Objectives. Static radiostereometric analysis (RSA) using implanted markers is considered the most accurate system for the evaluation of prosthesis migration. By using CT bone models instead of markers, combined with a dynamic RSA system, a non-invasive measurement of joint movement is enabled. This method is more accurate than current 3D skin marker-based tracking systems. The purpose of this study was to evaluate the accuracy of the CT model method for measuring knee joint kinematics in static and dynamic RSA using the marker method as the benchmark. Methods. Bone models were created from CT scans, and tantalum beads were implanted into the tibia and femur of eight human cadaver knees. Each specimen was secured in a fixture, static and dynamic stereoradiographs were recorded, and the bone models and marker models were fitted to the stereoradiographs. Results. Results showed a mean difference between the two methods in all six degrees of freedom for static RSA to be within -0.10 mm/° and 0.08 mm/° with a 95% limit of agreement (LoA) ranging from ± 0.49 to 1.26. Dynamic RSA had a slightly larger range in mean difference of -0.23 mm/° to 0.16 mm/° with LoA ranging from ± 0.75 to 1.50. Conclusions. In a laboratory-controlled setting, the CT model method combined with dynamic RSA may be an alternative to previous marker-based methods for kinematic analyses. Cite this article: K. Stentz-Olesen, E. T. Nielsen, S. De Raedt, P. B. Jørgensen, O. G. Sørensen, B. L. Kaptein, M. S. Andersen, M. Stilling. Validation of static and dynamic radiostereometric analysis of the knee joint using bone models from CT data. Bone Joint Res 2017;6:376–384. DOI: 10.1302/2046-3758.66.BJR-2016-0113.R3

An accurate geometrical three-dimensional (3D) model of human bone is required in many medical procedures including Total Knee Arthroplasty (TKA) and computer-assisted surgical navigation. Segmentation of Computed Tomography (CT) datasets is commonly used to obtain such models. However, such a method is expensive and time consuming. We herein propose a novel method for patient specific bone model reconstruction using standard x-ray fluoroscopy, a cheaper and widely available imaging alternative. Fluoroscopic images are taken at multiple arbitrary viewpoints to provide sufficient information for bone reconstruction. The viewpoints can be obtained by either rotating the imaging source and detector or the patient’s limb of interest. The bone’s pose within the radiological scene in each of the captured images can be estimated by tracking a set of metallic calibration markers within a calibration target, rigidly attached to the limb of interest. Having acquired the required calibration data, a complex iterative scheme is executed to optimize a statistical bone atlas of the bone of interest and the relative pose between the bone and the calibration target. In order to verify our method, we performed a cadaveric study. A set of rigidly attached fiducial markers were attached to a cadaveric leg. The leg was imaged using x-ray fluoroscopy while being rotated axially to provide us with the images required for bone model reconstruction. Distal femur and proximal tibia bone models were reconstructed from the fluoroscopy images. Furthermore, the leg was CT-scanned and segmented to provide us with the ground-truth required for reconstruction accuracy assessment. Results show the adequacy of the proposed method for surgical applications

Background. Periprosthetic femoral fractures following total hip arthroplasty are relatively uncommon but are associated with significant morbidity. With an increasing number of total hip arthroplasties being carried out in an aging population we need to ensure correct implants are chosen for our patients. A recent review of NJR data suggested a significantly higher revision risk for the Zimmer CPT stems due to periprosthetic fractures when compared to the Stryker Exeter stems. Objectives. Our aim was to compare the biomechanics of periprosthetic fractures around the CPT and Exeter V40 stems in a composite saw bone model to identify if a difference in fracture risk exists between the two stems. We also compared the engineering design of the two implants in order to analyse the possible effect this may have on fracture risk. Study Design & Methods. Fourteen composite femurs were divided into two groups and cemented using Palacos R cement with either the CPT or Exeter V40 stem by a single surgeon. The implanted femurs were then mounted onto an Instron machine and were axially loaded and torqued to fracture with an axial compressive force of 2000N over 10 seconds followed by a rotation of 40 degrees applied over 1 second. A power calculation from a previous composite saw bone model study suggested that a minimum of 6 implanted femurs would be required in each group. Results. The implanted femurs invariably sustained fracture patterns similar to the Vancouver B2 periprosthetic fracture which are commonly seen in clinical practice. Implanted femurs with CPT stems suffered periprosthetic fractures with less rotation when compared to those femurs with the Exeter V40 stem (20.10 versus 33.60, p<0.01). We also found that CPT implanted femurs were fracturing at significantly lower torque values when compared to the Exeter V40 implanted femurs (124Nm Versus 174Nm, p<0.01). The energy release rate (G111) for CPT stems was 21.8Nm compared to 61.2Nm for Exeter V40 stems. The higher energy release with Exeter stems led to more comminuted fractures in Exeter implanted femurs when compared to the CPT femurs, which fractured earlier, but with simpler fracture patterns. Finite element method (FEM) simulation analysis showed that fractures initiated between the prosthesis and cement at the proximal end of the femur. Two dimensional sections at the same height showed a difference in bone-cement-implant geometrics at the critical point of failure suggesting that a design cause may be the reason for the higher risk of periprosthetic fractures in CPT implanted femurs. Conclusions. Our observations may explain the higher revision risk secondary to periprosthetic fractures that has been observed with the CPT stem when compared to the Exeter V40 stem

