Aims. This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night. Methods. In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation. Results. Micro-CT and histological evaluation showed that the bone microscopic parameters of femoral metaphysis trabecular bone and bone tissue around the titanium rod in the OVX + MD group demonstrated higher bone mineral density, bone volume fraction, trabecular number, connective density, trabecular thickness, and lower trabecular speculation (p = 0.004) than the OVX + MN group. Moreover, the biomechanical parameters of the OVX + MD group showed higher pull-out test and three-point bending test values, including fixation strength, interface stiffness, energy to failure, energy at break, ultimate load, and elastic modulus (p = 0.012) than the OVX + MN group. In addition, the bone metabolism index and oxidative stress indicators of the OVX + MD group show lower values of Type I collagen cross-linked C-telopeptide, procollagen type 1 N propeptide, and malondialdehyde (p = 0.013), and higher values of TAC and SOD (p = 0.002) compared with the OVX + MN group. Conclusion. The results of our study suggest that systemic administration with melatonin at 9 am may improve the initial osseointegration of titanium rods under osteoporotic conditions more effectively than administration at 9 pm. Cite this article: Bone Joint Res 2022;11(11):751–762

Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440

PEEK rods construct has been proposed to allow better load sharing among spinal components when compared to the more traditional Titanium rods constructs. However, such proposal has largely derived from single-load in-vitro testing and the biomechanical differences between the two constructs when subjected to fatigue loading remain unknown. Current study comparatively analyzed the in-vitro biomechanical performance of PEEK and Titanium rod constructs as spinal implants through a 5 hour fatigue loading test. The disc height and intradiscal pressure of the instrumented and adjacent levels pre- and post-loading were recorded for analysis. The stress levels on the rods and bone stress near the screw-bone interface were also collected to investigate the likely failure rates of the two constructs. The results showed that the Titanium rods construct demonstrated a minimum amount of loss of disc height and intradiscal pressure at the instrumented level, however, a significant loss of the disc height and intradiscal pressure at adjacent levels compared to the intact spine were identified. In contrast, the disc height and intradiscal pressure of the PEEK rods were found to be comparable to those of the intact spine for all levels. The PEEK rods group also showed significantly less bone stress near the screw-bone interface compared to the Titanium rods group. Current study has demonstrated the potential benefits of the PEEK rods construct in reducing the risks of adjacent segment disease and implant failure rates when compared to the more traditional Titanium rods construct

Introduction: Recombinant human bone morphogenetic protein-2 (rhBMP-2) (Infuse) has been shown to cause osteolysis rather than accelerated fusion in some series. This paper reports two cases of vertebral osteolysis in patients undergoing anterior cervical corpectomy with stabilization using titanium prosthesis where rhBMP-7 (OP1) has been used in high concentration. Methods: Case series and review of literature. Results: OP1 was used in 23 patients undergoing anterior cervical surgery. Each case had at least two CT scans during the first twelve months of follow-up. The two cases of osteolysis were identified amongst a subgroup of 8 patients undergoing anterior cervical corporectomy and reconstruction using a titanium rod and buttress implant. The first case was a 71 year old man who underwent C4-T1 corpectomy for spondylotic cord compression and the second case was a 62 year old man who underwent C3-T1 corpectomy for spondylotic cord compression. In both cases a bottle of OP1 (3.5mg) was mixed with 5mls of carboxy-methyl-cellulose/tri-calcium phosphate (CMC/TCP) putty, approximately half of which was then applied to the ends of the titanium rod and buttress prosthesis and compressed between the buttress end and the vertebral endplate, and some residual OP1-containing putty was placed at the sides of each buttress. CT scans performed at 3 months postoperative in case 1 and 3.5 months postoperatively in case 2 demonstrated osteolysis in the vertebral bodies adjacent to the implant. In both cases however, CT scans performed 12 months post-operatively showed that the osteolytic cysts were beginning to resolve and fusion at the bone-titanium junction may have begun. No other cases of cystic osteolysis were found amongst other anterior cervical cases or 115 posterior lumbar interbody fusion (PLIF) cases similarly followed-up with serial CT scans. The concentration of rhBMP-7 used in a subgroup of 8 corpectomy cases undergoing anterior cervical corporectomy and reconstruction using a titanium rod and buttress implant was at least twice the concentration used in other anterior cervical cases and approximately one quarter to one fifth the concentration used in lumbar interbody PLIF cages. Discussion: These are the first reported cases of osteolysis associated with the use of BMP-7. Osteolysis has been described in association with the use of rhBMP-2. Following these reports, the manufacturers of rhBMP-2 have advised surgeons strongly not to use more than the (recently) recommended dose, despite there being no published evidence that osteolysis is dose-related. Similar recommendations have not been made regarding the use of BMP-7 (OP1). The concentration of BMP-7 (OP1) which led to osteolysis in these cases was much greater than used elsewhere in the spine, where OP1 (3.5mg) is usually mixed with 10–15 mls of finely-milled autograft. This suggests that the concentration achieved by mixing 3.5 mg of OP1 with 5 mls of CMC/TPC putty may increase the risk of osteolysis when inserted into the anterior cervical spine

