The <i>in vivo</i> effect of a porous titanium alloy flange with hydroxyapatite, silver and fibronectin coatings on soft-tissue integration of intraosseous transcutaneous amputation prostheses

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

Fast plasma sintering delivers functional graded materials components with macroporous structures and osseointegration properties

We explored the osseointegration potential of two macroporous titanium surfaces obtained using fast plasma sintering (FPS): Ti macroporous structures with 400-600 µmØ pores (TiMac400) and 850-1000 µmØ pores (TiMac850). They were compared against two surfaces currently in clinical use: Ti-Growth® and air plasma spray (Ti-Y367). Each surface was tested, once placed over a Ti-alloy and once onto a CoCr bulk substrate. Implants were placed in medial femoral condyles in 24 sheep. Samples were explanted at four and eight weeks after surgery. Push-out loads were measured using a material-testing system. Bone contact and ingrowth were assessed by histomorphometry and SEM and EDX analyses. Histology showed early osseointegration for all the surfaces tested. At 8 weeks, TiMac400, TiMac850 and Ti-Growth® showed deep bone ingrowth and extended colonisation with newly formed bone. The mechanical push-out force was equal in all tested surfaces. Plasma spray surfaces showed greater bone-implant contact and higher level of pores colonisation with new bone than FPS produced surfaces. However, the void pore area in FPS specimens was significantly higher, yet the FPS porous surfaces allowed a deeper osseointegration of bone to implant. FPS manufactured specimens showed similar osseointegration potential to the plasma spray surfaces for orthopaedic implants. FPS is a useful technology for manufacturing macroporous titanium surfaces. Furthermore, its capability to combine two implantable materials, using bulk CoCr with macroporous titanium surfaces, could be of interest as it enables designers to conceive and manufacture innovative components. FPS delivers functional graded materials components with macroporous structures optimised for osseointegration

Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4

OBJECTIVES: Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. METHODS: MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts. RESULTS: MSCs from OVX rats migrate significantly (p < 0.05) less towards SDF-1 (9%, sd 5%) compared with MSCs from adult (15%, sd 3%) and young rats (25%, sd 4%). Cells transfected with CXCR4 migrated significantly more towards SDF-1 compared with non-transfected cells, irrespective of whether these cells were from OVX (26.5%, sd 4%), young (47%, sd 17%) or adult (21%, sd 4%) rats. Transfected MSCs differentiated to osteoblasts express CXCR4 but do not migrate towards SDF-1. CONCLUSIONS: MSC migration is impaired by age and osteoporosis in rats, and this may be associated with a significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by upregulating CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients

Sheep condyle model evaluation of bone marrow cell concentrate combined with a scaffold for repair of large osteochondral defects

AIMS: Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. METHODS: The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. RESULTS: The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. CONCLUSION: Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677-689

Augmenting the osseointegration of endoprostheses using laser-sintered porous collars: an in vivo study

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

A novel closed-loop electromechanical stimulator to enhance osseointegration with immediate loading of dental implant restorations

Abstract: The degree of osseomechanical integration of dental implants is acutely sensitive to their mechanical environment. Bone, both as a tissue and structure, adapts its mass and architecture in response to loading conditions. Therefore, application of predefined controlled loads may be considered as a treatment option to promote early maturation of bone/implant interface prior to or in conjunction with crown/prosthesis attachment. Although many studies have established that the magnitude, rate of the applied strain, and frequency have significant effects on the osteogenic response, the actual specific relationships between strain parameters and frequency have not yet been fully defined. The purpose of this study was to develop a stimulator to apply defined mechanical stimuli to individual dental implants in vivo immediately after implantation, exploring the hypothesis that immediate controlled loading could enhance implant integration. An electromechanical device was developed, based on load values obtained using a two-dimensional finite element analysis of the bone/implant interface generating 1000 to 4000 me and operated at 30 and 3 Hz respectively. The device was then tested in a cadaveric pig mandible, and periosteal bone surface strains were recorded for potential future comparison with a three-dimensional finite element model to determine loading regimens to optimize interface strains and iterate the device for clinical use

Patient and surgery related factors associated with fatigue type polyethylene wear on 49 PCA and DURACON retrievals at autopsy and revision

<p>Abstract</p> <p>Background</p> <p>Polyethylene wear is an important factor for longevity of total knee arthroplasty. Proven and suspicious factors causing wear can be grouped as material, patient and surgery related. There are more studies correlating design and/or biomaterial factors to in vivo wear than those to patient and surgery related factors. Many retrieval studies just include revision implants and therefore may not be representative. This study is aimed to correlate patient- and surgery- related factors to visual wear score by minimizing design influence and include both autopsy and revision implants. Comparison between the groups was expected to unmask patient and surgery-related factors responsible for wear.</p> <p>Methods</p> <p>The amount of joint side wear on polyethylene retrievals was measured using a modification of an established visual wear score. Fatigue type wear was defined as summation of the most severe wear modes of delamination, pitting and cracks. Analysis of patient and surgery related variables suspicious to cause wear included prospectively sampled patient activity which was measured by self reported walking capacity. Statistical analysis was done by univariate analysis of variance. Activity level and implantation time were merged to an index of use and correlated to the wear score.</p> <p>Results</p> <p>Wear score after comparable implantation time was significantly less in the autopsy group. Even so, fatigue type wear accounted for 84 and 93 % of total wear score on autopsy and revision implants respectively. A highly significant influence on wear score was found in time of implantation (p = 0.002), level of activity (p = 0.025) and inserts belonging to revision group (p = 0.006). No influence was found for the kind of patella replacement (p = 0.483). Body mass index and accuracy of component alignment had no significant influence on visual wear score. Fatigue-type wear in the medial compartment was closely correlated to the index of use in the autopsy (R²= 0.383) and the revision group (R²= 0.813).</p> <p>Conclusion</p> <p>The present study's finding of substantial fatigue type wear in both autopsy and revision retrievals supports the theory that polyethylene fatigue strength is generally exceeded in this type of prosthesis. Furthermore, this study correlated fatigue-type polyethylene wear to an index of use as calculated by activity over time. Future retrieval studies may use activity over time as an important patient related factor correlated to the visual wear score. When evaluating total knee arthroplasty routine follow up, the surgeon must think of substantial wear present even without major clinical signs.</p

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes