Periprosthetic infection remains a clinical challenge that may lead to revision surgeries, increased spending, disability, and mortality. The cost for treating hip and knee total joint infections is anticipated to be $1.62 billion by 2020. There is a need for implant surface modifications that simultaneously resist bacterial biofilm formation and adhesion, while promoting periprosthetic bone formation and osseointegration.

In vitro research has shown that nanotextured titanium promotes osteoblast differentiation, and upregulates metabolic markers of osteoblast activity and osteoblast proliferation. In vivo rat studies confirmed increased bone-implant contact area, enhanced de novo bone formation on and adjacent to the implant, and higher pull-out forces compared to non-textured titanium. The authors have advanced a benign electrochemical anodization process based on ammonium fluoride that creates a nanotube surface in as little as 10 minutes (Fig. 1), which can also integrate antibacterial nanosilver (Fig. 2).

The work reported here summarizes in vitro post-inoculation and in vivo post-implantation studies, showing inherent inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by titanium surfaces with nanotubes (TiNT), nanotubes with nanosilver (TiNT+Ag), plain (Ti), and thermal plasma sprayed (TPS) titanium. Ti6Al4V was the base material for all surfaces. In vitro studies evaluated Ti, TPS, four TiNT groups with varying nanotube diameters (60nm, 80nm, 110nm, 150nm), and TiNT+Ag. After seeding with MRSA (10⁵, 10⁶, and 10⁸ CFU/mL), the 110nm diameter nanotubes showed MRSA inhibition up to three-orders of magnitude lower than the Ti and TPS surfaces at 2, 6, and 48 hours.

Following on the in vitro results, New Zealand White rabbits underwent a bilateral implantation of intramedullary tibial implants of the four material groups (4 mm outside diameter; 110nm NT diameter on TiNT and TiNT+Ag implants). One intramedullary canal was inoculated with clinically-derived MRSA (10⁵ CFU in broth) at the time of implantation; one canal had only culture media introduced (control). At a 2-week endpoint, limbs were harvested for analysis, including implant sonication with sonicant bacterial cultured, histology, and microcomputed chromatography. In the sonicant analysis cohort, TPS showed the lowest average MRSA count, while TiNT and TiNT+Ag were the highest. There was one sample each of TPS, TiNT and TiNT+Ag that showed no MRSA. After an additional 24-hour implant incubation, the TiNT and TiNT+Ag samples had no bacteria, but the TPS grew bacteria; therefore, the authors hypothesize that MRSA more readily releases from the TiNT and TiNT+Ag implants during sonication, indicating weaker biofilm adhesion and development. Histologic analysis is currently underway. In a therapeutic experiment, rabbits underwent bilateral implantation, followed by 1 week of infection development, and then 1 week of vancomycin treatment. At the endpoint, implants were sonicated and bacteria was quantified from the sonicant. TiNT showed viable MRSA at only 30% that of TPS-coated levels, while TiNT+Ag implants showed viable MRSA at only 5% that of TPS-coated levels (Fig. 3). These early results indicate that the TiNT and TiNT+Ag surfaces have some inherent antibacterial activity against MRSA, which may increase the efficacy of systemic antibiotic treatments in the setting of periprosthetic joint infections.

Aim. The use of medical devices has grown significantly over the last decades, and has become a major part of modern medicine and our daily life. Infection of implanted medical devices (biomaterials), like titanium orthopaedic implants, can have disastrous consequences, including removal of the device. For still not well understood reasons, the presence of a foreign body strongly increases susceptibility to infection. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. Formation of biofilms on the biomaterial surface is generally considered the main reason for these persistent infections, although bacteria may also enter the surrounding tissue and become internalized within host cells. To prevent biofilm formation using a non-antibiotic based strategy, we aimed to develop a novel permanently fixed antimicrobial coating for titanium devices based on stable immobilized quaternary ammonium compounds (QACs). Method. Medical grade titanium implants (10×4×1 mm) were dip-coated in a solution of 10% (w/v) hyperbranched polymer, subsequently in a solution of 30% (w/v) polyethyleneimine and 10 mM sodium iodide, using a dip-coater, followed by a washing step for 10 min in ethanol. The QAC-coating was characterized using water contact angle measurements, scanning electron microscopy, FTIR, AFM and XPS. The antimicrobial activity of the coating was evaluated against S. aureus strain JAR060131 and S. epidermidis strain ATCC 12228 using the JIS Z 2801:2000 surface microbicidal assay. Lastly, we assessed the in vivo antimicrobial activity in a mouse subcutaneous implant infection model with S. aureus administered locally on the QAC-coated implants prior to implantation to mimic contamination during surgery. Results. Detailed material characterization of the titanium samples showed the presence of a homogenous and stable coating layer at the titanium surface. Moreover, the coating successfully killed S. aureus and S. epidermidis in vitro. The QAC-coating strongly reduced S. aureus colonization of the implant surface as well as of the surrounding tissue, with no apparent macroscopic signs of toxicity or inflammation in the peri-implant tissue at 1 and 4 days after implantation. Conclusions. An antimicrobial coating with stable quaternary ammonium compounds on titanium has been developed which holds promise to prevent BAI. Non-antibiotic-based antimicrobial coatings have great significance in guiding the design of novel antimicrobial coatings in the present, post-antibiotic era