To date, all surgical techniques used for reconstruction of the pelvic ring following supra-acetabular tumour resection produce high complication rates. We evaluated the clinical, oncological and functional outcomes of a cohort of 35 patients (15 men and 20 women), including 21 Ewing’s sarcomas, six chondrosarcomas, three sarcomas not otherwise specified, one osteosarcoma, two osseous malignant fibrous histiocytomas, one synovial cell sarcoma and one metastasis. The mean age of the patients was 31 years (8 to 79) and the latest follow-up was carried out at a mean of 46 months (1.9 to 139.5) post-operatively. We undertook a functional reconstruction of the pelvic ring using polyaxial screws and titanium rods. In 31 patients (89%) the construct was encased in antibiotic-impregnated polymethylmethacrylate. Preservation of the extremities was possible for all patients. The survival rate at three years was 93.9% (95% confidence interval (CI) 77.9 to 98.4), at five years it was 82.4% (95% CI 57.6 to 93.4). For the 21 patients with Ewing’s sarcoma it was 95.2% (95% CI 70.7 to 99.3) and 81.5% (95% CI 52.0 to 93.8), respectively. Wound healing problems were observed in eight patients, deep infection in five and clinically asymptomatic breakage of the screws in six. The five-year implant survival was 93.3% (95% CI 57.8 to 95.7). Patients were mobilised at a mean of 3.5 weeks (1 to 7) post-operatively. A post-operative neurological defect occurred in 12 patients. The mean Musculoskeletal Tumor Society score at last available follow-up was 21.2 (10 to 27). This reconstruction technique is characterised by simple and oncologically appropriate applicability, achieving high primary stability that allows early mobilisation, good functional results and relatively low complication rates. Cite this article: Bone Joint J 2013;95-B:1410–16

Despite the myriad new spinal instrumentation systems, scoliosis can rarely be fully corrected, especially when the curves are stiff. A novel superelastic nickel-titanium (nitinol) rod that maximises the ability to slowly correct spinal deformities by utilising the viscoelastic properties of the spine has been developed. This parallel, double-blinded, randomised controlled trial compared the safety and efficacy of these new rods to conventional titanium rods in 23 patients with adolescent idiopathic scoliosis. The superelastic nitinol rods were found to be safe, could gradually correct scoliosis curves, and ultimately resulted in better coronal and sagittal alignments compared to traditional rods. Despite the myriad new spinal instrumentation systems, scoliosis can rarely be fully corrected, especially when the curves are stiff. A novel superelastic nickel-titanium (nitinol) rod that maximises the ability to slowly correct spinal deformities by utilising the viscoelastic properties of the spine has been developed. This parallel, double-blinded, randomised controlled trial compared the safety and efficacy of these new rods to conventional titanium rods in 23 patients with adolescent idiopathic scoliosis. The superelastic nitinol rods were found to be safe, could gradually correct scoliosis curves, and ultimately resulted in better coronal and sagittal alignments compared to traditional rods