Introduction and Objective. Calcium phosphates are among the most commonly used bone graft substitute materials. Compositions containing predominantly monetite (∼84.7%) with smaller additions of beta-tricalcium phosphate (β-TCP; ∼8.3%) and calcium pyrophosphate (Ca-PP; ∼6.8%) have previously been demonstrated to exhibit osteoinductive properties. Such a multi-component calcium phosphate bioceramic was fashioned in the form of hollowed-out, dome-shaped devices (15 mm diameter, 4 mm height), each reinforced with a 3D printed Ti6Al4V ELI frame. With the aim to induce bone formation beyond the skeletal envelope, these devices were investigated in vivo using a sheep (Ovis aries) occipital bone model. Materials and Methods. The bioceramic composition was prepared from a mixture of β-TCP/dicalcium pyrophosphate and monocalcium phosphate monohydrate powders mixed with glycerol. The Ti6Al4V ELI frame was positioned into a dome-shaped mould and bioceramic paste was poured over the frame and allowed to set, in sterile water, prior to removal from the mould. In adult female sheep (n=7), the devices were positioned directly over the bone and stabilised using self-drilling screws. After 52 weeks, the devices were retrieved, resin embedded, and used for X-ray micro-computed tomography (micro-CT), histology, backscattered electron scanning electron microscopy (BSE-SEM), energy dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR). Results. The bioceramic composition (Ca/P: ∼0.85 at. %) transforms to carbonated apatite (Ca/P: ∼1.2 at. %, Mg/Ca: ∼0.03 at. %), in vivo, largely at the expense of monetite and Ca-PP whereas β-TCP remains detectable. Discrete particles of Ca-PP are identified by correlative BSE-SEM and micro-Raman spectroscopy. Together with chemical transformation, physical degradation is evident within the bulk of the bioceramic. Beyond the confines of the skeletal envelope, de novo bone occupies ∼53–84% (∼73 ± 11%; mean ± standard deviation) of the hollowed-out space. Low porosity and the arrangement of remodelled bone into a concentric lamellar pattern is indicative of cortical-like structure. Such areas are typically surrounded by yet unremodelled, and microstructurally disordered, woven bone that stains intensely with blue cationic dyes, owing to relatively higher acid phosphate content. This pattern indicates a recurring sequence of woven bone formation followed by remodelling. Bone formation is also visible within the bioceramic. Recently remodelled and areas of ongoing remodelling are identified by relatively lower mineral density than the surrounding woven bone. Dendritic extensions of osteocytes appear to extend into the bioceramic surface. Both micro-Raman spectroscopy and FTIR reveal little, if any, detectable difference between the mineral and organic phases of the extracellular matrix, between de novo and native bone. Conclusions. The bioceramic composition undergoes physical degradation, but remains largely intact by 52 weeks in vivo, and only partially transforms to carbonated apatite. In addition to very high bone volume within the hollowed-out bioceramic device, the overall composition and microstructure of de novo bone are similar to native bone. Notably, the mineral phase of bone in response to, and in direct contact with the β-TCP, monetite, and Ca-PP, remains exclusively carbonated apatite

