Aims. The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants. Methods. We compared two groups, one made via 3D-printing (n = 7) and the other using conventional techniques (n = 7). We collected implant details, type of surgery and removal technique, patient demographics, and clinical history. Bone integration was assessed by macroscopic visual analysis, followed by sectioning to allow undecalcified histology on eight sections (~200 µm) for each implant. The outcome measures considered were area of bone attachment (%), extent of bone ingrowth (%), bone-implant contact (%), and depth of ingrowth (%), and these were quantified using a line-intercept method. Results. The two groups were matched for patient sex, age (61 and 63 years), time to revision (30 and 41 months), implant size (54 mm and 52 mm), and porosity (72% and 60%) (p > 0.152). There was no difference in visual bony attachment (p = 0.209). Histological analysis showed greater bone ingrowth in 3D-printed implants (p < 0.001), with mean bone attachment of 63% (SD 28%) and 37% (SD 20%), respectively. This was observed for all the outcome measures. Conclusion. This was the first study to investigate osseointegration in retrieved 3D-printed acetabular implants. Greater bone ingrowth was found in 3D-printed implants, suggesting that better osseointegration can be achieved. However, the influence of specific surgeon, implant, and patient factors needs to be considered. Cite this article: Bone Joint Res 2021;10(7):388–400

Aims. To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. Methods. 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. Results. iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). Conclusion. iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260–269

Aims. Osseointegrated prosthetic limbs allow better mobility than socket-mounted prosthetics for lower limb amputees. Fractures, however, can occur in the residual limb, but they have rarely been reported. Approximately 2% to 3% of amputees with socket-mounted prostheses may fracture within five years. This is the first study which directly addresses the risks and management of periprosthetic osseointegration fractures in amputees. Methods. A retrospective review identified 518 osseointegration procedures which were undertaken in 458 patients between 2010 and 2018 for whom complete medical records were available. Potential risk factors including time since amputation, age at osseointegration, bone density, weight, uni/bilateral implantation and sex were evaluated with multiple logistic regression. The mechanism of injury, technique and implant that was used for fixation of the fracture, pre-osseointegration and post fracture mobility (assessed using the K-level) and the time that the prosthesis was worn for in hours/day were also assessed. Results. There were 22 periprosthetic fractures; they occurred exclusively in the femur: two in the femoral neck, 14 intertrochanteric and six subtrochanteric, representing 4.2% of 518 osseointegration operations and 6.3% of 347 femoral implants. The vast majority (19/22, 86.4%) occurred within 2 cm of the proximal tip of the implant and after a fall. No fractures occurred spontaneously. Fixation most commonly involved dynamic hip screws (10) and reconstruction plates (9). No osseointegration implants required removal, the K-level was not reduced after fixation of the fracture in any patient, and all retained a K-level of ≥ 2. All fractures united, 21 out of 22 patients (95.5%) wear their osseointegration-mounted prosthetic limb longer daily than when using a socket, with 18 out of 22 (81.8%) reporting using it for ≥ 16 hours daily. Regression analysis identified a 3.89-fold increased risk of fracture for females (p = 0.007) and a 1.02-fold increased risk of fracture per kg above a mean of 80.4 kg (p = 0.046). No increased risk was identified for bilateral implants (p = 0.083), time from amputation to osseointegration (p = 0.974), age at osseointegration (p = 0.331), or bone density (g/cm2, p = 0.560; T-score, p = 0.247; Z-score, p = 0.312). Conclusion. The risks and sequelae of periprosthetic fracture after press-fit osseointegration for amputation should not deter patients or clinicians from considering this procedure. Females and heavier patients are likely to have an increased risk of fracture. Age, years since amputation, and bone density do not appear influential. Cite this article: Bone Joint J 2020;102-B(2):162–169

Aims. Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods. Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results. NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition (Pad4-/-) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion. This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135–144

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

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

Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114

The development and pre-clinical evaluation of nano-texturised, biomimetic, surfaces of titanium (Ti) implants treated with titanium dioxide (TiO. 2. ) nanotube arrays is reviewed. In vitro and in vivo evaluations show that TiO. 2. nanotubes on Ti surfaces positively affect the osseointegration, cell differentiation, mineralisation, and anti-microbial properties. This surface treatment can be superimposed onto existing macro and micro porous Ti implants creating a surface texture that also interacts with cells at the nano level. Histology and mechanical pull-out testing of specimens in rabbits indicate that TiO. 2. nanotubes improves bone bonding nine-fold (p = 0.008). The rate of mineralisation associated with TiO. 2. nanotube surfaces is about three times that of non-treated Ti surfaces. In addition to improved osseointegration properties, TiO. 2. nanotubes reduce the initial adhesion and colonisation of Staphylococcus epidermidis. Collectively, the properties of Ti implant surfaces enhanced with TiO. 2. nanotubes show great promise. Cite this article: Bone Joint J 2018;100-B(1 Supple A):9–16

Aims. This study describes the Osseointegration Group of Australia’s Accelerated Protocol two-stage strategy (OGAAP-1) for the osseointegrated reconstruction of amputated limbs. Patients and Methods. We report clinical outcomes in 50 unilateral trans-femoral amputees with a mean age of 49.4 years (24 to 73), with a minimum one-year follow-up. Outcome measures included the Questionnaire for persons with a Trans-Femoral Amputation, the health assessment questionnaire Short-Form-36 Health Survey, the Amputation Mobility Predictor scores presented as K-levels, 6 Minute Walk Test and timed up and go tests. Adverse events included soft-tissue problems, infection, fractures and failure of the implant. Results. Our results demonstrated statistically significant improvements in all five outcome measures. A total of 27 patients experienced adverse events but at the conclusion of the study, all 50 were walking on osseointegrated prostheses. Conclusion. These results demonstrate that osseointegrated prostheses are a suitable alternative to socket-fit devices for amputees experiencing socket-related discomfort and that our strategy offers more rapid progress to walking than other similar protocols. Cite this article: Bone Joint J 2016;98-B:952–60

Introduction. Approximately 2,000 Skeletal transcutaneous osseointegration (STOI) procedures have been performed worldwide as of 2020, more than half of which have been performed by the Osseointegration Group of Australia using a press-fit technique with either ILP or OPL implant designs. Despite the consistently demonstrated clinical benefits, concerns regarding potential complications following STOI have slowed its widespread adoption. As more patients are followed for a longer period of time, longitudinal studies have confirmed complication rates are very acceptable, similar to those of total ankle and total elbow replacements. One of the major risk category is implant removal. The primary goal of this study was to investigate the complications and technical issues associated with transtibial osseointegration implant removal due to any cause. The focus here will be on the press-fit ILP and OPL implants, including the indications for removal and patient outcomes following removal. Materials & Methods. A review of our osseointegration registry between November 2010 and March 2022 was performed. Inclusion criteria were patients who have undergone removal of a transtibial osseointegration implant due to any cause. Selected patients either had a follow-up of at least two years or had their index osseointegration surgery at least two years prior to when the study was performed. Patients who have had osseointegration at other anatomic levels, and patients who underwent simultaneous total knee replacement with transtibial osseointegration were excluded from the registry search. Results. There were a total of 148 transtibial osseointegration procedures performed during the study period, with 97 (65.5%) performed in males and 51 (34.5%) performed in females. The average age at first stage osseointegration procedure is 50.4 years (range 16.8–87.9, SD 14.1). In the study cohort of 22 cases requiring implant removals, 12 (54.5%) were male and 10 (45.5%) were female. The average age at first stage osseointegration procedure in this cohort is 51.3 (range 37.4–82.6, SD 10.7) and average BMI 30.3 (range 21.9–40.9, SD 5.8). Although men comprised the majority of removals, women had a greater relative risk (Fisher exact test p=0.032). The average duration from time of STOI to removal was 2.6 years (range 0.1–6.8, SD 1.9) within this 11.5 year follow-up period. The most frequent indication was infection (54.6%, n=12) followed equally by pain (13.6%, n=3), aseptic loosening (13.6%, n=3) and implant fracture (13.6%, n=3), and lastly failure to integrate (4.6%, n=1). Conclusions. Of the 22 removals, 12 were reimplanted at the same anatomical level (10 were reimplanted within 6 months, 1 within 12 months, and 1 within 24 months). 11 of these cases currently wear their prosthetic legs for more than 13 hours daily. 1 case was recently reimplanted and still completing their loading program. Of the patients who were not reimplanted at the same anatomical level, 1 required proximal amputation with transfemoral osseointegration. 3 patients converted to traditional socket prostheses (TSP) due to pain, and 1 underwent proximal amputation and converted to TSP due to infection. 3 cases are currently awaiting transtibial osseointegration reimplantation, and 1 patient was deceased. 1 patient was lost to follow-up

Aims. Hydroxyapatite (HA)-coated collars have been shown to reduce aseptic loosening of massive endoprostheses following primary surgery. Limited information exists about their effectiveness in revision surgery. The aim of this study was to radiologically assess osteointegration to HA-coated collars of cemented massive endoprostheses following revision surgery. Methods. Retrospective review of osseointegration frequency, pattern, and timing to a specific HA-coated collar on massive endoprostheses used in revision surgery at our tertiary referral centre between 2010 to 2017 was undertaken. Osseointegration was radiologically classified on cases with a minimum follow-up of six months. Results. In all, 39 patients underwent radiological review at mean 43.5 months; 22/39 (56.4%) showed no osseointegration to the collar. Revision endoprostheses for aseptic loosening were less likely to show osseointegration compared with other indications for revision. Oncological cases with previous or current infection were more likely to show osseointegration to ≥ 1 collar side than those without evidence of prior infection. Conclusion. This seven-year review identified osseointegration of HA-coated collars after revision surgery is less likely (43.6%, 17/39) than after primary surgery. Young patients who undergo revision surgery following initial oncological indication may benefit the most from this collar design. Use in revision oncological cases with a history of infection may be beneficial. HA-coated collars showed limited benefit for patients undergoing revision for failed arthroplasty with history of infection. Cite this article: Bone Jt Open 2021;2(6):371–379

Introduction. Percutaneous EndoProsthetic Osseointegration for Limbs (PEPOL) facilitates improved quality of life (QOL) and objective mobility for most amputees discontent with their traditional socket prosthesis (TSP) experience. Some amputees desiring PEPOL have residual bone much shorter than the currently marketed press-fit implant lengths of 14–16 cm, potentially a risk for failure to integrate. We report on the techniques used, complications experienced, the management of those complications, and the overall mobility outcomes of seven patients who had femur distraction osteogenesis (DO) with a Freedom nail followed by PEPOL. Materials & Methods. Retrospective evaluation of a prospectively maintained database identified nine patients (5 females) who had transfemoral DO in preparation for PEPOL with two years of follow-up after PEPOL. Six patients had traumatic causes of amputation, one had perinatal complications, one was performed to manage necrotizing fasciitis and one was performed as a result of osteosarcoma. Results. The average age at which DO commenced was 39.4±15.9 years, and seven patients had their amputation more than ten years prior (average 25.5±18.8 years). The residual femurs on average started at 102.2±39.7 mm and were lengthened 58.1±20.7 mm, 98±45% of goal (99±161% of the original bone length). Five patients (56%) had a complication requiring additional surgery: four events of inadequate regenerate were managed with continued lengthening to desired goal followed by autograft placement harvested from contralateral femur reaming; one patient had the cerclage wires break which required operative replacement. All patients had osseointegration performed, at 355±123 days after the initial lengthening nail surgery. One patient had K-level >2 before DO, at a mean of 3.4±0.6 (2.6–4.4) years following osseointegration six patients had K-level >2. The 6 Minute Walk Test remained unchanged (267±56 vs 308 ± 117 meters). Patient self-rating of prosthesis function, problems, and amputee situation did not significantly change from before DO to after osseointegration. Six patients required additional surgery following osseointegration: six to remove fixation plates placed to maintain distraction osteogenesis length at osseointegration; two required irritation and debridement for infection. Conclusions. Extremely short residual femurs which make TSP use troublesome can be lengthening with externally controlled telescoping nails, and successfully achieve osseointegration. However, it is imperative to counsel patients that additional surgery to address inadequate regenerate or to remove painful hardware used to maintain fixation may be necessary. This may improve the amputee's expectations before beginning on a potentially arduous process

Percutaneous EndoProsthetic Osseointegration for Limbs (PEPOL) facilitates improved quality of life (QOL) and objective mobility for most amputee's discontent with their traditional socket prosthesis (TSP) experience. Some amputees desiring PEPOL have residual bone much shorter than the currently marketed press-fit implant lengths of 14-16 cm, potentially a risk for failure to integrate. We report on the techniques used, complications experienced, the management of those complications, and the overall mobility outcomes of seven patients who had femur distraction osteogenesis (DO) with a Freedom nail followed by PEPOL. Retrospective evaluation of a prospectively maintained database identified nine patients (5 females) who had transfemoral DO in preparation for PEPOL with two years of follow-up after PEPOL. Six patients had traumatic causes of amputation, one had perinatal complications, one was performed to manage necrotizing fasciitis and one was performed as a result of osteosarcoma. The residual femurs on average started at 102.2±39.7 mm and were lengthened 58.1±20.7 mm, 98±45% of goal (99±161% of the original bone length). Five patients (56%) had a complication requiring additional surgery. At a mean of 3.4±0.6 (2.6-4.4) years following osseointegration six patients had K-level >2. The 6 Minute Walk Test remained unchanged (267±56 vs 308 ± 117 meters). Patient self-rating of prosthesis function, problems, and amputee situation did not significantly change from before DO to after osseointegration. Six patients required additional surgery following osseointegration: six to remove fixation plates placed to maintain distraction osteogenesis length at osseointegration; two required irritation and debridement for infection. Extremely short residual femurs which make TSP use troublesome can be lengthening with externally controlled telescoping nails, and successfully achieve osseointegration. However, it is imperative to counsel patients that additional surgery to address inadequate regenerate or to remove painful hardware used to maintain fixation may be necessary. This may improve the amputee's expectations before beginning on a potentially arduous process

Introduction. Transtibial osseointegration (TFOI) for amputees has limited but clear literature identifying superior quality of life and mobility versus a socketed prosthesis. Some amputees have knee arthritis that would be relieved by a total knee replacement (TKR). No other group has reported performing a TKR in association with TTOI (TKR+TTOI). We report the outcomes of nine patients who had TKR+TTOI, followed for an average 6.5 years. Materials & Methods. Our osseointegration registry was retrospectively reviewed to identify all patients who had TTOI and who also had TKR, performed at least two years prior. Four patients had TKR first the TTOI, four patients had simultaneous TKR+TTOI, and one patient had 1 OI first then TKR. All constructs were in continuity from hinged TKR to the prosthetic limb. Outcomes were: complications prompting surgical intervention, and changes in daily prosthesis wear hours, Questionnaire for Persons with a Transfemoral Amputation (QTFA), and Short Form 36 (SF36). All patients had clinical follow-up, but two patients did not have complete survey and mobility tests at both time periods. Results. Six (67%) were male, average age 51.2±14.7 years. All primary amputations were performed to manage traumatic injury or its sequelae. No patients died. Five patients (56%) developed infection leading to eventual transfemoral amputation 36.0±15.3 months later, and 1 patient had a single debridement six years after TTOI with no additional surgery in the subsequent two years. All patients who had transfemoral amputation elected for and received transfemoral osseointegration, and no infections occurred, although one patient sustained a periprosthetic fracture which was managed with internal fixation and implant retention and walks independently. The proportion of patients who wore their prosthesis at least 8 hours daily was 5/9=56%, versus 7/9=78% (p=.620). Even after proximal level amputation, the QTFA scores improved versus prior to TKR+TTOI, although not significantly: Global (45.2±20.3 vs 66.7±27.6, p=.179), Problem (39.8±19.8 vs 21.5±16.8, p=.205), Mobility (54.8±28.1 vs 67.7±25.0, p=.356). SF36 changes were also non-significant: Mental (58.6±7.0 vs 46.1±11.0, p=.068), Physical (34.3±6.1 vs 35.2±13.7, p=.904). Conclusions. TKR+TTOI presents a high risk for eventual infection prompting subsequent transfemoral amputation. Although none of these patients died, in general, TKR infection can lead to patient mortality. Given the exceptional benefit to preserving the knee joint to preserve amputee mobility and quality of life, it would be devastating to flatly force transtibial amputees with severe degenerative knee joint pain and unable to use a socket prosthesis to choose between TTOI but a painful knee, or preemptive transfemoral amputation for transfemoral osseointegration. Therefore, TTOI for patients who also request TKR must be considered cautiously. Given that this frequency of infection does not occur in patients who have total hip replacement in association with transfemoral osseointegration, the underlying issue may not be that linked joint replacement with osseointegrated limb replacement is incompatible, but may require further consideration of biological barriers to ascending infection and/or significant changes to implant design, surgical technique, or other yet-uncertain factors

Failure of osseointegration and periprosthetic joint infection (PJI) are the two main reasons of implant failure after total joint replacement (TJR). Nanofiber (NF) implant surface coating represents an alternative local drug eluting device that improves osseointegration and decreases the risk of PJI. The purpose of this study was to investigate the therapeutic efficacies of erythromycin (EM)-loaded coaxial PLGA/PCL-PVA NF coating in a rat S. aureus-infected tibia model. NF coatings with 100mg and 1000mg EM were prepared. NF without EM was included as positive control. 56 Sprague Dawley rats were divided into 4 groups. A titanium pin (1.0-mm x 8 mm) was placed into the tibia through the intercondylar notch. S. aureus (SA) was introduced by both direct injection of 10 μl broth (1 × 10. 4. CFU) into the medullary cavity and single dip of Ti pins into a similar solution prior to insertion. Rats were sacrificed at 8 and 16 weeks after surgery. The outcome measurements include μCT based quantitative osteolysis evaluation and hard tissue histology. Results: EM-NF coating (EM100 and EM1000) reduced osteolysis at 8 and 16 weeks, compared to EM0 and negative control. The effective infection control by EM-NFs was further confirmed by hard tissue section analysis. The Bone implant contact (BIC) and bone area fraction Occupancy (BAFO) within 200 µm of the surface of the pins were used to evaluate the osseointegration and new bone formation around the implants. At 16 weeks, the bone implant contact (BIC) of EM 100 (35.08%) was higher than that of negative control (3.43%) and EM0 (0%). The bone area fraction occupancy within 200 µm (BAFO) of EM100 (0.63 mm2) was higher than that of negative control (0.390 mm2) and EM0 (0.0 mm. 2. ). The BAFO of EM100 was also higher than that of EM1000 (0.3mm. 2. ). There was much less osteolysis observed with EM100 and EM1000 NF coatings at 16 weeks, as compared to EM0 positive control, p=0.08 and p=0.1, respectively. Osseointegration and periprosthetic bone formation was enhanced by EM-NFs, especially EM100. Data from this pilot study is promising for improving implant surface fabrication strategies