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

Introduction. With the use of each pedicle screw for surgical correction of adolescent idiopathic scoliosis (AIS), there is an increase in instrumentation-related costs, operative time, risk of neural injury, and overall health-care expenses. As such, alternate level screw strategy (ALSS) has been reported as a potential alternative to contiguous multilevel screw strategy (CMSS). Moreover, studies have shown the importance in accounting for the flexibility of the curve based on the fulcrum bending radiograph when assessing postoperative curve correction. Therefore, this study addressed a radiographic and cost analysis comparing CMSS with ALSS for the treatment of thoracic AIS with titanium screws and rod application. Methods. 77 patients with AIS underwent surgery (range 6–15 levels). 35 patients received CMSS, which was characterised as bilateral screw fixation at every level. 42 patients underwent ALSS, which entailed bilateral screw fixation at alternate levels. Titanium rods were used in all cases. Preoperative and postoperative posteroanterior and fulcrum bending radiographic Cobb angles were obtained for all patients. The fulcrum flexibility and the fulcrum bending correction index (FBCI) were assessed. Cost analysis was also done. Results. We recorded a statistically significant difference between screw strategy-type to that of preoperative and postoperative Cobb angles, and postoperative curve correction (p<0·05). No statistically significant difference was noted between screw strategy-type and fulcrum flexibility (CMSS mean 66·9%; ALSS mean 62·7%; p>0·05). The mean FBCIs of the CMSS and ALSS were 126·1% and 122·1%, respectively, and did not differ significantly (p=0·734). Compared with CMSS, ALSS was associated with pedicle screw cost reductions of up to 46·2%. Conclusions. This study is the first to show that irrespective of curve rigidity, ALSS with fewer pedicle screws can achieve comparable FBCI as CMSS. We attribute this finding to the relatively flexible titanium rods used in this study. Thus, ALSS is as effective as CMSS in terms of coronal curve correction, and it has the added benefits of reducing operative time and neurological complication risk. Furthermore, it offers the possibility of better kyphosis restoration compared with the lordosing effect of CMSS

The purpose of this study is to evaluate risk factors for distal construct failure (DCF) in posterior spinal instrumented fusion (PSIF) in adolescent idiopathic scoliosis (AIS). We observed an increased rate of DCF when the pedicle screw in the lowest instrumented vertebra (LIV) was not parallel to the superior endplate of the LIV, however this has not been well studied in the literature. We hypothesise a more inferiorly angled LIV screw predisposes to failure and aim to find the critical angle that predisposes to failure. A retrospective cohort study was performed on all patients who underwent PSIF for AIS at the Starship Hospital spine unit from 2010 to 2020. On a lateral radiograph, the angle between the superior endplate of the LIV was measured against its pedicle screw trajectory. Data on demographics, Cobb angle, Lenke classification, instrumentation density, rod protrusion from the most inferior screw, implants and reasons for revision were collected. Of 256 patients, 10.9% (28) required at least one revision. The rate of DCF was 4.6% of all cases (12 of 260) and 25.7% of revisions were due to DCF. The mean trajectory angle of DCF patients compared to all others was 13.3° (95%CI 9.2° to 17.4°) vs 7.6° (7° to 8.2°), p=0.0002. The critical angle established is 11°, p=0.0076. Lenke 5 and C curves, lower preoperative Cobb angle, titanium only rod constructs and one surgeon had higher failure rates than their counterparts. 9.6% of rods protruding less than 3mm from its distal screw disengaged. We conclude excessive inferior trajectory of the LIV screw increases the rate of DCF and a screw trajectory greater than 11° predisposes to failure. This is one factor that can be controlled by the surgeon intraoperatively and by avoiding malposition of the LIV screw, a quarter of revisions can potentially be eliminated