Aims: Does PHILOS (Proximal Humeral Internal Locking system) construct provides better þxation than Clover leaf plate and T-plate in a simulated 2-part fracture of proximal humerus, in an osteoporotic bone model?Materials and Methods: Biomechanical laboratory study. Third generation composite Humerus model was used, with short e-glass epoxy þbres forming cortex and polyurethane cancellous core. Low density polyure-thane core (1.2gm/cc) was used to simulate an osteoporotic model. Osteotomy at surgical neck of humerus was carried out to create 2-part fracture of proximal humerus. Samples were randomised to receive one of the implants. Following þxation samples were placed in a custom made jig to þx proximal and distal ends without interfering with implants and osteotomy site. All samples were subjected to cyclical torque, Torque to failure, Cyclical compression and Compression loading to failure. Results were entered in a database. Results: PHILOS provided signiþcantly better þxation in ÔTorque to failureñ experiment. PHILOS construct shows less plastic deformation in cyclical torque and cyclical compression. Locking screws did not Ôback offñ in any of the experiments involving PHILOS construct, however ordinary screws did back off both in Ôtoque and compressionñ testing. Conclusions: PHILOS construct provides better stability in Torque and compression as compared to conventional plating devices, in an osteoporotic bone model

This study aimed to characterise the microarchitecture of bone in different species of animal leading to the development of a physiologically relevant 3D printed cellular model of trabecular (Tb) and cortical bone (CB). Using high resolution micro-computed tomography (μ-CT) bone samples from multiple species were scanned and analysed before creating in silico models for 3D printing. Biologically relevant printing materials with physical characteristics similar to that of in vivo bone will be selected and tested for printability.

Porcine and murine bone samples were scanned using μ-CT, with a resolution of 4.60 μM for murine and 11 μM for porcine and reconstructed to determine the architectural properties of both Tb and CB independently. A region of interest, 1 mm in height, will be used to generate an in-silico 3D model with dimensions (10 mm³) and suitable resolution before being translated into printable G code using CAD assisted software.

A 1 mm section of each bone was analysed, to determine the differences in the microarchitecture with the intent of setting a benchmark for the developmental 3D in vitro model to be comparable against. In contrast, porcine caudal vertebrae (PCV) have an increased volume due to the size of the bone sample. Interestingly, BV/TR for Tb is similar between species in all samples except murine femur. Murine tibia and PCV have a similar Tb. number and thickness, however different SMI shape and separation.

μ-CT scanning and analysis permits tessellation of the 3D output which will lead to the generation of an in silico printable model. Biomaterials are currently under optimisation to allow printability and shape integrity to reflect the morphological and physiological properties of bone.

Summary Statement. Vitamin E-UHMWPE particles have a reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Introduction. Ultra high-molecular weight polyethylene (UHMWPE) particle-induced osteolysis is one of the major causes of arthroplasty revisions. The lack of particle clearance from the joint inevitably leads to the upregulation of the inflammatory cascade, resulting in bone resorption and implant loosening. Recent in vitro findings (Bladed CL et al. ORS 2011 and J Biomed Mater Res B Appl Biomater, 2012) have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis. This is of significant importance since VE-stabilised cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear debris from this new generation of implants. In this study we hypothesised that particles from VE-stabilised, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methods. Study groups were the following: 1) Radiation cross-linked VE-UHMWPE, approximately 0.8% by weight, diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Shams. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions (Oak Park, IL) for particle generation. After IACUC approval, C57BL/6 mice (n=12 for each group) received equal amount of particulate debris (3mg) overlying the calvarium and were euthanised after 10 days. Micro-CT scans: High resolution micro-CT scans were performed using an X-Tek HMX ST 225 with a set voltage of 70 kV and current of 70 µA. Topographical Grading Scale: Each calvarial bone (interparietal, right and left parietal, right and left frontal) was blindly scored using the following scale: 0=No osteolysis, defined as intact bone; 1=Minimal osteolysis, affecting 1/3 or less of the bone area; 2=Moderate osteolysis, affecting at least 2/3 of the bone area; 3=Severe osteolysis, defined as completely osteolytic bone. Histological Analysis: H&E and TRAP staining was performed on tissue to confirm the micro-CT findings and to quantify osteoclasts. Statistical Analysis: Inter-rater analysis was performed using Cohen's kappa analysis. An inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. A p-value<0.05 was considered statistically significant. Results. More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 µm in mean particle size. The mean particle size for VE-UHMWPE was 1.12 µm (range 0.28 to 79.08 µm), while virgin UHMWPE particles measured 1.22 µm (range 0.28 to 82.04 µm). There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. The micro-CT findings were confirmed histologically. A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p = 0.002) but no difference in osteoclast count (p = 0.293). Discussion/Conclusion. This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Arthroplasty procedures using VE-UHMWPE might be less susceptible to peri-prosthetic loosening caused by wear debris

