-up period was 10.1 and 10.4 years for the Type T and C, respectively. The all-polyethylene socket was fixed by bone cement, and the femoral head material was alumina or CoCr (22 or 26 mm). Results. One hip was revised in Type C. Japanese orthopaedic association (JOA) score improved from 39/37 to 84/77 points (Type T/C). Postoperative complication was dislocation in one case (Type C; 1). Socket loosening was not observed radiographically. Stem loosening was observed in one hip in Type C, demonstrating osteolysis at the distal end of the stem. In this case, revision THA was performed 3.5 years postoperatively. Bone resorption was more frequently observed in Type C than Type T. Cortical hypertrophy was observed in 7.7% in Type T and 25% in Type C. Discussion. The middle-term clinical results of K-MAX HS-3 taper stem (Type T) was excellent. The osteolysis at the stem tip was not observed in this type, which was observed in a few cases in previous Type C. From the X-ray finding, it was suggested that Type T had more uniform stress distribution to the femoral bone than Type C. Moreover, the problems associated with titanium alloy usage were not observed. From the present investigation, good long-term results of the tapered titanium stem (Type T) was expected. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Introduction. Following amputation, residual stumps used to attach the external prostheses can be associated with sores, infection and skin necrosis. These problems could be overcome by off loading the soft tissues. Intraosseous transcutaneous amputation prostheses (ITAP) attach external implants directly to residual bone reducing these complications. However, a tight seal at the skin implant interface is crucial in preventing epithelial down-growth and infection. Fibronectin (Fn) and laminin 332 (Ln), enhance early cell growth and adhesion of keratinocytes. Silanization to titanium alloy (Ti) allows these proteins to bond to the metal directly. We hypothesize that silanized dual coatings of fibronectin and laminin (SiFnLn) will be more durable than absorbed proteins and that keratinocyte adhesion will be increased compared with Ti controls and single silanized proteins. Methods. 10 mm diameter Ti alloy discs were polished, sterilized and silanized. The kinetics of silanized single and dual protein coating attachment onto titanium alloy was quantified using radio-labelled Fn(125I-Fn) and Ln(125I-Ln). Coating durability was assessed when soaked in fetal calf serum (FCS) for 0, 1, 24, 48, 72hrs. Data was compared to un-silanized Ti discs with the same amount of adsorbed proteins. In order to study cell attachment 20 × 103 keratinocytes were seeded on the discs (n = 6): silanized (Si), silanized fibronectin (SiFn), silanized laminin (SiLn), silanized dual coating (SiFnLn) for 1, 4 and 24hrs. Adhesion of cells was assessed using mouse vinculin antibody for 2hrs and alexafluor for 1hr which stains focal adhesions responsible for attaching cells to surfaces. Axiovision Image Analysis software was used to measure cell area, vinculin markers per cell unit and per unit cell area on 15 cells per disc. Data was analysed in SPSS and significance was assumed at the 0.05 level. Results. Silanized dual coatings bonded to Ti alloy in significantly larger quantities compared with adsorbed coatings (all p values < 0.05). When proteins were combined on silanized discs the same amount of each protein was attached as when used as a single coating (i.e. non competitive binding). Keratinocytes cultured on silanized dual coatings were significantly larger, produced more vinculin markers per unit cell and per cell area compared with single coatings at all time points. Conclusion. This study has demonstrated that silanized using dual proteins on Ti alloy enhances early keratinocyte growth and attachment in vitro. It also shows that there is non-competitive binding of laminin to Ti alloys in presence of fibronectin. This may lead to improved epidermal attachment to ITAP creating a tight seal at the implant interface, which will prevent migration of the epithelium and subsequent infection in vivo

Introduction. Intraosseous transcutaneous amputation prostheses (ITAP) provide an alternative means of attaching artificial limbs for amputees. Conventional stump-socket devices are associated with soft tissue complications including; pressure sores and tissue necrosis. ITAP resolves these problems by attaching the exo-prosthesis transcutaneously to the skeleton. The aim of this study is to increase the attachment of dermal fibroblasts to titanium alloy in vitro. Fibronectin (Fn) and laminin 332 (Ln) enhance early cell growth and adhesion. We hypothesize that silanized dual coatings of fibronectin and laminin (SiFnLn) will be more durable when compared with adsorbed dual coating (AdFnLn), and will enhance early fibroblast growth and adhesion compared to single coatings. Methods. The kinetics of dual single and dual protein coating attachment onto titanium alloy was quantified on silanized 10mm diameter discs using radiolabelled Fn (125I-Fn) and Ln (125I-Ln). Sixty discs were polished, sterilized and silanized. Coating durability was assessed when soaked in fetal calf serum (FCS) for 0, 1, 24, 48 and 72hrs. Data was compared to un-silanized Ti discs with the same coatings. Five thousand human dermal fibroblasts were seeded on discs (n = 6) of Ti polished alone (Pol), Ti with adsorbed fibronectin (AdFn), Ti with adsorbed laminin (AdLn), Ti adsorbed dual coating (AdFnLn), Ti silanized (Si), Ti silanized with fibronectin (SiFn), Ti silanized with laminin (SiLn), Ti silanized with a dual coating (SiFnLn) for 24hrs. In order to measure cell adhesion fibroblasts were fixed, vinculin stained using mouse vinculin antibody and alexa fluor. Axiovision Image Analysis software was used to measure cell area, vinculin focal adhesion markers per cell and per unit cell area. Data was analysed in SPSS and significance was assumed at the 0.05 level. Results. Silanized dual coatings bonded to Ti alloy in significantly larger quantities compared with adsorbed coatings at all time points (all p values < 0.05). Fibroblasts cultured on dual coatings were significantly larger, produced more vinculin markers per cell, and per unit cell area compared with single coatings. Cells on SiFnLn were larger with more numerous vinculin markers per cell, and per unit cell area compared with AdFnLn (p<0.05). Conclusion. This study has demonstrated that covalently bonding both fibronectin and laminin to Ti alloy provides a durable, dual coating that enhances early fibroblast growth and attachment compared with either protein coating alone in vitro. Our study showed that there is non-competitive binding of laminin on Ti surfaces in the presence of fibronectin. Dual coatings may be applied to the skin-penetrating region of transcutaneous devices to improve the skin seal and this may have positive implications for the development of ITAP

Introduction. During revision surgery, the active electrode of an electrocautery device may get close to the implant, potentially provoking a flashover. Incidents have been reported, where in situ retained hip stems failed after isolated cup revision. Different sizes of discoloured areas, probably induced by electrocautery contact, were found at the starting point of the fracture. The effect of the flashover on the implant material is yet not fully understood. The aim of this study was to investigate the fatigue strength reduction of Ti-6Al-4V titanium alloy after electrocautery contact. Material and Methods. 16 titanium rods (Ti-6Al-4V, extra low interstitial elements, according to DIN 17851, ⊘ 5 mm, 120 mm length) were stress-relief annealed (normal atmosphere, holding temperature 622 °C, holding time 2 h) and cooled in air. An implant specific surface roughness was achieved by chemical and electrolytic polishing (Ra = 0.307, Rz = 1.910). Dry (n = 6) and wet (n = 6, 5 µl phosphate buffered saline) flashovers were applied with a hand-held electrode of a high-frequency generator (Aesculap AG, GN 640, monopolar cut mode, output power 300 W, modelled patient resistance 500 Ω). The size of the generated discoloured area on the rod's surface - representative for the heat affected zone (HAZ) - was determined using laser microscopy (VK-150x, Keyence, Japan). Rods without flashover (n = 4) served as control. The fatigue strength of the rods was determined under dynamic (10 Hz, load ratio R = 0.1), force-controlled four-point bending (FGB Steinbach GmbH, Germany) with swelling load (numerical bending stress 852 MPa with a bending moment of 17.8 Nm) until failure of the rods. The applied bending stress was estimated using a finite-element-model of a hip stem during stumbling. Metallurgical cuts were made to analyse the microstructure. Results. The control rods failed at the pushers of the setup (median: 94,550, range: 194,000 cycles). The rods with flashover failed directly at the HAZ significantly earlier than the control rods (p = 0.018). The analysis of the microstructure showed a transformation of the equiaxed α+β microstructure to a bimodal state. The size of the HAZs were equal for the dry (median: 1.51 mm. 2. , range: 5.68 mm. 2. ) and wet flashovers (median: 0.92 mm. 2. , range: 2.50 mm. 2. , p = 0.792). The cycles to failure were smaller for the dry flashover (median: 22,650 cycles, range: 5,700) than the wet flashover but not reaching statistical significance (median: 32,200, range: 57,900; p = 0.052). No correlation between the dimension of the HAZs and the cycles to failure was found (dry: r. 2. = 0.019, p = 0.8; wet: r. 2. = 0.015, p = 0.721). Discussion. Flashovers induced by an electrocautery device reduce the fatigue strength of Ti-6Al-4V. Since no correlation between the size of the HAZs and the cycles to failure was found, every contact between electrocautery devices and metal implants should be avoided. For any figures or tables, please contact authors directly