Purpose: Many surgical techniques have been described for the treatment of pathological fractures due to aggressive unicameral bone cysts in order to varying rates of success and incomplete healing or recurrence. Many Authors suggested curettage and bone grafting as effective treatment in case of active lesion in children 8 – 12 years old, adjacent to the physis with width of the lesion exceeds that of the adjacent physis and recurrence or persistence. Due to invasive nature of operation this method non is preferred by several Authors : we preferred minimally invasive treatment consisting closed reduction and flexible with titanium rod (Nancy)intramedullary fixation for low operative morbidity whether for the fracture or for the cyst; in case of recurrence of the cyst the closed curettage of the cyst with arthroscopic technique can be applied successful. Methods: Between 2002–2004 40 aggressive unicameral cysts were observed as pathologic fractures in patients between 5–15 years old in these cases there was a significant loss of bone stock. The site of involvement was in 33 patients the metadiaphysis of humerus, in 7 the femur; radiograms reveal expanding lesion in metaphyseal-diaphyseal site with cortex tinned from its inner surface and erosion with infraction with displacement. The parents were informed about contextual presence of two lesions: the fracture and cyst. The proposed internal fixation with Nancy titanium rods heals the first and might heal the second lesion ; in case of failure this method do not exclude another possibility of treatment as arthroscopic curettage. The Nancy flexible intramedullary fixation was performed with retrograde access 3 0 4 mm. diameter. Two nails with “ Eiffel Tower” construction were inserted by two miniportals 1 centimetres far from the physis. Follow up of treated lesion was made with periodic x rays performed every 45 days. Results: In 36 patients after a 2-year period of observation the cyst has completely or incompletely healed but with a sufficient bone stock in the remainder four cases the arthroscopic procedure was performed. Curettage of cystic wall by trimmer blade and multiple miniportals 4,5 millimetres is the best way to treat all the cyst. In all the cases we used the standard optical cannula 30°. Conclusions: In conclusion minimally invasive treatment by Nancy rods and artrhoscopy can be effective because assure high incidence of favourable results by decompression-scaffolding of the lesions, the patient quickly recover natural life and school attendance

Objective: To emphasize the need to provide a controlled method of intra-operative reduction to correct fixed cervical flexion deformities in ankylosing spondylitis and to describe the technique involved. Design: The treatment of severe fixed cervical flexion deformity in ankylosing spondylitis represents a challenging problem that is traditionally managed by a corrective cervicothoracic osteotomy. The authors describe a method of controlled surgical reduction of the deformity, which eliminates saggital translation and reduces the risk of neurological injury. Subjects: 2 male patients aged 39 and 45 years old with ankylosing spondylitis presented with severe fixed flexion deformity of the cervical spine. Both patients had previously undergone a lumbar extension osteotomy to correct a severe thoracolumbar kyphotic deformity. As a result of the fixed cervical flexion deformity, marked restriction in forward gaze with ‘chin on chest’ deformity, feeding difficulties and personal hygiene were encountered in both. Their respective chin-brow to vertical angle was 60 and 72°. Somatosensory and motor evoked potentials were used throughout surgery. A combination of cervical lateral mass screws and thoracic pedicle screws were used. Interconnecting malleable rods were then fixed at the cervical end, thereby allowing them to slide through the thoracic clamps thus achieving a safe method of controlled closure of the cericothoracic osteotomy. When reduction was achieved, definitive pre-contoured titanium rods were interchanged. Halo-jacket was not considered necessary in view of the segmental fixation used. Results: Good anatomical reduction was achieved, with near complete correction of the deformities, restoration of saggital balances and forward gazes. There were no neurological deficits in either patient and the postoperative recoveries were uneventful. Both osteotomies united with no deterioration noted at 2 years. Conclusions: We illustrate a controlled method of surgical reduction during corrective cervicothoracic osteotomy of fixed cervical kyphosis in ankylosing spondylitis. This has been achieved with the use of a combination of cervical lateral mass screws and thoracic pedicle screws with interconnecting malleable rods that were later replaced with titanium rods. The authors believe that the unique technique described remains a technically demanding but adequate and safe approach for correcting such challenging deformities