Introduction. Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. The purpose of this study is to establish a clinically representative GN-PJI model that can reliably recapitulate biofilm formation on titanium implant surface in vivo. We hypothesized that biofilm formation on an implant surface will affect its ability to osseointegrate. Methods. The model was developed using 3D-printed titanium hip implants, to replace the femoral head of male Sprague-Dawley rats. GN-PJI was induced using two bioluminescent Pseudomonas aeruginosa strains: a reference strain (PA14-lux) and a mutant biofilm-defective strain (ΔflgK-lux). Infection was monitored in real-time using the in vivo imaging system (IVIS) and Magnetic Resonance Imaging (MRI). Bacterial loads on implant surface and in periprosthetic tissues were quantified utilizing viable-colony-count. Field-emission scanning-electron-microscopy of the explanted implants was used to visualize the biofilm formation at the bone-implant-interface. The implant stability, as an outcome, was directly assessed by quantifying the osseointegration in vitro using microCT scan, and indirectly assessed by identifying the gait pattern changes using DigiGait. TM. system in vivo. Results. Localized infection was established within the hip joint and was followed by IVIS in real-time. There was a quantitative and qualitative difference in the bacterial load and biofilm formation between PA14-lux and ΔflgK-lux. This difference in the ability to persist in the model between the two strains was reflected in the gait pattern and implant osseointegration. Conclusions. We developed a novel uncemented hip hemiarthroplasty, GN-PJI rat model. To date, the proposed in vivo biofilm-based model is the most clinically representative for GN-PJI since animals can bear weight on the implant and poor osseointegration correlates with biofilm formation. In addition, localized PJI was detected by various modalities. Clinical Relevance. The proposed in vivo GN-PJI model will allow for more reliable testing of novel biofilm-targeting therapeutics

We present the indications and outcomes of a series of custom 3D printed titanium acetabular implants used over a 9 year period at our institution (Sydney, Australia), in the setting of revision total hip arthroplasty. Individualised image-based case planning with additive manufacturing of pelvic components was combined with screw fixation and off-the-shelf femoral components to treat patients presenting with failed hip arthroplasty involving acetabular bone loss. Retrospective chart review was performed on the practices of three contributing surgeons, with an initial search by item number of the Medicare Benefits Scheme linked to a case list maintained by the manufacturer. An analysis of indications, patient demographics and clinical outcome was performed. The cohort comprised 65.2% female with a median age of 70 years (interquartile range 61–77) and a median follow up of 32.9 months (IQR 13.1 - 49.7). The indications for surgery were infection (12.5%); aseptic loosening (78.1%) and fracture (9.4%), with 65.7% of cases undergoing previous revision hip arthroplasty. A tumour prosthesis was implanted into the proximal femur in 21.9% of cases. Complications were observed in 31.3% of cases, with four cases requiring revision procedures and no deaths reported in this series. Kaplan-Meier analysis of all-cause revision revealed an overall procedure survival of 88.7% at two years (95%confidence interval 69 - 96.2) and 83.8% (95%CI 62 - 93.7) at five years, with pelvic implant-specific survival of 98% (95%CI 86.6 - 99.7) at two and five year follow up. We conclude that an individualised planning approach for custom 3D printed titanium acetabular implants can provide high overall and implant-specific survival at up to five years follow up in complex cases of failed hip arthroplasty and acetabular bone loss

Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. To date, there are no animal models that can fully recapitulate how a biofilm is challenged in vivo in the setting of GN-PJI. The purpose of this study is to establish a clinically representative GN-PJI in vivo model that can reliably depict biofilm formation on titanium implant surface. We hypothesized that the biofilm formation on the implant surface would affect the ability of the implant to be osseointegrated. The model was developed using a 3D-printed, medical-grade titanium (Ti-6Al-4V), monoblock, cementless hemiarthroplasty hip implant. This implant was used to replace the femoral head of a Sprague-Dawley rat using a posterior surgical approach. To induce PJI, two bioluminescent Pseudomonas aeruginosa (PA) strains were utilized: a reference strain (PA14-lux) and a mutant strain that is defective in biofilm formation (DflgK-lux). PJI development and biofilm formation was quantitatively assessed in vivo using the in vivo imaging system (IVIS), and in vitro using the viable colony count of the bacterial load on implant surface. Magnetic Resonance Imaging (MRI) was acquired to assess the involvement of periprosthetic tissue in vivo, and the field emission scanning electron microscopy (FE-SEM) of the explanted implants was used to visualize the biofilm formation at the bone-implant interface. The implant stability, as an outcome, was directly assessed by quantifying the osseointegration using microCT scans of the extracted femurs with retained implants in vitro, and indirectly assessed by identifying the gait pattern changes using DigiGaitTM system in vivo. A localized prosthetic infection was reliably established within the hip joint and was followed by IVIS in real-time. There was a quantitative and qualitative difference in the bacterial load and biofilm formation between PA14 and DflgK. This difference in the ability to persist in the model between the two strains was reflected on the gait pattern and implant osseointegration. We developed a novel uncemented hip hemiarthroplasty GN-PJI rat model. This model is clinically representative since animals can bear weight on the implant. PJI was detected by various modalities. In addition, biofilm formation correlated with implant function and stability. In conclusion, the proposed in vivo GN-PJI model will allow for more reliable testing of novel biofilm-targeting therapetics