An experimental study is reported of fracture healing in the femora of 36 Beagle dogs, comparing the results of using stainless steel plates with those of using less rigid titanium alloy plates. The alloy plates led to the appearance of a small amount of periosteal callus without any histological evidence of fracture instability, thus allowing the radiological assessment of fracture union. This also produced less bone loss during the remodelling phase. Radiological measurements 24 weeks after osteotomy showed cortical thickness to be reduced by six per cent under titanium alloy and by 19 per cent under stainless steel, while histological measurements showed a total bone loss of 3.7 per cent under titanium alloy and of 11 per cent under stainless steel plates. Removal of the titanium alloy plates after eight weeks followed by a recovery period of 16 weeks produced an increase of cortical thickness of 69 per cent and a gain in total bone mass of 30 per cent. Titanium alloy plates also produced less soft-tissue reaction than stainless steel plates. It is concluded that this alloy is a promising material for internal fixation devices

Introduction: Cell adhesion to titanium alloy implants is important in osseointegration [1,2] and attachment of the soft tissues to skin penetrating implants e.g. external fixator pins and Intraosseous Transcutaneous Amputation Prostheses [3,4]. Cell adhesion can be assessed using cell area data and immunolocalisation of focal contact proteins e.g. vinculin; however no method of assessing biophysical attachment is performed routinely. Cell adhesion can be enhanced with adhesion proteins including fibronectin (Fn)[5]. We have previously shown that covalently binding Fn to titanium also increases cell adhesion, and produces a more robust protein coating [6]. However the strength of adhesion of cells to this coating has not been measured. Our hypothesis was that biophysical cell adhesion measured using novel radial flow apparatus would correlate with cell area and focal contact data and that covalently bound fibronectin substrates would increase cell adhesion compared with adsorbed and uncoated controls. Method: Dermal fibroblasts were cultured for 1, 4, and 24 hours on 30mm and 10mm diameter polished titanium alloy discs (n = 6). Cells on 30mm discs were calcein stained and subjected to shear stress in a submerged, media filled, custom-made radial flow apparatus at 37¬C at 1.66ml/s for 15s. Cells were fixed in 10% formal saline and photographs were taken using a tangential light source. Fluorescent microscopy was performed at 2mm intervals along two perpendicular diameters. Using image analysis, the central cell free zone was measured and radial distance and shear stress calculated. Cells on 10mm discs were fixed, permeablised and vinculin stained (mouse vinculin antibody (1:200) 2hrs; FITC mouse antibody (1:100)1hr). Images were analyzed with a Zeiss microscope linked to image analysis software and the number of focal contacts were counted per cell area. The medians of the radial flow data were compared with data for cell area and focal contact production at the same time points using Spearman¡s regression correlation. This method was subsequently used to compare cell adhesion at one hour with adsorbed and covalently bound Fn substrates (10¥ìg/disc). Results/Discussion: The shear strength of cells increased between 4 and 24hrs (p=0.002) on polished untreated control substrates. Attachment values (dynes/cm2) were 84.90 (73.98–97.19), 96.30 (91.66–100.89), and 136.69 (134.68–140.30) for 1, 4 and 24 hours respectively. At 1hr, covalently bound Fn (509.90 dynes/cm2 (490.55–528.49) significantly increased cell adhesion compared with adsorbed Fn(434.45 dynes/cm2(385.25–465.62)) and control substrates(p=0.002). There was significant correlation between shear stress and focal contacts/cell (1.00(p< 0.01)) and focal contacts/cell area (0.900(p=0.037)), but not cell area (0.600(p=0.285)). Conclusion: Radial flow measurement is a useful direct method to quantify cell adhesion to orthopaedic implants and correlates well with other methods of measurement. Covalently bound Fn significantly increases biophysical cell attachment compared with adsorbed and uncoated controls

Introduction. Periprosthetic joint infection (PJI) remains the main cause of failure in primary and revision total knee arthroplasties (TKAs). Local delivery of antibiotics, mainly antibiotic-loaded bone cement (ALBC), is commonly employed to prevent PJI. Over the past decade, tantalum and porous titanium have been successfully utilized as metaphyseal fixation devices to address bone loss and improve biologic fixation during revision TKA. However, no study has examined the antimicrobial properties compared to bone cement. The purpose of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement (ALBC) and smooth titanium alloy (STA) to inhibit Staphylococci bacterial agents in an in vitro medium environment, based on the evaluation of the zone of inhibition (ZOI) and the antibacterial activity duration. Our study hypothesis was that we will found no significant difference between groups to inhibit Methicillin-Sensitive or Methicillin-Resistant Staphylococcus aureus (MSSA/MRSA) agents. Methods. Thirty beads made of 3 different materials (tantalum/ 3D porous titanium/ STA) were bathed during 1hour inside of a solution made of 1g vancomycin with 20-mL of sterile water for injection (bath concentration: 50 mg/mL). Ten 1cm. 3. cylinders were also created mixing standard surgical cement with 1g of Vancomycin in standardized sterile molds (ALBC beads). Finally, thirty beads made of tantalum/ 3D porous titanium/ STA were bathed in phosphate buffered saline solution to act as a control group. Cylinders were then placed on agar plates inoculated with MSSA and MRSA. Inhibition zone diameters were measured each day and cylinders were transferred onto a new inoculated plate. Inhibition zones were measured with a manual Vernier caliper and with automated software. The mean inhibition zones between groups were compared using the Wilcoxon Test. Results. The inter-class coefficient correlation values indicated an optimal intra-observer and inter-observer reproducibility for ZOI measurement (ICC 0.96 and ICC 0.98). For MSSA and MRSA, no inhibitory effect was found in the control group and antibiotic-loaded STA beads exhibited a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads exhibited larger inhibition zones than cement beads (all p<0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After 6 days, ALBC presented larger inhibition zone than the 3D porous titanium, but no difference was found with tantalum. For MRSA, both tantalum and 3D porous titanium beads had significantly larger inhibition zones than ALBC each day until day 6 for tantalum (all p<0.01) and until day 3 for 3D porous titanium (all p<0.04). ALBC presented larger inhibition zone than tantalum and 3D porous titanium from day 7 to 9 (all p<0.04). Conclusion. Our results demonstrate that porous metal implants can deliver local antibiotics over slightly varying time frames based on our in vitro analysis. Antibiotic-impregnated tantalum and 3D porous titanium constructs exhibited superior antimicrobial properties when compared to STA. Future goals include impregnating porous metals with antibiotics for intraoperative use during revision TKA. For figures, tables, or references, please contact authors directly

Aim. To control the growth and function of osteoblasts on Titanium alloy surfaces produced by electrochemical patterning. Methods. Samples of Ti6Al4V were prepared with three different finishes; no surface preparation following machining, polishing on a grinding wheel with sequential grit papers up to 4000 to achieve a mirror finish and treatment in a flat electrochemical cell with a 3M sulphuric acid in methanol using 9V supplied over 60 seconds to produce a surface with defined nano/microscale roughness. Glass coverslips were used as control surfaces. Surfaces were seeded with primary rat calvarial osteoblasts and incubated in Dulbecco's Modified Eagle Medium with 10% (v/v) sera for 24 hours before fixing and performing immunofluorescence staining with anti-vinculin antibody. Photomicrographs of the surfaces were analysed with Image J and analySIS FIVE programs. Results for cell number, cell area, focal adhesion area and polarity (lack of roundness) were analysed (using the Mann Whitney test) for ANOVA using SPSS. Results. Cells adhered to all surfaces with the most cells on the polished surface and the fewest on the glass and 9V60s surfaces. There were significant differences in cell number only between the polished surface and the glass control (p=0.026) and the 9V60s surface (p=0.006). Cells grown on the glass control surfaces exhibited the largest areas (mean = 840micron2) whilst those on the machined surface were the smallest (mean = 601micron2). A significant difference in cell area was seen between the machined and polished surfaces (p=0.025). The area of the focal adhesions was significantly different between the cells on 9V60s surface and the glass control (p=0.004), machined (p=0.003) and polished surfaces (p=0.006). Significant differences in polarity were seen between the cells on machined surface and the glass control (p=0.004), polished (p=0.004) and 9V60s surfaces (p=0.004). Discussion. Differences in cell numbers on glass and two of the Ti surfaces may be explained by the smooth nature of the glass coverslips in comparison to the nanoscale topography on the polished and 9V60s treated surfaces. Cell area was noted to be different between the machined and smoother polished surface. This may be explained by the grooves present on the machined surfaces preventing normal cell spreading by the process of contact guidance. There was a marked difference in polarity between the most polarised cells on the machined surface and the more rounded cells on the smoother surfaces, again consistent with the behaviour of contact guidance, with cells growing in the direction of the surface grooves. Focal adhesions present on the 9V60s treated surface were very small in comparison to those on other surfaces. Several features of implant surfaces may affect osteoblast growth, including surface roughness, chemical composition, surface charge and surface energy. These features influence the adsorption of proteins onto the surfaces, in turn influencing the growth and behaviour of the adherent cell population. Conclusion. Mechanical and electrochemical treatment of titanium alloy can significantly affect the growth and behaviour of osteoblasts grown on the surface. This has potential applications in arthroplasty and fracture fixation