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

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

The gold standard for PJI treatment comprises the use of antibiotic-loaded bone cement spacers, which are limited in their load bearing capacity[1]. Thus, developing an antibiotic-eluting UHMWPE bearing surface can improve the mechanical properties of spacers and improve the quality of life of PJI patients. In this study, we incorporated vancomycin into UHMWPE to investigate its elution characteristics, mechanical properties and its efficacy against an acute PJI in an animal model. Vancomycin hydrochloride was incorporated into UHMWPE (2 to 14%) by blending and consolidation. We studied drug elution with blocks in PBS and UV-Vis spectroscopy at 280 nm. We determined the tensile mechanical properties and impact strength [3]. We implanted osteochondral plugs in rabbits using either control UHMWPE, bone cement (40g) containing vancomycin (1g) and tobramycin (3.6g) or vancomycin-eluting UHMWPE (n=5) plugs in the patellofemoral groove of rabbits. All rabbits received a beaded titanium rod in the tibial canal. All groups received two doses of 5×10. 7. cfu of bioluminescent S. aureus in the distal tibial canal prior to insertion of the rod and the articular space after closure of the joint capsule. No intravenous antibiotics were used. Bioluminescence signal was measured when the rabbits expired, or at 21-day post-op. Hardware, polyethylene implants, and joint tissues were sonicated to further quantify live bacteria via plate seeding. Vancomycin elution increased with increasing drug loading. Vancomycin elution above MIC for 3 weeks and optimized mechanical properties were obtained at 6–7 wt% vancomycin loading in UHMWPE. In our lapine acute infection model using bioluminescent S. aureus, knees treated with UHMWPE without antibiotics and bone cement containing vancomycin and tobramycin had significantly higher bioluminescence compared to those treated with vancomycin-eluting UHMWPE. These results suggest that an antibiotic-eluting UHMWPE spacer with acceptable properties as a bearing surface could be used to treat periprosthetic joint infection in lieu of bone cement spacers and this could allow safer load bearing and a higher quality of life for the patients during treatment. In addition, this presents a safer alternative in cases where the second stage surgery for the implantation of new components is hindered

Introduction. Radiation cross-linking of ultrahigh molecular weight polyethylene (UHMWPE) has reduced the in vivo wear and osteolysis associated with bearing surface wear (1), significantly reducing revisions associated with this complication (2). Currently, one of the major and most morbid complications of joint arthroplasty is peri-prosthetic infection (3). In this presentation, we will present the guiding principles in using the UHMWPE bearing surface as a delivery device for therapeutic agents and specifically antibiotics. We will also demonstrate efficacy in a clinically relevant intra-articular model. Materials and Methods. Medical grade UHMWPE was molded together with vancomycin at 2, 4, 6, 8, 10 and 14 wt%. Tensile mechanical testing and impact testing were performed to determine the effect of drug content on mechanical properties. Elution of the drug was performed in phosphate buffered saline (PBS) for up to 8 weeks and the detection of the drug in PBS was done by UV-Vis spectroscopy. A combination of vancomycin and rifampin in UHMWPE was developed to address chronic infection and layered construct containing 1 mm-thick drug-containing UHMWPE in the non-load bearing regions was developed for delivery. In a lapine (rabbit) intra-articular model (n=6 each), two plug of the layered UHMWPE construct were placed in the trochlear grove of the rabbit femoral surface and a porous titanium rod with a pre-grown biofilm of bioluminescent S. Aureus was implanted in the tibia. Bioluminescent imaging was employed to visualize and quantify the presence of the bacteria up to 3 weeks. Results and Discussion. Increasing drug content decreased both the ultimate tensile strength (UTS) and the impact toughness of vancomycin-containing UHMWPE (Figure 1). Elution data and structural analysis suggested that a percolation threshold was reached at above 6 wt% drug in UHMWPE, which resulted in sustained drug delivery above the minimum inhibitory concentration (MIC; 1 mg/ml) for up to 8 weeks (Figure 2). The layered constructs implanted in rabbits were able to eradicate all detectable bacteria from the biofilm on the titanium surfaces implanted on the counterface (Figure 3), suggesting clinically relevant efficacy. Significance. To our knowledge, this is the first study showing the design and efficacy of an antibiotic-eluting UHMWPE bearing surface. Such a device has the potential of reducing all two-stage revisions to single-stage treatment with load-bearing components, enhancing the mobility and quality of life for the patients and reducing the cost of infection treatment in arthroplasty. For figures/tables, please contact authors directly.