Aims

Cementless acetabular components rely on press-fit fixation for initial stability. In certain cases, initial stability is more difficult to obtain (such as during revision). No current study evaluates how a surgeon’s impaction technique (mallet mass, mallet velocity, and number of strikes) may affect component fixation. This study seeks to answer the following research questions: 1) how does impaction technique affect a) bone strain generation and deterioration (and hence implant stability) and b) seating in different density bones?; and 2) can an impaction technique be recommended to minimize risk of implant loosening while ensuring seating of the acetabular component?

Introduction. According to proposal of Noble, the femoral bone marrow cavity form of patients who underwent Total Hip Arthroplasty (THA) can be classified under 3 categories; those are Stovepipe, Normal and Champagne-fluted. We developed typical sodium chloride femoral model was created by 3D prototyping technique. The purpose was to identify the relationship of pressure zone of the surrounding areas between femoral bone marrow cavity form and hip stem. Materials and Method. As opponent clarified stem design concept Zweymüller type model was used. According to CT data with the patients who underwent THA, the sodium chloride femoral model was custom-made and selected as the representative model based on Noble's 3 categories. Eight models of each category were used to performed mechanical test. Result. In mechanics test, the result of comparison between the contact pressure zones of zone 1–7, significant differences of contact pressure zones were identified between the Stovepipe group and Normal group in zone 3, 4 and 5. In zone 3 and 5, such significant differences were also identified between Champagne-fluted group and Normal group. In Stovepipe group, a significant difference of the contact pressure zone was observed at the proximal and distal. In Champagne-fluted group and the Normal group, a significant difference was observed in the contact pressure in distal femur (3, 4, 5 Zone) and (Zone1, 2, 6, 7) proximal femur. Discussion. Although in most studies Sawbone® is used for femoral models, the focus of this research is of those who possess a characteristic femur with marrow cavity form. Therefore, sodium chloride bone model was used instead. In comparison in terms of applicability between sodium chloride bone model and regular model, the failure of all 24 joints of sodium chloride bone model were unconfirmed in mechanics test. Moreover, the possibility that its performance in mechanics test is equivalent to Sawbone®is considered. The design concept for Zweymüller type achieves the ability to load distribute within a wide range of cortical bone across the middle position to distal femur. It's determined by the concept that a wide range of contact pressure was admitted at middle position and distal femur in the Champagne-fluted group and the Normal group. On the other hand, the contact pressure zone of Stovepipe was not able to meet the expected level at distal femur. The method of this research is control its stress condition within the stem design. By this point, it is considered possible that the stability of various stem design was able to be forecasted and the assessment of stableness was positive. Conclusion. On the basis of Noble's categories, 3 types of bone models were created by 3D prototyping technique, and pressure distribution measurement were performed. The result from the pressure distribution indicated that even in Zweymüller stem had anxiety of securing force in Champagne-fluted type and Stovepipe type canal. We believe the method of in vivo study can develop to assess the stability of implant preoperatively

Introduction. In vitro findings (Bladed CL et al. ORS 2011 and J Biomed Mater Res B Appl Biomater, 2012) have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased osteolytic potential. Currently, there is no in vivo data determining the effects of wear debris from this new generation of implants. In this study we hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methods. Study groups: 1). Radiation cross-linked VE-UHMWPE, 0.8% by weight, diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Shams. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions for particle generation. After IACUC approval, C57BL/6 mice (n = 12 for each group) received 3 mg of particulate debris overlying the calvarium and euthanized after 10 days. Micro-CT scans: Performed using an X-Tek-HMX-ST-225 with 70 kV voltage and 70 μA current. Topographical Grading Scale: Each calvarial bone was blindly scored with the following scale: 0 = No osteolysis, defined as intact bone; 1 = Minimal osteolysis, affecting 1/3 or less of the bone area; 2 = Moderate osteolysis, affecting at least 2/3 of the bone area; 3 = Severe osteolysis, defined as completely osteolytic bone. Histology H&E and TRAP staining was performed. Statistical Analysis: Inter-rater analysis was performed using Cohen's kappa analysis. Inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. A p-value<0.05 was considered statistically significant. Results. More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 μm in mean particle size. There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. The micro-CT findings were confirmed histologically (Fig. 1). A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p = 0.002) but no difference in osteoclast count (p = 0.293). Discussion/Conclusion. This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model