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls. . Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively

Our aim was to determine whether in vitro studies would detect differences in the cellular response to wear particles of two titanium alloys commonly used in the manufacture of joint replacement prostheses. Particles were of the order of 1 μm in diameter representative of those found adjacent to failed prostheses. Exposure of human monocytes to titanium 6-aluminium 4- vanadium (TiAlV) at concentrations of 4 x 10. 7. particles/ml produced a mean prostaglandin E. 2. release of 2627.6 pM; this was significantly higher than the 317.4 pM induced by titanium 6-aluminium 7-niobium alloy (TiAlNb) particles (p = 0.006). Commercially-pure titanium particles induced a release of 347.8 pM. In addition, TiAlV stimulated significantly more release of the other cell mediators, interleukin-1, tumour necrosis factor and interleukin-6. At lower concentrations of particles there was less mediator release and less obvious differences between materials. None of the materials caused significant toxicity. The levels of inflammatory mediators released by phagocytic cells in response to wear particles may influence the amount of periprosthetic bone loss. Our findings have shown that in vitro studies can detect differences in cellular response induced by particles of similar titanium alloys in common clinical use, although in vivo studies have shown little difference. While in vitro studies should not be used as the only form of assessment, they must be considered when assessing the relative biocompatibility of different implant materials

Objectives: The purpose of this biomechanical study was to compare the mechanical properties of locked nails and screws made from either stainless steel or titanium alloy. Methods: The specially designed locked nails and screws with the same structures were made from either stainless steel or titanium alloy. The structural factors investigated included inner diameter and root radius for locking screws and outer diameter and nail hole size for locked nails. The mechanical properties investigated included bending stiffness, strength, and fatigue life. Finite element models were used to simulate the mechanical tests and compute the stress concentration factors. Results: Increasing the root radius and the inner diameter could effectively increase the fatigue strength of the locking screws. Fatigue strength increased more in titanium than in stainless steel screws, especially when the inner diameter was increased. In contrast, the titanium locked nails were much weaker than their stainless steel counterparts. Finite element models could closely predict the results of the biomechanical tests with a correlation coefficient that ranged from −0.58 to −0.84 for screws and was −0.98 for nails. The stress concentration factors ranged from 1 to 1.81 for screws and from 3.06 to 4.17 for nails. Conclusions: With larger root radius and inner diameter, titanium locking screws could provide much stronger fatigue strength than stainless steel counterparts. However, titanium locked nails might lose their advantages of superior mechanical strength because of high notch sensitivity and this limitation should be a critical concern clinically. Finite element analyses could be reliably used in research and development of locked nails and locking screws

INTRODUCTION. Biomaterial-related infections are an important complication in orthopaedic surgery [1], and Staphylococcus sp. accounts for more than half of the prosthetic joint infection cases [2]. Adhesion of bacteria to biomaterial surfaces is a key step in pathogenesis of such infections [3]. Titanium alloys are widely used in orthopaedic implants because their biocompatibility [4]. Surface incorporation of ions with antimicrobial properties, like fluorine, is one strategy previously studied with good results [5]. MATERIAL AND METHODS. A 18mm diameter rod of Ti–6Al–4V alloy ELI grade according to the standard ASTMF136-02 supplied by SURGIVAL was cut into 2 mm thick disk specimens, ground through successive grades of SiC paper to 1200 grade, degreased with a conventional detergent and rinsed in tap water followed by deionised water. The specimens were then chemically polished (CP). The disks were anodized only on one side by using a two electrode cell in a suitable electrolyte. TiO. 2. barrier layers, without fluoride (BL), were produced by anodizing in 1 M H. 2. SO. 4. at 15 mA cm-2 to 90 V, reaching 200 nm of thickness. Fluoride barrier layers (FBL) were produced in an electrolyte containing 1 M NH. 4. H. 2. PO. 4. and 0.15 M NH. 4. F, at constant voltage controlled at 20 V for 120 min at 20°C; the thickness of the layer is 140 nm. Laboratory biofilm-forming strains of Staphylococcus aureus 15981 [6] and Staphylococcus epidermidis ATCC 35984 were used in adherence studies, which were performed using the protocol by Kinnari et al [7]. Photographs obtained were studied by ImageJ software. Statistical analysis was performed by EPI-INFO software. The experiments were performed in triplicates. RESULTS. Lower adherence was detected when compared FBL with unmodified controls (CP and BL). A statistical significant difference (p<0.01) was detected in the adhesion to modified material between both species, being the adherence of S. aureus lower than that of S. epidermidis (Figure 1). DISCUSSION & CONCLUSIONS. There is currently a discussion about the actual antibacterial properties of fluorine when incorporated in biomaterial surfaces. In this study we have demonstrated that both S. aureus and S. epidermidis strains showed a decrease of bacterial adhesion to modified surfaces with fluorine, a decrease that cannot be due to other surface modifications. Further studies, including adhesion studies with clinical strains [8], must be performed to confirm these results, which can lead to the development of new materials with a potential use in orthopaedic surgery

Introduction: Transcutaneous Amputation Prosthesis (ITAP) is an alternative for transfemoral amputees to conventional stump-socket prostheses which have many problems. These include: poor fit, stump pressure sores, pain, infections and unnatural gait. ITAP aims to overcome these by being osseointegrated into the femoral medulla with a pin protruding through the skin to which the external prosthesis attaches. Thus, the forces normally encountered by the stump soft tissues are now transferred directly to the skeleton. However, the transcutaneous pin produces a route for infection from the external to internal environment. Therefore, a key feature to the success of the ITAP is to produce a biological seal at the transcutaneous interface. Epithelial cells have been shown to attach to dental transcutaneous titanium devices via hemidesmosomes (HD).2 Focal contacts (FC) are also important in cell adhesion and to the underlying substratum.3 We grew human keratinocytes on different titanium surfaces to assess their morphology, ability to proliferate and produce HD and FC. Hypothesis: Surface topography influences keratinocytes morphology and proliferative capacity and expression of HD and FC. Materials and Methods: 4 titanium alloy (Ti6Al4V) surface topographies were used (10mm x 4mm discs): polished, machine finished, sandblasted and hydrofluoric acid etched (HF) and a control – plastic thermanox. Surface roughness profiling of titanium discs were measured (Mitutoyo Surftest SV-400). HaCaT keratinocytes were grown on disc surfaces in wells of culture medium at +37oC, 5% CO2 and analysed at 1, 2, 3 and 4 days. Cells were processed to visualise HD with fluorescence microscopy using antibodies to the 6-integrin and plec-tin. Anti-vinculin antibodies were used to visualise FC. Fluorescein isothiocyanate (FITC) secondary antibodies enabled counting of structures (all product: Sigma-Aldrich, UK). Alamar blue (Serotec, UK) measured cell proliferation and SEM (surface morphology, cell area) and TEM were also performed. Cells grown on polished, machined and thermanox discs supported a regular, confluent layer with many cytoplasmic processes and dividing cells. HF and sandblasted discs grew an irregularly layer with fewer cytoplasmic processes and fewer dividing cells (not quantified). Day 3 TEM revealed HD, FC and desmosomes; cells on polished and thermanox were more closely packed and in layers. Conclusion: Keratinocytes are significantly influenced by titanium surface topography. Smooth polished titanium alloy may be the ideal surface for a transcutaneous pin in the ITAP. Further experiments into isolating favourable biological components needed to encourage keratinocytes to attach onto titanium should be carried out. Results: No significant difference shown in cell proliferation between titanium discs but cells on thermanox grew significantly more (p< 0.05). FC and HD numbers increased on all surfaces (days 1–3); a negative correlation between surface roughness and HD and FC numbers observed (lower Ra values = more HD and FC expressed)