Massive irreparable rotator cuff tears often lead to superior migration of the humeral head, which can markedly impair glenohumeral kinematics and function. Although treatments currently exist for treating such pathology, no clear choice exists for the middle-aged patient demographic. Therefore, a metallic subacromial implant was developed for the purpose of restoring normal glenohumeral kinematics and function. The objective of this study was to determine this implant's ability in restoring normal humeral head position. It was hypothesized that (1) the implant would restore near normal humeral head position and (2) the implant shape could be optimized to improve restoration of the normal humeral head position. A titanium implant was designed and 3D printed. It consisted of four design variables that varied in both implant thickness (5mm and 8mm) and curvature of the humeral articulating surface (high constraint and low constraint. To assess these different designs, these implants were sequentially assessed in a cadaver-based biomechanical testing protocol. Eight cadaver specimens (64 ± 13 years old) were loaded at 0, 30, and 60 degrees of glenohumeral abduction using a previously developed shoulder simulator. An 80N load was equally distributed across all three deltoid heads while a 10N load was applied to each rotator cuff muscle. Testing states included a fully intact rotator cuff state, a posterosuperior massive rotator cuff tear state (cuff deficient state), and the four implant designs. An optical tracking system (Northern Digital, Ontario, Canada) was used to record the translation of the humeral head relative to the glenoid in both superior-inferior and anterior-posterior directions. Superior-Inferior Translation. The creation of a posterosuperior massive rotator cuff tear resulted in significant superior translation of the humeral head relative to the intact cuff state (P=0.016). No significant differences were observed between each implant design and the intact cuff state as all implants decreased the superior migration of the humeral head that was observed in the cuff deficient state. On average, the 5mm low and high constraint implant models were most effective at restoring normal humeral head position to that of the intact cuff state (-1.3 ± 2.0mm, P=0.223; and −1.5 ± 2.3mm, P=0.928 respectively). Anterior-Posterior Translation. No significant differences were observed across all test states for anterior-posterior translation of the humeral head. The cuff deficient on average resulted in posterior translation of the humeral head, however, this was not statistically significant (P=0.128). Both low and high constraint implant designs were found to be most effective at restoring humeral head position to that of the intact cuff state, on average resulting in a small anterior offset (5mm high constraint: 2.0 ± 4.7mm, P=1.000; 8mm high constraint: 1.6 ± 4.9mm, P=1.000). The 5mm high constraint implant was most effective in restoring normal humeral head position in both the superior-inferior and anterior-posterior directions. The results from this study suggest the implant may be an effective treatment for restoring normal glenohumeral kinematics and function in patients with massive irreparable rotator cuff tears. Future studies are needed to address the mechanical efficiency related to arm abduction which is a significant issue related to patient outcomes

Aim. Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty. While research has focused on developing better tests for disease diagnosis, treatment options have stayed relatively constant over the years with high failure rates ranging from 30%–50% and are due in part to the protective biofilm produced by some bacterial species. Current treatment options are compromised by the presence of biofilm, emphasizing the need for novel treatment strategies to be developed. Our group has developed a novel treatment (PhotothermAA) which has demonstrated in vitro its ability to target bacterial biofilm. The purpose of this study was to test this PhotothermAA technology in vivo in a rabbit model of PJI for its efficacy in eradicating biofilm. Method. Rabbits were fitted with a titanium implant into the tibial plateau and inoculated with 5×10. 6. CFU Xen36 (luminescent Staphylococcus aureus). At two weeks, rabbits underwent irrigation and debridement and treatment with PhotothermAA gel for two hours and subsequently laser heated using an 808 nm laser for 10 minutes. Gel was washed out and implant was removed for quantitative biofilm coverage analysis via scanning electron microscopy (SEM, n=3 for control and n=2 for PhotothermAA treated). Periprosthetic tissue was collected before and after treatment for toxicity studies via hemotoxylin and eosin (H&E) staining and scored for necrosis by three blinded reviewers (n=5 per group). Student's t-test was used for statistical analysis. Results. Implants isolated after PhotothermAA gel treatment had less biofilm coverage on the surface of the implant compared to non-treated control via SEM analysis (36.9% vs. 55.2%, p<0.14). PhotothermAA gel treatment and subsequent laser treatment was not harmful to surrounding tissue as no increase in necrotic tissue was observed. Conclusions. PhotothermAA gel and laser treatment safely decreases biofilm coverage on infected knee implants in a rabbit PJI model

