A scoring system to evaluate stability of percutaneous osseointegrated implants for transfemoral amputation with validation in the ITAP clinical trial.

Percutaneous osseointegrated implants for individuals with lower limb amputation can increase mobility, reduce socket related pain, and improve quality of life. It would be useful to have an evaluation method to assess the interface between bone and implant. We assessed outpatient radiographs from the Intraosseous Transcutaneous Amputation Prosthesis clinical trial using an interface scoring system which summed and weighted equally measures of implant collar cortical ongrowth and radiolucency along the implant stem/bone interface. Radiographs from 12 participants with unilateral transfemoral amputations (10 males, 2 females, mean age = 43.2, SD = 7.4 years) in the clinical trial from cohort I (implanted in 2008/09) or cohort II (implanted in 2013/14) were collated (mean image span = 7.2, SD = 2.4 years), scale normalised, zoned, and measured in a repeatable way. Interface scores were calculated and then compared to clinical outcomes. Explanted participants received the lowest interface scores. A higher ratio of stem to residuum and shorter residuum's produced better interface scores and there was an association (weak correlation) between participants with thin cortices and the lowest interface scores. A tapered, cemented, non curved stem may provide advantageous fixation while stem alignment did not appear critical. In summary, the interface score successfully demonstrated a non-invasive evaluation of percutaneous osseointegrated implants interfaces when applied to the Intraosseous Transcutaneous Amputation Prosthesis clinical trial. The clinical significance of this work is to identify events leading to aseptic or septic implant removal and contribute to clinical guidelines for monitoring rehabilitation, design and surgical fixation choices.

Open-porous magnesium-based scaffolds withstand in vitro corrosion under cyclic loading: A mechanistic study.

The successful application of magnesium (Mg) alloys as biodegradable bone substitutes for critical-sized defects may be comprised by their high degradation rate resulting in a loss of mechanical integrity. This study investigates the degradation pattern of an open-porous fluoride-coated Mg-based scaffold immersed in circulating Hanks' Balanced Salt Solution (HBSS) with and without in situ cyclic compression (30 N/1 Hz). The changes in morphological and mechanical properties have been studied by combining in situ high-resolution X-ray computed tomography mechanics and digital volume correlation. Although in situ cyclic compression induced acceleration of the corrosion rate, probably due to local disruption of the coating layer where fatigue microcracks were formed, no critical failures in the overall scaffold were observed, indicating that the mechanical integrity of the Mg scaffolds was preserved. Structural changes, due to the accumulation of corrosion debris between the scaffold fibres, resulted in a significant increase (p < 0.05) in the material volume fraction from 0.52 ± 0.07 to 0.47 ± 0.03 after 14 days of corrosion. However, despite an increase in fibre material loss, the accumulated corrosion products appear to have led to an increase in Young's modulus after 14 days as well as lower third principal strain (εp3) accumulation (-91000 ± 6361 µÎµ and -60093 ± 2414 µÎµ after 2 and 14 days, respectively). Therefore, this innovative Mg scaffold design and composition provide a bone replacement, capable of sustaining mechanical loads in situ during the postoperative phase allowing new bone formation to be initially supported as the scaffold resorbs.

Multi-scale mechanical and morphological characterisation of sintered porous magnesium-based scaffolds for bone regeneration in critical-sized defects.

Magnesium (Mg) and its alloys are very promising degradable, osteoconductive and osteopromotive materials to be used as regenerative treatment for critical-sized bone defects. Under load-bearing conditions, Mg alloys must display sufficient morphological and mechanical resemblance to the native bone they are meant to replace to provide adequate support and enable initial bone bridging. In this study, unique highly open-porous Mg-based scaffolds were mechanically and morphologically characterised at different scales. In situ X-ray computed tomography (XCT) mechanics, digital volume correlation (DVC), electron microscopy and nanoindentation were combined to assess the influence of material properties on the apparent (macro) mechanics of the scaffold. The results showed that Mg exhibited a higher connected structure (38.4mm-3 and 6.2mm-3 for Mg and trabecular bone (Tb), respectively) and smaller spacing (245µm and 629µm for Mg and Tb, respectively) while keeping an overall appropriate porosity of 55% in the range of trabecular bone (30-80%). This fully connected and highly porous structure promoted lower local strain compared to the trabecular bone structure at material level (i.e. -22067 ± 8409µÎµ and -40120 ± 18364µÎµ at 6% compression for Mg and trabecular bone, respectively) and highly ductile mechanical behaviour at apparent level preventing premature scaffold failure. Furthermore, the Mg scaffolds exceeded the physiological strain of bone tissue generated in daily activities such as walking or running (500-2000µÎµ) by one order of magnitude. The yield stress was also found to be close to trabecular bone (2.06MPa and 6.67MPa for Mg and Tb, respectively). Based on this evidence, the study highlights the overall biomechanical suitability of an innovative Mg-based scaffold design to be used as a treatment for bone critical-sized defects. STATEMENT OF SIGNIFICANCE: Bone regeneration remains a challenging field of research where different materials and solutions are investigated. Among the variety of treatments, biodegradable magnesium-based implants represent a very promising possibility. The novelty of this study is based on the characterisation of innovative magnesium-based implants whose structure and manufacturing have been optimised to enable the preservation of mechanical integrity and resemble bone microarchitecture. It is also based on a multi-scale approach by coupling high-resolution X-ray computed tomography (XCT), with in situ mechanics, digital volume correlation (DVC) as well as nano-indentation and electron-based microscopy imaging to define how degradable porous Mg-based implants fulfil morphological and mechanical requirements to be used as critical bone defects regeneration treatment.