Introduction. In THA, fretting corrosion at the head-stem taper junction has emerged as a clinical concern that may result in adverse local tissue reactions, even in patients with a metal-on-polyethylene bearing [1]. Taper junctions that employ a ceramic head have demonstrated reduced corrosion at the interface [2]. However, during revision surgery with a well-fixed stem, a titanium sleeve is used in conjunction with a ceramic head to ensure proper fit of the head onto the stem and better stress distribution. In vitro testing has suggested that corrosion is not a concern in sleeved ceramic heads [3]; however, little is known about the in vivo fretting corrosion of the sleeves. The purpose of this study was to investigate fretting corrosion in sleeved ceramic heads. Materials and Methods. Between 2001 and 2014, 35 sleeved ceramic heads were collected during revision surgery as part of a multi-center retrieval program. The sleeves were all fabricated from titanium alloy and manufactured by 4 companies (CeramTec (n=14), Smith & Nephew (Richards, n=11), Stryker (n=5), and Zimmer (n=5)). The femoral heads were made from 3 ceramics (Alumina (n=7), Zirconia (n=11), and Zirconia-toughened Alumina (n=17)). Sleeve dimensions (length and thickness) were measured using calibrated calipers. Fretting corrosion of the sleeves and available associated stems was scored using a 4-point, semi-quantitative scoring system [4], with 1 being little-to-no damage, and 4 corresponded to severe fretting corrosion. Five sleeves could not be extracted; thus the external surface was not scored. Results. Moderate-to-severe fretting corrosion scores (Score ≥ 2) were observed in 97% (34/35) of internal tapers (sleeve-femoral stem contact), 57% (17/30) of external tapers (sleeve-femoral head contact), and 65% (11/17) of the stems. The internal sleeve had higher fretting corrosion scores than the external taper (Mean Score Difference [MSD] = 1.1; p = 0.001) and stem (MSD = 0.7; p = 0.016). Fretting corrosion scores were correlated with implantation time at all surfaces (Rho ≥ 0.53; p ≤ 0.015). Scores were not correlated with sleeve dimensions (p > 0.05). Fretting corrosion scores of the external sleeve correlated directly with activity level (p = 0.005) and inversely with patient age (p = 0.03). Discussion. The retrieval data shows that fretting corrosion can occur in these components, particularly on the internal surface of the sleeve. The corrosion scores were similar to levels observed in prior studies of tapers in CoCr heads [2]. Implantation time was the main predictor of increased fretting corrosion. The impact of ceramic material and sleeve design currently remain unclear as the analyses were confounded with implantation time. Thus, more detailed and quantitative analyses are required to fully determine the factors that influence fretting corrosion of sleeved ceramic heads in THA

Thirteen total hip replacements with titanium alloy femoral components required revision for loosening at an average of two years after implantation. At revision the soft tissues around the implant were darkly stained and a proliferative membrane had invaded the cement-bone interface. The femoral components showed polishing of parts of their shot-blasted surfaces. Histology showed a fibroblastic reaction with abundant titanium lying free and within histiocytes, and a scanty foreign-body giant-cell reaction. Surface analysis of the removed femoral components and chemical analysis of the excised tissues is described. Tissue reaction in response to the metal-wear debris may have contributed to the early failure of these implants

Background: Osseointegrated amputation prostheses avoid soft tissue complications associated with traditional socket prostheses. Forces are transmitted directly to the skeleton resulting in improved function. However, approximately 50% of transcutaneous implants become infected due to the lack of a successful skin-implant seal. Intraosseous Transcutaneous Amputation Prostheses (ITAP) are designed to integrate with the skin preventing epithelial downgrowth and infection. Fibronectin adsorption enhances fibroblast adhesion in vitro; however, in vivo, fibronectin becomes desorbed from the implant surface. Covalent attachment of fibronectin by silanisation has been shown to be durable in vitro. The silanisation process for fibronectin includes a stage of passivation with sulphuric acid which alters surface characteristics. Aims: The aim of this study was to determine if in vitro fibroblast adhesion to silanised fibronectin (SiFn) titanium alloy could be improved by omitting or reducing the length of time of passivation. The study also assessed the effects of SiFn on dermal attachment in vivo comparing the results with adsorbed fibronectin substrates and with uncoated controls. Methods: Scanning electron microscopy, Ra profilometry and contact angle measurement (n=6) were used for topographical characterization of surfaces. Anti-vinculin antibodies were used to immunolocalize fibroblast adhesion sites after 24 hours. The morphology of fibroblasts on each surface was evaluated using scanning electron microscopy. Subcutaneous plates were implanted onto the tibiae of an ovine model (n=3) in order to evaluate the performance of the modified SiFn surface in vivo. Hydroxyapatite (HA) and adsorption of fibronectin to HA (HAFn) were also tested because HA coatings are currently applied to the dermal section of ITAP in clinical trials. After four weeks, a histological assessment of the percentage of soft-tissue attachment and cell alignment relative to the implant was performed. Results: Passivation produced rougher, more hydrophobic surfaces with numerous microcracks and was associated with poorer fibroblast adhesion and spreading than un-passivated controls in vitro. SiFn with passivation resulted in poorer cell adhesion than SiFn without passivation. Reducing the time period for passivation did not reduce the detrimental effects of passivation In vivo, HAFn and SiFn resulted in higher median values for soft-tissue attachment than simple adsorption of fibronectin; however, the differences were not statistically significant. Cell alignment was significantly different for HAFn and SiFn compared with controls (p< 0.05), with cells on the fibro-nectin treated surfaces orientated more perpendicular to the implant surface. Conclusion: Omission of passivation improves fibro-blast adhesion to SiFn surfaces in vitro. Coating with fibronectin either by silanisation onto titanium alloy or by adsorption onto HA surfaces affected the orientation of cells in vivo, implying that tissue attachment was enhanced. A time course may be of value to determine if fibronectin coatings are lost over time in vivo

Introduction: The S-ROM. ®. modular hip system (DePuy, Warsaw, IN) has a cementless femoral component made of titanium alloy with a distally fluted and slotted stem. The stem mates with a sleeve that is implanted in the proximal femur. No reports exist in the literature of intraoperative difficulties in disengaging the sleeve-stem interface. Induced by the impossibility of intraop-eratively disconnecting the sleeve-stem interface in one patient leading to unintended revision of a well-fixed sleeve, we asked whether in vivo evidence for fretting or mechanically-assisted crevice corrosion of the mating surfaces could be found in retrieved components and whether its appearance is influenced by factors such as length of implantation. Methods: The sleeve-stem combinations were retrieved from 1998 to 2008 as part of our IRB-approved implant retrieval system. Twenty-two sleeve-stem interfaces of S-ROM. ®. femoral components were located in our retrieval collection. Seven sleeve-stem combinations were still mated when retrieved; 2 were disengaged by hammering the sleeve away from the stem, the remaining 5 had to be cut longitudinally with a diamond saw to disengage the sleeve from the stem. All disengaged sleeves were also cut to expose their inner surfaces. The surfaces of the taper region and the corresponding inner surfaces of the split sleeves were inspected macroscopically and assigned to the following groups: severe corrosion; moderate surface changes; and few or no evidence of surface changes. Microscopic examination was used to grade fretting and corrosion using an established subjective scale (Goldberg et al., 2002). The surface of the taper and the sleeve was divided into 12 regions each and every region was evaluated separately. The mean score of all 24 regions was calculated and opposed to the implantation time of the respective femoral component. Statistical analysis of correlation between the mean score and implantation length was performed using the Pearson product moment correlation. Additionally, the surface of the taper regions of 6 specimens underwent detailed analysis with SEM and EDAX. Results: In 3 of 22 sleeve-stem interfaces severe corrosion accounting for at least 80% of the surface area was detected. Furthermore, ten sleeve-stem interfaces showed moderate surface changes. Nine sleeve-stem interfaces showed few or no surface changes. There was no correlation between presence of corrosion and implantation length (r=0.13; p=0.56). Conclusion: In 3 of 22 retrieved sleeve-stem interfaces severe corrosion was found at the stem-sleeve interface. Though apparently not the rule, failure to disengage the stem from the sleeve undermines an important advantage of this type of modularity in total hip replacement and suggests that alternative procedures should be anticipated when planning for revision surgery of such (or a similar) modular femoral component