Traditional socket prosthesis (TSP) rehabilitation for amputees is associated with substantial dissatisfaction due to poor mobility and pain from soft tissue squeezing. Osseointegration (OI), eliminates skin compression and prosthesis fit issues, providing superior mobility and quality of life (QOL) for most amputees. The potential for OI to benefit patients with exceptionally poor mobility is understudied. To address this knowledge gap, this project investigated the mobility and QOL changes. A retrospective review was performed to identify transfemoral amputees who presented with wheelchair-bound mobility (K0) and had at least five years of post-osseointegration follow-up. Outcome measures included changes in mobility (K-level, daily prosthesis wear hours, Timed Up and Go (TUG), 6 minute walk test (6MWT)) and QOL (Questionnaire for persons with a Transfemoral Amputation (QTFA); Short Form Health Survey 36 (SF36). Adverse events recorded included debridement for infection, implant revision surgery, fractures, and implant failures. 9 patients with mean age 48.2±7.7 (range 34-59) years were included. The proportion of patients achieving K-level >2 improved from 0/9=0% to [9/9=100%], p<0.001. The 6MWT improved from 0±0 to 320.65±57 meters (p<0.001). The TUG improved from incapable to 10.68±2.7 seconds (p<0.001). Statistically significant QOL metrics included QTFA global score (33.33±31 vs 68.52±21, p=0.039), SF36 physical component score (30.03±6.3 vs 42.34±12, p=0.023) and the SF36 mental component score (47.89±8.8 vs 51.95±10.4, p=0.332). Six patients required operative intervention to address complications. Five developed infections: three had debridement, and 2 required implant removal and reimplantation. Osseointegration does confer significant sustained mobility and quality of life improvement for wheelchair bound transfemoral amputees. All 9 K0 patients had statistically improved mobility and QOL after osseointegrated reconstruction. This supports osseointegration as an effective rapid and long-term rehabilitation alternative for patients who have the neurologic and muscular capacity to walk but are unable due to issues related to their TSP

The use of implant biomaterials for prosthetic reconstructive surgery and osteosynthesis is consolidated in the orthopaedic field, improving the quality of life of patients and allowing for healthy and better ageing. However, there is the lack of advanced innovative methods to investigate the potentialities of smart biomaterials, particularly for the study of local effects of implant and osteointegration. Despite the complex process of osseointegration is difficult to recreate in vitro, the growing challenges in developing alternative models require to set-up and validate new approaches. Aim of the present study is to evaluate an advanced in vitro tissue culture model of osteointegration of titanium implants in human trabecular bone. Cubic samples (1.5×1.5 cm) of trabecular bone were harvested as waste material from hip arthroplasty surgery (CE AVEC 829/2019/Sper/IOR); cylindrical defects (2 mm Ø, 6 mm length) were created, and tissue specimens assigned to the following groups: 1) empty defects- CTR-; 2) defects implanted with a cytotoxic copper pin (Merck cod. 326429)- CTR+; 3) defects implanted with standard titanium pins of 6 µm-rough (ZARE S.r.l) -Ti6. Tissue specimens were cultured in mini rotating bioreactors in standard conditions, weekly assessing viability. At the 8-week-timepoint, immunoenzymatic, microtomographic, histological and histomorphometric analyses were performed. The model was able to simulate the effects of implantation of the materials, showing a drop in viability in CTR+, differently from Ti6 which appears to have a trophic effect on the bone. MicroCT and histological analysis supported the results, with lower BV/TV and Tb.Th values observed in CTR- compared to CTR+ and Ti6 and signs of matrix and bone deposition at the implant site. The collected data suggest the reliability of the tested model which can recreate the osseointegration process in vitro and can therefore be used for preliminary evaluations to reduce and refine in vivo preclinical models. Acknowledgment: This work was supported by Emilia-Romagna Region for the project “Sviluppo di modelli biologici in vitro ed in silico per la valutazione e predizione dell'osteointegrazione di dispositivi medici da impianto nel tessuto osseo”

Introduction. The use of osseointegrated limb replacement prostheses for amputees are rapidly growing in popularity due to the many benefits over conventional sockets. Many institutions worldwide are beginning to provide this surgical option to their patients and are advertising the service online. The aim of this study was to assess the quality and reading level of related information available online. Materials & Methods. A search was performed using the 3 most popular English language search engines reviewing the top 40 websites from each, using the term osseointegration on. Duplicates, videos, medical journal articles and dentistry websites were excluded. All included websites were assessed for reading using the FKGL, G-Fog and FRE. Quality was assessed using the JAMA benchmark criteria, HONC erificate and a novel 16-point scoring system developed specifically for limb replacement osseointegration. Results. The search resulted in 9,985,000 websites, 120 were assessed. 23 websites were included after removal of duplicates, medical journals and dentistry websites. None with reading grades of 6 or lower. Mean FKGL grade was 11.3/18. Mean FRE was 38.83/100. Mean G-FOG was 12.57/20. No websites had HONC. Mean JAMA score was 1.76/4. Mean HSSOIS was 5.70/16. Most provided information on indications(16/23) and explanation of osseointegration 17/23) but few discussed costs(3/23) or restrictions(9/23). Conclusions. There is already a large amount of information available online regarding osseointegrated prostheses. However, the most accessible information may exceed most patients’ reading levels, limiting is usefulness. Further, the information available is generally of low quality, The quality of information and the readability of online content should be improved to ensure more effective patient education

Introduction. Transfemoral osseointegration (TFOI) for amputees has substantial literature proving superior quality of life and mobility versus a socketed prosthesis. Some amputees have hip arthritis that would be relieved by a total hip replacement (THR). No other group has reported performing a THR in association with TFOI (THR+TFOI). We report the outcomes of eight patients who had THR+TFOI, followed for an average 5.2 years. Materials & Methods. Our osseointegration registry was retrospectively reviewed to identify all patients who had TFOI and also had THR, performed at least two years prior. Six patients had TFOI then THR, one simultaneous, one THR then TFOI. All constructs were in continuity from hip to prosthetic limb. Outcomes were: complications prompting surgical intervention, and changes in subjective hip pain, K-level, daily prosthesis wear hours, Questionnaire for Persons with a Transfemoral Amputation (QTFA), and Short Form 36 (SF36). All patients had clinical follow-up, but one patient did not have complete mobility and quality of life survey data at both time periods. Results. Four (50%) were male, average age 52.7±14.8 years. Three patients (38%) had amputation for trauma, three for osteosarcoma, one each (13%) infected total knee and persistent infection after deformity surgery. One patient died one year after THR+TOFA from subsequently diagnosed pancreatic cancer. One patient had superficial debridement for infection with implant retention after five years. No implants were removed, no fractures occurred. All patients reported severe hip pain preoperatively versus full relief of hip pain afterwards. K-level improved from 0/8=0% K>2 (six were wheelchair-bound) to 5/8=63% (p=.026). At least 8 hours of prosthesis wear was reported by 2/7=29% before TOFA vs 5/7=71% after (p=.286). The QTFA improved in all categories, but not significantly: Global (40.0±21.6 vs 60.0±10.9, p=.136), Problem (50.2±33.2 vs 15.4±8.4, p=.079), and Mobility (35.9±26.8 vs 58.3±30.7, p=.150). The SF36 also improved minimally and not significantly: Mental (53.6±12.0 vs 54.7±4.6, p=.849) and Physical (32.5±10.9 vs 36.3±11.2, p=.634). Conclusions. THR+TFOI is a successful reconstruction option for amputees who desire relief from severe pain related to hip joint degeneration, and also the opportunity for improved mobility and quality of life that TFOI typically confers. In our cohort, the procedure proved safe: no associated deaths, no removals, one soft tissue debridement. Mobility improved markedly. Quality of life improved, but not to significant thresholds as measured by the surveys. THR+TFOI appears safe and reasonable to offer to transfemoral amputees with painful hip joint degeneration

Introduction. Patients with aseptic loosening, a cause of failure in uncemented total joint arthroplasty (TJA), often present with fibrous tissue at the bone-implant interface. 1. In this study, we characterize the presence of neutrophil extracellular traps (NETs) in the intramedullary fibrotic membrane of aseptic loosening patients. We further explore the role of NETs, mediated by peptidyl arginine deiminase (PAD4), in peri-implant fibrosis and osseointegration failure through a murine model of unstable tibial implantation. 2–4. Methods. Peri-implant membrane was retrieved from five patients during total hip revision surgery and analyzed for the presence of NETs (citH3+ with extracellular DNA) via immunofluorescence. A Ti-6Al-4V implant was inserted in an oversized drill-hole in the right proximal tibia of 8-week-old C57BL/6J and PAD4 knockout mice (n=3 per group). Fourteen days later, all mice were euthanized, and implanted tibias were dissected. Fibrosis and osseointegration at the bone-implant interface were assessed by micro-computed tomography (microCT) and hematoxylin and eosin (H&E) staining. H&E samples were scored blindly by the investigator and another observer for signs of poor (score=0) to excellent osseointegration (score=3) using a rubric established in our lab. Results. NETs were found in peri-implant membrane collected from aseptic loosening patients (Figure 1a) and at the bone-implant interface in a murine model (Figure 1b). Unstable implants in wild type mice failed to osseointegrate, indicated by presence of fibroblast-like cells (dashed arrow), immature bone matrix (Figure 1c), low bone volume fraction (BV/TV) and bone surface area (BS) (Figure 1e). Unstable implants in PAD4. −/−. mice showed signs of good osseointegration such as mature trabeculae (solid arrow) (Figure 1d), higher BV/TV (p<0.10) and BS (p<0.05) (Figure 1f). Histological osseointegration scoring indicated wildtype mice exhibited an average score of 0.83 and PAD4. −/−. exhibited an average score of 2.5 (p<0.05, weighted Cohen's kappa = 0.714) (Figure 1g). Conclusion. NETs were characterized in fibrotic tissue in both aseptic loosening patients and in a murine model of unstable tibial implantation. NET inhibition was able to successfully prevent peri-implant fibrosis and osseointegration failure, leading the way for a potential novel non-invasive therapeutic approach for the treatment of aseptic loosening. For any figures, tables, or references, please contact the authors directly

3D Printed polyether-ether-ketone (PEEK) has gained widespread use in clinical practice due to its excellent biocompatibility, biomechanical compatibility, and personalization. However, pre-printed PEEK implants are not without their flaws, including bioinert, optimization distortion of 3D printing digital model and prosthetic mismatching. Recent advancements in mechanical processing technology have made it possible to print bone implants with PEEK fused deposition, allowing for the construction of mechanically adaptable implants. In this study, we aimed to synthesize silanized polycitrate (PCS) via thermal polymerization and in situ graft it to PEEK surface to construct an elastomer coating for 3D printed PEEK implants (PEEK-PCS). This incorporation of PCS allows the implant to exhibit adaptive space filling ability and stress dispersal. In vivo and in vitro results, PEEK-PCS exhibited exceptional osseointegration and osteogenesis properties along with macrophage M2 phenotypic polarization, inflammatory factors reducing, promotion of osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). Additionally, PEEK-PCS displays good autofluorescence properties in vitro and in vivo, with stable fluorescence for 14 days, suggesting potential bioimaging applications. The study confirms that PEEK in situ grafting with thermo-polymerized PCS elastomers is a viable approach for creating multifunctional (bone defect adaptation, bioimaging, immune regulation, and osseointegration) implants for bone tissue engineering

Due to unsatisfactory results and reported drawbacks of anterior cruciate ligament (ACL) reconstruction new regenerative approaches based on tissue-engineering strategies are currently under investigation. It was the purpose of this study to determine if a novel silk fiber-based ACL scaffold is able to initiate osteointegration in the femoral and tibial bone tunnels under in vivo conditions. Furthermore we tested if the osteointegration process will be improved by intraoperatively seeding the scaffolds with the autologous stromal vascular fraction, an adipose-derived, stem cell-rich isolate from knee fat pads. In this controlled laboratory study, 33 sheep underwent ACL resection and were then randomly assigned to 2 experimental groups: ACL reconstruction with a scaffold alone and ACL reconstruction with a cell-seeded scaffold. Half of the sheep in each group were randomly chosen and euthanized 6 months after surgery and the other half at 12 months. To analyze the integration of the silk-based scaffold in the femoral and tibial bone tunnels, hard tissue histology and micro-computed tomography measurements were performed. The histological workup showed that in all treatment groups, with or without the application of the autologous stromal vascular fraction, an interzone of collagen fibers had formed between bone and silk-based graft. This collagen-fiber continuity partly consisted of Sharpey fibers, comparable with tendon-bone healing known for autografts and allografts. Insertion sites were more broad based at 6 months and more concentrated on the slightly protruding, bony knoblike structures at 12 months. Histologically, no differences between the treatment groups were detectable. Analysis of micro-computed tomography measurements revealed a significantly higher tissue density for the cell-seeded scaffold group as compared with the scaffold-alone group in the tibial but not femoral bone tunnel after 12 months of implantation. The novel silk fiber-based scaffold for ACL regeneration demonstrated integration into the bone tunnels via the formation of a fibrous interzone similar to allografts and autografts. Histologically, additional cell seeding did not enhance osteointegration. No significant differences between 6 and 12 months could be detected. After 12 months, there was still a considerable amount of silk present, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed

Surgical failure, mainly caused by loosening implants, causes great mental and physical trauma to patients. Improving the physicochemical properties of implants to achieve favourable osseointegration will continue to be the focus of future research. Strontium (Sr), a trace element, is often incorporated into hydroxyapatite (HA) to improve its osteogenic activity. Our previous studies have shown that miR-21 can promote the osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway. The aim of this study is to fabricate a SrHA and miR-21 composite coating and it is expected to have a favorable bone healing capability. Ti discs (20 mm diameter and one mm thickness for the in vitro section) and rods (four mm diameter and seven mm length for the in vivo section) were prepared by machining pure Ti. The Ti cylinders were placed in a Teflon-lined stainless-steel autoclave for treating at 150°C for 24 h to form SrHA layer. The miR-21 was encapsulated in nanocapsules. The miR-21 nanocapsules were mixed with CMCS powder to form a gel-like sample and uniformly coated on the SrHA modifed Ti. Osteoblast-like MG63 cells were cultured on SrHA and miR-21 modified Ti, Cell proliferation activity and osteogenesis-related gene expression were evaluated. A bone defect model was established with mature New Zealand to evaluate the osseointegration. Cylindrical holes (four mm in diameter) were created at the distal femur and tibial plateau. Each rabbit was implanted with four of the aforementioned rods (distal femur and tibial plateau of the hind legs). After implantation for one, two and three months, the rabbits were observed by X-ray and scanned using u-CT. Histological and Immunohistochemical analysis were performed to examine the osteogenic markers. A biomechanical push-in test was used to assess the bone-implant bonding strength. Both SrHA nanoparticles with good superhydrophilicity and miR-21 nanocapsules with uniform sizes were distributed evenly on the surface of the Ti. In vitro experiments revealed that the composite coating was beneficial to osteoblast proliferation, differentiation and mineralization. In vivo evaluations demonstrated that this coating could not only promote the expression of angiogenic factor CD31 but also enhance the expression of osteoblastic genes to facilitate angio-osteogenesis. In addition, the composite coating also showed a decreased RANKL expression compared with the miR-21 coating. As a result, the SrHA/miR-21 composite coating promoted new bone formation and mineralization and thus enhanced osseointegration and bone-implant bonding strength. A homogeneous SrHA and miR-21 composite coating was fabricated by generating pure Ti through a hydrothermal process, followed by adhering miR-21 nanocapsules. This coating combined the favorable physicochemical properties of SrHA and miR-21 that synergistically promoted angiogenesis, osteogenesis, osseointegration, bone mineralization and thus bone-implant bonding strength. This study provided a new strategy for surface modification of biomedical implants

Aims. Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses. Materials and Methods. The two novel designs of porous SLS collars, one with small pores (Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared in an ovine tibial diaphyseal model. Osseointegration of these collars was compared with that of a clinically used solid, grooved design (G). At six months post-operatively, the ovine tibias were retrieved and underwent radiological and histological analysis. Results. Porous collars provided a significantly greater surface (p < 0.001) for the ingrowth of bone than the standard grooved design. Significantly greater extracortical pedicle formation was seen radiologically around the grooved design (length p = 0.002, thickness p < 0.001, surface area p = 0.002) than around the porous collars. However, the ingrowth of bone occurred from the transection site into the porous structure of both types of collar. A fivefold increase in integration was seen with the SP and a threefold increase in the LP design when compared with G (p < 0.001). Conclusion. SLS porous collars allow the direct ingrowth of more bone and are better than current designs which rely on surface ongrowth and ECBB. Cite this article: Bone Joint J 2017;99-B:276–82

Abstract. Introduction. The long-term biological success of cementless orthopaedic prostheses is highly dependent on osteointegration. Pre-clinical testing of new cementless implant technology however, requires live animal testing, which has anatomical, loading, ethical and cost challenges. This proof-of-concept study aimed to develop an in vitro model to examine implant osteointegration under known loading/micromotion conditions. Methods. Fresh cancellous bone cylinders (n=8) were harvested from porcine femur and implanted with additive manufactured porous titanium implants (Ø4 × 15 mm). To simulate physiological conditions, n=3 bone cylinders were tested in a bioreactor system with a cyclic 30 µm displacement at 1Hz for 300 cycles every day for 15 days in a total of 21 days culture. The chamber was also perfused with culture medium using a peristaltic pump. Control bone cylinders were cultured under static conditions (n=5). Samples were calcein stained at day 7. Post-testing, bone cylinders were formalin fixed and bony ingrowth was measured via microscopy. Results. Viability of the freshly harvested ex vivo bone cylinders was maintained for up to 28 days. Two samples remain unanalysed due to COVID lockdown, one in each group. Similar to osteointegration seen in live animal models, evidence of bony ingrowth was seen more markedly at the bone-implant interface under dynamic conditions. This was evident by a greater intensity of calcein staining, confirming the deposition of new bone, at the bone-implant interface. In comparison, under static conditions, calcein staining was observed randomly all over the cylinder. Conclusion. This proof-of-concept study demonstrates that implant bony adaptation and ingrowth can be measured in vitro under known cyclic micromotion/loading conditions. This comparatively low cost, low ethical impact, controlled loading laboratory method has potential to accelerate the rate of implant development whilst conforming with the principles of NC3Rs. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Hypoxic Inducible Factor and Hypoxic mimicking agents (HMA) trigger the initiation and promotion of angiogenic-osteogenic cascade events. However, there has been paucity of studies investigating how HIF could be over expressed under chronic hypoxic conditions akin to that seen in sickle cell disease patients to help form a template for tackling the matter of macrocellular avascular necrosis. Angiogenesis and osteogenesis are tightly coupled during bone development and regeneration, and the hypoxia-inducible factor-1 alpha (HIF-1) pathway has been identified as a key component in this process studies have shown. There are still no established experimental models showing how this knowledge can be used for the evaluation of bone implant integration and suggest ways of improving osseointegration in sickle cell disease patients with hip arthroplasty and thereby prevent increased implant loosening. The aim of this study is to help develop an in vitro experimental model which would mimic the in vivo pathologic state in the bone marrow of sickle cell disease patients. It also seeks to establish if the hypoxic inducible factor (HIF) could be over expressed in vitro and thus enhancing osseointegration. MG63 osteoblastic cells were cultured under normoxia and hypoxic conditions (20%; and 1% oxygen saturation) for 48 and 72 hours. Cobalt chloride was introduced to the samples in order to mimic true hypoxia. Cells cultured under normoxic conditions and without cobalt chloride was used as the control in this study. The expression of the hypoxic inducible factor was assessed using the reverse transcriptase qualitative polymerase chain reaction (RT-qPCR). There was increased expression of HIF1-alpha at 72hours as compared to 48hours under the various conditions. The level of expression of HIF increased from 48hrs (mean rank= 4.60) to 72hrs (mean rank =5.60) but this difference was not statistically significant, X2(1) = 0.24, p =0.625. The mean rank fold change of HIF in hypoxic samples decreased compared to the normoxic samples but this difference was not statistically significant, X2(1) = 0.54, p= 0.462. Therefore, the expression of HIF is only increased with prolonged hypoxia as seen in the 72hours samples. The expression of HIF increased in samples with CoCl2 (mean rank=5.17), compared with samples without CoCl2 (mean rank 4.67), however this was not statistically significant, X2(1) = 0.067, p=0.796, p value > 0.05. The over expression of HIF was achieved within a few days (72hours) with the introduction of Cobalt Chloride, which is a mimetic for hypoxia similar to the in vivo environment in sickle cell disease patients. This is an in vitro model which could help investigate osseointergation in such pathologic bone conditions