Abstract

Introduction: Correct alignment in both coronal and sagittal planes has been shown to be associated with longevity of total knee arthroplasty. The majority of procedures are performed using an intramedullary rod with a femoral cutting jig, with a 5°–7° offset depending upon the anatomical and mechanical axes. The cutting jig rotates around the rod and therefore the rotational alignment of the jig will also affect the cut and final component position (in addition to the rod entry point). It is interesting that rotational alignment of the femoral component is often assessed after the distal resection has been made. The distal resection plane determines the final position of the femoral component, influences patellar tracking and medial/lateral, flexion/extension balancing. This study measures the resultant effect on the distal femoral resection when entry point and jig rotation are varied.

Materials and Methods: The distal femoral resection was carried out in sawbones with three different entry points (central, inferior and superolateral) in neutral alignment and rotations of 10° (internal and external) about the transepicondylar axis. The resulting plane of the cut was assessed by a graphical method measuring the changes in orientation of the alignment rod in space before and after the distal cut. A computer navigation system was used to measure the varus/valgus and flexion/extension angles of the distal cut. This experiment was done thrice, in a total of 27 sawbones and the average values were recorded.

Results: The results varied considerably in the sagittal plane with central and inferior entry points. Internal rotation of the jig around a central entry point produced hyperextension (mean 3.3°) and external rotation caused flexion (mean 1.8°). Using an inferior entry point, flexion of the distal plane improved from an average 3° in neutral rotation to 1.6° on internal rotation; external rotation worsened flexion to an average of 4.3°. The angles digressed in both sagittal and coronal planes with a superolateral entry point; rotations of the distal cutting jig caused hyperextension (maximum of 7.5°). Coronal alignment ranged from 4.5° of varus to 5° of valgus in neutral alignment and rotations around a superolateral entry point.

Conclusion: The study demonstrates that there is a possibility of a compound error from misplaced entry point and that malrotation prior to distal resection is real. This error would invariably be extrapolated in the subsequent steps of conventional knee arthroplasty. Computer assisted arthroplasty may have a role in avoiding this surgical error.

Background: Aseptic loosening of total joint arthroplasty is characterised by osteolysis, which is caused by osteoclasts and macrophages. Collagen cross link molecules N Telopeptides (NTx) are released during osteolysis and represents a highly specific marker for bone resorption. NTx could be a potential marker in the laboratory investigation of aseptic loosening with the advantage of being cheaper and easier to perform compared to present established markers. The aim of this study was to show that NTx generated during osteolysis by cells extracted from human interface membranes of aseptically loosened hips correlates with the established radiolabelled 45Ca bone resorption model.

Methods: Cells from human interface membranes of aseptic loosened hip joints were cultured with dead radiolabelled (45Ca) mice calvaria discs and in the control culture no cells were added to the culture system. Calvaria discs used in each experiment comparison were from the same parietal bone. The supernatant culture medium were extracted on day 3,7,10 & 14 and assayed for NTx and by scintillation counting. On day 14 the remaining culture medium and cells were assayed by scintillation counting and the total remaining 45Ca in the bone were measured.

Results: All results were expressed as the ratio of bone exposed to cells (BC)/bone only (B). Supernatant samples for 45Ca and NTx showed a rise in BC/B ratio with time. These were 0.83, 0.88, 0.97 & 1.08 (p=0.0001) and 1.06, 1.21, 1.41 & 1.40 (p = 0.03) respectively. In the bottom sampling for 45Ca the mean ratio of BC/B was 1.8 (p=0.0001) and the mean BC/B ratio for the remaining 45Ca in the bone at the end of the culture was 0.81 (p=0.0007). There was a strong correlation between 45Ca and NTx (r = 0.88).

Discussion: The initial drop of calcium levels can be explained by calcium uptake by the cells. We believe this is the first time human interface membrane cells have been shown to release NTx during osteolysis in an in vitro model. Replacing 45Ca radilabelled bone with NTx as a marker represents an important step towards simplifying and reducing the cost of an in in vitro model of particle induced osteolysis.