Introduction: Intraosseous Transcutaneous Amputation Prostheses (ITAP) could overcome the problems associated with conventional stump-socket prostheses for amputees (pressure sores, pain, infections and unnatural gait), by attaching the external prosthesis directly to the skeleton via a skin penetrating abutment. Despite this, the skin breach introduces a potential route for infection. For success, a biological seal at the skin-ITAP interface is essential. The protein Laminin-5 (L-5) is a ‘biological glue’, which is integral to epitheial cell adhesion. Covalently bonding L-5 to the ITAP titanium alloy (Ti6Al4V), may enhance the strength of the skin-ITAP interface. Silanisation, a chemical technique that covalently bonds proteins to metals, could be used to bond L-5 to Ti6Al4V. We have assessed the characteristics L-5 silanised Ti6Al4V as a potential substrate for ITAP. Method: To determine the maximum quantity of L-5 that could be silanised to Ti6Al4V, and its relative stability when soaked in foetal calf serum (FCS) over time; polished Ti6Al4V discs were silanised by immersing in aminopropyltriethoxysilane followed by glutaraldehyde. Radiolabelled rat laminin-5-I125 was then added. Discs were immersed in FCS for 4 days (37 C) and analysed at 24 hour intervals in a liquid scintillation counter. Un-silanised discs were used as controls. Results: L-5 was successfully covalently bound to Ti6Al4V. 10ng, 100ng, 250ng and 500ng droplets yielded significantly more silanised L-5 (p< 0.05), but no difference was observed between 750ng and 1000ng. Percentage L-5 covalently bound ranged from 33% and 65%. A small decrease in bound L-5 occurred after 24 hours of FCS soaking (p< 0.05), but subsequent to this no significant reduction was observed for 4 days (p< 0.05). Controls showed a significantly larger reduction after 24 hours (p< 0.05). Conclusion: Covalently bonding L-5 to Ti6Al4V by silanisation can be achieved with predictable results. Large enough quantities can be immobilised to influ-ence cellular function. L-5 silanised to Ti6Al4V remains stable in vitro over time and is not removed. Following the study of cellular interactions with silanised L-5, a stable skin seal may be achieved at the transcutaneous portion of the ITAP

Objectives. Ultraviolet (UV) light-mediated photofunctionalisation is known to improve osseointegration of pure titanium (Ti). However, histological examination of titanium alloy (Ti6Al4V), which is frequently applied in orthopaedic and dental surgery, has not yet been performed. This study examined the osseointegration of photofunctionalised Ti6Al4V implants. Methods. Ti and Ti6Al4V implants were treated with UV light, and the chemical composition and contact angle on the surfaces were evaluated to confirm photofunctionalisation. The implants were inserted into femurs in rats, and the rats were killed two or four weeks after the surgery. For histomorphometric analysis, both the bone–implant contact (BIC) ratio and the bone volume (BV) ratio were calculated from histological analysis and microcomputed tomography data. Results. The amount of carbon and the contact angle on both implants were significantly reduced after UV irradiation. The BIC ratios for both UV light-treated implants significantly increased at two weeks, but there was no significant difference at four weeks. There was no significant difference in the BV ratios between the UV light-treated and control implants at two or four weeks. Conclusions. This study suggests that photofunctionalisation of Ti6Al4V implants, similar to that of Ti implants, may promotes osseointegration in early but not in the late phase of osseointegration. Cite this article: R. Yamauchi, T. Itabashi, K. Wada, T. Tanaka, G. Kumagai, Y. Ishibashi. Photofunctionalised Ti6Al4V implants enhance early phase osseointegration. Bone Joint Res 2017;6:331–336. DOI: 10.1302/2046-3758.65.BJR-2016-0221.R1

Additive manufacturing (AM) techniques have gained attraction in orthopedic implant design with their ability to create unique shapes and structures. Depending on the application, there are different mechanical properties required. This study evaluated the mechanical properties of direct metal laser sintered (DMLS) Titanium alloy (Ti6Al4V) with and without hot isostatic pressure (HIP) treatment. Three dimensional computer modeling and the DMLS manufacturing assisted in building net or near-net samples for testing. The material testing consisted of uniaxial tension, Charpy impact, rotating beam fatigue (RBF), density, and hardness. Two sets of Ti6Al4V samples were created for testing using a DMLS process and stress relieved in a vacuum furnace prior to removal from the build platform. One set of samples were HIP treated. The two sets of samples were tested and the material properties of the non-HIP treated samples were compared to those with HIP treatment. Tension testing was conducted on fifteen (15) samples per treatment according to ASTM E8/E8M on as-built samples designed to a round specimen 3 per the standard. Fifteen (15) Charpy impact samples per treatment were built to near-net shapes. A low stress grind was performed on all surfaces and a notch was placed in the sample to comply with ASTM E23 and testing was performed in accordance with the standard. Fifteen (15) samples were built per treatment and machined for RBF per ISO 1143. RBF was performed on all samples at a frequency of 100 Hz with run out conditions of 10M cycles or failure. Density and hardness was measured on three (3) samples from each set using Archimedes' Principle and Rockwell hardness techniques respectively. The average (standard deviation) tensile strengths between the two groups were statistically different (p < 0.05). The non-HIP treated samples had an average ultimate strength of 956(10) MPa, yield strength of 896(13) MPa, and modulus of 118(2) GPa (Table 1). The HIP treated samples had an average ultimate strength of 909(4) MPa, yield strength of 832(9) MPa, and modulus of 112(3) GPa (Table 1). There was also statistical differences in the impact strength with the HIP treatment samples having a higher required force of 23.4(1.6) J compared to the non-HIP treated group of 19.8(1.8) J (Table 1). The fatigue strength of the samples HIP treated compared to the non-HIP treated group was 650 MPa and 396 MPa respectively (Table 1). This study shows that the HIP treatment of DMLS Ti6Al4V diminishes some mechanical strengths while greatly improving the fatigue life of the material. As we continue to evaluate these “new” materials for orthopedic devices, these mechanical and physical properties will help us understand the capabilities of this process and material

Introduction. One of the major concerns in the use of modular hip prostheses is the structural failure of one or more components of the prosthesis, with total mechanical failure. In literature there are sporadic cases of breakage of the prosthetic neck in patients with high functional demand. Material and methods. In our experience we have implanted a model of modular hip prostheses in 38 patients. In 17 of these patients it was implanted a neck made of titanium alloy, while in the remaining 21 was utilised a CrCo neck. In 5 of the 17 patients with neck titanium it has been a spontaneous rupture of the neck in a time ranging from 12 to 24 months. We proceeded with the replacement of the titanium neck with similar neck made of CrCo alloy in 5 patients with failed neck, and we decided to call the remaining 12 patients with titanium neck, offering them the revision of the system. All patients accepted the revision surgery. Results. implants explanted and subject to breakage of the neck were analyzed by an independent metallurgical laboratory which has produced a document in which were found the main signs of wear which led to the deterioration of metal involved. Conclusions. The rupture of the modular hip prostheses is a possible event both because of the high functional loads required by some types of patients, that of the building materials and design of the modular components. In this study we are presented the results of the laboratory tests that allow us to pose hypotheses about the causes and failure mechanisms of modular hip prostheses

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1α), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1α expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1α in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1α were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1α inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty

Aim:. To compare the degree of deformity correction achieved using cobalt chromium versus titanium alloy rods in patients with Adolescent Idiopathic Scoliosis. Method:. A retrospective comparison of two cohorts of patients with Adolescent Idiopathic Scoliosis treated with posterior segmental pedicle screw fixation using either Titanium or Cobalt Chromium rods. The radiographs of 50 patients treated before 2009 (Ti group) and 50 patients after 2009 (CoCr group) were reviewed for changes in: Main Coronal Curvature Sagittal Balance (C7 Plumb Line) Kyphosis (T5-12). Results:. Thirteen were excluded because of incomplete radiographs. 38 patients received CoCr, 45 Ti and 4 patients received hybrid constructs. Correction rate of curves measuring >50 was significantly improved with CoCr (81% vs 69%, p=0.02). Sagittal balance was improved in both groups (CoCr 27.8, Ti 28.0 mm) but no significant difference was seen (p=0.84). Within the Ti group 12 patients moved for normal kyphosis (20–40) to abnormal (<20, >40) while 9 patients moved from abnormal to normal (p=0.66). Within the CoCr Group 10 patients were normalised while only 2 patients moved from normal to abnormal (p=0.04). Mean change in kyphosis showed a trend towards improved correction with CoCr (4.2 vs 2.9) but failed to reach significance (p=0.62). Discussion:. We have demonstrated that CoCr rods significantly improve coronal correction in patient with >50 curves. No difference in overall sagittal balance was seen between metal alloys. There is a trend towards better restoration of T5-12 kyphosis with CoCr however it is unclear if this small difference is clinically relevant. Conflict Of Interest Statement: No conflict of interest