Proximal femoral focal deficiency is a congenital disorder of malformation of the proximal femur and/or the acetabulum. Patients present with limb length discrepancy and clinical features along a spectrum of severity. As these patients progress through to skeletal maturity and on to adulthood, altered biomechanical demands lead to progression of arthropathy in any joint within the lower limb. Abnormal anatomy presents a challenge to surgeons and conventional approaches and implants may not necessarily be applicable. We present a case of a 62-year-old lady with unilateral proximal femoral focal deficiency (suspected Aitken Class A) who ambulated with an equinus prosthesis for her entire life. She presented with ipsilateral knee pain and instability due to knee arthritis but could not tolerate a total knee arthroplasty due to poor quadriceps control. A custom osteointegration prosthesis was inserted with a view to converting to the proximal segment to a total hip replacement if required. The patient went on to develop ipsilateral symptomatic hip arthritis but altered acetabular anatomy required a custom tri-flange component (Ossis, Christchurch, New Zealand) and a custom proximal femoral component to link with the existing osseointegration component (Osseointegration Group of Australia, Sydney, Australia) were designed and implanted. The 18 month follow up of the custom hip components showed that the patient had Oxford hip scores that were markedly improved from pre-operatively. Knee joint heights were successfully restored to equal when the patient's prosthesis was attached. The patient describes feeling like “a normal person”, walks unaided for short distances and can ambulate longer distances with crutches. Advances in design and manufacture of implants have empowered surgeons to offer life improving treatments to patients with challenging anatomy. Using a custom acetabular tri-flange and osseointegration components is one possible solution to address symptomatic ipsilateral hip and knee arthropathy in the context of PFFD in adulthood

Focal knee resurfacing implants (FKRIs) are typically intended to treat focal cartilage defects in middle-aged patients. All currently available FKRIs are (partly) composed of metal, which potentially leads to degeneration of the opposing articulating cartilage and hampers follow-up using magnetic resonance imaging (MRI). The purpose of this study was to investigate the in vivo osseointegration process of a novel non-degradable thermoplastic polycarbonate-urethane (TPU) osteochondral implant. Bi-layered implants measuring 6 mm in diameter, with a double-curvature to match the approximate curvature of the goat medial femoral condyle were fabricated. TPU implants were composed of an articulating Bionate® II 80A top layer, and a Bionate® 75D bottom layer (DSM Biomedical, Geleen, the Netherlands) which is intended to osseointegrate. A biphasic calcium phosphate coating formulation, optimized during a prior in vitro study, was applied to half of the TPU implants, while the other half was left uncoated. Bi-layered metal implants (articulating cobalt-chromium top layer and titanium bottom layer) were used as positive control implants. Eight implants per group were implanted bilaterally in the medial femoral condyle of the stifle joints in 12 Dutch milk goats. 18F-sodium fluoride (18F-NaF) positron emission tomography-computed tomography (PET-CT) scanning was performed at 3 and 12 weeks postoperatively, and the corrected maximum standard uptake values (cSUVmax) was calculated to assess the peri-implant bone metabolism. After sacrifice 12 weeks postoperatively, bone histomorphometric analysis was performed to assess the bone-to-implant contact area (BIC). Student's T-test was used in case of normal distribution and the Mann-Whitney-U-test was used in case of abnormal distribution for comparison of BIC and cSUVmax. The BIC value of 10.27 ± 4.50% (mean ± SD) for the BCP-coated TPU implants was significantly (P=0.03) higher than the 4.50 ± 2.61% for the uncoated TPU implants. The uncoated TPU implants scored significantly (P=0.04) lower than the BIC of 12.81 ± 7.55% for the metal implants, whereas there was no significant difference between BCP-coated TPU implants and the metal implants (P=0.68). There was a strong correlation between the cSUVmax values and the BIC values at 12 weeks (Pearson's R=0.74, P=0.001). The cSUVmax values significantly decreased between 3 and 12 weeks for the metal implants (p=0.04). BCP-coated TPU implants followed a similar trend but did not reach statistical significance (p=0.07). cSUVmax in the uncoated TPU implants did not show a significant difference between the time-points (p=0.31). Osseointegration of BCP-coated TPU implants did not significantly differ from metal implants. 18F-NaF PET-CT is a feasible modality to assess osseointegration patterns and showed a similar trend between the BCP-coated and metal implants. Hence, an implant fully composed of TPU may avoid the typical metal-related drawbacks of currently available FKRIs. Long-term follow-up studies are advocated to address the effects of the implant to the opposing cartilage, and are therefore warranted

Introduction. Poor osseointegration of cementless implants is the leading clinical cause of implant loosening, subsidence, and replacement failure, which require costly and technically challenging revision surgery. The mechanism of osseointegration requires further elucidation. We have recently developed a novel titanium implant for the mouse tibia that maintains in vivo knee joint function and allows us to study osseointegration in an intra-articular, load-bearing environment. Vascular endothelial growth factor (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. It also plays critical roles in skeletal development and bone repair and regeneration. A specialized subset of vascular endothelium, CD31. hi. EMCN. hi. cells displaying high cell surface expression of CD31 and Endomucin, has been reported to promote osteoblast maturation and may be responsible for bone formation during development and fracture healing. Because of their potential role in osseointegration, the aim of this study was to use our mouse implant model to investigate the role of VEGF and CD31. hi. EMCN. hi. endothelium in osseointegration. Methods. Under an IACUC-approved protocol, the implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (N = 38). The mice were then randomized into 2 groups: Control group (N=19) and Anti-VEGFR group (N=19). A cocktail of VEGFR-1 antibody (25mg/kg) and VEGFR-2 antibody (25mg/kg) was given to the mice in the Anti-VEGFR group by intraperitoneal injection every third day starting immediately after surgery until euthanasia. An equivalent amount of an isotype control antibody was given to the control group. Flow cytometric (N = 4/group) and immunofluorescencent (N = 3/group) analyses were performed at 2 weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium in the peri-implant bone. Pull-out testing was used at 4 weeks post-implantation to determine the strength of the bone-implant interface. Results. Flow cytometry revealed that Anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium percentage in the peri-implant bone vs. control (p = 0.039) at 2 weeks post-implantation (Fig. 1). This was confirmed by the decrease of CD31 and EMCN double positive cells detected with immunofluorescence at the same time point (Fig. 2). More importantly, anti-VEGFR treatment decreased the maximum load of pullout testing compared with control (p = 0.042) (Fig. 3). Conclusion. VEGF is a key mediator of osseointegration and the development of CD31. hi. EMCN. hi. endothelium. This may provide a new drug target for the enhancement of osseointegration. We have also developed a system to run flow cytometric analysis and perform fluorescent staining on the limited tissue around the implant in this mouse model. This will be a powerful platform for future mechanistic studies on osseointegration. For any figures or tables, please contact authors directly

Abstract. Objectives. Currently, total hip replacement surgery is an effective treatment for osteoarthritis, where the damaged hip joint is replaced with an artificial joint. Stress shielding is a mechanical phenomenon that refers to the reduction of bone density as a result of altered stresses acting on the host bone. Due to solid metallic nature and high stiffness of the current orthopaedic prostheses, surrounding bones undergo too much bone resorption secondary to stress shielding. With the use of 3D printing technology such as selective laser melting (SLM), it is now possible to produce porous graded microstructure hip stems to mimics the surrounding bone tissue properties. Method. In this study we have compared the physical and mechanical properties of two triply periodic minimal surface (TPMS) lattice structure namely gyroid and diamond TPMS. Based on initial investigations, it was decided to design, and 3D print the gyroid and diamond scaffolds having pore size of 800 and 1100 um respectively. Scaffold of each type of structure were manufactured and were tested mechanically in compression (n=8), tension (n=5) and bending (n=1). Results. Upon FEA validation of the scaffold in Abaqus, the desired scaffold for hip implant application was evaluated to have a young's modules of 12.15 GPa, yield strength of 242 MPa and porosity of 55%. Topology and lattice optimization were performed using nTopology to design an optimised graded porous hip implant based on stress shielding reduction. It was understood that the designed optimised hip implant can reduce the stress shielding effect by more than 65% when compared to the conventional generic implant. Conclusions. The designed hip implant presented in this work shows clinical promise in reducing bone loss while having enhanced osseointegration with the surrounding cortical bones. Hence, this will help reduce the risk of periprosthetic fracture and the probability of revision surgery

Introduction:. Non-cemented, porous-coated metaphyseal sleeves have been designed to improve biologic fixation and stability in revision total knee arthroplasty (TKA) with major bone defects. The aim of this study was to evaluate the clinical results and osteointegration of these sleeves in major bone loss. Materials and Methods:. Between 2008 and 2011, 24 revision TKAs with major bone loss were reconstructed with non-cemented, porous-coated proximal sleeve (DePuy, Warsaw, IN). All patients were prospectively followed for a minimum of 2 years. Indications for use of sleeves were major metaphyseal tibial and femoral bone loss, younger age, and higher activity level. Osteointegration around the sleeves were classified as: . –. Grade 1: Complete osteointegration in all views without any demarcation. –. Grade 2: Sleeves that are not completely osteointegrated but they are stable. Grade 2A: Demarcation less than 2 mm on any view. Grade 2B: Demarcation more than 2 mm on any view . –. Grade 3: Sleeves that are not osteointegrated and unstable with evidence of subsidence. Grade 3A: Subsidence less than 2 mm on any view. Grade 3B: Subsidence more than 2 mm on any view. Results:. Mean range of motion and Knee Society Scores were 108 degrees and 92 respectively. 14 cases were revised for aseptic loosening and 10 cases for infection (which were treated with two stage revision arthroplasty). There was no malalignment, subsidence or re-revision at final follow-up. All sleeves were osteointegrated with majority grade 1 or 2a. Discussion and conclusion:. Short-term results of non-cemented metaphyseal sleeves in major bone loss for loosening of infection demonstrated excellent clinical results and osteointegration

Aseptic loosening is the most common cause of failure in load bearing orthopaedic implants. This is most often attributed to stress shielding, which is caused by a mismatch in mechanical properties between the implant and bone, predominantly stiffness. The implant causes a redistribution of the forces through the bone leading to localised tissue resorption in low stress areas and over time loosening of the implant. To address this, the implant design may be modified to introduce porous structures that reduced overall stiffness. Conventional methods of creating porous structures include the space holder method and gas foaming, although these allow control of the pore size and volume fraction, the position of the voids is random and potentially non-uniform, creating unpredictable mechanical properties. Using additive manufacture predictable porous lattice structures can be built. Two methods for creating lattice structure are explored here: controlled stochastic lattices, and layers of repeating unit cells. Due to the predictable nature of these design methods the mechanical properties can be tailored to suit the needs of the implants. In addition to mechanical optimisation the porous lattice structures can be optimised for osseointegration properties. The ability of the tissue to grow into the implant are affected by; the size of the pores, how interconnected the pores are, the overall void fraction (porosity), the shape and roughness of the pores, and whether the structure is coated. Although additive manufacture allows great design freedoms, there are also some manufacturing constraints to consider including resolution which is determined by powder and laser spot size, and strut angle since these cannot be too close to horizontal or they will collapse during the build unless supported. This preliminary work uses Finite Element Analysis to model the compressive properties of lattice structures with different design parameters, with the intention to optimise for mechanical, osseointegration and manufacturability properties. Cylinders of the lattice structures were generated in Simpleware ScanIP (Synopsys, Exeter, UK) and their compression was modelled in Ansys Workbench 18.2 (Canonsburg, PA, USA) in accordance with ISO 13314. Stress distributions for each lattice structure were produced which showed the stochastic lattice did not undergo banded deformation unlike the repeating unit cell based lattices. Future work will physically test the lattices and feed that data back into the model for further optimisation. Other relevant mechanical testing will be modelled and performed in order to choose the optimal lattice design for future implants

Introduction. Extensive bone loss and poor residual bone quality can make implant fixation difficult to achieve in revision of failed megaprostheses. While newer porous components are available to address various periarticular cavitary and segmental defects, diaphyseal fixation remains challenging without resorting to cemented techniques, or cementless fully-coated stems that achieve fixation over long segments of bone. In cases of previous infection, it may be advantageous to avoid the use of such devices as they can be difficult to remove and may result in even greater bone loss if the infection were to persist. Compressive osseointegration technology has been become a valuable device in the management of these challenging situations. Objectives. We aimed to evaluate the short-term results of compressive osseointegration when used for reconstruction of massive diaphyseal and segmental bone defects. We believe that compressive osseointegration provides predictable, strong endoprosthesis fixation in the short-term and that osseointegration can be evaluated radiogrphically. Methods. We retrospectively reviewed a total of 32 implants (spindles) in 28 patients with failed prior megaprosthetic reconstructions. Procedures were performed at two institutions by six surgeons. Data recorded included patient demographics, indication for surgery, diaphyseal segment and joint reconstructed, and any complications. Results. Average patient age and body mass index at time of surgery were 48 years (range 14–68) and 28.1 m2 (range 17–58), respectively. Indications included aseptic loosening (18), loosening and infection (11), and allograft-prosthetic composite nonunion (3). The reconstructions consisted of distal femoral replacement (16), proximal femoral replacement (10), distal humeral replacement (4) and proximal ulnar replacement (2). There were five spindle failures in 4 patients. Three were converted to a Compress device, two were successful one converted to a cemented stem and another patient was also converted to a cemented stem. Other complications that required repeat surgery included hinge failure (2), arthrofibrosis (1), segment taper adapter fracture (2), persistent chronic deep wound infection (1)and superficial wound infection (1). Fixation at the bone-implant interface remained intact in each of these cases. There was 1 deep infection in this series in spite of a large number of index infected megaprostheses. Twenty-six of twenty-eight patients (92.8%) achieved stable osteointegration and we had an overall spindle osteointegration failure rate of 15.6% (5 of 32) at a mean follow-up length of 16.7 months (range 0.5–57.4). The cortex/spindle ratio of these increased from 0.33 (SD 0.9) immediately postoperatively to 0.53 (SD 0.15) at final follow-up (p < 0.001). At most recent follow-up, these patients reported satisfaction and painless function of the operative limb. Conclusion. Use of compressive osseointegration for revision of failed massive segmental bone defects (See Fig 1 and 2) provides reliable short term fixation, and may prove to be bone conserving in cases that require future re-revision. The cortex/spindle ratio reliably increases over time as fixation is achieved. It has become our device of choice for failed limb salvage reconstructions

Purpose: Radiographic signs of osseointegration have been well established for cementless femoral components, but not for cementless acetabular components. At our institution using principles similar to those applied to cementless femoral components, we have observed apparent radiographic signs of osseointegration of porous-coated cups. We then hypothesized that these signs could be used to predict bone ingrowth of porous-coated acetabular components. Methods: In a series of 119 total hip arthroplasties with porous-coated cementless cups, we reviewed post-primary and prerevision serial radiographs and proposed five radiographic signs for detecting osseointegration of a porous-coated acetabular component: absence of radiolucent lines, presence of a superolateral buttress, medial stress shielding, radial trabeculae, and an infero-medial buttress. We compared the predictability of each sign to intraoperative findings of cup stability and measured the sensitivity, specificity, and intra-observer agreement of each sign. Results: . In our population, ninety-eight cups had three to five radiographic signs of osseointegration; of these, ninety-five cups (97%) were found to be bone-ingrown at the revision operation. Conversely, twelve cups had only one or no sign; of these, ten (83%) were clinically unstable at the revision operation. Conclusions: We concluded these five, readily detectable signs of acetabular osseointegration are very useful in predicting acetabular component stability found at surgery

Few studies have been reported focusing on developing implant surface nanofiber (NF) coating to prevent infection and enhance osseointegration by local drug release. In this study, coaxial doxycycline (Doxy)-doped polycaprolactone/polyvinyl alcohol (PCL/PVA) NFs were directly deposited on the titanium (Ti) implant surface during electrospinning. The bonding strength of Doxy-doped NF coating on Ti implants was confirmed by a stand single-pass scratch test. The improved implant osseointegration by PCL/PVA NF coatings in vivo was confirmed by scanning electron microscopy, histomorphometry and micro computed tomography at 2, 4 and 8 weeks after implantation. The bone contact surface (%) changes of NF coating group (80%) is significantly higher than that of no NF group (< 5%, p<0.05). Finally, we demonstrated that Doxy-doped NF coating effectively inhibited bacterial infection and enhanced osseointegration in an infected (Staphylococcus aureus) tibia implantation rat model. Doxy released from NF coating inhibited bacterial growth up to 8 weeks in vivo. The maximal push-in force of Doxy-NF coating (38 N) is much higher than that of NF coating group (6.5 N) 8 weeks after implantation (p<0.05), which was further confirmed by quantitative histological analysis and micro computed tomography. These findings indicate that coaxial PCL/PVA NF coating doped with Doxy and/or other drugs have great potential in enhancing implant osseointegration and preventing infection

Background. Following endosteal uncemented orthopaedic device implantation, the initial implant/bone interface retains spaces and deficiencies further exacerbated by pressure necrosis and resultant bone resorption. This implant-bone space requires native bone infill through the process of de novo osteogenesis. New appositional bone formation on the implant surface is known as contact osteogenesis and is generated by osteogenic cells, including skeletal stem cells (SSCs), colonising the implant surface and depositing the extracellular bone matrix. Surface nanotopographies provide physical cues capable of triggering SSC differentiation into osteoblasts, thus inducing contact osteogenesis, translated clinically into enhanced osseointegration and attainment of secondary stability. The current study has investigated the in vitro and in vivo effects of unique nanotopographical pillar substrates on SSC phenotype and function. Methods. Adult human SSCs were immunoselected, enriched using STRO-1 antibody and cultured on control and test surfaces for 21 days in vitro. The test groups comprised Ti-coated substrates with planar or modified surfaces with nanopillar. Osteoinductive potential was analysed using qPCR and immunostaining to examine gene expression and protein synthesis. Results. Following in vitro (n=5) culture on nanopillars, the expression of osteogenic genes (ALP, Collagen 1, OPN and OCN) and of Osteopontin protein (a bone matrix protein), on Ti pillars were both significantly enhanced when compared to control or Ti planar surfaces. Conclusions. Discrete raised surface nanopillars modulate adult SSC populations in the absence of any chemical cues and enhance their osteogenic properties, an effect not observed on planar Ti constructs. Hence, these findings herald exciting opportunities to improve the implant surface design, implant osseointegration, and, ultimately, implant survival. Level of evidence. Original experimental study

Silicon nitride spinal fusion cages have been successfully used in the treatment or correction of stenosis, disc herniation, trauma, and other deformities of the spinal column since 2008. To date over 14,000 devices have been implanted with perioperative and postoperative complication rates of less than 0.2%. This remarkable achievement is due in part to the material itself. Silicon nitride is an ideal interbody material, possessing high strength and fracture toughness, inherent phase stability, biocompatibility, hydrophilicity, excellent radiographic imaging, and bacterial resistance. These characteristics can lead to implants that aid in prevention of nosocomial infections and achieve rapid osteointegration. In this paper, we will review the various in vitro and in vivo studies that demonstrate silicon nitride's effective bacteriostatic and osteointegration characteristics, and compare these to the two most common cage materials – titanium and poly-ether-ether-ketone (PEEK). Human case studies will be also reviewed to contrast the clinical performance of these biomaterials. In comparison to the traditional devices, silicon nitride shows lower infection rates, higher bone apposition, and essentially no fibrous tissue growth on or around the implant. To better understand the mechanisms underlying these benefits, surface characterization studies using scanning electron microscopy coupled with XPS chemical analyses, sessile water drop techniques and streaming zeta potential measurements will be reported. Data from these studies will be discussed in relation to the physiochemical reasons for the observed behavior. Silicon nitride is a non-oxide ceramic in its bulk; but possesses a protective Si-N-O transitional layer at its surface. It will be shown that the chemistry and morphology of this layer can be modified in composition, thickness and structure resulting in marked changes in chemical species, surface charge, isoelectric points and wetting behavior. It is postulated that the needle-like grain structure of silicon nitride coupled with its enhanced wettability play important roles in inhibiting biofilm formation, while its surface chemical environment consisting of silicon diimide Si(NH). 2. , silicic acid Si(OH). 4. , and derivatives of ammonia, NH. 3. , NH. 4. OH, lead to improved bone reformation and bacteriostasis, respectively. Few materials have this combination of properties, making silicon nitride a unique biomaterial that provides improved patient care and outcomes with low comorbidities

