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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
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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


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 868 - 873
1 Jul 2020
Yang G Dai Y Dong C Kang H Niu J Lin W Wang F

Aims

The purpose of this study was to explore the correlation between femoral torsion and morphology of the distal femoral condyle in patients with trochlear dysplasia and lateral patellar instability.

Methods

A total of 90 patients (64 female, 26 male; mean age 22.1 years (SD 7.2)) with lateral patellar dislocation and trochlear dysplasia who were awaiting surgical treatment between January 2015 and June 2019 were retrospectively analyzed. All patients underwent CT scans of the lower limb to assess the femoral torsion and morphology of the distal femur. The femoral torsion at various levels was assessed using the a) femoral anteversion angle (FAA), b) proximal and distal anteversion angle, c) angle of the proximal femoral axis-anatomical epicondylar axis (PFA-AEA), and d) angle of the AEA–posterior condylar line (AEA-PCL). Representative measurements of distal condylar length were taken and parameters using the ratios of the bianterior condyle, biposterior condyle, bicondyle, anterolateral condyle, and anteromedial condyle were calculated and correlated with reference to the AEA, using the Pearson Correlation coefficient.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 185 - 189
1 Feb 2012
Lim H Bae J Park Y Park Y Park J Park J Suh D

The purpose of this study was to evaluate the long-term functional and radiological outcomes of arthroscopic removal of unstable osteochondral lesions with subchondral drilling in the lateral femoral condyle. We reviewed the outcome of 23 patients (28 knees) with stage III or IV osteochondritis dissecans lesions of the lateral femoral condyle at a mean follow-up of 14 years (10 to 19). The functional clinical outcomes were assessed using the Lysholm score, which improved from a mean of 38.1 (sd 3.5) pre-operatively to a mean of 87.3 (sd 5.4) at the most recent review (p = 0.034), and the Tegner activity score, which improved from a pre-operative median of 2 (0 to 3) to a median of 5 (3 to 7) at final follow-up (p = 0.021). The radiological degenerative changes were evaluated according to Tapper and Hoover’s classification and when compared with the pre-operative findings, one knee had grade 1, 22 knees had grade 2 and five knees had grade 3 degenerative changes. The overall outcomes were assessed using Hughston’s rating scale, where 19 knees were rated as good, four as fair and five as poor.

We found radiological evidence of degenerative changes in the third or fourth decade of life at a mean of 14 years after arthroscopic excision of the loose body and subchondral drilling for an unstable osteochondral lesion of the lateral femoral condyle. Clinical and functional results were more satisfactory.