Periprosthetic fractures present an increasing workload as more hip arthroplasties are performed. They are often challenging to treat due to poor bone stock and patient frailty. We compare the early clinical and radiological results in 2 centres of 24 consecutive periprosthetic hip fractures in 24 patients, using a cannulated interlocked long stemmed titanium alloy femoral component with or without a hydroxyapatite (HA) coating (Cannulok revision prosthesis). The mean age at the time of operation was 79 years (range 65 to 92.4 years). The average length of follow up was 1.17 years (range 3 months to 5.3 years). All patients receiving a Cannulok revision stem with a minimum follow up of 3 months were included regardless of their primary aetiology and number of previous surgical procedures. Patients were reviewed and scored using the Merle d’Aubigne and Postal Score, Harris Hip Score and the WOMAC index at latest review. Periprosthetic fractures were classified using the Vancouver classification. At latest radiological review we measured subsidence, new bone formation (including presence of callus), osteolysis and radiolucent lines in all areas of the stem. Of the 24 fractures, 22 healed. In the 14 who had HA coated implants there was a 50% increase in bone. In the non-HA coated stems there was a 36% increase in bone radiologically. The mean Harris hip score was 74 at the latest post-operative review. The mean WOMAC and MDP scores were 48.7 and 7.7 respectively. The mean pain visual analogue score was 1.6 overall and 0 specifically for mid-thigh pain. We present encouraging early clinical and radiological results of the Cannulok stem system for treatment of complex periprosthetic fractures. This implant provides early fracture stability and subsequent biological bonding with an improvement in bone mass

We present the extended follow-up (≥ 20 years) of a series of fully hydroxyapatite-coated femoral components used in 72 primary total hip replacements (THRs). Earlier results of this cohort have been previously published. All procedures were performed between 1986 and 1991. The series involved 45 women and 15 men with 12 bilateral procedures. Their mean age at the time of surgery was 60 years (46 to 80) and the mean duration of follow-up was 22.5 years (20 to 25). At final follow-up, the mean Merle d’Aubigné and Postel hip scores were 5.5 (4.5 to 6), 3.8 (3.5 to 5) and 3.3 (3.0 to 5.0) for pain, mobility and function, respectively. Of the patients 92% were very satisfied at the time of final follow-up.

There were seven revisions: six of the acetabular component for aseptic loosening and one of both the stem and the acetabular component for loosening due to deep infection. The survival of this prosthesis at 22.5 years with revision for any reason as the endpoint was 91.7% (95% confidence interval (CI) 84 to 99). Survival with aseptic loosening of the stem as the endpoint was 100% (95% CI 90 to 100).

This prosthesis provides pain relief in the long term. Survival of this component is comparable to the best results for primary THR with any means of fixation.

Cite this article: Bone Joint J 2013;95-B:467–71.

Prosthetic joint infections (PJI) occur infrequently, but they represent the most devastating complication with high morbidity and substantial cost. Staphylococcus aureus and coagulase-negative S. epidermidis are the most commonly infecting agents associated with PJI. Nowadays, Gram-negative species like Escherichia coli and Pseudomonas aeruginosa are gaining relevance.

The use of TiO2 conical nanotubular doped with fluorine and phosphorous (FP-cNT) surfaces is an interesting approach to prevent surface bacterial colonization during surgery and favouring the osseointegration. Despite of there are serum markers related with PJI, to date there is described no biomaterial-related marker that allows detecting PJI. Here we describe the adherence and the bactericidal effect of FP-cNT and its capacity of marking the non-fermenting bacteria that have been in contact with it by Al. This metal is delivered by FP-cNT in non-toxic concentrations (between 25 and 29 ng/mL).

F-P-cNT layers on Ti6Al4V alloy were produced as described previously by our group. Ti6Al4V chemical polishing (CP) samples without nanostructure were used as control and produced as described previously.

S. aureus 15981, S. epidermidis ATCC 35984, E. coli ATCC 25922, and P. aeruginosa ATCC 27853 strains adherence study was performed using the protocol described by Kinnari et al. in 0.9% NaCl sterile saline with a 120 min incubation. After incubation, the samples were stained with LIVE/DEAD BacLight Bacterial Viability Kit. Proportion of live and dead bacteria was calculated and studied by using ImageJ software. The experiments were performed in triplicate. The aluminum concentration was estimated in the supernatant after incubation and in the 0.22 µm filtered supernatant by atomic absorption in graphite furnace.

The statistical data were analyzed by nonparametric Kruskal-Walis test and by pairwise comparisons using the nonparametric unilateral Wilcoxon test with a level of statistical significance of p<0.05. The values are cited as medians.

Our results show that the bacterial adherence of all tested species significantly decreased on FP-cNT compared to CP except P. aeruginosa ATCC 27853: 19.8% for S. aureus 15981, 45.3% for S. epidermidis ATCC 35984 and 8.1% for E. coli ATCC 25922. The bacterial viability decreased 2-fold for S. aureus 15981, and 5-fold for S. epidemidis ATCC 35984, but increased 95% for P. aeruginosa ATCC 27853 and there no was variation for E. coli ATCC 25922 on FP-cNT compared to CP. Only supernatant P. aeruginosa ATCC 27853 shows significant Al detection after 120 min incubation (p<0.05).

In summary, F-P cNT is a promising biomaterial that besides favoring osseointegration and potential usefulness as drug carrier, present bactericidal, non-stick ability (at least for staphylococci and E. coli) and is able to mark P. aeruginosa with Al, which could be potentially monitored in serum and urine in patients with PJI.

The osseointegration of implants is related to the early interactions between osteoblastic cells and titanium surfaces. The behavior of osteoblast cells was compared on four different titanium surfaces in vitro and in vivo: machined, blasted, plasma spray and micro-arc oxidation.

X-ray diffraction and scanning electron microscope investigations were performed in order to assess the structure and morphology. Biologic and morphologic responses to the osteoblast cell lines (Saos-2) were then examined, using Promega proliferation assay, alkaline phosphatase activity, vβ3 integrin expression and cytoskeleton staining (Rhodamine-Phallodine). The analysis of gene expression for osteocalcin and collagen I was done through RT-PCR. In addition, differential histologic evaluation and interfacial strength at the bone-implant interfaces were then evaluated in the distal femur of four beagle dogs.

In conclusion, micro-arc oxidation of titanium appears to exhibit more favorable osteoblast adhesion and stronger interfacial strength than the compared groups in vitro and in vivo as well.

We have examined 26 retrieved, failed titanium-alloy femoral stems. The clinical details, radiological appearances and the histology of the surrounding soft tissues in each patient were also investigated.

The stems were predominantly of the flanged design and had a characteristic pattern of wear. A review of the radiographs showed a series of changes, progressive with time. The first was lateral debonding with subsidence of the stem. This was followed by calcar resorption and fragmentation or fracture of the cement. Finally, osteolysis was seen, starting with a radiolucency at the cement-bone interface and progressing to endosteal cavitation.

Three histological appearances were noted: granulomatous, necrobiotic and necrotic. We suggest that an unknown factor, possibly related to the design of the stem, caused it to move early. After this, micromovement at the cement-stem interface led to the generation of particulate debris and fracture of the cement. A soft-tissue reaction to the debris resulted in osteolysis and failure of fixation of the prostheses.

In rabbits and goats, test implants with a porous surface of two layers of Tl-6A;-4V beads were examined at intervals for bond strength with bone. Half of the implants were coated with hydroxyapatite by plasma spray. The bonding strength with bone in the coated specimens was about four times greater than that of the uncoated specimens at two weeks, and twice as strong at six weeks. Twelve weeks after implantation, the strengths were similar. The hydroxyapatite coating of the beads provided earlier and stronger fixation.

Introduction

Adverse Local Tissue Reactions (ALTR) have been reported in association with both wear and corrosion. Tissue reactions have been reported in association with corrosion at CoCr head-CoCr neck, CoCr head-TiAl6V4 neck, and CoCr modular neck on beta-titanium (TMZF) stem junctions. The current abstract reports on 3 cases of ALTR in association with CoCr modular necks on convention titanium (TiAl6V4) stem junctions.

Case 1. A 67 year old male (87 kg, 1.73 m, BMI 29.1) presented with new onset hip irritation 11 months after surgery. Radiographs show no abnormalities. Further investigation revealed the following: ESR = 95, CRP = 5, Cr level = 1.0, Co level = 4.1, leukocyte transformation testing = highly reactive to nickel. Hip aspiration was culture negative with 11,250 wbc. Metal artifact reduction MR showed cystic local reaction in the region of the greater trochanter.

Case 2. A 52 year old male (89 kg, 1.83 m, BMI 26.5) presented with new onset hip irritation 30 months after surgery. Radiographs show no abnormalities. Further investigation revealed the following: ESR = 7, CRP = 5.4, Cr level = 2.1, Co level = 4.8, leukocyte transformation testing = reactive to nickel. Hip aspiration was culture negative with 3995 wbc. Metal artifact reduction MR showed cystic local reaction in the region of the iliopsoas.

Case 3. A 52 year old male (104 kg, 1.85 m, BMI 30.1) presented with new onset hip irritation 26 months after surgery. Radiographs show no abnormalities. Further investigation revealed the following: ESR = 33, CRP = 34.9, Cr level = 1.0, Co level = 3.7, leukocyte transformation testing = no reactivity to any of the biomaterials. Hip aspiration was culture negative with 3,780 wbc. Metal artifact reduction MR showed cystic local reaction in the region of the iliopsoas.

