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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 22 - 22
1 Nov 2021
Belvedere C Leardini A Gill R Ruggeri M Fabbro GD Grassi A Durante S Zaffagnini S
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Introduction and Objective

Medial Knee Osteoarthritis (MKO) is associated with abnormal knee varism, this resulting in altered locomotion and abnormal loading at tibio-femoral condylar contacts. To prevent end-stage MKO, medial compartment decompression is selectively considered and, when required, executed via High Tibial Osteotomy (HTO). This is expected to restore normal knee alignment, load distribution and locomotion. In biomechanics, HTO efficacy may be investigated by a thorough analysis of the ground reaction forces (GRF), whose orientation with respect to patient-specific knee morphology should reflect knee misalignment. Although multi-instrumental assessments are feasible, a customized combination of medical imaging and gait analysis (GA), including GRF data, rarely is considered. The aim of this study was to report an original methodology merging Computed-Tomography (CT) with GA and GFR data in order to depict a realistic patient-specific representation of the knee loading status during motion before and after HTO.

Materials and Methods

25 MKO-affected patients were selected for HTO. All patients received pre-operative clinical scoring, and radiological/instrumental assessments; so far, these were also executed post-operatively at 6-month follow-up on 7 of these patients. State-of-the-art GA was performed during walking and more demanding motor tasks, like squatting, stair-climbing/descending, and chair-rising/sitting. An 8-camera motion capture system, combined with wireless electromyography, and force platforms for GRF tracking, was used together with an own established protocol. This marker-set was enlarged with 4 additional skin-based non-collinear markers, attached around the tibial-plateau rim. While still wearing these markers, all analyzed patients received full lower-limb X-ray in standing posture a CT scan of the knee in weight-bearing Subsequently, relevant DICOMs were segmented to reconstruct the morphological models of the proximal tibia and the additional reference markers, for a robust anatomical reference frame to be defined on the tibia. These marker trajectories during motion were then registered to the corresponding from CT-based 3D reconstruction. Relevant registration matrices then were used to report GRF data on the reconstructed tibial model. Intersection paths of GRF vectors with respect to the tibial-plateau plane were calculated, together with their centroids.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 113 - 113
1 Mar 2021
George A Ellis M Gill R
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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.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 101 - 101
1 Nov 2018
George A Ellis M Gill R
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It is well documented that implant loosening rate in sickle cell disease patients is higher than that seen in patients with hip arthroplasty from other indications. The Hypoxic inducible factor(HIF) - is activated in the microcellular hypoxic environment and this through a cascade of other enzymatic reactions promotes the activity of other factors and further help enhance angiogenesis and osteogenesis. The aim of this study was to investigate and propose a potential model for investigating osseointegration in a hypoxic microcellular environment using osteoblasts(MG63).

Human MG63 osteoblastic cells were cultured under normoxia and hypoxic conditions (20%; and 1% oxygen saturation) for 72 hours under two different condition- with and without cobalt chloride. The samples cultured under normoxic condtions without cobalt chloride acted as control. Using qualitative polymerase chain reaction-(qPCR) - HIF expression was assessed under the above conditions in relation to the control.

The results showed there was significant expression of the HIF 1 alpha protein under hypoxic condition with cobalt chloride in comparison with the control samples- all at 72hours incubation. Mann-Whitney U test was used to deduce level of significance of fold change.(p=0.002; <0.05). This was deemed as being a significant difference in the level of expression of HIF compared to the control.

The results show that the hypoxic inducible factor can be expressed using the above tested

experimental invitro-model with significant results which can be a foundation for further research into improving hip implant prosthesis design to help enhance osseo-integration in sickle cell disease patient with AVN.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 10 - 10
1 Apr 2018
Gosiewski J Gheduzzi S Gill R
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Introduction

The THR is the second most successful and cost-effective surgical procedure of all time. Data shows that hip cup failure is a significant problem. The aim of this study is to improve methods of cemented cup fixation through validation experiments and FEA.

Methods

Five Sawbones composite pelves with cemented UHMWPE cups were tested. Each pelvis was instrumented with triaxial strain gauges at four locations of predicted high strain. Each sample (n = 5) was bolted at the sacroiliac joint in a uniaxial testing machine. A load of 500 N was applied in the direction of the peak force during normal walking, for five repetitions. The directional surface strains were used to evaluate the equivalent strain. Specimen specific finite element models were developed based on CT scan data using ScanIP. Each mesh consisted of an average of 2.5 million linear tetrahedral elements and was solved in ANSYS.