Background. One of the serious postoperative complications associated with joint replacement is bacterial infection. In our recent investigations, iodine supported titanium implants demonstrated antibacterial activity in both in vitro studies and clinical trials. But it is not clear whether iodine treated titanium implants produce strong bonding to bone. This study evaluated the bone bonding ability of titanium implants with and without iodine surface treatments. Methods. Titanium rods were implanted in intramedullary rabbit femur models, in regard to the cementless hip stem. The implant rods were 5mm in diameter and 25mm in length. Half of the implants were treated with iodine (ID implants) and the other half were untreated (CL implants). The rods were inserted into the distal femur; ID implants into the right femur and CL implants into the left. We assessed the bonding strength by a measuring pull-out test at 4, 8, and 12 weeks after implantation. The bone-implant interfaces were evaluated at 4 weeks after implantation. Results. Pull-out test results of the ID implants were 202, 355, and 344 N, at 4, 8, and 12 weeks, respectively, significantly higher than those of the CL implants (102, 216, and 227 N). Histological examination revealed that new bone formed on the surface of both types of implants, but significantly more bone made direct contact with the surfaces of the ID implants. Conclusion. This research showed that new type of coating, iodine coated titanium has low toxicity and good osteoconductivity

Introduction: The mechanobiology and response of bone formation to strain under physiological loading is well established, however investigation into exceedingly soft scaffolds relative to cancellous bone is limited. In this study we designed and 3D printed mechanically-optimised low-stiffness implants, targeting specific strain ranges inducing bone formation and assessed their biological performance in a pre-clinical in vivo load-bearing tibial tuberosity advancement (TTA) model. The TTA model provides an attractive pre-clinical framework to investigate implant osseointegration within an uneven loading environment due to the dominating patellar tendon force. A knee finite element model from ovine CT data was developed to determine physiological target strains from simulated TTA surgery. We 3D printed low-stiffness Ti wedge osteotomy implants with homogeneous stiffness of 0.8 GPa (Ti1), 0.6 GPa (Ti2) and a locally-optimised design with a 0.3 GPa cortex and soft 0.1 GPa core (Ti3), for implantation in a 12-week ovine tibial advancement osteotomy (9mm). We quantitatively assessed bone fusion, bone area, mineral apposition rate and bone formation rate. Optimised Ti3 implants exhibited evenly high strains throughout, despite uneven wedge osteotomy loading. We demonstrated that higher strains above 3.75%, led to greater bone formation. Histomorphometry showed uniform bone ingrowthin optimised Ti3 compared to homogeneous designs (Ti1 and Ti2), and greater bone-implant contact. The greatest bone formation scores were seen in Ti3, followed by Ti2 and Ti1. Results from our study indicate lower stiffness and higher strain ranges than normally achieved in Ti scaffolds stimulate early bone formation. By accounting for loading environments through rational design, implants can be optimised to improve uniform osseointegration. Design and 3D printing of exceedingly soft titanium orthopaedic implants enhance strain induced bone formation and have significant importance in future implant design for knee, hip arthroplasty and treatment of large load-bearing bone defects

Prosthetic joint infection (PJI) is a complex disease that causes significant damage to the peri-implant tissue. Developing an animal model that is clinically relevant in depicting this disease process is an important step towards developing novel successful therapies. In this study, we have performed a thorough histologic analysis of peri-implant tissue harvested post Staphylococcus aureus (S. aureus) infection of a cemented 3D-printed titanium hip implant in rats. Sprague-Dawley rats underwent left hip cemented 3D-printed titanium hemiarthroplasty via posterior approach under general anesthesia. Four surgeries were performed for the control group and another four for the infected group. The hip joint was inoculated with 5×10. 9. CFU/mL of S. aureus Xen36 prior to capsule closure. The animals were scarified 3 weeks after infection. The femur was harvested and underwent micro-CT and histologic analysis. Hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) stains were performed. Immunohistochemistry (IHC) using rabbit antibody for S. aureus was also used to localize bacterial presence within femur and acetabulum tissue . The histologic analysis revealed strong resemblance to tissue changes in the clinical setting of chronic PJI. IHC demonstrated the extent of bacterial spread within the peri-implant tissue away from the site of infection. The H&E and MT stains showed 5 main features in infected bone: 1) increased PMNs, 2) fibrovascular inflammation, 3) bone necrosis, and 4) increased osteoclasts 5) fibrosis of muscular tissue and cartilage. Micro CT data showed significantly more osteolysis present around the infected prosthesis compared to control (surgery with no infection). This is the first clinically relevant PJI animal model with detailed histologic analysis that strongly resembles the clinical tissue pathology of chronic PJI. This model can provide a better understanding of how various PJI therapies can halt or reverse peri-implant tissue damage caused by infection