The Masquelet technique is a variable method for treating critical-sized bone defects, but there is a need to develop a technique for promoting bone regeneration. In recent studies of bone fracture healing promotion, macrophage-mesenchymal stem cell (MSC) cross-talk has drawn attention. This study aimed to investigate macrophage expression in the induced membrane (IM) of the Masquelet technique using a mouse critical-sized bone defect model. The study involved a 3-mm bone defect created in the femur of mice and fixed with a mouse locking plate. The Masquelet (M) group, in which a spacer was inserted, and the Control (C) group, in which the defect was left intact, were established. Additionally, a spacer was inserted under the fascia of the back (B group) to form a membrane due to the foreign body reaction. Tissues were collected at 1, 2, and 4 weeks after surgery (n=5 in each group), and immunostaining (CD68, CD163: M1, M2 macrophage markers) and RT-qPCR were performed to investigate macrophage localization and expression in the tissues. The study found that CD68-positive cells were present in the IM of the M group at all weeks, and RT-qPCR showed the highest CD68 expression at 1 week. In addition, there was similar localization and expression of CD163. The C group showed lower expression of CD68 and CD163 than the M group at all weeks. The B group exhibited CD68-positive cells in the fibrous capsule and CD163-positive cells in the connective tissue outside the capsule, with lower expression of both markers compared to the M group at all weeks. Macrophage expression in IM in M group had different characteristics compared to C group and B group. These results suggest that the IM differs from the fibrous capsules due to the foreign body reaction, and the macrophage-MSC cross-talk may be involved in Masquelet technique

Objectives. We aimed to further evaluate the biomechanical characteristics of two locking screws versus three standard bicortical screws in synthetic models of normal and osteoporotic bone. Methods. Synthetic tubular bone models representing normal bone density and osteoporotic bone density were used. Artificial fracture gaps of 1 cm were created in each specimen before fixation with one of two constructs: 1) two locking screws using a five-hole locking compression plate (LCP) plate; or 2) three non-locking screws with a seven-hole LCP plate across each side of the fracture gap. The stiffness, maximum displacement, mode of failure and number of cycles to failure were recorded under progressive cyclic torsional and eccentric axial loading. Results. Locking plates in normal bone survived 10% fewer cycles to failure during cyclic axial loading, but there was no significant difference in maximum displacement or failure load. Locking plates in osteoporotic bone showed less displacement (p = 0.02), but no significant difference in number of cycles to failure or failure load during cyclic axial loading (p = 0.46 and p = 0.25, respectively). Locking plates in normal bone had lower stiffness and torque during torsion testing (both p = 0.03), but there was no significant difference in rotation (angular displacement) (p = 0.84). Locking plates in osteoporotic bone showed lower torque and rotation (p = 0.008), but there was no significant difference in stiffness during torsion testing (p = 0.69). Conclusions. The mechanical performance of locking plate constructs, using only two screws, is comparable to three non-locking screw constructs in osteoporotic bone. Normal bone loaded with either an axial or torsional moment showed slightly better performance with the non-locking construct

Adrenomedullin is a peptide hormone that has attracted attention with its proliferative and anti-apoptotic effects on osteoblasts in recent years. We investigated the effect of adrenomedullin on healing of the segmental bone defect in a rat model.

36 Wistar rats were randomly divided in six groups based on follow-up periods and administered dose of adrenomedullin hormone. In each group, a 2 mm bone defect was created at the diaphysis of radius, bilaterally. NaCl solution was administered to sham groups three times a week for 4 and 8 weeks, intraperitoneally. Adrenomedullin was administered to study groups three times a week; 15 µg-4 weeks, 15 µg-8 weeks, 30 µg-4 weeks and 30 µg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric (new bone area (NBA)) and micro-tomographic (bone volume (BV), bone surface (BS), bone mineral density (BMD)) analysis.

Although 4 and 8 weeks 15 μg administered study groups had higher NBA values than the other study and control groups, histomorphometric analysis did not reveal any statistical difference between the control and study groups in terms of new bone area (p > 0.05). In micro-tomographic analysis, BV was higher in 15 μg – 4 weeks group than 30 μg – 4 weeks group (296.9 vs 208.5, p = 0.003) and BS was lower in 30 μg – 4 weeks than 4 week - control group (695.5 vs 1334.7, p = 0.005) but in overall, no significant difference was found between the control and study groups (p > 0.05). Despite these minor differences in histomorphometric and micro-tomographic criteria indicating new bone formation, BMD values of 15 µg-4 and −8 weeks study groups showed significant increase comparing with the control group (p = 0.04, p = 0.001, respectively).

