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