Buechel and Pappas invented a modified version of LCS RP system (Co-Cr) with light material (Titanium), axial rotation limiting bar and improved conformity. The purpose of this prospective randomized study was to compare the minimum 3-year clinical outcomes including lightness, preference, and instability between the Co-Cr implant system and the Titanium implant system in bilateral total knee arthroplasty. We prospectively enrolled 108 patients and 20 patients were lost to follow-up. Therefore, 88 patients (176 knees; mean age, 69.9±6.0years) were included in the study. The range of motion and clinical scores such as Knee Society score (KSS), Hospital for Special Surgery score (HSS) and Western Ontario and McMaster University (WOMAC) scores were measured preoperatively and postoperatively. At each follow-up, patients also complete a Likert scale questionnaire regarding subjective pain, lightness, left-right side preference (naturalness and satisfaction) and subjective instability. There were no significant differences in all preoperative variables between two groups (p>.05). Mean follow-up period was 46.3±8.8 (36 to 72) months. The mean weight of Titanium implants was three times lighter than that of Co-Cr implants (133.9g versus 390.1g, p<.01). At the minimum of 3-year follow-up, there were no significant differences in pain, range of motion (ROM), clinical scores including KSS, HSS, and WOMAC between both groups. Also, the study showed no significant differences with subjective pain, lightness, preference (convenience, naturalness, and satisfaction), and subjective instability between the Co-Cr protheses and the Titanium protheses (p>.05). No differences in clinical outcomes as well as subjective side-to-side differences between the Co-Cr prostheses and the Titanium prostheses were observed in the minimum 3-year follow-up. This implies that patients do not feel differently with two different weighted implants in mid-term follow-up

Introduction. Recent advances in nano-surface modification technologies are improving osseointegration response between implant materials and surrounding tissue. Living cells have been shown to sense and respond to cues on the nanoscale which in turn direct stem cell differentiation. One commercially practical surface treatment technique of particular promise is the modification of titanium implant surfaces via electrochemical anodization to form arrays of vertically aligned, laterally spaced titanium oxide (TiO2) nanotubes on areas of implants where enhanced implant–to-bone fixation is desired. Foundational work has demonstrated that the TiO2 nanotube surface architecture significantly accelerates osteoblast cell growth, improves bone-forming functionality, and even directs mesenchymal stem cell fate. The initial in vitro osteoblast cell response to such TiO2 nanotube surface treatments and corresponding in vivo rabbit tissue response are evaluated. Methods. Arrays of 30, 50, 70, 100nm diameter TiO2 nanotubes formed onto titanium surfaces were compared to grit blasted titanium controls in vitro (Figure 1). SEM micrographs of bovine cartilage chondrocytes (BCCs) on the nanotube surfaces were evaluated after 2 hours, 24 hours, and 5 days of culture. Additionally 20 samples each of various nanotube diameters and the non-nanotube treated titanium controls were evaluated after exposure to human mesenchymal stem cell (hMSC) after 2 hours and 24 hours. The left tibia and right tibia of four rabbits were implanted with disk shaped titanium implants (5.0 mm dia. × 1.5 mm) with and without TiO2 nanotubes. The front side of each implant faced the rabbit tibia bone and the back side of the implant had screw holes for post-in vivo tensile testing. After 4 weeks, the bones with implants were retrieved for mechanical testing and histology analysis. Comparative osteogenic behavior on metal oxide nanotube surfaces applied to other implant material surface chemistries including ZrO2, Ta, and Ta2O5 were also evaluated along with TiO2 nanotubes formed on a thin films of titanium on the surface of zirconia and CoCr alloy orthopedic implants. Results. A striking difference in ECM fibril formation and cell clustering on the nanotube substrates is evident in larger diameter nanotubes compared to non-treated titanium as shown by the arrows in Figure 2. The average fracture strength was significantly higher for TiO2 nanotube implants (10.8 N) compared to the grit blasted titanium control implants (1.2 N). The histology at week 4 shown in Figure 3 confirms direct bonded growth of new bone onto the nanotubes with a significantly less trapped amorphous tissue at the implant-bone interface compared to the control. Conclusions. The TiO2 nanotubes significantly enhanced the adhesion and growth of osteoblast cells (in vitro) by 300 to 400% as compared to non-nanostructure surfaces. In vivo implant tests indicate enhanced osseointegration of new bone cells on the TiO2 nanotube implant surface, with a 600% improvement in adhesion strength compared to conventional sand-blasted titanium surfaces. Discussion. Both in vitro and in vivo analysis indicates that TiO2 nanotubes enhance the speed and proliferation of osseointegration. This surface treatment technique can be applied to non-porous or porous surfaces on implants where optimized bone fixation is desired