Introduction. The following study start from an idea of the evaluation of the osteointegration in the bone cage of the Equinoxe Reverse shoulder prosthesis. The aim of the study is to assess the values of Bone Mineral Density (BMD) in periprosthetic areas, in patients undergoing shoulder arthroplasty with implants of the Equinoxe system by Excatech, Inc. To better understand the steps of osteointegration time of the bone cage with the glenoid. The objectives of the work are not only expanded to the value of osteointegration, but could also be useful for the evaluation of both mechanical and septic loosening of the stem of the glenoid. Materials and Methods. In the period from November 2011 to May 2012, 15 patients were evaluated. All patients were subjected to bone densitometry type of DXA within the first 15 days after surgery and at 3 months after surgery. The patients are all part of a homogeneous group for anatomical glenoid. Were excluded from the study all patients who were no significant alterations of the head and the glenoid. The acquisitions were performed with the patient in an oblique position, with limb in a neutral position, in order to obtain images in the coronal plane “true” of the joint. Were subsequently calculated values of BMD is around the stem with the 7 areas used by Gruen for the hip prosthesis and peripherally to the central peg using 3 areas, superiorly, medially and inferiorly to the same. Results. The values obtained showed a significant increase in the time of bone density peripherally to the central peg demonstrating a significant osteointegration. Being a prospective study these values will be integrated with new acquisition DXA to 6, 9, 12 months, 2, 3 and 5 years. Conclusions. Although preliminary, through our study it was possible to obtain the standard values of BMD in patients with prosthetic replacement has been successful. These BMD values represent a standard of reference for the physiological osseointegration; in the future must be evaluated for their variation in patients with prosthetic loosening and / or with infectious processes, in order to allow an early diagnosis of these diseases by studying DXA. Also in future studies BMD values obtained by us of the Equinoxe prosthesis can be compared with those obtained in other models of the shoulder prosthesis to detect any advantages or disadvantages in terms of osteointegration

Introduction. Trabecular Titanium™ is a highly porous biomaterial with a regular hexagonal cell structure, which has shown excellent mechanical properties. Several in vitro studies reported promising data on its osteoinductive and osteoconductive properties. Furthermore, it has demonstrated in vivo to enhance bone in-growth. Aim of this multicentre prospective study was to assess Trabecular Titanium™ osseointegration by measuring change in bone mineral density (BMD) around a cementless DELTA-TT cup with dual-emission X-ray absorptiometry (DXA). Methods. 89 patients (91 hips) underwent primary THA with DELTA-TT cups (Lima Corporate) between 2009 and 2010. There were 46 (52%) men and 43 (48%) women, with a median (IQR) age of 67 (57–70) years and a median (IQR) BMI of 26 (24–29) kg/m. 2. Right side and left side were affected in 44 (48%) and 47 (52%) cases, respectively. Underlying pathology was primary osteoarthritis in 80 (88%) cases, osteonecrosis in 5 (6%), post-traumatic osteoarthritis in 3 (3%), developmental dysplasia of the hip in 2 (2%) and oligoarthritis in 1 (1%). BMD was determined by DXA using DeLee and Charnley 3 Regions of Interest (ROI) at 7 days, 3, 6, 12 and 24 months. Clinical evaluation (Harris Hip Score, HHS), patient health status survey (SF-36) and radiographic assessment were performed preoperatively and at the same time-points. Data were analyzed using non-parametric tests (Mann-Whitney, Wilcoxon signed-rank) and a p < 0.05 as threshold for statistical significance. Results. Excellent results were observed in terms of pain relief and functional recovery. Median (IQR) HHS improved from 48 (39–62) before surgery, to 99 (96–100) at 24 months, with a statistical significant increase of 96% (p < 0.05, Wilcoxon signed-rank). Median (IQR) SF-36 improved from 49 (37–62) preoperatively to 86 (79–92) at 24 months, with a statistical significant increase of 95% (p < 0.05, Wilcoxon signed-rank), indicating a considerable improvement in patients' quality of life. After an initial decrease of BMD values from baseline at 7 days (median [IQR] ROI I: 1.44 [1.21–1.67]; ROI II: 1.23 [0.99–1.49]; ROI III: 1.11 [0.85–1.48] g/cm. 2. ) to 6 months (ROI I: 1.27 [1.08–1.52]; ROI II: 1.14 [0.89–1.37]; ROI III: 1.05 [0.73–1.35] g/cm. 2. ), BMD slightly increased in ROI I, the most loaded area, and stabilized in ROI III. BMD in ROI II increased after 12 months and stabilized at 24 months (ROI I: 1.30 [1.11–1.55]; ROI II: 1.12 [0.96–1.36]; ROI III: 1.04 [0.80–1.25] g/cm. 2. ). Radiographic analysis showed evident signs of bone remodeling and osseointegration, with presence of supero-lateral and infero-medial bone buttress and of radial trabeculae perpendicular to the cup surface in ROI I/II. No radiolucent lines, loosening or osteolysis were observed. All cups were stable and no revision was carried out. Conclusion. BMD patterns and radiographic evaluation showed signs of an effective osseointegration around DELTA-TT cups at 24 months. Although clinical outcomes, functional recovery and stability are very satisfactory, longer follow-ups are necessary to assess survivorship

Purpose: Osseointegration is crucial for favorable outcomes after total hip arthroplasty (THA) using cement-less femoral components. Osseointegration is recognized on radiographs as the endosteal spot weld, which is the bony bridge between the implant and surrounding bone (Engh et al, CORR, 1989). The purpose of this study is to evaluate the clinical and radiographic results for patients who had hydroxyapatite (HA)-coated rough surfaced implants compared with those who had identical implants without HA-coating at three-year minimum follow-up. Methods: Ninety-one patients, one hundred and two hips who had primary THA with titanium arc sprayed rough surfaced femoral implants were retrospectively studied. Sixty-four hips had received HA-coated implants (HA) and 38 hips had an identical component but without HA (Non-HA). Radiographical parameters analyzed included 1) endosteal spot welds, 2) radiolucent lines, 3) calcar responses, 4) pedestal formation, 5) implant loosening, 6) endosteal osteolysis. Results: At a minimum follow up of 3 years after operation (mean, 5.5 years), the mean Harris hip score was 89.4 points in the HA group and 89.0 points in the Non-HA group. The radiographic analysis did show the significantly earlier appearance of the endosteal spot welds in HA group. The spot welds at 1 and 2 year after operation were present in 48% and 70% of HA group, while 13% and 42% of Non-HA group. There was no significance at 3 years (71% vs 66%). More than 80% of the spot welds were seen at Gruen zone 6 in the both groups. No differences were noted regarding the radiolucent lines, calcar response, pedestal formation between the groups. There were no implant loosening and osteolysis in both groups. Conclusions: These results suggest that the use of HA-coating does provide improved fixation in the early periods and the possibility of improved durability

Degree of early integration of titanium alloy implants into bone is an important predictor of long term implant success in arthroplasty. The correlation between observations on early cell adhesion and the ability of modified surfaces to affect osseointegration of implants in in vivo models is unclear. We hypothesised that observation of increased focal adhesion complexes in early cultures of osteoblasts would correlate with increased osseointegration of treated implants in an animal model. Longer term culture of rat osteoblasts for alkaline phosphatase activity indicated that cells cultured on the 9V treated surfaces were displaying greater alkaline phosphatase activity at 14 days. Bone nodule formation at 28 days demonstrated a trend towards smaller area of bone nodules on the surfaces treated at 9V then those treated at 3V and 5V. A rat model was employed for testing mechanical push-out strength of experimental implants and demonstrated a trend towards increased yield strength of the bone-implant interface for implants treated at 3V180s and 5V180s. Histomorphometry was performed and no statistically significant differences in percentage area of contact with mineralised bone matrix were seen, although there was a trend for greater mineralised matrix contact on the polished and 9V180s treated implants. Previous experiments demonstrated cells on the 9V treated surfaces were well spread and had significantly increased size and number of focal adhesions. This was regarded as indicating more successful cell adhesion. The above results demonstrate that this early trend disappeared in longer term culture did not persist in experiments in an animal model

Proximally-coated non-cemented tapered femoral stems have demonstrated excellent long-term clinical results. However, there is sparse literature reporting the incidence of failure of osteointegration in patients with this stem design. The aim of this study is to report this incidence and identify factors which may increase its risk. 206 elective primary total hip arthroplasties were performed consecutively with a single stem design over a three-year period. All patients were evaluated clinically and radiographically. Radiographic parameters were analyzed for any potential risk factors that may predispose to failure of osteointegration. Three of 206 hips failed to osteointegrate and subsequently underwent revision surgery, for an incidence of 1.5%. The average time to revision was 1.2 years. The presenting complaint was persistent pain and radiographs revealed a progressive linear lucency at the proximal implant-bone interface in all three patients. Each patient had been implanted with a large-sized stem that had achieved a diaphyseal fit radiographically. This cohort had a statistically lower canal-flare index (p < 0.05) when compared to the rest of the study group. At the time of surgery, all stems were found to be loose and were easily removed. Failure of osteointegration in this type of stem is an uncommon but serious complication that may necessitate revision surgery. Risk factors predisposing to a failure to osteointegrate are a mismatch between the patient’s proximal femoral geometry and the stem, specifically a large stem in a Dorr type C femur, leading to a diaphyseal rather than a metaphyseal wedge

Summary Statement. Preoperative bone-marrow-derived cell mobilization by G-CSF is a safe orthopaedic procedure and allows circulation in the blood of high numbers of CD34+ve cells, promoting osseointegration of a bone substitute. Introduction. Granulocyte-colony-stimulating-factor(G-CSF) has been used to improve repair processes in different clinical settings for its role in bone-marrow stem cell(CD34+ and CD34-) mobilization. Recent literature suggests that G-CSF may also play a role in skeletal-tissue repair processes. Aim of the study was to verify the feasibility and safety of preoperative bone-marrow cell (BMC) mobilization by G-CSF in orthopaedic patients and to evaluate G-CSF efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy(HTVO) for genu varum. Patients/Methods. 24 patients were enrolled in a prospective phase II trial. The osteotomy gap was filled by a hydroxyapatite-tricalciumphosphate bone substitute(HATriC). Patients were randomised to receive (GROUP A) or not receive (GROUP B) preoperatively a daily dose of 10µg/kg of G-CSF for three consecutive days, with an additional dose 4 hours before surgery. BMC-mobilization was monitored by white blood cell (WBC)-count, flow-cytometry analysis of circulating CD34+cells and Colony-forming cell assays. Patients were evaluated by: Lysholm and SF-36 scores preoperatively and at 1, 2, 3, 6, and 12 months after surgery;. X-ray evaluation preoperatively and at 1, 2, 3, 6, and 12 months after surgery, in order to compare the percentage of osseointegration of the bone-graft junction using the semi-quantitative score of Dallari[1]. CT-scan of the host bone-substitute interface at 2 months, in order to estimate the quality of the newly formed bone at the bone-graft junction by a quantitative measure of bone density (by Hounsfield unit) at the proximal and distal bone-graft junctions. Results. All patients completed the treatment program without major side effects; G-CSF was well tolerated. BMC-mobilization occurred in all Group A patients, with median peak values of 110/µL (range 29–256) of circulating CD34+ve cells. Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant improvement in the SF-36-Role-Physical scale and in the Lysholm score was recorded at follow-up in Group A compared to Group B(p<0.05). At the X-ray-evaluation, there was a significant increase in osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months post-surgery compared to Group B(p<0.05). CT-scans of the grafted area at 2 months post-surgery showed no significant difference in the quality of the newly formed bone between the two Groups. Discussion/Conclusions. These results suggest that G-CSF can be safely administered preoperatively in subjects undergoing HTVO. In addition, the clinical, radiographic and CT monitoring indicate that preoperative G-CSF administration promotes bone graft substitute osseointegration. Enhanced osseointegration might be the result of the direct activity of G-CSF on the host bone or a cellular effect mediated by bone marrow-derived progenitors mobilised by G-CSF, or by a combination of all these factors. This study is a proof-of-principle that preoperative G-CSF might be an alternative treatment option to enhance bone regeneration in the field of bone marrow stem cell therapy and reconstructive orthopaedic surgery

Osteointegration of HA coated devices is well demonstrated. An abundant experimental material exists, allowing to describe the various properties of HA (early osteointegration, sealing effect, gap healing effect, etc…). Various side-effects have been described (third body wear of HA debris, delamination of the proximal coating etc…). Thus controversy still exists, despite a more and more convincing clinical experience. The role of human retrievals is therefore crucial to determine the exact role of all these parameters in the natural life of the implant throughout the years. 49 human well-functioning explants have been retrieved during systemic autopsies in elderly patients previously operated for a displaced fracture of the neck with a Corail® implant. Delays of implantation vary from 5 days to 10 years. All these specimens have been processed for optical microscopy, electronic microscopy with backscattering. This constitutes the longest report on one single implant and the retrievals are evenly distributed over this ten-year period. Several histomorphometric parameters were measured in the different Gruen’s zones: cortical bone density, cortical bone thickness, density of endosteal bone. 3 steps are recognized:. Bone formation around the implant appears early after surgery. Multiple units of bone formation go to coalescence as soon as 6 weeks and develop thereafter, leading to osteointegration. Bone remodelling reorganizes the architecture of connecting trabeculae according to the mechanical stresses resulting from the presence of the implant. Compression areas are generally the seat of broad and interconnected trabeculae, whereas tensile stresses areas display the presence of long, thin, unconnected and often parallel trabeculae. Very broad and short trabeculae are often seen at the level of the corners. Coating resorption is seen in every specimen beyond one year of implantation, predominantly in the areas with less bone coverage. Release of HA particles in the joint cavities was never encountered. Some metallic particles, originating from the femoral ball are commonly seen in the polyethylene. HA particles (presumably scratched off the prosthesis during insertion?...) have never been identified in the heterotopic ossifications. We conclude that the osteointegration of the Corail stems is a reliable phenomenon with a reproducible sequence of events. It lasts even after the disappearance of the coating in a 5–10 years period. The presence of the stem provokes a remodelling of the cortices but the presence of a total coating and its longer duration at the level of the tip does not induce a disappearance of the proximal bone or a loose of the proximal fixation

Aims: Hydroxyapatite coatings have been proven to improve the osteointegration of metal implants however they are not stable and they might delaminate from the metal surface when challenged by the mechanical stresses experienced by the implant. Therefore, efforts of different researchers are being devoted to find more stable coatings or surface treatments that could replace HA. In particular, spontaneous calcium phosphate deposition on titanium surfaces from aqueous electrolyte containing calcium and phosphate ions, such as simulated body fluid solutions, has been observed and is believed to be related to the excellent bonding capability in contact with bone tissue. In the present study, a new multiphase anodic spark deposition (ASD) method combined with chemical etching is presented It has been optimized and such modified titanium surface exhibited high mineralisation potential, selective protein adsorption, quicker and more intensive osteoblasts adhesion and differentiation. Such treatements was labelled BioSpark™ and consisted in a thick calcium-phosphate-doped oxide film growth on the titanium bulk. This oxide layer exhibits anatase lattice, micro-porosity and a thin nano-roughened texture. Methods: The effect of this process, was investigated invitro and in vivo in cortical and spongy bone of 12 adult sheep. Histomorphometric and microhardness measurement were carried out at each experimental time (4, 8, 12 weeks) to quantify the bone-to-implant contact around the implants, the bone ingrowth as well as the newly bone hardness and bone maturation index. Results: Data suggests that the BioSpark treatment produces a modification of the Ti surface, which represents good bioactivity and may be suitable for achieving a stable implant osseointegration. Conclusions: Such surface modification treatments was applied in the last two years on dental implants with great success and is now being tested in human being for histological studies. In the future, it will be applied on orthopaedic prostheses devices in order to improve device osteintegration. The data demonstrate that this type of surface improves the material osteointegration potential when compared to conventional surfaces while offering high mechanical stability

In an experimental clinical study, 25 implants of pure titanium were inserted into the proximal tibia of 11 volunteer patients, four with rheumatoid arthritis and seven with osteoarthritis. The implants were removed from five weeks to 24 months later and detailed histological analysis was performed. The implants generally healed with direct bone-metal contact, showing so-called osseointegration. Only one of the 21 implants which had been in place for over five months did not show osseointegration, probably because of inadequate primary contact with bone. The presence of rheumatoid disease did not prevent osseointegration, but accompanying osteoporosis seemed to be a risk factor

Introduction. Modular tantalum augments have been introduced to manage severe bone defects in hip and knee revision surgery. The porous surfaces of tantalum augments are intended to enhance osseointegration and a number of studies have documented their excellent biocompatibility. However, the characteristics of tantalum augment osseointegration on human ex vivo specimens from re-revision procedures have not been reported so far. Methods. Out of a total number of 324 hip and knee revisions with a tantalum augment performed in our institution between 2007 and 2010 four patients had to be re-revised at a mean followup time of 15 months. The causes for re-revision were a periprosthetic acetabular fracture in one, a loosening of a tibial component in one and periprosthetic hip infections in two cases. To characterize osseointegration of the tantalum augments, they were removed during revision surgery and subjected to undecalcified processing. All specimens were analysed by contact radiography, histology (toluidine blue, von Kossa) and quantitative histomorphometry. Results. In all specimens trabecular ingrowth was apparent along the former bone-augment-interface. The depth of bone ingrowth into the porous microarchitecture of the augments reached up to 2000 μm. Thin-section analysis revealed scattered and partially mineralized bone forming units within the interior of the augments. Conclusions. To the best of our knowledge this is the first histomorphometric analysis on the osseointegration of tantalum augments in human ex vivo specimens. In the presented series porous tantalum showed excellent osteoconductive characteristics on the histological level. These early ex vivo histological findings are promising, but structural analysis of later re-revision cases is needed