Aim:. To evaluate the effect of a stiffer rod in normalising thoracic hypokyphosis in adolescent idiopathic scoliosis (AIS). Methods:. A retrospective review of AIS cases performed at our institution was carried out. In order to reduce variability, the analysis included only Lenke 1 cases which had all pedicle screw constructs, with similar constructs and implant density. Cases that underwent anterior release were excluded. All cases had the same implant (Expedium 5.5, Depuy-Synthes, Raynham, USA). The rod material differed in that some cases had 5.5 titanium, whilst others had 5.5 cobalt chrome. The preoperative and postoperative sagittal Cobb angle was measured. Results:. 35 patients met the inclusion criteria. 15 had titanium rods and 20 had cobalt chrome rods. The mean fulcrum correction index was similar between groups. The preoperative coronal and sagittal Cobb was similar between the two groups. There was no statistically significant difference in the postoperative sagittal Cobb between the two groups (ANOVA one way test). Discussion:. Despite the theoretical advantage of a stiffer construct improving the sagittal profile in AIS, this study identified no such benefit despite closely matching the two groups. All pedicle screw constructs do not seem to improve the sagittal profile despite the use of a stiffer rod. Conflict of interest:. Depuy-Synthes fund a fellow in this unit. Conflict Of Interest Statement: No conflict of interest

Currently, no clinical options are available to prevent infections on uncemented orthopedic implants. Therefore we investigated the efficacy of DAC-hydrogel (disposable antibacterial coating(1), Novagenit, Italy) as carrier for various agents to prevent infections in an in vivo implant-model. Titanium rods were implanted in the left tibiae in New Zealand White rabbits. Prior to implantation, the implant bed was contaminated with 10∧5 colony forming units S. aureus. In the experimental groups, the hydrogel was loaded prior to be coated on the rods with: 2%(w/v) vancomycin (Van2 group, N=6), 5%(w/v) vancomycin (Van5 group, N=6), 10%(w/v) bioactive glass (BonAlive, Finland) (BAG group, N=6), which is antibacterial(2) and osteoconductive(3), or 0.5%(w/v) N-acetyl cysteine (NAC group, N=6), which inhibits bacterial growth and decreases biofilm formation(4). In the control group, empty hydrogel was applied (Gel group, N=12). Blood values were measured weekly. Following explantation on day 28, the anterior tibia was processed for bacterial culture. The posterior tibia and rod were used for measuring bone-implant contact using micro-CT and for histopathology. Results of the experimental groups were compared to the Gel group results. The blood values in the Van2 and Van5 groups were lower on day 7. Moreover, culture results demonstrated less animals with an infection in both groups at day 28. In accordance, these groups showed lower grades for infection. Further, the Van2 group demonstrated more bone-implant contact. These results suggest that infection was reduced in the Van2 and Van5 groups. In contrast, blood values, histological grades, and bone-implant contact of the BAG and NAC groups were comparable with the Gel group. These results suggest that infection was not prevented in the BAG and NAC groups. Local application of vancomycin-loaded DAC-hydrogel successfully reduced implant-related infections. Loading of the hydrogel with BAG or NAC did not prevent infection. It is possible that BAG in powder form, as used in the present study, dissolved before the antibacterial effect could take place. Instead, BAG granules may be a viable alternative. Next, it is possible that the NAC concentration was too low to prevent infections in an in vivo environment, although this concentration was proven effective in vitro for its antibacterial properties

