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The Bone & Joint Journal
Vol. 101-B, Issue 7_Supple_C | Pages 108 - 114
1 Jul 2019
Ji G Xu R Niu Y Li N Ivashkiv L Bostrom MPG Greenblatt MB Yang X

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 CD31hiEMCNhi endothelium. RNA sequencing analysis was performed using sorted CD31hiEMCNhi 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.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_12 | Pages 44 - 44
1 Oct 2018
Ji G Xu R Niu Y Turajane K Li N Greenblatt MB Yang X Bostrom M
Full Access

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, CD31hiEMCNhi 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 CD31hiEMCNhi 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 CD31hiEMCNhi 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.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 96 - 96
1 Mar 2010
Dong N Li N Thakore M Wang A Manley M Morris H
Full Access

Previous studies suggested that the shallow Ultra High Molecular Weight Polyethylene (UHMWPE) acetabular socket liner or the liner with no head centre inset can significantly increase the risk of hip joint dislocation. Independent to the traditional neck impingement models, the purpose of this study was to investigate an additional dislocation force pushing the femoral head out of UHMWPE acetabular liner bearing under direct hip joint loading and the factors including the head centre inset affecting the magnitude of this force. The 3 D Finite Element Analysis (FEA) models were constructed by (30) 10 mm thick UHMWPE liners with six inner bearing diameters ranging from 22 mm to 44 mm and five head centre insets in each bearing size from 0 mm to 2 mm. A load of 2 446 N was applied through the corresponding CoCr femoral head to the rim of the liner. The DF was recorded as a function of head centre inset and head diameter. The results were verified by the physical tests of two 28 mm head bearing liners with 0 and 1.5 mm head centre insets respectively.

The results showed that the highest DF was 1 269N in 0 mm head centre inset and 22 mm head. The lowest DF was 171 N in 2 mm head centre inset and 44 mm head. The DF decreased as the head centre inset and head size increased. When head centre inset increased from 0 mm to 1 mm, the DF was reduced more than 50%. Two experimental data points were consistent with the trend of DF curve found in the FEA.

We concluded that the new intrinsic dislocating force DF can be induced by the rim directed joint loading force alone and can reach as high as 51% of the femoral loading force. This can be the addition to the dislocating moment generated by the neck impingement. A head inset above 1mm can effectively reduce DF to less than 25% of the joint force. Furthermore, the larger head diameter generates less DF. The DF is likely caused by the wedge effect between the deformed polyethylene bearing and the femoral head. The inset allows the femoral head to be separated from the spherical bearing surface, thus reducing the wedge effect. Our observation of the stabilizing effect trend of the head centre inset was consistent with reported clinical data. However, the increased height of the capture wall also reduces the range of motion. It is therefore necessary to minimize the inset height with the maximum benefit of the stabilize effect. This study suggested the larger femoral head has the advantage of reducing the DF and the stabilizing effect is more effective when combining with the inset wall. The result of this study should provide the guidance to improve acetabular poly liner design for better joint stability.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 473 - 474
1 Sep 2009
Dong N Li N Thakore M Wang A Manley M Morris H
Full Access

Previous studies suggested the lack of capture wall of acetabular Ultra High Molecular Weight Polyethylene (UHMWPE) liner can significantly increase the risk of hip joint dislocation. To date, the dislocation studies have been focused on the femoral neck impingement models. The purpose of this study was to identify a new Dislocating Force (DF) generated by rim directed joint force alone and investigate the factors to affect the magnitudes of the DF. The 3 D Finite Element Analysis (FEA) models were constructed by (30) 10 mm thick UHMWPE liners with six inner bearing diameters ranging from 22 mm to 44 mm and five capture wall heights in each bearing size from 0 mm to 2 mm. A load of 2 446 N was applied through the corresponding CoCr femoral head to the rim of the liner. The DF was recorded as a function of capture wall height and head diameter. The results were verified by the physical tests of two 28 mm head bearing liners with 0 and 1.5 mm capture wall heights respectively.

The results showed that the highest DF was 1 269N in 0 mm capture wall and 22 mm head. The lowest DF was 171 N in 2 mm capture wall and 44 mm head. The DF decreased as the capture wall and head size increased. When capture wall increased from 0 mm to 1 mm, the DF was reduced more than 50%. Two experimental data points were consistent with the trend of DF curve found in the FEA.

We concluded that the new intrinsic dislocating force DF can be induced by the rim directed joint loading force alone and can reach as high as 51% of the femoral loading force. A capture wall height above 1mm can effectively reduce DF to less than 25% of the joint force. In addition, the larger head diameter also resulted in less DF generation.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 474 - 474
1 Sep 2009
Dong N Li N Schmidt W Kester M Wang A Nogler M Krismer M
Full Access

High tensile stress has been considered as a contributing factor to the rim fracture of polyethylene acetabular cup liner. We performed the 3 D Finite Element Analysis (FEA) to compare the stress patterns at the polyethylene liner rim as a function of polyethylene thicknesses and whether or not rim was supported by the titanium acetabular shell extension. Two 3.1 mm thick generic 52 mm titanium alloy acetabular shells with and without 2 mm high rim support extension were modelled. Six corresponding Ultra High Molecular Weight Polyethylene (UHMWPE) liners with inner bearing diameters ranging from 22 mm to 44 mm and same outer diameters, were fixed in the shells. A 2 450 N load was applied through the corresponding CoCr femoral heads to the rims of liners while the acetabular shells were fixed on the outer spherical surface. The FEA was performed in half body of the assembly. The maximum principal stresses at the rim regions of UHMWPE liners were recorded.

The results showed that in all rim supported conditions, the maximum principal stress were in compressive patterns, a preferred pattern to reduce the potential polyethylene liner fracture. In rim unsupported conditions, the stresses was in tensile on the internal bearing surface when polyethylene liner thickness was bellow 5 mm, or was bellow 9 mm if the average maximum principal stress cross the rim was considered.

We conclude that the metal rim support changes the stress pattern in the rim region of UHMWPE liner to compressive for all liner thicknesses. The stress pattern turns to tensile, or there will be a higher potential for rim fracture, if UHMWPE liner is unsupported and the polyethylene rim thickness is less than 9 mm.

Although components used this study did not include the locking details which add higher stress concentrations, the trend of stress patterns should follow the results found in this study.