Introduction: Despite advances in endoprosthesis fixation by implant surface alteration, the problem of aseptic implant loosening still exists. Especially in patients with revisions osseointegration and filling of gaps at the bone-implant interface is mandatory for implant survival. Simple BMP-2 immersion has been introduced previously to act as an osteoinductive coating for advanced osseointegration. However, because of the uncontrolled release kinetics and subsequent molecular action and activity of BMP-2, purely osteoinductive actions are hard to differentiate from osteoclastic BMP-actions leading to bone remodelling, which could counteract the implant fixation process and might be the reason for failed attempts to use BMP-2 for implant fixation. In this study we investigated the osteoinductive potency of BMP-2 bound to titanium surfaces by a highly controlled molecular coupling with specifically designed polymers, allowing a slow controlles release kinetics. We present the first results of two different polymers that were implanted in the tibia and femora of New Zealand White Rabbits. Methods: In this study we designed cylindrical titanium-implants with an inner thread (Ti6-Alï·& #8220;4V, 3 mm hight x 3 mm diameter) and an electropolished outer surface that were coated with different polymers. The polymers were fixed to the surface using the photochemical method of grafting. The implants were implanted in the proximal tibia and distal femora of New Zealand White Rabbits. The anatomical locations of the implants were alternated to test their osseointegration in different quality of bone (cancellous vs. cortical bone). After 4 weeks the animals were sacrificed and DEXA-scans (Dual-energy X-ray absorptiometry), micro-CT and histological analysis were performed. ANOVA and t-test were used for statistic analysis. Results: In high-resolution DEXA-scans we found a difference in bone mineral density (BMD) between PVBP and a control implant in the distal femora (PVBP 0,720 g/cm², control 0,661 g/cm²) and in the proximal tibia (PVBP 0,633 g/cm², control 0,431 g/cm²) with an increase of bone mineral density. In the histological investigation we found an increase of osteoblasts around the implants coated with PVBP and PVBP-Co-Acryloxysuccimid. Furthermore, the micro-CT scans showed an increase of BV/TV (bone volume/total volume) for both polymers. Discussion: In this study we present the first results of the investigation of polymer-coated titanium-implants implanted in the proximal tibia and distal femora of New Zealand White Rabbits. The results of DEXA-scans, micro-CT and histological analysis showed an increase of osseointegration. We suggest that controlled release kinetics after coupling of these polymers with BMP-2 can additionally increase osseointegration. To get a closer look on the polymers, their characteristics in-vivo, and coupling with BMP-2 further investigations are conducted

Purpose. To review prospectively collected data on patients undergoing primary total hip arthroplasty utilizing two different cementless acetabular components. Materials & Methods. All patients undergoing primary total hip replacement surgery at our institution are entered prospectively into a database which includes history and physical examination, radiology, WOMAC and SF-36 scores. The patients are re-examined, re-x-rayed and re-scored at 3 months, 6 months and 1 year after surgery and yearly thereafter. Using this database we are able to identify patients who have undergone total hip replacement using one of two geometric variants of the acetabular component. The first design is hemispherical and the second design has a peripheral rim expansion designed to increase initial press-fit stability. Results. Five hundred and twenty-seven consecutive primary total hip replacements were identified using either of the geometric variants of the acetabular component. Results at a mean of 7 years revealed a 95.6% survivorship with no significant difference between the two component designs with revision for aseptic loosening as the end point. Functional scores between the two groups of patients also demonstrated no statistically significant difference. Radiologic assessment, however, showed a difference between the two designs. The hemispherical design which matches the reamer line-to-line had 80% complete osseointegration on final radiologic review while the second design with a peripheral rim expansion had only 57% complete osseointegration. This was statistically significant. The peripherally expanded components also had a greater number of screws inserted at the time of surgery, felt by us to be a reflection of initial surgeon dissatisfaction with component stability at the time of insertion of the component

INTRODUCTION. Trabecular Titanium™ is an innovative material characterised by an high open porosity and composed by multi-planar regular hexagonal cells. It is not a traditional coating and its tri-dimensional structure has been studied to optimise osteointegration. Furthermore, it has excellent mechanical properties, as a very high tensile and fatigue resistance and an elastic module very similar to the that of the trabecular bone. The aim of this study is to evaluate the osteointegration and bone remodelling measuring the longitudinal pattern of change in BMD around a cementless acetabular cup made from Trabecular Titanium™ (Delta TT cup, Lima Corporate, Italy) in primary total hip arthroplasty (THA). METHODS. Dual-energy x-ray absorptiometry (DEXA) analysis, radiographic evaluation on standard AP and lateral views and clinical evaluation with Harris Hip Score (HHS) and SF-36 were performed at 1 week, 3, 6, 12 months after surgery. RESULTS. Between February 2009 and June 2010, 72 patients underwent primary THA with Delta TT cup at 4 centres. There were 36 (50%) female and 36 (50%) male with an average age of 63 (range 39-75). Preliminary results include 72 patients with 56 at 3 months, 42 at 6 months and 28 at 12 months. The mean HHS improved from 48 points (range 14-79) preoperatively to 88 (range 74-100) at 3 months, to 94 (range 71-100) at 6 months and to 97 (range 94-100) at 12 months. SF-36 reported a progressive improvement of all domains. An initial transient decrease of the bone mineral density (BMD) occurred between 1 week and 3 months after surgery, then bone mass returns to baseline values after 6 months and increased at 12 months. No radiolucent lines nor osteolysis have reported and no revision occurred. There were 2 complications not related to the implant on study: one dislocation solved with a close reduction and one dislocation solved with a revision of the neck and the head, but not compromising the cup. CONCLUSIONS. Delta TT acetabular cup allows to obtain a very good primary stability, thanks to the high friction coefficient of the Trabecular Titanium™, followed by a good and fast osteointegration, as reported by early DEXA outcomes. Preliminary results showed also a very good clinical and functional improvement. Long-term follow-up is ongoing in order to prove these promising results

To review prospectively collected data on patients undergoing primary total hip arthroplasty utilizing two different cementless acetabular components. All patients undergoing primary total hip replacement surgery at our institution are entered prospectively into a database which includes history and physical examination, radiology, WOMAC and SF-36 scores. The patients are re-examined, re-x-rayed and re-scored at 3 months, 6 months and 1 year after surgery and yearly thereafter. Using this database we are able to identify patients who have undergone total hip replacement using one of two geometric variants of the acetabular component. The first design is hemispherical and the second design has a peripheral rim expansion designed to increase initial press-fit stability. Five hundred and twenty-seven consecutive primary total hip replacements were identified using either of the geometric variants of the acetabular component. Results at a mean of 7 years revealed a 95.6% survivorship with no significant difference between the two component designs with revision for aseptic loosening as the end point. Functional scores between the two groups of patients also demonstrated no statistically significant difference. Radiologic assessment, however, showed a difference between the two designs. The hemispherical design which matches the reamer line-to-line had 80% complete osseointegration on final radiologic review while the second design with a peripheral rim expansion had only 57% complete osseointegration. This was statistically significant. The peripherally expanded components also had a greater number of screws inserted at the time of surgery, felt by us to be a reflection of initial surgeon dissatisfaction with component stability at the time of insertion of the component. The difference in screw numbers was also statistically significant. This study demonstrates that a hemispherical design with line-to-line contact between the acetabular component surface and the acetabular bone is statistically superior in terms of bone ingrowth and probably statistically superior in terms of initial press-fit stability when compared to a peripherally expanded component. Peripherally expanded components appear to offer no advantage over hemispherical components in terms of clinical outcome and are statistically inferior to hemispherical components in radiologic parameters at 7 years follow-up

Introduction. Studies have documented encouraging results with the use of fluted, tapered, modular, titanium stems in revision hip arthroplasty with bone loss. However, radiographic signs of osseointegration and patterns of reconstitution have not been previously categorized. Materials and Methods. 64 consecutive hips with index femoral revision using a particular stem of this design formed the study cohort. Serial radiographs were retrospectively reviewed by an independent observer. Bone loss was determined by Paprosky's classification. Osseointegration was assessed by a slight modification of the criteria of Engh et al. Femoral restoration was classified according to Kolstad et al. Pain and function was documented using Harris Hip Score (HHS). Results. Mean patient age was 68.3 years and radiographic follow-up 6.2 years. 74% femora had type 3 or 4 bone loss. All distal segments were radiographically osseointegrated. Proximal segment radiolucent lines were frequent (40%). Early minor subsidence occured in 4 (6.2%) hips. Definite bony regeneration was documented in 73% femora and stress-shielding in 26%. HHS improved from a pre-operative mean of 50.1 points to 86.2 at most recent follow-up. Discussion. A consistent pattern of bony remodeling and osseointegration occurred which could be applied for assessment of fixation and stability of this stem. The well established criteria of osseointegration for cylindrical cobalt-chrome stems may have to be altered for application to these stems as the mechanism of load transfer is entirely different. Stems with diameter of 18mm or greater are clearly predisposed to stress shielding, predominantly at the mid-shaft region

Summary Statement. A porcine model using Yucatan minipigs was found to be very promising for the investigation of healing around transcutaneous osseointegrated implants. Pigs demonstrated surprising agility and adaptability including the ability to ambulate on three legs during the immediate postoperative period. Introduction. Previous non weight-bearing and weight-bearing caprine, canine and ovine models have evaluated design, material, and biological coating variations in an attempt to improve the wound healing and skin-implant seal around transcutaneous osseointegrated implants. Although these models have primarily been used as a window into the application of transcutaneous osseointegrated implants in humans, some important model characteristics affecting wound healing and infection have been missing including: 1) replication of the physiological tissue response, and 2) availability of a transcutaneous site with sufficient soft tissue coverage. Pig skin, like human, is relatively hairless, tightly attached to the subcutaneous tissue, vascularised by a cutaneous blood supply, and healed by means of epithelialization. Swine have been extensively utilised for superficial and deep wound healing studies and can offer ample soft tissue coverage following a lower limb amputation. Development of a porcine model is important for continued understanding and improvement of weight-bearing transcutaneous osseointegration. Methods. Two male Yucatan mini-pigs (9 months, 36kg) were fit with transcutaneous osseointegrated prostheses using a single-stage transtibial amputation and prosthesis implantation procedure. The endo-prosthesis consisted of a cylindrical intraosseous threaded section and a smooth transcutaneous section. The transcutaneous sections were smooth to promote epithelialization and deter direct skin-implant adhesion. The implants were custom manufactured from medical grade Ti-6Al-4V alloy. The exo-prosthesis, consisting of an adjustable length leg and foot, was attached by clamp to the supercutaneous portion of the implant following either one or two days of sling constraint to limit initial weight-bearing. Various exo-prosthesis designs and configurations were trialed. The animals’ behavior and gait were closely observed. Weight-bearing was monitored using a force plate. At 5 and 8 weeks, clinical, microbiological, and histological data were examined to assess wound healing and infection at the skin-bone-implant interface. Results. The pigs demonstrated surprising agility and adaptability. They were able to successfully ambulate on three legs during the post-op period before weight-bearing was permitted. They adapted quickly to changes in exo-prosthesis design, position, and length. Although bacterial colonization was verified, neither of the animals exhibited clinical signs of infection over the respective eight and five week studies. Histological results indicated that there was no skin to implant adhesion but that epithelial growth was progressing towards the implant in one animal. Healing of the transcutaneous wound site showed substantial progress but a definitive skin seal was non-existent at the eight week time point. Discussion/Conclusion. This is likely the first animal model developed, having soft tissue characteristics similar to those found in humans, in which an axially-loaded, weight-bearing implant was successfully used. Results indicated that this porcine model offers many advantages over previous models for the development, evaluation, and comparison of the various techniques being advocated to achieve successful transcutaneous osseointegration in humans. The Yucatan miniature pig's ability to ambulate on three legs during the immediate post-operative period and quickly adjust to changes in the exo-prosthesis design, coupled with their physiological similarity to humans, makes them a valuable model for future studies

Glenoid loosening is a major problem in total shoulder arthroplasty. Failure of osteointegration, osteolysis and loosening are potential problems with concerning reports of these complications with earlier metal back designs. CT scans have been reported as more accurate than plain x-rays in examining fixation of components. This study examines the medium term osteointegration of the SMR (Lima) metal back glenoid component. 20 consecutive patients operated on by the same surgeon (KM) were evaluated at a mean of 3 years 9 months (range 3-5 years) using CT analysis. Films were read by a musculoskeletal radiologist (AS). 8 zones were described and the interface graded as ‘osteointergrated’, ‘lucent zone < 1mm’, ‘lucent zone 1-2mm’, ‘lucent zone > 2mm osteolysis’. Loosening was defined as lucent line on all zones > 1mm or migration of implant. No components were loose. All components were osteointegrated around the central peg. Osteointegration was observed in 85% of zones. 4% of the zones were graded as osteolysis, all in the one patient. This patient had osteolysis 4 years post-surgery with superior subluxation of the humeral head and polyethlylene and metal wear. The glenoid component was not loose at revision surgery. Problems with this technique of assessment include radiation exposure and artefact. Small lucent zones often had a well contoured margin suggesting that the component did not seat perfectly on the bone surface in these areas. These results confirm that reliable medium term osteointegration does occur with the SMR metal back glenoid in anatomical total shoulder replacement. Osteolysis can occur and longer term follow up is ongoing

Purpose. Internal fixation of fractures in the presence of osteopenia has been associated with a failure rate as high as 25%. Enhancing bone formation and osseointegration of orthopaedic hardware is a priority when treating patients with impaired bone regenerative capacity. Fibroblast Growth Factor (FGF) 18 regulates skeletal development and could therefore have applications in implant integration. This study was designed to determine if FGF 18 promotes bone formation and osseointegration in the osteopenic FGFR3−/− mouse and to examine its effect on bone marrow derived mesenchymal stem cells (MSCs). Method. In Vivo: Intramedullary implants were fabricated from 0.4 × 10mm nylon rods coated with 300nm of titanium by physical vapour deposition. Skeletally mature, age matched female FGFR3−/− and wild type mice received bilateral intramedullary femoral implants. Left femurs received an intramedullary injection of 0.1μg of FGF 18 (Merck Serono), and right femurs received saline only. Six weeks later, femurs were harvested, radiographed, scanned by micro CT, and processed for undecalcified for histology. In Vitro: MSCs were harvested from femurs and tibiae of skeletally mature age matched FGFR3−/− and wild type mice. Cells were cultured in Alpha Modified Eagles Medium (αMEM) to monitor proliferation or αMEM supplemented with ascorbic acid and sodium beta-glycerophosphate to monitor differentiation. Proliferation was assessed through cell counts and metabolic activity at days 3, 6 and 9. Differentiation was assessed through staining for osteoblasts and mineral deposition at days 6, 9 and 12. Results. Wild type mice exhibited more peri-implant bone formation compared to FGFR3−/− mice. Peri-implant bone formation at the proximal metaphyseal-diaphyseal junction was increased in FGF18 treated femurs compared with contralateral control femurs in wild type (p = NS) and FGFR3−/− (p = 0.04) mice. Histological analysis corroborated micro CT findings, with FGF 18 treated FGFR3−/− femurs forming peri-implant bone instead of the fibrous response seen in controls. In vitro studies showed that FGF18 significantly increased MSC proliferation and metabolism in a dose dependent manner in wild type and FGFR3−/− mice. Osteoblast differentiation was inhibited by FGF18 in wild type MSCs, but was increased at physiological concentrations in cells harvested from FGFR3−/− mice. Conclusion. FGF 18 increases bone formation and osseointegration of intramedullary implants in osteopenic mice and increases MSC proliferation in both the presence and absence of FGFR3. FGF18 also promoted osteoblast differentiation in the absence of FGFR3 signalling, most likely via FGFR1 or 2. Additional work is needed to confirm the identity of the alternate FGFR and to evaluate its capacity to improve osseous healing in unfavourable in-vivo environments

Aim of the study: The aim of our study is to provide a clinical and x-ray review of the Nexgen tantalum tibial plate prosthesis which have been implanted from 2004 to 2007 at our department, evaluating the short term osteointegration of the tantalum surface. Instruments and methods: 17 Nexgen PTG have been implanted without sacrifice of the posterior ligament with tantalum tibial plateau. The tibial component is constituted by a tantalum and polythene monoblock: it is implanted a press-fit through two pegs. The evaluation has been conducted with a minimum of 12 months follow-up. We considered a total of 13 prosthesis implanted in 12. The average patients age is 59.9 years (SD of 3.5 years) and within the range 52–67 years. 77% of the prosthesis (10 prosthesis) has been implanted in female patients. In 100% of situations, the pathology at the origin of the implementation was the primary gonar-thritis. For the clinic evaluation we used the HSS scheme; for the X-ray evaluation we used the “Knee Society TKA Roentgenographic evaluation and scoring system”. Results: clinical evaluation: the average HSS score we got at control (using the average score after 3months, 6months, 1 year and at present) is 91.7 (OS +/−7.6). The difference between the pre-surgery and at control score is about 27.6 scores. At check up every patient was free from pain with a complete operational recovery (11.19/12 scores). Nobody was using aids. The average pre-surgery articolarity was about 93 degrees, at check up we measured an average inflection extension of about 114.1 degrees. All the score differences between pre-surgery and post-surgery are statistically significant (P< =0.001). To conduct our study we used the statistical program SAS (v.8, Sas inc., North Carolina, USA). X-ray evaluation: we didn’t find any unstuck part, neither periprosthesis osteolysis nor prosthesis mobilisation. We didn’t find any periprosthesis radiolucency line bigger than 1mm and none of the previous ones had any complication at control. The absence of pain (subjective evaluation) and absence of radiolucency lines (an objective evaluation) represent two indirect parameters that we considered valid to evaluate the osteointegration of the implant. Discussion: The improvement of the surgical technique, either technical either instrumental, associated with a lower degree of pain, let us suggest that the prosthesis implantation is indicated also in young patients with high operational demands, who need a fast and complete operational recovery. For the same reason, it’s important to guarantee a good osteointegration and a long survival of the implant, with maximum care of bond tissue, forecasting a subsequent review surgery. The features of tantalum seem to respond pretty well at these requirements, being quite similar in terms of structural characteristics to the spongious bond. The reliability of the material is assured by its use in the prosthesis surgery since a couple of years ago. The design of the prosthesis is convenient in order to save at most the bond tissue. The high friction coefficient against the bone and the physical and mechanical features of the tantalum tibial plateau guarantee a fast osteointegration of the prosthesis. Although it’s proven that the implant survival with or without cost of the posterior ligament is the same, the prosthesis without cost of the posterior ligament has been chosen because the maintenance of the patient ligament offers an intrinsic knee stability. The optimal clinical and x-ray results, even if they are at short term, considered as indices of a good osteointe-gration, push us to believe that the use of the tantalum tibial plateau could be a good solution for any young patient with a gonarthrosis

Purpose. To review prospectively collected data on patients undergoing primary total hip arthroplasty utilizing two different cementless acetabular components. Method. All patients undergoing primary total hip replacement surgery at our institution are entered prospectively into a database which includes history and physical examination, radiology, WOMAC and SF-36 scores. The patients are re-examined, re-x-rayed and re-scored at 3 months, 6 months and 1 year after surgery and yearly thereafter. Using this database we are able to identify patients who have undergone total hip replacement using one of two geometric variants of the acetabular component. The first design is hemispherical and the second design has a peripheral rim expansion designed to increase initial press-fit stability. Results. Five hundred and twenty-seven consecutive primary total hip replacements were identified using either of the geometric variants of the acetabular component. Results at a mean of 7 years revealed a 95.6% survivorship with no significant difference between the two component designs with revision for aseptic loosening as the end point. Functional scores between the two groups of patients also demonstrated no statistically significant difference. Radiologic assessment, however, showed a difference between the two designs. The hemispherical design which matches the reamer line-to-line had 80% complete osseointegration on final radiologic review while the second design with a peripheral rim expansion had only 57% complete osseointegration. This was statistically significant. The peripherally expanded components also had a greater number of screws inserted at the time of surgery, felt by us to be a reflection of initial surgeon dissatisfaction with component stability at the time of insertion of the component. The difference in screw numbers was also statistically significant. Conclusion. Cementless acetabular components in total hip replacement have become increasingly popular because of ease of insertion, use of differing bearing surfaces and ease of revision. Longevity of implanted acetabular components appears related to some extent to the quality and extent of bone ingrowth. This study demonstrates that a hemispherical design with line-to-line contact between the acetabular component surface and the acetabular bone is statistically superior in terms of bone ingrowth and probably statistically superior in terms of initial press-fit stability when compared to a peripherally expanded component. Peripherally expanded components appear to offer little advantage over hemispherical components in terms of clinical outcome and are statistically inferior to hemispherical components in radiologic parameters at 7 years follow-up