Introduction. The use of Additive Manufacturing (AM) to 3D print titanium implants is becoming widespread in orthopaedics, particularly in producing cementless porous acetabular components that are either custom-made or off-the-shelf; the primary design rationale for this is enhanced bony fixation by matching the porosity of bone. Analysis of these retrieved components can help us understand their performance; in this study we introduce a non-destructive method of the retrieval analysis of 3D printed implants. Material and methods. We examined 11 retrieved 3D printed acetabular cups divided into two groups: “custom-made” (n = 4) and “off-the-shelf” (n = 7). A macroscopic visual analysis was initially performed to measure the area of tissue ongrowth. High resolution imaging of each component was captured using a micro-CT scanner and 3D reconstructed models were used to assess clinically relevant morphometric features of the porous structure: porosity, porous structure thickness, pore size and strut thickness. Optical microscopy was also used as a comparison with microCT results. Surface morphology and elemental composition of the implants were investigated with a Scanning Electron Microscope (SEM) coupled with an Energy Dispersive X-ray Spectroscope (EDS). Statistical analysis was performed to evaluate possible differences between the two groups. Results. We found a spread of tissue coverage, median of 81% (23 – 95), with a trend with time in situ. Custom implants showed a higher spread of porosity, with median value of 74.11% (67.94 – 81.01), due to the presence of differently designed porous areas. Off-the-shelf cups had median porosity of 72.49% (66.67 – 73.07), but there was no significant difference between the two groups (p = 0.164). There was a significant difference in the thickness of the porous structure of the two groups, which were 3.918 mm (3.688 – 4.102) and 1.289 mm (1.235 – 1.364), respectively (p = 0.006). SEM output showed specific morphological features of 3D printed object; EDS analysis suggested that no chemical modifications occurred in vivo, with elemental ratios (Ti/Al = 14; Ti/V = 21; Al/V = 1.51) comparable to previously published results. Conclusion. This is one of the first retrieval studies of 3D printed orthopaedic implants. We introduced a method for the investigation of these components and micro-CT scanning enabled the non-destructive assessment of the porous structure. This work represents the first step in understanding the performance of 3D printed implants

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

Additive manufacturing has enabled a radical change in how surgeons reconstruct massive acetabular defects in revision hip surgery. We report on the early clinical and radiological results from our methods for surgical planning, design, and implantation of 3D printed trabecular titanium implants in a cohort of patients with large unclassifiable pelvic defects. We set up a prospective investigation involving 7 consecutive patients. Inclusion criteria was the following: 1) A history of previous total hip replacement; and 2) Current imaging showing at least a Paprosky 3B defect. Planned acetabular inclination and version was 40° and 20° respectively. Post operatively all patients had a CT scan which was analysed with software to determine component position and compared to planned. Outpatient review was done at 2 weeks (For wound), 6 weeks (for weight bearing and fixation) and 52 weeks (for fixation and infection) post-operative. The median age at surgery was: 65 years (40–78). The median bone defect volume was 140cm. 3. Median surgery length was 5.2 hours (3–6.25). Median blood loss was 1300mL (450– 2000). Radiologically, components were stable and no screw breakages were identified. Achieved inclination was 41.0° (29.0–55.6) and achieved version was 15.8° (3.8–43.6). Median Oxford Hip score improved from 9 (2–44) to 25 (18–32). We have demonstrated a new series of pre, intra and post-operative methods for reconstruction of unclassifiable acetabular bony defects. Initial clinical and radiological results are excellent considering the severity of the bony defects. We recommend the use of our or similar methods when trying to reconstruct these defects