Titanium alloys are one of the most used for orthopaedic implants and the fabrication of them by 3D printing technology is a raising technology, which could effectively resolve existing challenges. Surface modification of Ti surfaces is often necessary to improve biocorrosion resistance, especially in inflammatory conditions. Such modification can be made by coatings based on hydrogels, like alginate (Alg) - a naturally occurring anionic polymer. The properties of the hydrogel can be further enhanced with calcium phosphates like octacalcium phosphate (OCP) as a precursor of biologically formed hydroxyapatite. Formed Alg-OCP matrices have a high potential in wound healing, delivery of bioactive agents etc. but their effect on 3D printed Ti alloys performance was not well known. In this work, Alg-OCP coated 3D printed samples were studied with electrochemical measurements and revealed significant variations of corrosion resistance vs. composition of the coating. The potentiodynamic polarization test showed that the Alg-OCP-coated samples had lower corrosion current density than simple Alg-coated samples. Electrochemical impedance spectroscopy indicated that OCP incorporated hydrogels had also a high value of the Bode modulus and phase angle. Hence Alg-OCP hydrogels could be highly beneficial in protecting 3D printed Ti alloys especially when the host conditions for the implant placement are inflammatory. AcThis work was supported by the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions GA860462 (PREMUROSA). The authors also acknowledge the access to the infrastructure and expertise of the BBCE – Baltic Biomaterials Centre of Excellence (European Union Horizon 2020 programme under GA857287)

Fracture of contemporary femoral stems is a rare occurrence. Earlier THR stems failed due to design issues or post manufacturing heat treatments that weakened the core metal. Our group identified and analyzed 4 contemporary fractured femoral stems after revision surgery in which electrochemical welds contributed to the failure. All four stems were proximally porous coated titanium alloy components. All failures occurred in the neck region post revision surgery in an acetabular cup exchange. All were men and obese. The fractures occurred at an average of 3.6 years post THR redo (range, 1.0–6.5 years) and 8.3 years post index surgery (range, 5.5–12.0 years). To demonstrate the effect of electrocautery on retained femoral stems following revision surgery, we applied intermittent electrosurgical currents at three intensities (30, 60, 90 watts) to the polished neck surface of a titanium alloy stem under dry conditions. At all power settings, visible discoloration and damage to the polished neck surface was observed. The localized patterns and altered metal surface features exhibited were like the electrosurgically-induced damage priorly reported. The neck regions of all components studied displayed extensive mechanical and/or electrocautery damage in the area of fracture initiation. The use of mechanical instruments and electrocautery was documented to remove tissues in all 4 cases. The combination of mechanical and electrocautery damage to the femoral neck and stem served as an initiation point and stress riser for subsequent fractures. The electrocautery and mechanical damage across the fracture site observed occurred iatrogenically during revision surgery. The notch effect, particularly in titanium alloys, due to mechanical and/or electrocautery damage, further reduced the fatigue strength at the fractured femoral necks. While electrocautery and mechanical dissection is often required during revision THA, these failures highlight the need for caution during this step of the procedure in cases where the femoral stem is retained

Aims. This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys. Methods. Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment. Results. On stainless steel, both nonactivated and activated cell groups were shown to have a significant increase in metal ion release for Cr, Fe, and Ni (p < 0.001, p = 0.002, and p = 0.020 respectively) compared with medium only and showed macrophage-sized corrosive pits on the stainless steel surface. On titanium alloy discs there was a significant increase in aluminum (p < 0.001) among all groups compared with medium only. Conclusion. These results indicated that macrophages were able to attach to and affect the oxide surface of stainless steel and titanium alloy discs. Cite this article: Bone Joint J 2020;102-B(7 Supple B):116–121

Aims. Here we used a mature seven-day biofilm model of Staphylococcus aureus, exposed to antibiotics up to an additional seven days, to establish the effectiveness of either mechanical cleaning or antibiotics or non-contact induction heating, and which combinations could eradicate S. aureus in mature biofilms. Methods. Mature biofilms of S. aureus (ATCC 29213) were grown on titanium alloy (Ti6Al4V) coupons for seven days and were subjected to the following treatments or their combinations: antibiotics, mechanical cleaning, or heat shock by induction heating of 60°C for one minute. Experiments were repeated at least five times. Results. In the untreated biofilm, growth up to 1.8×10. 11. colony-forming units (CFU)/cm. 2. was observed. Treatment with ciprofloxacin, flucloxacillin, vancomycin, cefuroxime, and amoxicillin all with rifampicin gave 6.0 log, 6.1 log, 1.4 log, 4.8 log, and 3.6 log reduction in CFU/cm. 2. , respectively. Mechanical cleaning alone resulted in 4.9 log reduction and induction heating in 7.3 log reduction. There was an additional effect of ciprofloxacin, flucloxacillin, and induction heating when used in combinations. There was no additional effect for mechanical cleaning. No bacterial growth could be detected after induction heating followed by seven days of ciprofloxacin with rifampicin. Conclusion. Mechanical cleaning, antibiotics, and non-contact induction heating reduced the bacterial load of mature S. aureus biofilms with approximately 5 log or more as a single treatment. The effect of mechanical cleaning on mature S. aureus biofilms was limited when used in combination with antibiotics and/or induction heating. Cite this article: Bone Joint Res 2022;11(9):629–638

Abstract. Objectives. Additive manufacturing has led to numerous innovations in orthopaedic surgery: surgical guides; surface coatings/textures; and custom implants. Most contemporary implants are made from titanium alloy (Ti-6Al-4V). Despite being widely available industrially and clinically, there is little published information on the performance of this 3D printed material for orthopaedic devices with respect to regulatory approval. The aim of this study was to document the mechanical, chemical and biological properties of selective laser sintering (SLS) manufactured specimens following medical device (TOKA®, 3D Metal Printing LTD, UK) submission and review by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). Methods. All specimens were additively manufactured in Ti-6Al-4V ELI (Renishaw plc, UK). Mechanical tests were performed according to ISO6892-1, ISO9585 and ISO12107 for tensile (n=10), bending (n=3) and fatigue (n=16) respectively (University of Bath, UK). Appropriate chemical characterisation and biological tests were selected according to recommendations in ISO10993 and conducted by external laboratories (Wickham Labs, UK; Lucideon, UK; Edwards Analytical, UK) in adherence with Good Lab Practise guidelines. A toxicological review was conducted on the findings (Bibra, UK). Results. The mechanical tests demonstrated that the material performed to the specification for conventionally manufactured titanium alloy of this type (ISO5832-3). The toxicology review concluded that there were no significant concerns for the health of the patients identified in this evaluation and implantation of the TOKA® device would not result in a significant health risk to patients. Conclusions. Reflecting on our MHRA experience, additive manufacture of orthopaedic devices is still considered to be a ‘novel’ process by regulatory bodies, requiring additional safety evidence. Despite this, our findings demonstrate that there is no difference, mechanically or chemically, to the traditionally manufactured alloy material. We hope to support the widening use of 3D printed titanium alloy orthopaedic devices by publishing our route to regulatory approval. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Aims. Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results. Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion. Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection. Cite this article: Bone Joint Res 2024;13(3):101–109

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 cm. 3. 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. Results. For MSSA and MRSA, no inhibitory effect was found in the control group, and antibiotic-loaded smooth titanium alloy beads showed a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads showed significantly larger mean ZOIs than cement beads (all p < 0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After six days, antibiotic-loaded cement had significantly larger mean ZOIs than the 3D porous titanium (p = 0.027), but no significant difference was found with tantalum (p = 0.082). For MRSA, both tantalum and 3D porous titanium beads had significantly larger mean ZOIs than antibiotic-loaded cement each day until day 6 for tantalum (all p < 0.01) and until day 3 for 3D porous titanium (all p < 0.04). Antibiotic-loaded cement had significantly larger mean ZOIs than tantalum and 3D porous titanium from day 7 to 9 (all p < 0.042). Conclusion. These results show that porous metal implants can deliver local antibiotics over slightly varying time frames based on in vitro analysis. Cite this article: Bone Joint J 2020;102-B(6 Supple A):158–162

AM specifically allows for cost-efficient production of patient-specific Orthopaedic medical devices with unusual designs and properties. A porous design allows to adjust the stiffness of metallic implants to that of the host bone. Beyond traditional metals, like titanium alloys, this talk will review the present state-of-the-art of directly printed absorbable metal families. Physicochemical, mechanical and biological properties of standardized design prototypes from all currently available metal families will be compared and their clinical application potential discussed. The impact of in vitro test environments on comparative corrosion behavior, post manufacturing aspects, and the recent status quo in biocompatibility testing and present knowledge gaps will be addressed