Advances in military surgery have led to significant numbers of soldiers surviving with bilateral above knee amputations. Despite advances in prosthetic design and high quality rehabilitation not all amputees succesfully ambulate. Five patients (10 stumps) with persisting socket fit issues were selected for osseointegration (OI) using a transcutaneous prosthesis with press-fit fixation in the residual femur. Prior to surgery all five were primarily/exclusively wheelchair users. Follow up was from 7 to 25 months (mean 12.2). There were no deaths, episodes of sepsis or osteomyelitis. There was one proximal femoral fracture secondary to a fall. One stump required soft tissue refashioning. Cellulitis needing oral antibiotics occurred in four cases. Functional improvement occurred in all cases with all currently primarily prosthetic users, the majority all day users. Three patients are still completing rehabilitation. Six minute walk tests (SMWT) improved by a mean of 20%. Three are now graded mobility SIGAM F (normal gait) and two SIGAM D-b (limited terrain; with one stick). This cohort suggests that OI may have a role in the treatment of military blast amputees. A larger scale clinical evaluation is planned in the UK blast related amputee population to further establish the benefits and risks of this technique

Uncemented porous-coated total hip prostheses rely on osseointegration or bone ingrowth into the pores for a stable interface and long term fixation. One of the criteria for achieving this is good initial stability, with failure often being associated with migration and excessive micromotion. This has particularly been noted for long stem prostheses. To minimize micromotion and increase primary stability, a short stemmed implant ‘PROXIMA’(DePuy; Leeds, UK) with a prominent lateral flare was developed with the aim of providing a closer anatomical fit, more physiological loading and limiting bone resorption due to stress shielding. This study aims to simulate bone ingrowth and tissue differentiation around a well fixed porouscoated short stemmed implant using a mechanoregulatory algorithm and finite element analysis (FEA). Specific emphasis is made on the design of the implant and its effect on osseointegration. An FE model of the proximal femur was generated using computer tomography (CT) scans. The PROXIMA was then implanted into the bone maintaining a high neck cut and adequate cancellous bone on the lateral side to accommodate the lateral flare and for osseointegration. A granulation tissue layer of 0.75mm was created around the implant corresponding to the thickness of the porous coating used. The mechanoregulatory hypothesis of Carter et al (J. Orthop, 1988) originally developed to explain fracture healing was used with selected modifications, most notably the addition of a quantitative module to the otherwise qualitative algorithm. The tendency of ossification in the original hypothesis was modified to simulate tissue differentiation to bone, cartilage or fibrous tissue. Normal walking and stair climbing loads were used for a specified number of cycles reflecting typical patient activity post surgery. The majority of the tissue type predicted to be formed, simulating a month in vivo, is fibrous and indicates a weak interface proximally after this period. The stronger tissues, bone and cartilage occupy the mid-lower regions, indicating a strong interface distally. This can be explained by the unique lateral flare that provides extra stability to the distal regions of the implant, especially on the lateral side. The percentage of bone ingrown around the implant at different stages is also important and there was a significant rise from 15% after 10 cycles to about 30% after 30 cycles, simulating a month in vivo. It was also noted that initial bone formation was very high, even after a few cycles, which leads to a stronger interface early on. Fibrous tissue occupied around 45% at almost all stages and did not vary considerably. Cartilage however, was replaced by bone as tissue differentiation occurred, reducing from about 30% after 10 cycles to 20% after 30 cycles. This further indicates the trend of tissue ossification through the regions of stronger tissues, gradually proceeding in the direction of the weaker tissues. The unique lateral flare design and the seating of the implant entirely in the cancellous bed without any diaphyseal fixation provides contrasting results in terms of bone ingrowth around the implant. The lateral flare minimises micromotion and provides better stress distribution at the interface under the region. This accounts for a large percentage of the mid to distal regions under the flare being covered with either bone or cartilage. From the predictions of the algorithm, the significant lateral flare of the PROXIMA helps in stabilizing the implant and provides better osseointegration in the distal regions around the implant

We implanted nails made of titanium (Ti6Al4V) and of two types of glass ceramic material (RKKP and AP40) into healthy and osteopenic rats. After two months, a histomorphometric analysis was performed and the affinity index calculated. In addition, osteoblasts from normal and osteopenic bone were cultured and the biomaterials were evaluated in vitro. In normal bone the rate of osseointegration was similar for all materials tested (p > 0.5) while in osteopenic bone AP40 did not osseointegrate (p > 0.0005). In vitro, no differences were observed for all biomaterials when cultured in normal bone-derived cells whereas in osteopenic-bone-derived cells there was a significant difference in some of the tested parameters when using AP40. Our findings suggest that osteopenic models may be used in vivo in the preclinical evaluation of orthopaedic biomaterials. We suggest that primary cell cultures from pathological models could be used as an experimental model in vitro

The osteointegration of a new three-dimensional reticular titanium material, Trabecular Titanium™, was assessed using a bilateral cancellous (distal femur, proximal tibia) and cortical (tibia diaphysis) bone drill hole model in 18 sheep. TT is a novel Ti6Al4V material characterized by a high open porosity and composed of multi-planar regular hexagonal cells. Two 5.0 mm diameter, 12 mm long cylinders (TT1 & TT2) of two different porosities (TT1:650 μm, TT2:1250 μm) were tested and compared to two solid predicate 5.0 mm diameter, 12 mm long Ti cylinders (PT1 & PT2) coated with porous Ti (PT1: vacuum-plasma spray coating; PT2: inert-gas shielding arc spray coating). Each implant type was surgically implanted at 4 separate locations in each sheep (16 implants per sheep). Three timepoints of 4, 16 and 52 weeks (n=6 sheep per timepoint) were used. Bone-implant interface was analyzed ex vivo by the determination of: 1) the shear strength (SS) measured during a push out test, 2) the percentage of bone in-growth (%B) using histomorphometry, 3) the bone apposition rate using fluorochrome labelling analysis and 4) the bone-implant contact using backscattered scanning electron microscopy (SEM). An ANOVA with a Bonferroni Post hoc test were used to detect differences between tested and predicate implants. P values 0.05 were considered significant. At 4 weeks, 5 out of the 6 TT1 could be pushed out of the cortical bone (COB) samples. The remaining TT1 collapsed during testing. All TT1 could be pushed of the cancellous bone (CAB) samples. Four out of the 6 TT2 could be pushed out of CAB and of the COB samples. At 16 and 52 weeks, only one TT1 and one TT2 could be pushed out of the bone samples, the remaining implants collapsed during testing. All the PTs were successfully pushed out at all timepoints. The mean %B of PT1 and PT2 did not significantly increase over time. For both materials, the mean %B ranged between 1.7% and 4.4% at 4 weeks and between 5.7% and 6.5% at 52 weeks. The mean %B of TT1 significantly increased over time in both COB (10.2% at 4 weeks, 46.2% at 16 weeks, 50.5% at 52 weeks) and CAB (5.8%, 23.9%, 24.3%). Similarly, the mean %B of TT2 significantly increased over time in both COB (7.8%, 48.6%, 65%) and CAB (4.5%, 24.1%, 38.6%). Bone apposition rates for the TT implants remained superior to 2 μm/day for the entire duration of the study. SEM showed an intimate bone-implant contact for all implant types at all timepoints. At 16 and 52 weeks, histomorphometry revealed an extensive osteointegration of the TT specimens. Bone-implant interface strength was so high for the TT implants that they could not be pushed out of the bone samples. The results of this study would indicate that the TT implants provide a good scaffold for bone in-growth

It is well documented that implant loosening rate in sickle cell disease patients is higher than that seen in patients with hip arthroplasty from other indications. The Hypoxic inducible factor(HIF) - is activated in the microcellular hypoxic environment and this through a cascade of other enzymatic reactions promotes the activity of other factors and further help enhance angiogenesis and osteogenesis. The aim of this study was to investigate and propose a potential model for investigating osseointegration in a hypoxic microcellular environment using osteoblasts(MG63). Human MG63 osteoblastic cells were cultured under normoxia and hypoxic conditions (20%; and 1% oxygen saturation) for 72 hours under two different condition- with and without cobalt chloride. The samples cultured under normoxic condtions without cobalt chloride acted as control. Using qualitative polymerase chain reaction-(qPCR) - HIF expression was assessed under the above conditions in relation to the control. The results showed there was significant expression of the HIF 1 alpha protein under hypoxic condition with cobalt chloride in comparison with the control samples- all at 72hours incubation. Mann-Whitney U test was used to deduce level of significance of fold change.(p=0.002; <0.05). This was deemed as being a significant difference in the level of expression of HIF compared to the control. The results show that the hypoxic inducible factor can be expressed using the above tested. experimental invitro-model with significant results which can be a foundation for further research into improving hip implant prosthesis design to help enhance osseo-integration in sickle cell disease patient with AVN

Introduction. A modified anodisation technique where a titanium surface releases bactericidal concentrations of silver was developed and called Agluna. Our hypothesis was that silver incorporation was bactericidal and had no effects on the viability of fibroblasts and osteoblasts, would have no negative effect on interfacial shear strength and bone contact in an in vivo trans-cortical implant ovine model. Methods. In vitro: Titanium alloy discs were either polished (Ti), anodised (Ano), anodised or Agluna treated (Ag) or anodised and Agluna treated followed by a conditioning step (Ag C). Conditioning was achieved by incubating discs in culture fluid for 48 hrs. The bactericidal effect of these discs was tested by measuring the zone of inhibition of different bacteria grown on agar. Live/dead staining was carried out and silver levels measured using atomic emission spectroscopy. 8 implants were inserted into each sheep (60 in total (n=5)). Grit blasted Titanium alloy (Gb) and Agluna treated grit blasted titanium alloy (Ag) at a silver concentration of 4-6 micrograms/cm2 were compared at 6 weeks. Gb implants, Ag (at 4-6micrograms/cm2), high dose Agluna implants with silver concentrations at 15-20micrograms/cm2 (HdAg) and a grit blasted anodised titanium alloy (Ano) were compared at 12 weeks. Pullout strength and bone-implant contact was quantified. Results. On Ti, Ano and Ag C surfaces the number of live fibroblasts was significantly greater than on Ag (non-conditioned) surfaces. Data from pull out tests at 6 weeks showed a lower but significant interfacial shear strength in the Ag group (310.4N) when compared with the Gb group (561.2N) (p=0.01). At 12 weeks, there were no significant differences between each of the 4 treatment groups. Histological analysis showed no significant differences in bone-implant contact between groups at 6 and 12 weeks. Discussion. The initial non-conditioned Agluna surface is bactericidal and cytotoxic but on conditioning, osteoblasts and fibroblasts attached and remained viable. The condition Agluna surface remains bactericidal. Silver incorporation at a concentration up to 20 micrograms/cm2 has no adverse toxic effect on osteointegration and the interfacial shear strength of implants. This coating has been used clinically in situations where the infection rate is high

The aim of hip revison surgery is to restore biomechanical parameters: rotation centre, muscle arm lever and leg length; homologous bone grafting is often necessary. It is possible to bioenhance grafts, resulting in better osteointegration speed and quality. We propose the use of our platelet gel protocol. Care was given to assess the cost-benefit rate of the method. We performed densitometric analysis of homologous bioenhanced grafts vs homologous grafts, with a specific acetabular bone loss indication, randomising two groups of patients (rct study). The “intention to treat” was to decide the benefit of the method in order to extend use to all patients. Densitometric analysis was implemented with radiographic analysis using a modified Cook’s scale. We used clinical scores, too. The clinical and plain radiographic results did not differ significantly between the two groups or with our historical group (7 years/23 implants, already published). The synthesis of all instruments used indicates that the use of bioenhanced bone is promising for enhanced osteointegration; however, the study group must be extended and observed for a longer time to achieve appropriate study power

The durable fixation of an uncemented cup is due to two major factors: the primary stability obtained by the design of the cup and the secondary fixation obtained by the features of the surface of the cup. The CSF (cancellous screws fixation) cup is an emispheric press-fit Hydroxyapatite coated cup that has 5 holes for screws. This permit to insert screws not only in the superior part of the acetabulum but also in the inferior and supero-medial. This theoretically guarantee, also in those cases in which a perfect press-fit was non achievable, a good primary fixation. This primary fixation permit the osteo-conductive function of the HA coating in order to gain secondary e more stable fixation. From january 1999 to september 2003 we per-formed130 uncemented THR with the CSF cup and the Furlong stem. In the first 100we always insert three screws. In the next 30 only in case of a non perfect-press-fit (10). The mean age was 65 years (14–80). The follow-up varying from 5 years to 6 months. The study is retrospective. At the last follow-up all implants resulted well integrated.. The formation of new trabecular bone bonding the cup was noted on the X-ray since the third month’s control. There was no complication due to the position of the screws. All patients regained full authonomy. Primary stability is mandatory in order to obtain a good secondary fixation by osteointegration. The possibility to insert additional screws in a triaxial fashion permit to obtain good primary stability. in all the cases. The screws must be inserted carefully under X-ray in order to avoid complications. Hydroxyapatite, guiding the growth of new trabecular bone bonding the cup to the pelvic bone, guarantee a good secondary fixation

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

The influence of controlled mechanical loading on osseointegration was investigated using an in vivo device implanted in the distal lateral femur of five male rabbits. Compressive loads (1 MPa, 1 Hz, 50 cycles/day, 4 weeks) were applied to a porous coated titanium cylindrical implant (5mm diameter, 2mm width, 75% porosity, 350ìm average pore diameter) and the underlying cancellous bone.. The contralateral limb served as an unloaded control. MicroCT scans at 28 μm resolution were taken of a 4 × 4mm cylindrical region of interest that included cancellous bone below the implant. A scanning electron microscope with a backscattered electron (BSE) detector was used to quantify the percent bone ingrowth and periprosthetic bone in undecalcified sections through the same region of interest. A mixed effects model was used to account for the correlation of the outcome measures within rabbits.. The percent bone ingrowth was significantly greater in the loaded limb (19 +/− 4%) compared to the unloaded control limb (16 +/− 4%, p=0.016) as measured by BSE imaging. The underlying cancellous periprosthetic tissue bone volume fraction was not different between the loaded (0.26 +/− 0.06) and unloaded control limb (0.27 +/− 0.07, p=0.81) by microCT. BSE imaging also showed no difference in the percent area of periprosthetic bone (27 +/− 10% loaded vs. 23 +/− 10% unloaded, p=0.25). Cyclic mechanical loading significantly enhanced bone ingrowth into a titanium porous coated surface compared to the unloaded controls

The aim was to study the evolution of radiographic patterns of osteointegration of tapered wedge stems and determine if there is correlation with bony morphology and initial stem fit. We reviewed primary total hip replacements performed by two surgeons using a single cementless tapered wedge design and that had a complete series of radiographs (defined as preoperative, 6 weeks, 1 year and 5 or more years). Signs of bony remodeling were recorded at each Gruen zone. Calcar remodeling, changes in cortical thickness, evidence of subsidence and pedestal formation were recorded (Figure 1). 57 hips (50 patients) were available for analysis with a mean follow up of 5.03 years. Mean changes in cortical thickness were positive in zones 2(7.51) and 6(5.36) and negative in zones 1(−7.53) and 7(−13.51). Radiolucent lines were found in gruen zones 3,4(39%), and 5. Femoral neck cancellization was seen in zone 7 in 8 patients (14%) in year 1 and 36 (63%) by year 5. Correlations were seen with proximal canal fill and radiolucent lines at zones 3 (0.278; p0.36) and 5 (0.258; p 0.05) and with distal canal fill and hypertrophy of the cortex in zone 3 (0.429; p0.001) and 5. Cortical hypertrophy around the midstem, lack of radiolucent lines around the proximal stem and cancellization of the calcar are all radiographic patterns which occur routinely. A positive correlation with distal canal fill and hypertrophy of zones 3 and 5 was noted. There was no significant correlation with preoperative boney morphology or initial stem fit proximally

Titanium is a popular orthopaedic implant material, but it requires surface modification techniques to improve osseointegration and long term functionality. This project compares a new method of modifying surface topography (nano-patterning) with an existing clinical technology (grit-blasting and acid-etching (GAE)). Titanium discs were blasted with aluminium oxide and etched in sulphuric and acetic acid. Injection moulded discs (with two different nano-patterns) were coated in titanium by evaporation. The topography and chemistry of the discs was assessed using atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle measurements, and X-ray photo-electron spectroscopy (XPS). Two discs were plated bilaterally onto a flattened area of the tibiae of 12 rabbits. Tibiae were removed after 4 and 8 weeks for histological assessment of the bone-implant contact (BIC) ratio. AFM and SEM demonstrated a difference in pattern between the square array of nano-pits (SQ) and the randomly positioned nano-pits (RAND). The GAE implants exhibited increased surface roughness (Ra = 570nm) compared to the titanium coated SQ and RAND implants (Ra = 12nm). Water contact angle measurements showed the surface had comparable wettability and XPS demonstrated similar chemical compositions, except GAE surfaces contained 6.8% aluminium. Histological samples analysed at 4 weeks showed a BIC ratio of 36% for GAE, 56% for SQ, and 48% for RAND. At 8 weeks, the BIC ratio was 52% for GAE, 80% for SQ, and 72% for RAND implants. This increase in BIC at 8 weeks for both SQ and RAND implants compared to GAE was statistically significant (P < 0.05). This project demonstrated there was an increase in interfacial bone to implant contact when using a nano-scale topography incorporating nano-pits compared to conventional grit-blasted acid-etched micro-scale topographies. This enhancement of BIC may reduce long term loosening of orthopaedic implants due to mechanical and biological attrition at the interface

Trabecular TitaniumTM is a tri-dimensional material composed by multi-planar regular hexagonal cells and characterised by a highly open porosity that has been studied to optimise bone osteointegration. The aim of this study is to evaluate bone remodelling measuring BMD changes around an acetabular cup made from Trabecular TitaniumTM in primary total hip arthroplasty (THA). Between February 2009 and December 2010, 89 patients (91 hip) underwent primary THA with a modular acetabular cup in Trabecular TitaniumTM (DELTA-TT cup, Limacorporate, Villanova di San Daniele, Italy). The average age was 63.5± 9.4 years, the average height and weight were 75.9± 12.9 kg and 168.8± 8.9 cm, respectively (av. BMI 26.8± 4.2). There were 46 (51.7%) males and 43 (48.3%) females affected by primary coxarthrosis in 80 (87.9%) cases, avascular necrosis in 5 (5.5%), posttraumatic coxarthrosis in 3 (3.3%), dysplasia in 2 (2.2) and oligoarthritis in 1 (1.1%) case. The study includes the clinical evaluation with Harris Hip Score (HHS) and SF-36, radiographic evaluation and dual-energy x-ray absorptiometry (DEXA) analysis preoperatively and postoperatively at 1 week, 3, 6, 12 and 24 months. Preliminary results are currently available for 47 patients at 12 months, 68 at 6 months and 80 at 3 months. The average HHS significantly improved from 48.7± 14.99 preoperatively to 93.8± 5.91 at 12 months, with a constant progression in the intermediate follow-ups. All patients showed a significant ROM increase, with an average flexion from 86.6°± 15.9° preoperatively to 105°±13.14 at 12 months. Sf-36 highlighted a satisfactory improvement of general health status from an average preoperative value of 50.8± 18.7 to 80.7± 12.9 at 12 months (from 42.9 to 80.1 for physical health; from 58.4 to 81.3 for mental one). All cups were stable at 12 months with no radiolucent lines. Preliminary DXA analysis reported an initial bone mineral density decrease from 1 week baseline values (BMD R1: 1.40± 0.37; R2: 1.20± 0.45; R3:1.16± 0.31) to 3 months (BMD R1: 1.31± 0.41; R2: 1.17± 0.3; R3: 1.06± 0.37) followed by BMD recovery up to initial values (BMD R1: 1.37± 0.3; R2:1.18± 0.34; R3: 1.12± 0.36) at 12 months. Trabecular TitaniumTM demonstrates a good primary and secondary stability. Preliminary densitometric outcome confirms an optimal osseointegration of the DELTA-TT cup and early clinical and patient subjective results are very promising at a short term follow-up. However, the completions of follow-up evaluation are necessary to draw a conclusive analysis