The effect of increased microporosity on bone formation within silicate-substituted scaffolds in an ovine posterolateral spinal fusion model.

This study compared the bone forming capacity of the same formulation of silicate-substituted bone graft substitute materials with different microporosity in an instrumented posterolateral spinal fusion ovine model. Materials with a strut porosity of (i) 22.5% (SiCaP) or (ii) 36.0% (SiCaP(+)) were packed along either side of the spine. Bone apposition rates, % new bone formation, % bone-implant contact, and % graft resorption were quantified at 8, 12, and 24 weeks post surgery. Computed Tomography (CT) was used to grade the formation of fusion bridges between vertebrae. Results showed no significant difference in bone apposition rates, % new bone formation, and % bone-implant contact when the two materials were compared. However, at 8 weeks, a significantly higher CT score was obtained in the SiCaP(+) group (0.83 ± 0.17) when compared with the SiCaP group (0.17 ± 0.17; p = 0.027). Significantly less scaffold remained in the SiCaP(+) group at 12 weeks (p = 0.018). Both SiCaP and SiCaP(+) formulations augmented bone formation. Increasing the strut porosity did not significantly increase bone formation however, at 8 weeks it promoted the formation of more highly mineralized bone resulting in a significantly higher CT score, suggesting the bone tissue formed was more mature. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 805-814, 2017.

Long-term survival of cemented distal femoral endoprostheses with a hydroxyapatite-coated collar: a histological study and a radiographic follow-up.

BACKGROUND: The objective of this study was to examine the degree of osteointegration into a hydroxyapatite-coated collar and relate this finding to aseptic loosening in patients with a distal femoral replacement used to treat primary bone cancer. Our hypothesis was that the implant collar would increase osteointegration and reduce the rate of aseptic implant loosening. METHODS: Sixty-one patients treated with a primary cemented distal femoral prosthesis between 1992 and 2001 were included in this study. The mean duration of follow-up was 8.5 years (range, two to eighteen years). Extracortical bone growth into the grooved hydroxyapatite-coated collar was quantified radiographically. Histological sections through four hydroxyapatite-coated collars and four implants with no collar, retrieved following amputation due to local recurrence or at autopsy at a mean of 3.5 years (range, 1.4 to 6.1 years) after implantation, were evaluated as well. RESULTS: Five (8%) of the implants were revised because of aseptic loosening, 3% of the implants fractured, and 3% were revised because of infection. Six limbs (10%) required amputation because of local tumor recurrence. On radiographs, osteointegration into the collar was seen to have occurred in 70% of the patients and did not correlate with sex, age, diagnosis, or length of time postoperatively. Histological analysis showed mature lamellar bone within the grooves of the hydroxyapatite-coated collar, and bone was observed in direct contact with the hydroxyapatite coating. Extracortical bone failed to make direct contact with the surface of the implants manufactured without a collar. CONCLUSIONS: The use of cemented distal femoral massive bone tumor prostheses with a hydroxyapatite-coated collar located at the shoulder of the implant was followed by a low (8%) rate of revision due to aseptic loosening. The use of hydroxyapatite grooved collars may lead to osteointegration of the implant shoulder (collar) and may reduce the rate of aseptic loosening.

The effect of adherens junction components on keratinocyte adhesion in vitro: potential implications for sealing the skin-implant interface of intraosseous transcutaneous amputation prostheses.

Amputation places a significant burden on healthcare systems worldwide as patients suffer life-long complications associated with the stump-socket interface. Skin penetrating, osseointegrated implants like intraosseous transcutaneous amputation prostheses, could overcome this, however, they rely on the formation and maintenance of an infection-free seal at the skin-implant interface. Epithelial cell migration around transcutaneous implants creates downgrowth, which leads to infection and implant failure. Epithelial cells form cell-cell attachments via adherens junctions and desmosomes that prevent cell migration via contact inhibition. If epithelial cells formed cell-cell attachments with an implant surface, it could facilitate stronger cell attachment and prevent downgrowth. In adherens junctions, E-cadherin is essential in homotypic cell attachment. In this study, we have demonstrated that cell-cell adherens junctions can be formed on substrates adsorbed with E-cadherin. We have assessed the effects of two E-cadherin peptides and determined an optimal concentration for increasing cell attachment via adherens junctions. We have demonstrated that adsorption of 15 µg/mL of the full extracellular domain of E-cadherin to titanium alloy significantly increases metabolic activity, cell area, and attachment of murine keratinocytes in vitro, with a fourfold increase in attachment via adherens junctions at 24, 48, and 72 h.