Introduction. About 2% of primary total joint replacement arthroplasty (TJA) procedures become infected. Periprosthetic joint infection (PJI) is currently one of the main reasons requiring costly TJA revisions, posing a burden on patients, physicians and insurance companies. 1. Currently used drug-eluting polymers such as bone cements offer limited drug release profiles, sometimes unable to completely clear out bacterial microorganisms within the joint space. For this study we determined the safety and efficacy of an antibiotic-eluting UHMWPE articular surface that delivered local antibiotics at optimal concentrations to treat PJI in a rabbit model. Materials and Methods. Skeletally mature adult male New Zealand White rabbits received either two non-antibiotic eluting UHMWPE (CONTROL, n=5) or vancomycin-eluting UHMWPE (TEST, n=5) (3 mm in diameter and 6 mm length) in the patellofemoral groove (Fig. 1). All rabbits received a beaded titanium rod in the tibial canal (4 mm diameter and 12 mm length). Both groups received two doses of 5 × 10. 7. cfu of bioluminescent S. aureus (Xen 29, PerkinElmer 119240) in 50 µL 0.9 % saline in the following sites: (1) distal tibial canal prior to insertion of the rod; (2) articular space after closure of the joint capsule (Fig. 1). None of the animals received any intravenous antibiotics for this study. Bioluminescence signal (photons/second) was measured when the rabbits expired, or at the study endpoint (day 21). The metal rods were stained with BacLight. ®. Bacterial Live-Dead Stain and imaged using two-photon microscopy to detect live bacteria. Hardware, polyethylene implants and joint tissues were sonicated to further quantify live bacteria via plate seeding. Results. All control rabbits expired within 7 days (Fig. 2a). One rabbit in the test group expired at day 7 and another at day 15. All control rabbits had positive bioluminescence (live bacteria), while none of the test rabbits did (Fig 2b). Kidney (creatinine and BUN) and liver functions (ALT and ALP) remained normal for all rabbits. All control rabbits showed positive bacterial culture after sonication, while all test rabbits were negative. Two-photon imaging showed 75±10 % viability for bacteria adhered to the metal rods in the control and no viability in the test group. Discussion. This rabbit model showed that vancomycin eluted from UHMWPE is sufficient to eradicate S. aureus in joint space and in between the bone-implant interface of tibial canal. One limitation of this study is the lack of intravenous antibiotic treatment, which is standard clinical practice. In addition, joint infections are often associated with already formed biofilms, which were not tested in this study. However, safety data (normal kidney and liver functions) and complete eradication of S. aureus is an encouraging finding. Conclusion. Vancomycin-eluting UHMWPE effectively eliminated bacteria in a rabbit model of acute peri-prosthetic joint infection. This material is promising as a replacement liner to treat joint infections in revision surgery. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Introduction and Aims: To determine differences in metal memory, at physiological temperatures, between 6mm stainless steel and titanium rods as a function of construct failure in scoliosis surgery. Method: Different length Ti and SST rods were contoured at room temperature with a radius of curvature of 30cm and incubated at 37±2°C. Rods were photographed biweekly over graph paper with a digital camera. The images were processed using Jandel Sigma Scan. A best-fit regression polynomial was used to calculate the average curvature. After 36 weeks, the curvature of each rod was normalised against the initial curvature and plotted against time, with a linear regression performed to assess changes in curvature, expressed as percent of change per year. Results: Changes in both SST rods and pre-bent Ti rod were within measurement error (0.52% increase for long SST, 0.26% decrease for short SST). In contrast, both manually bent Ti rods changed markedly (decreases of 6.76% and 5.2% for long and short Ti rods respectively). Conclusion: Continuous physiologic heat conduction may contribute to a loss of curvature in Ti rods due to memory properties. The ideal implant should retain the intended contour. Ti rods, subjected to physiologic heat, lost correction. The use of custom contoured Ti rods for the surgical correction of spinal deformities should be questioned