Introduction. Total hip arthroplasty has seen a transition from cemented acetabular components to press-fit porous coated components. Plasma sprayed titanium implants are often press-fit with 1mm under-reaming of the acetabulum; however, as porous coating technologies evolve, the amount of under-reaming required for initial stability may be reduced. This reduction may improve implant seating due to lowered insertion loads, and reduce the risk of intraoperative fracture. The purpose of this study was to investigate the initial fixation provided by a high porosity coating (P2, DJO Surgical), and a plasma sprayed titanium coating under rim loading with line-to-line and 1mm press-fit surgical preparation. Methods. Five, 52mm high porosity acetabular cups (60% average porosity) and five 52mm plasma sprayed titanium coated cups were inserted into low density (0.24g/cc) biomechanical test foam (Pacific Research Laboratories). Foam test material was cut into uniform 90×90×40mm blocks. Reaming was performed using standard instrumentation mounted on a vertical mill. Cups were first inserted into foam blocks prepared with line-to-line (52mm) reaming. Following mechanical testing, cups were removed from the foam, cleaned, and inserted into foam blocks prepared with 1mm under reaming (51mm). In total 4 test conditions were evaluated:. Group A: P2 + line-to-line. Group B: Plasma sprayed + line-to-line,. Group C: P2 + 1mm under-reaming. Group D: Plasma sprayed + 1mm-under reaming. Acetabular cup impaction was carried out using a single axis servohydraulic test machine (Instron 8500). Cups were inserted at 1mm/s to a load of 5kN. Insertion load was calculated as a 0.1mm offset from the linear portion of the force/displacement curve; insertion energy was the area under the curve. Tangential rim loading was applied at 0.0254mm/s by a conical indenter to the implant rim. Load data were recorded at 1kHz. Cup displacement was recorded by a 3D, marker-based tracking system at 15Hz (DMAS, Spicatek). Six markers were attached to a disk secured in the acetabular cup (Figure 1). Yield failure was defined as 0.331o of angular displacement (150µm of relative displacement). Angular displacement was derived by calculating the normal vector of a best-fit plane based on marker centroids. Results. Under-reamed groups (C,D) showed statistically higher insertion loads and insertion energies than line-to-line groups (A,B), with group C requiring the highest insertion load. Despite greater ease of insertion, groups A and B attained comparable yield loads with group A statistically outperforming D. Group C attained the highest ultimate failure loads, outperforming A and D (Figure 2). Discussion. Implants with high porosity coating and line-to-line preparation required less effort for full seating and maintained yield and ultimate performance which exceeded, or was comparable to, plasma sprayed titanium coated implants in either under-reamed or line-to-line preparation. Limitations of this study include the use of a mill for foam block preparation and automated implant insertion. Initial results in three matched cadaveric acetabular pairs with line-to-line preparation indicate that the advantages of high porosity coating may be preserved in human tissue with average yield failure and ultimate failure load improvements of 108% and 73% respectively (Figure 3). Study is ongoing

Aim. The aim of this study was to establish an implant-associated osteomyelitis model in rats with the ability to quantify biofilm formation on implants for prospective evaluation of antibacterial effects on micro-structured implant surfaces. Method. Staphylococcus aureus (strain 36/07) suspension with infection concentrations of 106, 105, 104 and 10. 3. CFU/10µl, respectively was injected in the tibia of 32 rats (n=8 per group). Afterwards a titanium implant (0.8×0.8×12 mm) was inserted. 8 rats were implanted with a preincubated implant (107 CFU/ml, 12 h) and 8 rats served as a control (injection of 0.9% NaCl). During the follow up, clinical, radiographic and µ-CT examinations were conducted. On day 21 post op, all rats were sacrificed. Implant and tibia were explanted under sterile conditions. The implant was stained with green and red fluorescent nucleic acid dye (live/ dead) and analyzed by confocal microscopy. The amount of vivid and dead biomass as well as vivid bacteria on the implant surface was calculated with an image software*. Results. In all groups with artificial infection, local bacterial colonization could be detected without systemic infection. While clinical signs of infections (lameness, subcutaneous abscesses) decreased, the volume of bacterial colonization increased on the implant surface with decreasing initial infection CFU. Preincubated implants showed a similar bacterial colonialization of the surface as implants which were infected with 106 CFU as well as a similar bone disintegration due to ongoing osteomyelitis. Conclusions. Establishment of the implant-associated infection model in rats with subsequent quantification of the vivid bacterial volume via confocal microscopy was successful and is now applicable for the evaluation of micro-structured antibacterial implant surfaces. Pre incubation of implants with initiating biofilm formation was established as alternative onset of infection. This work was part of BIOFABRICATION for NIFE and funded by Volkswagen Foundation and MWK. * Imaris® ×64 6.2.1