Introduction. Modularity in femoral stem designs allow surgeons to independently control leg length, offset, and femoral version in revision or complex primary THA cases. Initial enthusiasm in these modular stems has been tempered by recognition of modular junction failures. This study evaluates mean 5-year clinical results and survival rates of a 3-part titanium alloy modular femoral implant with unique taper geometries and a metaphyseal plasma spray surface. The current results are presented after pre-market independent fatigue testing performed by Orthopaedic Laboratory (Greenwald) and previously published early clinical results in 2006. Low plasticity burnishing (LPB) was added in 2005 to further strengthen the neck metaphyseal modular junction. The modular stem component is a polished cylindrical splined clothespin design. Our hypothesis is that these unique modular junctions succeed in offering the advantages of modularity without failure at this midterm follow-up period. Methods. Between May 2010 and July 2016, 32 total hip arthroplasties were performed using a 3-part femoral stem with neck-metaphyseal-stem modular junctions. Surgeries were either the final stage of a two-stage revision for infection, revision THR for loosening, or a revision of a previous non-prosthetic replacement procedure. Patients were entered into an IRB-approved registry and followed with x-rays, HHS, Oxford scores, and patient satisfaction scores. Patients who failed to return for routine follow-up were contacted by phone or email. Two patients had died with their implants intact. Six patients could not be reached for an updated follow-up. One stem was revised for loosening at 33 months due to failed osseointegration in a patient with chronic renal failure. This removed stem was submitted for taper exam and sectioning. Results. There were 23 patients for evaluation at a mean 61 months (range 21–98). Mean patient age at implantation was 56 (range 25–88), BMI was 27 (range 20–40). There were no modular junction failures. Modular junctions examined in the retrieved implant did not demonstrate any abnormalities other than normal wear properties. HHS and OHS scores both improved between pre-op and final follow-up, 23 to 85 and 17 to 43, respectively. Average patient satisfaction score at final follow-up was 9.8 out of 10 (min 8, max 10). Radiographic examination showed stem subsidence > 2mm and radiolucencies around the metaphyseal cone in 1 patient, the same patient who required implant removal. Radiolucencies were seen along the polished stem tip in 43% of cases, spot welding at the distal metaphyseal cone in 67% of cases, and mild proximal-medial stress shielding in 33% of cases. Conclusion. This unique 3-part modular stem with metaphyseal fixation shows good functional and radiographic results at 5-year follow-up. There were no junctional failures. One stem was removed due to failure to osseointegrate and showed no worrisome taper abnormalities. Spot welding is common around the plasma spray metaphyseal cone. Implant removal, if necessary, only requires disruption of the metaphyseal fixation. Further follow-up will be important to confirm our confidence in this unique stem design

Introduction: Treatment of osteoarthritis by total joint replacement generally shows a high success rate; however challenges remain. Prostheses inserted without cement are popular worldwide. Insertion of uncemented implants is intended to be pressfit. Early bone growth on the implant is critical to long-term fixation. Parathyroid hormone (PTH) is a regulator of bone metabolism. When PTH is administered intermittently it induces strong anabolic effect by increasing osteoblastic activity. Our understanding of PTH is mainly based on research on osteoporosis, in which bone formation is known to be coupled to the bone resorption. In the orthopaedic situation of a joint replacement other conditions apply. We therefore find it of interest to examine PTH’s role as an adjuvant in implant surgery. We examine the effect of PTH on the osseointegration of an experimental orthopaedic implant in which the implant due to insertion initiates a bone repair in the implant bed. We hypothesize that parathyroid hormone will improve the bone ongrowth at the bone-implant interface. Methods: An unpaired canine study was carried out following approval of our Institutional Animal Care and Use Committee. In 20 skeletally mature dogs cylindrical titanium alloy porous coated implants (6×10mm) were inserted pressfit (0.1 mm under-drill) in the extraarticular cancellous bone site of the proximal tibia. Test animal were postoperatively randomised to daily treatment of placebo or parathyroid hormon rhPTH (1–34)(t eriparatide)(Bachem) 5 μg/kg s.c. After 4 weeks observation time specimen blocks were harvested, sectioned and evaluated by unbiased stereological histomorphometry (CAST-grid system (Olympus Denmark)). The endpoints were bone-to-implant contact and tissue density in a 500 μm region of interest. Since data were not normally distributed a non-parametric analysis two-sample Wilcoxon rank-sum test was applied with p-value < 0.05 considered statistically significant. Data are accordingly presented as median and interquartile ranges. Results: Two implants in the PTH group were excluded. At the implant interface tissue density for PTH was 0,193 (0,157–0,229) for bone, 0,796 (0,764–0,821) for marrow and 0 (0–0,009) for fibrous tissue, as for control 0,163 (0,141–0,193) for bone, 0,837 (0,805–0,859) for marrow and 0 (0-0) for fibrous tissue. Bone tissue showed no significant differences. In the peri-centric region the tissue fraction for PTH was 0,238 (0,211–0,276) for bone, 0,752 (0,724–0,785) for marrow and 0 (0–0,007) for fibrous tissue, as for control 0,223 (0,201–0,235) for bone, 0,777 (0,765–0,799) for marrow and 0 (0–0) for fibrous tissue. Conclusion: In conclusion parathyroid hormone does not show significantly induced bone formation at a titanium alloy implant that has a porous coating of titanium alloy and inserted pressfit

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

Despite advances in total hip arthroplasty, failure of acetabular cup remains a concern. The role of bone marrow stromal cells (BMSCs) to aid osseointegration of orthopaedic implants have been recently studied. We investigated the hypothesis that autologous BMSCs sprayed on the surface of acetabular cups would improve bone formation and bone implant contact. Total hip replacements were implanted in 11 sheep, randomly assigned to receive either acetabular implants sprayed with autologous BMSCs suspended in fibrin (study group) or fibrin only (control group). Sheep were sacrificed after six months and the acetabulum with the implant was retrieved and prepared for undecalcified histology. Implant bone contact in both groups was compared microscopically, by noting the presence or absence of new bone or fibrous tissue along the implant at 35 consecutive points (every 1000 μm). The observers undertaking the histological analysis were blinded. Significantly increased bone implant contact was noted in the BMSC treated group 30.71% ± 2.95 compared to the control group 5.14% ± 1.67 (p = 0.014). The mean thickness of fibrous tissue in contact with the implant was greater at the periphery 887.21mm ± 158.89 and the dome 902.45mm ± 80.67 of the implant in the control group compared to the BMSC treated group (327.49mm ± 20.38 at the periphery and 739.1 mm ± 173.72 at the centre). Conversely, direct bone contact with the implant surface was significantly greater around the cups with BMSCs. Our data demonstrate that BMSC sprayed on surface of acetabular implants improves bone implant contact. Spraying acetabular cups using stem cells could be used in humans where acetabular bone contact is compromised such as in revision procedures

In the reconstruction of the anterior cruciate ligaments of the knee, early loading of the leg is usually desirable. Thus, it is of a great interest to evaluate the early stability of screws used for tibial fixation of the ligament, rather than long-term stability of such devices when the neoligament is certainly integrated. The purpose of this study (controlled laboratory study) was to investigate the early osteointegration and biodegradation of hydroxyapatite (HA)/poly(L-lactide)(PLLA) (HA/PLLA) composite screws compared with tricalcium-phosphate (TCP)/PLLA (TCP/PLLA) composite screws used for tibial fixation in the reconstruction of the anterior cruciate ligaments. We used two types of resorbable screws: BioRCI (Smith& Nephew) composite screws (30% HA and 70% PLLA) and Biocryl (Mitek) composite screws (30% TCP and 70% PLLA) that were inserted into the distal femur of three skeletally mature sheep. Each animal received one HA/PLLA composite screw and one TCP/ PLLA composite screw. The three sheep were sacrificed 20, 40 and 60 days after surgery. Results were evaluated by radiological (RX, TC and RMN), histological and microradiographic analyses. The amount of bone tissue osteointegrating the screw was higher for TCP/PLLA screws than for HA/PLLA screws. No sign of real biodegradation was observed in any of the specimens. In conclusion, TCP/PLLA composite screws provide a favourable early osteointegration compared to HA/PLLA composite screws; this could provide an early loading of the leg, which is the primary goal of clinicians and patients in this case. In addition, this could provide a considerable reduction of medical expenses, due to the decrease in hospitalisation and rehabilitation time

Coating titanium alloy implants with titanium nitride (TiN) by the method of Powder Immersion Reaction Assisted Coating (PIRAC) produces a stable layer on their surface. We have examined the ability of the new TiN coating to undergo osseointegration. We implanted TiN-coated and uncoated Ti6Al4V alloy pins into the femora of six-month-old female Wistar rats. SEM after two months showed a bone collar around both TiN-coated and uncoated implants. Morphometrical analysis revealed no significant differences between the percentage of the implant-bone contact and the area and volume of the bone around TiN-coated compared with uncoated implants. Electron-probe microanalysis indicated the presence of calcium and phosphorus at the implant-bone interface. Mineralisation around the implants was also confirmed by labelling with oxytetracycline. Strong activity of alkaline phosphatase and weak activity of tartrate-resistant acid phosphatase were shown histochemically. Very few macrophages were detected by the non-specific esterase reaction at the site of implantation. Our findings indicate good biocompatibility and bone-bonding properties of the new PIRAC TiN coatings which are comparable to those of uncoated Ti6Al4V alloy implants

Aims. Safety concerns surrounding osseointegration are a significant barrier to replacing socket prosthesis as the standard of care following limb amputation. While implanted osseointegrated prostheses traditionally occur in two stages, a one-stage approach has emerged. Currently, there is no existing comparison of the outcomes of these different approaches. To address safety concerns, this study sought to determine whether a one-stage osseointegration procedure is associated with fewer adverse events than the two-staged approach. Methods. A comprehensive electronic search and quantitative data analysis from eligible studies were performed. Inclusion criteria were adults with a limb amputation managed with a one- or two-stage osseointegration procedure with follow-up reporting of complications. Results. A total of 19 studies were included: four one-stage, 14 two-stage, and one article with both one- and two-stage groups. Superficial infection was the most common complication (one-stage: 38% vs two-stage: 52%). There was a notable difference in the incidence of osteomyelitis (one-stage: nil vs two-stage: 10%) and implant failure (one-stage: 1% vs two-stage: 9%). Fracture incidence was equivocal (one-stage: 13% vs two-stage: 12%), and comparison of soft-tissue, stoma, and mechanical related complications was not possible. Conclusion. This review suggests that the one-stage approach is favourable compared to the two-stage, because the incidence of complications was slightly lower in the one-stage cohort, with a pertinent difference in the incidence of osteomyelitis and implant failure. Cite this article: Bone Jt Open 2023;4(7):539–550

Titanium-alloy is a metal with excellent biocompatibility, but its osteoconduction is not as efficient as hydroxyapatite materials. Calcium-ion (Ca-ion) implantation is a surface modification technique that can improve osteoconduction of titanium without an additional layer of coating. We studied the effects of Ca-ion-implantation on osseointegration of a titanium-alloy stem in a bilateral canine THA model. The stem surface was grit-blasted and Ca-ion-implanted by the ion mixing technique. Fifteen mongrel dogs had bilateral single-stage THAs, with a Ca-ion-implanted stem used in one side and a non-Ca-ion-implanted stem in the contralateral side. They were sacrificed at 1, 6, and 12 months postoperatively, and microradiographs were taken. Undecalcified cross-sections were evaluated histologically. For quantitative evaluation, the length of new bone apposition to the implant surface was obtained using computer image analysis. Most implants were well integrated, and there was no apparent qualitative difference between the two types of stems radiographically and histologically. However, Ca-ion-implanted stems had significantly greater new bone apposition than non-Ca-ion-implanted stems at 1 month, although the overall effect of Ca-ion-implantation was not significant. The results showed enhanced osteoconduction with Ca-ion-implantation only in the early postoperative period. This could be related to the previous data of immersion tests that the dissolution rate of Ca-ion from Ca-ion-implanted titanium decreases with time. Clinically, early osteoconduction is desirable and could accelerate rehabilitation and outcome. Although further improvement of the Ca-ion-implantation technique for a sustained osteoconductive effect is necessary, Ca-ion-implantation will be beneficial for early fixation of titanium-alloy implants

Periprosthetic joint infections (PJI) are one of the most common reasons for orthopedic revision surgeries. In previous studies, it has been shown that silver modification of titanium (Ti-6Al-4V) surfaces by PMEDM (powder mixed electrical discharge machining) has an antibacterial effect on Staphylococcus aureus adhesion. Whether this method also influences the proliferation of bacteria has not been investigated so far. Furthermore, the effect is only limitedly investigated on the ossification processes. Therefore, the aim of this work is to investigate the antibacterial effect as well as the in vitro ossification process of PMEDM machined surfaces modified by integration of silver.

In this study, we analyzed adhesion and proliferation of S. aureus in comparison to of surface roughness, silver content and layer thickness of the silver-integrated-PMEDM surfaces (N = 5). To test the in vitro ossification, human osteoblasts (SaOs-2) and osteoclasts (differentiated from murine-bone-marrow-macrophages) were cultured on the silver surfaces (N = 3).

We showed that the attachment of S. aureus on the surfaces was significantly lower than on the comparative control surfaces of pure Ti-6Al-4V without incorporated silver, independently of the measured surface properties. Bacterial proliferation, however, was not affected by the silver content. No influence on the in vitro ossification was observed, whereas osteoclast formation was drastically reduced on the silver-modified surfaces.

We showed that 1 to 3% of silver in the surface layer significantly reduced the adhesion of S. aureus, but not the proliferation of already attached bacteria. At the same time, no influence on the in vitro ossification was observed, while no osteoclasts were formed on the surface. Therefore, we state that PMEDM with simultaneous silver modification of the machined surfaces represents a promising technology for endoprostheses manufacturing to reduce infections while at the same time optimizing bone ingrowth.

Aims

For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel.

Aims:. To test the effect of different surface roughness and fluorohydroxyapatite (FHA) coating on osteoblast-like cell (MG63) viability, proliferation, differentiation and synthetic activity, then to compare the various surfaces tested and try to identify an osteoblast parameter that can better explain the different behaviour of the tested surfaces observed in previous in vivo studies. Methods: The tested materials were made of Ti6Al4V coated with Ti and with Ti plus FHA with different roughness; they can be divided into four groups: low roughness (LR; Ra: 5.9 B5m), low roughness plus FHA coating (LR+FHA; Ra: 5.6 B5m), high roughness (HR; Ra: 22.5 B5m), high roughness plus FHA coating (HR+FHA; Ra: 21.2 B5m). MG63 were cultivated on 6 samples of each group and on polystyrene as control; after 72 hours the proliferation assay (WST-1) was done, alkaline phosphatase activity (ALP) was determined and the synthesis of osteocalcin (OC), type 1 collagen (CICP), transforming growth factor α 1 (TGF-A71), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-a) were measured. Samples of each material were randomly processed for analysis with a scanning electron microscope (SEM). Results: Cells proliferated on biomaterials more slowly than in the control group (p < 0.0001), the proliferation rate was higher on FHA-coated LR than uncoated HR (p = 0.037). CICP production was positively affected by the LR surface (p = 0.001) as compared to controls, while it was significantly lower (p = 0.0001) in the HR surfaces. Compared to controls, LR and HR surfaces led to enhanced production of TGF-A71, further improved by FHA (FHA-coated LR: p = 0.007; FHA-coated HR p < 0.0001 respectively). ALP, OC, IL-6 levels were not significantly different from the controls. Conclusions: Results suggest that CICP production could be useful in predicting the in vivo osteointegration rate of biocompatible biomaterials observed in previous studies

Background: As the understanding of bone repair mechanics has advanced the integrity of the bone pin interface has emerged as a key factor in determining the success of external fracture fixation. The benefits of using pins coated with Hydroxyapatite (HA) are well documented however the thickness of the conventional plasma spray coating precludes its use for modification of the surface of fine features in implants. Consequently new electro-chemical techniques for pre-coating implants with a ‘biomimetic’ HA layer using simulated body fluids (SBF) have been pioneered. In this study we test the hypothesis that varying the technique for deposition of HA by electrolysis of SBF alters the morphology of the HA surface which will modify the level of osseointegration. Method: Three alternative methods of HA coating the Barerre, Redepenning and Kumar techniques were compared. Tantalum coated stainless steel pins were coated then used to stabilise a mid-diaphyseal osteotomy in three sheep using an orthofix fixator for a period of ten weeks. Insertion and extraction torques were measured to calculate the pin performance index (PPI). Sections of the bones were then examined using scanning electron microscopy to determine the percentage of bone in contact with the pin surface and the percentage of new bone formation. Results: The different coating protocols resulted in different HA crystal morphologies. The extraction torque exceeded the insertion torque for both the Barerre and Redepenning methods and their PPI exceeds that of plasma spray coatings. The Redepenning technique was shown to perform sig-nificantly better than both the Barerre (p=0,001) and Kumar (p=0,001) techniques with 49.4% of the pin surface in contact with bone. These results were mirrored on analysis of new bone formation with the Redepen-ning technique showing 70.2% of new bone formation compared to the Barerre (55.4%) and Kumar (53.8%) methods. Conclusion: These results indicate that the Redepenning technique is the most effective for creating a bio mimetic HA coating in terms of bonding to bone and promoting new bone formation. This technique holds significant advantages over the conventional plasma spray technique for example the coating thickness can be easily controlled and additional proteins such as bone morphogenic proteins and antibiotics can be incorporated. It may therefore represent a new era in the use of HA coating

All types of regenerative materials, including metal implants, porous scaffolds and cell-laden hydrogels, interact with the living tissue and cells. Such interaction is key to the settlement and regenerative outcomes of the biomaterials. Notably, the immune reactions from the host body crucially mediate the tissue-biomaterials interactions. Macrophages (as well as monocytes and neutrophils), traditionally best known as defenders, accumulate at the tissue-biomaterials interface and secrete abundant cytokines to create a microenvironment that benefits or inhibits regeneration. Because the phenotype of these cells is highly plastic in response to varying stimuli, it may be feasible to manipulate their activity at the interface and harness their power to mediate bone regeneration. Towards this goal, our team have been working on macrophage-driven bone regeneration in two aspects. First, targeting the abundant, glucan/mannan-recognising receptors on macrophages, we have devised a series of glucomannan polymers that can stimulate macrophages to secrete pro-osteogenic cytokines, and applied them as coating polymer of mesenchymal stem cells-laden hydrogels. Second, targeting the toll-like receptors (TLRs) on macrophages, we have screened TLR-activating polysaccharides and picked up zymosan (beta-glucan) to be modified onto titanium and glass implants. We evaluated both the efficacy of integration and safety of immune stimulation in both in vitro and in vivo models. Our future exploration lies in further elaborating the different roles and mechanisms of macrophages of various types and origins in the regenerative process.