Adrenomedullin seemed to have a positive effect on BMD at a certain dose (15 µg) but it alone is not considered sufficient for healing of the defect with new bone formation. Further studies are needed to assess its effects on bone tissue trauma.

This study was funded by Hacettepe University Scientific Research Projects Coordination Unit

Objectives. To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects. Materials and Methods. Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation. Results. A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 . sd. 1089 mm. 3. versus 782 . sd. 507 mm. 3. ; p = 0.09). Bone union was consistent with autograft (1960 . sd. 518 mm. 3. ). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% . sd. 5% versus 94% . sd. 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs. Discussion. Bone regeneration in critical-size defects could be obtained with full bioresorption of the scaffold using coral-based TECs in a large animal model. The superior performance of Acropora-TECs brings us closer to a clinical application, probably because of more suitable bioresorption kinetics. However, nonunion still occurred in nearly half of the bone defects. Cite this article: A. Decambron, M. Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V. Viateau. A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model. Bone Joint Res 2017;6:208–215. DOI: 10.1302/2046-3758.64.BJR-2016-0236.R1

Nitrogen-containing bisphosphonates such as Zoledronic Acid (ZA) are used clinically for the treatment of skeletal diseases related with increased bone resorption. The gold standard is to administrate the drug through a systemic pathway, however this is often associated with high dosages, risk of side-effects, reduced site-specific drug delivery and hence, limited drug-effectiveness. A controlled local drug delivery, via a biomimetic bone graft, could be beneficial by direct and time-regulated application of significantly lower drug dosage at the site of interest. Thus, higher efficacy and reduced side-effects could be expected. In this experimental in vivo study, we examined the effect of ZA when used together with a Calcium Sulphate/Hydroxyapatite biomaterial in a femoral condyle bone defect in rats and compared local to systemic administration. The following groups were used: group1: empty defect (no biomaterial & no treatment), group2: biomaterial alone, group3: biomaterial + systemic ZA (0.1mg ZA/kg – single subcutaneous injection), group4–6: biomaterial conjugated with ZA at different concentrations, (0.07 to 0.70 mg ZA/mL of paste, corresponding to 0.0024 to 0.024 mg ZA/kg). The animals were sacrificed at 6 weeks and toxicological examination was performed. Bone regeneration was evaluated using qualitative and quantitative micro-CT analysis and Histomorphometry. The results showed a significant difference between the groups, suggesting that ZA has an overall effect on bone healing. The most pronounced effect was seen with the local application of approximately 10 times less ZA-dosage when compared to systemic use (p<0.001). This study demonstrates the importance of local ZA administration in bone regeneration.

Long-term survival of massive prostheses used to treat bone cancers is associated with extra-cortical bone growth and osteointegration into a grooved hydroxyapatite coated collar positioned adjacent to the transection site on the implant shaft [1]. The survivorship at 10 years reduces from 98% to 75% where osteointegration of the shaft does not occur. Although current finite element (FE) methods successfully model bone adaption, optimisation of adventitious new bone growth and osteointegration is difficult to predict. There is thus a need to improve existing FE models by including biological processes of osteoconduction and osteoinduction. The principal bone adaptation criteria is based on the standard strain-energy remodeling algorithm, where the rate of remodeling is controlled by the difference in the stimulus against the reference value [3]. The additional concept of bone connectivity was introduced, to limit bone growth to neighbouring elements (cells) adjoining existing bone elements. The algorithm was developed on a cylindrical model before it was used on an ovine model. The geometry and material properties from two ovine tibiae were obtained from computed tomography (CT) scans and used to develop FE models of the tibiae implanted with a grooved collar. The bones were assigned inhomogeneous material properties based on the CT grey values and typical ovine walking load conditions were applied. The FE results show a region of bone tissue growth below the implanted collar and a small amount of osteointegration with the implant, which is in good agreement to clinical results. Some histological results suggest that further bone growth is possible and potential improvements to the model will be discussed. In summary, by including an algorithm that describes osteoconduction, adventitious bone growth can be predicted

Purpose

Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. VEGF has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological and microCT evaluations (Atesok, Li, Schemitsch 2010); EPC treatment of fractures resulted in a significantly higher strength by biomechanical examination (Li, Schemitsch 2010). In addition, cell-based VEGF gene transfer has been effective in the treatment of segmental bone defects in a rabbit model (Li, Schemitsch et al 2009); Purpose of this study: Evaluation of VEGF gene expression after EPC local therapy for a rat segmental bone defect.