Titanium knee, shoulder and hip implants are typically grit-blasted, thermal plasma spray coated, or sintered to provide ingrowth surface features having texture with pore sizes on the order of hundreds of micrometers. This provides macro and micro-mechanical locking upon bone remodeling. However, at the nanoscale and cellular level, these surfaces appear smooth. In vitro and in vivo research shows surfaces with nanoscale features result in enhanced osseointegration, greater bone-implant contact area and pullout force, and the potential to be bactericidal via a simple hybrid anodization surface modification process. Prior processes for creating nanotube nano-textured surfaces via electrochemical anodization relied on hydrofluoric acid electrolyte and platinum cathodes. This novel process uses ammonium fluoride electrolytes and graphite cathodes which are more cost effective and easier to handle during processing. Hybrid electrolytes with differing concentrations of ethylene glycol, water, and ammonium fluoride provide a variety of nanotube morphologies and sizes. Nano-tubular surfaces on knee tibial and femoral implants, hip stems and acetabular cups, bone screws and other 3D printed parts have been enhanced by this method of nano-texturing in as little as 30 minutes. In vivo work in a Sprague Dawley rat model showed bone-implant contact area up to 2.9-times greater, and uniaxial pullout forces up to 6.9-times greater, than implanted smooth titanium controls at 4 and 12-week time points. In these tests, 1.25mm Kirschner wires were implanted in the rat femora to simulate an intramedullary nail. Histomorphometry in the mid-shaft and distal regions showed greater trabecular thickness and bone tissue mineral density than controls. Axial pullout tests often resulted in bone failure before the bone-implant interface. In vitro evidence suggests that nanoscale surfaces may have an antibacterial effect due to surface energy changes that reduce the ability of bacteria to adhere. However, it is recognized that silver is highly antibacterial in appropriate concentrations. It is also recognized that nanosilver, approximately 10–20nm, is especially effective. Ammonium fluoride anodization is modified using a hybrid electrolyte that includes silver fluoride. By substituting some of the ammonium fluoride with silver fluoride, to maintain a constant total fluorine mass, nanosilver is integrated within and among the nanotubes in the same single process that forms the nanotubes. This hybrid process in nano-texturing titanium implants can be integrated into current manufacturing production at low cost

Aim. Implant-associated infection remains one of the biggest challenges facing orthopaedics and there is an urgent clinical need to develop new prophylactic strategies. We have previously shown that CSA-90, a broad-spectrum antimicrobial, prevented infection in an infected open fracture model. In this study we developed a novel model of implant-associated infection, in which to further test the potential of CSA-90 as a prophylactic agent. Method. All studies were approved by the local animal ethics committee. 3D-printed porous titanium implants were implanted into the distal femora of 18 week-old male Wistar rats under general anaesthesia. The treatment groups' (n=10) implants were pre-coated with 500μg CSA-90 in saline. Staphylococcus aureus* was inoculated either directly around the implant (1×104 CFU) or injected intravenously immediately post-operatively (1×105 CFU). No systemic antibiotic prophylaxis was used. The study ran for six weeks and animals were reviewed daily for signs of infection. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats demonstrating osteolysis and/or declining overall health were culled early at their instruction. The primary outcome was implant infection, incorporating survival, microbiological, radiological, and histological measures. Results. All untreated animals inoculated with S. aureus developed clinical and radiographic evidence of implant infection and were culled within 14 days of surgery (Figure 1A). CSA-90 treatment significantly increased median survival in groups inoculated with S. aureus (p<0.001). Swab culture demonstrated that CSA-90 treated implants had a significantly reduced rate of infection compared to untreated implants in both the local (p< 0.01) and systemic (p<0.001) groups (Figure 1B). Conclusions. This study demonstrates clinical potential for CSA-90 as a novel prophylactic antimicrobial for orthopaedics. Further in vivo evaluation is required in conjunction with existing systemic antibiotic prophylaxis. Acknowledgements. This work was funded by NHMRC grant 1106982. Implants and CSA-90 were donated in kind support from Stryker and N8 Medical respectively. For any figures and tables, please contact authors directly (click on ‘Info & Metrics’ tab above for contact details)

Introduction. Trabecular titanium implants are 3D printed with a high-friction ingrowth surface that is continuous with the rest of the acetabular shell. The ability to “face-change” following optimum seating of the component allows unprecedented levels of versatility in acetabular orientation. Bolt-on augments enable rapid trialling and definitive insertion of a monobloc construct. The use of these implants has rapidly increased in the National Joint Registry over the last three years with little published outcome data. We present one of the largest studies using this material. Objectives. This study assesses the early stability, ingrowth and clinical outcome of revision acetabular reconstruction with trabecular titanium. Methods. 120 consecutive acetabular revisions were prospectively evaluated radiographically and clinically with a 2 to 5 year follow-up. Results. The indications for revision were aseptic loosening (84) infection (20), dislocation/ instability (9), metallosis (6) and impingement (1). The defects were classified as type I in 2 cases, IIA in 26, IIB in 47, IIC in 15, IIIA in 25 and IIIB in 5. External augments were used in 16 cases and face changing liners in 40 cases. Mean preoperative Oxford Hip Score was 24 (range 13–33) with a postoperative mean score of 36 (range 13–46). No patients were lost to follow-up which was from 2 to 4 years (mean 3 years). Two cases were subsequently revised for infection and two for instability. One case was revised for material failure as a result of a cross-threaded screw. There were no cases of aseptic loosening and all remaining implants appear well-integrated radiographically. Conclusions. These early results are very encouraging with excellent initial stability clinically and radiographically. The versatility of face-changing liners, multiple bearing options and bolt-on augments allows rapid and accurate reconstruction. The data support the use of this material and we will continue to report the outcome of this series