Intramedullary nails (IMNs) are the current gold standard for treatment of long bone diaphyseal and selected metaphyseal fractures. Their design has undergone many revisions to improve fixation techniques, conform to the bone shape with appropriate anatomic fit, reduce operative time and radiation exposure, and extend the indication of the same implant for treatment of different fracture types with minimal soft tissue irritation. The IMNs are made or either titanium alloy or stainless steel and work as load-sharing internal splints along the long bone, usually accommodating locking elements – screws and blades, often featuring angular stability and offering different configurations for multiplanar fixation – to secure secondary fracture healing with callus formation in a relative-stability environment. Bone cement augmentation of the locking elements can modulate the construct stiffness, increase the surface area at the bone-implant interface, and prevent cut-through of the locking elements. The functional requirements of IMNs are related to maintaining fracture reduction in terms of length, alignment and rotation to enhance fracture healing. The load distribution during patient's activities is along the entire bone-nail interface, with nail length and anatomic fit being important factors to avoid stress risers

Previous studies have reported excellent results with tapered, titanium alloy, porous plasma-sprayed components in patients undergoing uncemented primary total hip arthroplasty (THA). The purpose of this study was to examine survival and clinical results at minimum 25-year follow-up. We reviewed all patients who underwent primary THA at our center through 1995 with a specific femoral component, the Mallory-Head Porous (MHP; Zimmer Biomet, Warsaw, IN). This device, marketed in the U.S. until December 2021, was essentially unchanged since its 1984 introduction, except the porous coating was continued circumferentially along the lateral aspect in 1987, a hydroxyapatite-coated option was offered in 1988, and an offset option was added in 1999 after the study period. Three hundred thirty-two patients (396 THA) had a minimum of 25-year follow-up. Mean age at surgery was 47.6 years (range, 21–70 years). Mean follow-up in non-failed patients was 28.7 years (range, 25 to 37 years). There were 31 femoral revisions (7.8%): 9 infection, 3 failure of ingrowth, 5 aseptic loosening, 8 osteolysis revised well-fixed, 2 periprosthetic fracture, 2 polyethylene wear with trochanteric avulsion, 1 component breakage, and 1 malalignment well-fixed. Kaplan-Meier survival with endpoint of stem revision for all causes was 94.8% (95% CI: ±0.9%) at 36.7 years, and survival with endpoint of aseptic loosening/failure of ingrowth was 98.7% (95% CI: ±0.5) at 36.7 years. Harris hip scores improved significantly from 43 preoperatively to 76 most recently. This tapered, titanium, porous plasma spray-coated femoral component continues to demonstrate high long-term survival with a low rate of femoral component revision for any reason or aseptic loosening/failure of ingrowth

Despite advancements, revision rates following total ankle replacement (TAR) are high in comparison to other total joint replacements. This explant analysis study aimed to investigate whether there was appreciable metal particulate debris release from various contemporary TARs by describing patterns of material loss. Twenty-eight explanted TARs (9 designs: 3 fixed and 6 mobile bearing), revised for any reason, were studied. The articulating surfaces of the metal tibial and talar components as well as the polyethylene insert were assessed for damage features using light microscopy. Based on the results of the microscopic analysis, scanning electron microscopy with energy dispersive X-ray spectroscopy was performed to determine the composition of embedded debris identified, as well as non-contacting 3D profilometry. Pitting, indicative of material loss, was identified on the articulating surfaces of 54% of tibial components and 96% of talar components. Bearing constraint was not found to be a factor, with similar proportions of fixed and mobile bearing metal components showing pitting. More cobalt-chromium than titanium alloy tibial components exhibited pitting (63% versus 20%). Significantly higher average surface roughness (Sa) values were measured for pitted areas in comparison to unpitted areas of these metal components (p<0.05). Additionally, metallic embedded debris (cobalt-chromium likely due to pitting of the tibial and talar components or titanium likely from loss of their porous coatings) was identified in 18% of polyethylene inserts. The presence of hard 3. rd. body particles was also indicated by macroscopically visible sliding plane scratching, identified on 79% of talar components. This explant analysis study demonstrates that metal debris is released from the articulating surfaces and the coatings of various contemporary TARs, both fixed and mobile bearing. These findings suggest that metal debris release in TARs may be an under-recognised issue that should be considered in the study of painful or failed TAR moving forwards

Infection in orthopedics is a challenge, since it has high incidence (rates can be up to 15-20%, also depending on the surgical procedure and on comorbidities), interferes with osseointegration and brings severe complications to the patients and high societal burden. In particular, infection rates are high in oncologic surgery, when biomedical devices are used to fill bone gaps created to remove tumors. To increase osseointegration, calcium phosphates coatings are used. To prevent infection, metal- and mainly silver-based coatings are the most diffused option. However, traditional techniques present some drawbacks, including scarce adhesion to the substrate, detachments, and/or poor control over metal ions release, all leading to cytotoxicity and/or interfering with osteointegration. Since important cross-relations exist among infection, osseointegration and tumors, solutions capable of addressing all would be a breakthrough innovation in the field and could improve clinical practice. Here, for the first time, we propose the use antimicrobial silver-based nanostructured thin films to simultaneously discourage infection and bone metastases. Coatings are obtained by Ionized Jet Deposition, a plasma-assisted technique that permits to manufacture films of submicrometric thickness having a nanostructured surface texture. These characteristics, in turn, allow tuning silver release and avoid delamination, thus preventing toxicity. In addition, to mitigate interference with osseointegration, here silver composites with bone apatite are explored. Indeed, capability of bone apatite coatings to promote osseointegration had been previously demonstrated in vitro and in vivo. Here, antibacterial efficacy and biocompatibility of silver-based films are tested in vitro and in vivo. Finally, for the first time, a proof-of-concept of antitumor efficacy of the silver-based films is shown in vitro. Coatings are obtained by silver and silver-bone apatite composite targets. Both standard and custom-made (porous) vertebral titanium alloy prostheses are used as substrates. Films composition and morphology depending on the deposition parameters are investigated and optimized. Antibacterial efficacy of silver films is tested in vitro against gram+ and gram- species (E. coli, P. aeruginosa, S. aureus, E. faecalis), to determine the optimal coatings characteristics, by assessing reduction of bacterial viability, adhesion to substrate and biofilm formation. Biocompatibility is tested in vitro on fibroblasts and MSCs and, in vivo on rat models. Efficacy is also tested in an in vivo rabbit model, using a multidrug resistant strain of S. aureus (MRSA, S. aureus USA 300). Absence of nanotoxicity is assessed in vivo by measuring possible presence of Ag in the blood or in target organs (ICP-MS). Then, possible antitumor effect of the films is preliminary assessed in vitro using MDA-MB-231 cells, live/dead assay and scanning electron microscopy (FEG-SEM). Statistical analysis is performed and data are reported as Mean ± standard Deviation at a significance level of p <0.05. Silver and silver-bone apatite films show high efficacy in vitro against all the tested strains (complete inhibition of planktonic growth, reduction of biofilm formation > 50%), without causing cytotoxicity. Biocompatibility is also confirmed in vivo. In vivo, Ag and Ag-bone apatite films can inhibit the MRSA strain (>99% and >86% reduction against ctr, respectively). Residual antibacterial activity is retained after explant (at 1 month). These studies indicate that IJD films are highly tunable and can be a promising route to overcome the main challenges in orthopedic prostheses

Orthopedic metallic medical devices are essential in the treatment of a wide range of skeletal diseases and disabilities. However, they are often related with surgery complications due to acute prosthetic joint infections (PJI) causing devastating complications. Gallium (Ga) antibacterial activity has been recently demonstrated: in aqueous solutions, Ga ionize in a trivalent form Ga. 3+. that can replace Fe. 3+. in bacterial metabolism thus leading to bacteria death. However, it is not yet clear whether such effect is typical to Ga. 3+. release, and how this would affect longer term performance. Here we investigated Ga addition into titanium alloys using metallurgical methods. The study has confirmed that metallurgical addition of gallium even in small amounts (1–2% wt.) to titanium alloys have highly efficient antibacterial function without any visible cytostatic or cytotoxic effects. The presence of gallium within the metal matrix might ensure that antibacterial effect will persist for a long time towards multi-drug resistant S. aureus, which might not be possible if gallium or other metal are only in thin degradable coatings or similar formulations. A 5-logs decrease in CFU number was detected for alloys with 2% Ga and more after 72 h (alamar blue and CFU count assays). The alloys also show to be in vitro cytocompatible with both mature U2OS osteoblasts and progenitor pre-osteoblasts hFOB. Since gallium is metallurgically analogous to aluminium in titanium alloys, it might be used without affecting other alloy properties