Aims. Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. Methods. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed. Results. A greater RLL score (p = 0.041) was observed at three years postoperatively, with those receiving chemotherapy showing greater radiological loosening compared with those not receiving chemotherapy. Chemotherapy patients experience osteolysis at the shoulder of the ingrowth collar over time (p < 0.001) compared with non-chemotherapy patients where osteolysis was not observed. A greater median percentage integration of the collar surface was observed in the non-chemotherapy group (8.6%, interquartile range (IQR) 0.0% to 37.9%; p = 0.021) at three years. Bone growth around the collar was observed in both groups, and no statistical difference in amount of extracortical bony bridging was seen. Conclusion. Multidrug chemotherapy affects the osseointegration of ingrowth collars and accelerates signs of radiological loosening. This may increase the risk of aseptic loosening in patients with massive segmental implants used to treat bone cancer. Cite this article: Bone Joint Res 2020;9(7):333–340

Aim

The first osseointegrated transfemoral amputation prosthesis operation was performed in Gothenburg in 1990. The aim is improving quality of life for patients who cannot use conventional socket prosthesis. In 1999 the prospective OPRA-study (Osseointegrated Prosthesis for Rehabiliation of Amputees) was initiated with standardized surgery, equipment and rehabilitation program.

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: Hip arthroplasty can present surgeons with difficult bone loss. Impacted allografting is a well-established way of initally securing implant stability. However subsequent bone integration and fusion can be prolonged. Also concerns relate on maintaining bone volume of allograft during integration.

Intermittent administration of parathyroid hormone (PTH) is bone anabolic and improves fracture healing. As adjuvant in implant surgery PTH has only recently been introduced experimentally predominantly showing improved implant integration within empty peri-implant bone defects.

Given the desire to improve the graft incorporation process, the purpose of our study is to examine whether PTH improves early implant integration by accelerating healing of peri-implant bone allograft. We test the hypothesis that systemic intermittent administration of PTH increases new bone formation in allograft inserted in a gap with impacted morselized bone allograft around an experimental orthopaedic implant. We hypothesize that parathyroid hormone will improve new bone formation in allograft and preserve allograft.

Methods: An unpaired canine study was carried out following approval of our Institutional Animal Care and Use Committee. In 20 skeletally mature dogs cylindrical titanium alloy porous coated implants (6x10mm) were inserted in a 2.5 mm circumferential gap in the extraarticular cancellous bone site of the proximal humeri. Cancellous bone was milled on fine setting and impacted in the gap. Test animal were postoperatively randomised to daily treatment of placebo or parathyroid hormon rhPTH (1–34)(teriparatide)(Bachem) 5 μg / kg s.c. After 4 weeks observation time specimen blocks were harvested, sectioned and evaluated by unbiased stereological histomor-phometry (newCast, Visiopharm, Horsholm, Denmark). The endpoints were bone-to-implant contact and tissue density in an outer gap region of 1500 μm and an inner gap region reaching the implant. Since data were not normally distributed a non-parametric analysis two-sample Wilcoxon rank-sum test was applied with p-value < 0.05 considered statistically significant. Data are accordingly presented as median and interquartile ranges.

Results: Two implants in the PTH group were excluded. In the peri-centric region new bone improved significantly (outer region: PTH 21.1 (12.9–16.3) / control 15.2 (13.9–16.2), inner region: PTH 19.8 (15.8–21.5)/control 14.0 (12.9–16.3)). There were no significant differences in the amount of allograft. At the implant interface new bone for PTH was 11.5 (8.1–14.0), as for control 10.5 (7.2–14.8). Old bone for PTH was 1.5 (0.8–2.0), and old bone 1.4 (0.8–1.7). Bone tissue showed no significant differences.

Conclusion: Parathyroid hormone shows promise in significant inducing bone formation in impacted morselized allograft around implant without resorbing it significantly retaining graft volume.

Introduction and Objectives: The goal of this study is to document radiographic changes occurring in patients with hydroxyapatite(HA)-coated total hip prostheses (THP).

Materials and Methods: From May 1990 to May 1993, 60 THP with complete (femoral and acetabular) HA-coating were implanted in 59 patients. Of these 59 patients, 36 were male and 23 female. Average age was 69.26 years. A retrospective study of these patients was done, with an average follow-up time of 11 years. Radiological follow-up was done at 1 month, 3 months, 6 months, 1 year, and annually thereafter. Available imaging methods included conventional radiography, direct digital radiography, digital processing, CT scan, bone scintigra-phy, and tomodensitometry. We used the first 3 of these techniques. The acetabular cup and femoral stem have been divided based on DeLee-Charnley zones (cup) and Gruen zones (femur). The following variables were tracked for the acetabular component: subchondral sclerosis, radiolucent lines, resorption, remodeling, and the appearance of osteolyic lesions. For the femoral component, the following were tracked: radiolucent lines, calcar resorption, periprosthetic cortical thickness, appearance and progression of the pedestal, appearance of osteo-lytic lesions, new intramedullary bone formation, and state of cancellous bone, with particular emphasis on periprosthetic trabeculation. We also assessed prosthetic positioning (normal, varus, valgus), angle of the acetabular component, changes in the polyethylene, and heterotopic ossification (Brooker’s classification). Radiographic studies were performed by 2 independent observers, blinded as to the clinical situation.

Results: Of the 60 THP with HA coating in our study, 5 could not be reviewed due to incorrect personal data on their clinical records, and 6 were deceased. With the cups, DeLee-Charnley zone 1 showed bone remodeling with frequent sclerotic changes, and zone 3 showed radiolucent lines of less than 1 mm. Femoral stems had a typical pattern of poor endosteal apposition around Gruen’s zone 6. Calcar remodeling was slowly progressive, with thinning of the cortex. Minimal resorption of the femoral neck was also observed. A periosteal reaction was noted in eccentrically loaded stems. Pedestals were common and did not seem to reflect loosening of the prosthesis in our data. Image digitalisation permitted the examination of newly-formed trabeculae, particularly in Gruen’s zones 2–3 and 5–6, which appeared at 3 months.

Discussion and Conclusions: Radiographic progression in most of the patients with THP with HA coating was satisfactory. Digitalisation of radiographic images permitted better visualization of changes occurring at the bone-prosthesis interface.

Background A biomaterial serves to support, organize and directly influence the behaviour of growing cells. Chitosan has the capability to be a very useful biomaterial in the speciality of orthopaedics, due to its excellent biocompatibility, and physical properties that allow topographical modification. Chitosan films have potential to be used to coat implant surfaces, regulating bone cells at the implant interface. Enhanced integration may therefore help towards solving problems such as aseptic loosening.

Method 85% deacylated chitosan (Sigma) was dissolved in 2% acetic overnight. The viscous chitosan was then sterilized by autoclaving for 10 minutes. PDMS patterned stamps produced from a silicon mould were added to the viscous chitosan and as the chitosan film forms the topographic impression is left on the surface. The gel was then dried for 36 hours in a sterile system. The pH is neutralized with NaOH1M for 24 hours. The gel was washed in sterile hanks balanced salt solution until the pH was 7.4. Osteoblasts were then grown on these surfaces in a cell culture system and analysed by light microscopy and image analysis.

Results We have successfully designed a protocol for the production of sterile topographically modified chitosan, with surface features that can be produced in the range of 1–100um. We have shown that cells on un-modified chitosan differentiate and form bone at a much slower rate than on chitosan with a modified surface. Findings supported by in-situ alkaline phosphatase levels. Control can be exerted on cell shape and inter-cellular interactions based upon shape and surface area between shapes; with a smaller surface area making adhesion more difficult.

Conclusion. Our data shows that osteoblasts can be controlled by altering chitosans surface topography. Being able to influence biology by changing biomaterial surface features will enhance interaction at the bone implant interface, allowing greater implant integration.

Aims. The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis. Methods. In this cohort study, all patients with a unilateral TFA treated with the Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) implant system in Sahlgrenska University Hospital, Gothenburg, Sweden, between January 1999 and December 2017 were included. The cohort comprised 111 patients (78 male (70%)), with a mean age 45 years (17 to 70). The main reason for amputation was trauma in 75 (68%) and tumours in 23 (21%). Patients answered the Questionnaire for Persons with Transfemoral Amputation (Q-TFA) before treatment and at two, five, seven, ten, and 15 years’ follow-up. A prosthetic activity grade was assigned to each patient at each timepoint. All mechanical complications, defined as fracture, bending, or wear to any part of the implant system resulting in removal or change, were recorded. Results. The Q-TFA scores at two, five, seven, and ten years showed significantly more prosthetic use, better mobility, fewer problems, and an improved global situation, compared with baseline. The survival rate of the osseointegrated implant part (the fixture) was 89% and 72% after seven and 15 years, respectively. A total of 61 patients (55%) had mechanical complications (mean 3.3 (SD 5.76)), resulting in exchange of the percutaneous implant parts. There was a positive relationship between a higher activity grade and the number of mechanical complications. Conclusion. Compared with before treatment, the patient-reported outcome was significantly better and remained so over time. Although osseointegration and the ability to transfer loads over a 15-year period have been demonstrated, a large number of mechanical failures in the external implant parts were found. Since these were related to higher activity, restrictions in activity and improvements to the mechanical properties of the implant system are required. Cite this article: Bone Joint J 2020;102-B(1):55–63

We investigated the hypothesis that autologous bone marrow stromal cells (BMSC) sprayed on the surface of acetabular cups would improve bone formation and bone implant contact.

Total hip replacements were implanted in 11 sheep, randomly assigned to receive either acetabular implants sprayed with autologous BMSCs suspended in fibrin (study group) or fibrin only (control group). Sheep were sacrificed after six months and the acetabulum with the implant was retrieved and prepared for undcalcified histology. Implant bone contact in both groups was compared, by microscopically noting the presence or absence of new bone or fibrous tissue along the implant at 35 consecutive points (every 1000 μm). The observers undertaking the histological analysis were blinded.

Significantly increased bone implant contact was noted in the BMSC treated group 30.71% ± 2.95 compared to the control group 5.14% ± 1.67 (p = 0.014). The mean thickness of fibrous tissue in contact with the implant was greater at the periphery 887.21mm ± 158.89 and the dome 902.45mm ± 80.67 of the implant in the control group compared to the BMSC treated group (327.49mm ± 20.38 at the periphery and 739.1 mm ±173.72 at the centre). Conversely direct bone contact with the implant surface was significantly greater around the cups with stem cells.

BMSC sprayed on surface of implants improves bone implant contact. Spraying acetabular cups using stem cells could be used in humans where acetabular bone contact is compromised such as in revision procedures.

Objectives. Enhanced micromotions between the implant and surrounding bone can impair osseointegration, resulting in fibrous encapsulation and aseptic loosening of the implant. Since the effect of micromotions on human bone cells is sparsely investigated, an in vitro system, which allows application of micromotions on bone cells and subsequent investigation of bone cell activity, was developed. Methods. Micromotions ranging from 25 µm to 100 µm were applied as sine or triangle signal with 1 Hz frequency to human osteoblasts seeded on collagen scaffolds. Micromotions were applied for six hours per day over three days. During the micromotions, a static pressure of 527 Pa was exerted on the cells by Ti6Al4V cylinders. Osteoblasts loaded with Ti6Al4V cylinders and unloaded osteoblasts without micromotions served as controls. Subsequently, cell viability, expression of the osteogenic markers collagen type I, alkaline phosphatase, and osteocalcin, as well as gene expression of osteoprotegerin, receptor activator of NF-κB ligand, matrix metalloproteinase-1, and tissue inhibitor of metalloproteinase-1, were investigated. Results. Live and dead cell numbers were higher after 25 µm sine and 50 µm triangle micromotions compared with loaded controls. Collagen type I synthesis was downregulated in respective samples. The metabolic activity and osteocalcin expression level were higher in samples treated with 25 µm micromotions compared with the loaded controls. Furthermore, static loading and micromotions decreased the osteoprotegerin/receptor activator of NF-κB ligand ratio. Conclusion. Our system enables investigation of the behaviour of bone cells at the bone-implant interface under shear stress induced by micromotions. We could demonstrate that micromotions applied under static pressure conditions have a significant impact on the activity of osteoblasts seeded on collagen scaffolds. In future studies, higher mechanical stress will be applied and different implant surface structures will be considered. Cite this article: J. Ziebart, S. Fan, C. Schulze, P. W. Kämmerer, R. Bader, A. Jonitz-Heincke. Effects of interfacial micromotions on vitality and differentiation of human osteoblasts. Bone Joint Res 2018;7:187–195. DOI: 10.1302/2046-3758.72.BJR-2017-0228.R1

Aims

Surgeons and most engineers believe that bone compaction improves implant primary stability without causing undue damage to the bone itself. In this study, we developed a murine distal femoral implant model and tested this dogma.

Aims

The purpose of this study was to evaluate the biological fixation of a 3D printed porous implant, with and without different hydroxyapatite (HA) coatings, in a canine model.

Aims. United Classification System (UCS) B2 and B3 periprosthetic fractures in total hip arthroplasties (THAs) have been commonly managed with modular tapered stems. No study has evaluated the use of monoblock fluted tapered titanium stems for this indication. This study aimed to evaluate the effects of a monoblock stems on implant survivorship, postoperative outcomes, radiological outcomes, and osseointegration following treatment of THA UCS B2 and B3 periprosthetic fractures. Methods. A retrospective review was conducted of all patients who underwent revision THA (rTHA) for periprosthetic UCS B2 and B3 periprosthetic fracture who received a single design monoblock fluted tapered titanium stem at two large, tertiary care, academic hospitals. A total of 72 patients met inclusion and exclusion criteria (68 UCS B2, and four UCS B3 fractures). Primary outcomes of interest were radiological stem subsidence (> 5 mm), radiological osseointegration, and fracture union. Sub-analysis was also done for 46 patients with minimum one-year follow-up. Results. For the total cohort, stem osseointegration, fracture union, and stem subsidence were 98.6%, 98.6%, and 6.9%, respectively, at latest follow-up (mean follow-up 27.0 months (SD 22.4)). For patients with minimum one-year of follow-up, stem osseointegration, fracture union, and stem subsidence were 97.8%, 97.8%, and 6.5%, respectively. Conclusion. Monoblock fluted stems can be an acceptable modality for the management of UCS B2 periprosthetic fractures in rTHAs due to high rates of stem osseointegration and survival, and the low rates of stem subsidence, and revision. Further research on the use of this stem for UCS B3 periprosthetic fractures is warranted to determine if the same conclusion can be made for this fracture pattern. Cite this article: Bone Jt Open 2023;4(8):551–558

Patients with transfemoral amputation (TFA) often experience problems related to the use of socket-suspended prostheses. The clinical development of osseointegrated percutaneous prostheses for patients with a TFA started in 1990, based on the long-term successful results of osseointegrated dental implants.

Between1999 and 2007, 51 patients with 55 TFAs were consecutively enrolled in a prospective, single-centre non-randomised study and followed for two years. The indication for amputation was trauma in 33 patients (65%) and tumour in 12 (24%). A two-stage surgical procedure was used to introduce a percutaneous implant to which an external amputation prosthesis was attached. The assessment of outcome included the use of two self-report questionnaires, the Questionnaire for Persons with a Transfemoral Amputation (Q-TFA) and the Short-Form (SF)-36.

The cumulative survival at two years’ follow-up was 92%. The Q-TFA showed improved prosthetic use, mobility, global situation and fewer problems (all p < 0.001). The physical function SF-36 scores were also improved (p < 0.001). Superficial infection was the most frequent complication, occurring 41 times in 28 patients (rate of infection 54.9%). Most were treated effectively with oral antibiotics. The implant was removed in four patients because of loosening (three aseptic, one infection).

Osseointegrated percutaneous implants constitute a novel form of treatment for patients with TFA. The high cumulative survival rate at two years (92%) combined with enhanced prosthetic use and mobility, fewer problems and improved quality of life, supports the ‘revolutionary change’ that patients with TFA have reported following treatment with osseointegrated percutaneous prostheses.

Cite this article: Bone Joint J 2014;96-B:106–13.

Introduction. Osseointegration has emerged as a promising alternative to rehabilitating with a traditional socket mounted prosthesis. Advantages have been reported to include improved functional mobility, better osseoperception, improved comfort, reduced pain, better biomechanical alignment and better gait, which all lead to a less restricted lifestyle and significantly improved quality of life. A major concern of the Osseointegrated approach lies in the risk of infections occurring from the permanent transcutaneous opening often referred to as the stoma. Several systematic reviews have indicated that the occurrence of minor infections can be quite common, serious complications are reported to be rare. In addition to commonly anticipated complications including fractures, surgical debridements or revisions, we have identified several significant events in which a patient may require to be readmitted and go through additional surgery. The objective of this study is to examine the rate of occurrence and reports on the best management practices of serious complications across a multi-centre review of more than 1000 osseointegration surgeries. Materials & Methods. A detailed analysis has been performed on all osseointegration surgeries performed by the Osseointegration Group of Australia and it's affiliates between since 2010. The majority of surgeries took place in Australia, the United States, the Middle East as well as in Europe. All events leading to a re-admission and subsequent re-operation have been identified through hospital operation records and pooled together for meta-analysis. Events identified include: revision of implants, periprosthetic fracture fixation, surgical debridement due to infections, neurectomies and soft- tissue refashioning. Results. Over 800 surgeries have been identified with a minimum 12-month follow-up time and included in this study. These included tibial, femoral and humeral, radial-ulnar and transpelvic osseointegration cases. The majority of these were performed using a single stage protocol. While general complications such as infection and soft tissue refashioning are common, serious events such as revision and fracture are rare. Interestingly, the rate of debridements and soft-tissue refashions were found to be higher among patients who were operated using a two-stage surgery. Among all cases, there were a total of 399 re-operation events recorded which occurred among 163 patients, indicating a high recurrence rate among the same patients. We recorded a total of 112 washouts, 93 neurectomies, 117 soft tissue refashions, 53 implant revisions and 24 periprosthetic fracture fixations. Conclusions. Many events leading to readmission after the primary surgery may not necessarily be graded as a complication of the osseointegration technique. This study has identified several addition possible reasons in which an osseointegration patient may need to be re-admitted into hospital for additional surgery. It was identified that through the implementation of improved surgical techniques and rehabilitation protocols, the rate of several of these re-operation events can be largely reduced, thus improving the overall outcomes of patients undergoing osseointegration surgery

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

Introduction. This study reports on minimum 2 year follow up outcomes on functional and quality of life of patients after undergoing bilateral osseointegration in comparison to traditional socket prosthesis. Materials & Methods. This is a prospective pilot study of 35 patients, consisting of 30 males and 5 females, aged 22–66 (mean 36) years at surgery, with minimum two-year follow-up. Selection criteria were age over 18 years, bilateral amputees who had socket-related problems or were wheelchair-bound with short stumps and non-reconstructable limb pathology. Principle outcome measures included the Questionnaire for persons with a Trans-Femoral Amputation (Q-TFA), Short Form Health Survey 36 (SF-36), Six Minute Walk Test (6MWT), Timed Up and Go (TUG), and K-levels. Adverse events were recorded including infection, revision surgery, fractures, and implant failures. Results. Comparisons were made using differences between the mean pre-operative and mean post-operative values for each outcome measure. Significant improvements in all validated outcome measures were observed. All patient who were wheelchair bound prior to the surgery were able to mobilise post operatively. The occurrence levels of adverse events, including the infection rate and revision rate within this patient cohort, were similar to other established trans-femoral osseointegration studies. Conclusions. These preliminary results indicate that osseointegration surgery is a safe and effective alternative treatment for bilateral amputees experiencing socket-related discomfort. Compared to the suboptimal outcomes of socket prostheses, osseointegration currently provides one of the best chances for any bilateral amputee to walk again and regain the ability to perform daily activities