Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft. 13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4). It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells. The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study

Remodeling of the cancellous bone is more active than that of the cortical bone. It is known that the remodeling is governed by the intracancellous fluid pressure. Particularly, the lacunocanalicular pore (PLC) fluid pressure (FP) is essential for survival of the osteocyte and communication of remodeling signals between the PLC and intertrabecular pore (PIT). As a result, knowledge about the PLCFP generation of trabeculae is required to understand human cancellous bone biology. At this moment, the PLCFP measurement of human trabeculae is not reported. The purpose of this study was a direct measurement of PLCFP generation of human proximal femoral trabeculae in the direction of superior-to-fovea. Twenty one microscopic cylindrical trabecular specimens from trabeculae of five fresh human proximal femur (75 to 77 years) were fabricated using a micro-milling machine composed of the laser (Teemphotonics: 532nm), 3-dimensional PZT stage (PI Gmbh, resolution: 0.5nm), and microscope (lens: Navitar, and CCD: Hitachi) with the image processor. The fabrication resolution of the micro-milling machine was 0.4 um. Based on the trabecular trajectory of femoral head, the specimens were obtained in the direction of superior-to-fovea. The cylindrical specimen size had 120 um in diameter and 240 um in length. The test methods described in the previous study were utilized. The used undrained uniaxial strain condition could induce the maximum PLCFP within the trabecular elastic limit. The measured trabecular PLCFP (±SD) at the strain of 0.4% was 693.7±79.1 kPa. Since this experiment is equivalent to the instantaneous response of PLCFP with free flow boundaries after application of an extremely fast loading speed such an ideal step loading, a PLCFP generation in the physiological condition will be much less than the results obtained in this study. Base on the linear isotropic poroelasticity, the obtained Skempton's coefficient is almost 0. Thus, the load bearing capability by trabecular PLC fluid is negligible. The Biot coefficient is 0.35 which is higher than that of the cortical tissue (0.14). As a result, the intraosseous fluid communication through trabecular surfaces is active compared to that through Haversian canal surfaces. This imply that mass transports from the trabecular PLC into the PIT and from the PIT into the trabecular PLC could be significantly affected by the PITFP (the physiological blood systolic and diastolic pressure: 16 and 11 kPa, respectively) that acts as the FP boundary condition for the PLC flow. It is known that the PLC flow generates the electrical charges on the trabecular surface (‘+’ for being spouted into the PIT and ‘−’ for being flown into the PLC), which control differentiation and proliferation of the osteoblast and mesenchymal stem cell. Thus, significant changes in the PITFT could cause changes in the intra-trabecular PLC flow characteristics, mass transports between the PLC and PIT, and electrical charges on the trabeculae. Eventually, these could result in pathologies related to the trabecular remodeling

Summary. These data suggest that PTH treatment for stimulation of bone healing after trauma is not much dependent on mechanical stimulation and therefore, roughly equal treatment effects might be expected in the upper and lower extremities in humans. Introduction. Stimulation of bone formation by PTH is known to, in part, act via increased mechanosensitivity. Therefore, unloading should decrease the response to PTH treatment in uninjured bone. This has served as a background for speculations that PTH might be less efficacious for human fracture treatment in unloaded limbs, e.g. for distal radial fractures. We analyzed if the connection with mechanical stimulation also pertains to bone formation after trauma in cancellous bone. Methods. 20 male SD rats, 8 weeks old, had one hind leg immobilised via Botox injections. At 10 weeks of age the rats received bilateral screw implants into their proximal tibiae. Half of the rats were given daily injections of 5µg/kg PTH(1–34). After two weeks of healing, the tibias and femurs were harvested. Mechanical testing of screw fixation (pull-out) and µCT of the cancellous bone of the distal femurs was performed. Results. The pull-out forces served as a read-out for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded (from 30 to 44 N). These force values are not limited by a ceiling effect, and the difference in relative effect of PTH was significant (p = 0.03). Discussion/Conclusion. PTH appeared to exert a greater effect on bone healing in the unloaded limbs, compensating for the lack of mechanical stimulation. These data suggest that PTH treatment for stimulation of bone healing after trauma is not much dependent on mechanical stimulation. Therefore, roughly equal treatment effects might be expected in the upper and lower extremities in humans

We obtained medial and lateral subchondral cancellous bone specimens from ten human postmortem proximal tibiae with early osteoarthritis (OA) and ten normal age- and gender-matched proximal tibiae. The specimens were scanned by micro-CT and the three-dimensional microstructural properties were quantified. Medial OA cancellous bone was significantly thicker and markedly plate-like, but lower in mechanical properties than normal bone. Similar microstructural changes were also observed for the lateral specimens from OA bone, although there had been no sign of cartilage damage. The increased trabecular thickness and density, but relatively decreased connectivity suggest a mechanism of bone remodelling in early OA as a process of filling trabecular cavities. This process leads to a progressive change of trabeculae from rod-like to plate-like, the opposite to that of normal ageing. The decreased mechanical properties of subchondral cancellous bone in OA, which are due to deterioration in architecture and density, indicate poor bone quality

Summary. At the clinical CT image resolution level, there is no influence of the image voxel size on the derived finite element human cancellous bone models. Introduction. Computed tomography (CT)-based finite element (FE) models have been proved to provide a better prediction of vertebral strength than dual-energy x-ray absorptiometry [1]. FE models based on µCTs are able to provide the golden standard results [2], but due to the sample size restriction of the µCT and the XtremeCT machines, the clinical CT-based FE models is still the most promising tool for the in vivo prediction of vertebrae's strength. It has been found [3] that FE predicted Young's modulus of human cancellous bone increases as the image voxel size increases at the µCT resolution level [3]. However, it is still not clear whether the image voxel size in the clinical range has an impact on the predicted mechanical behavior of cancellous bone. This study is designed to answer this question. Methods. For this study, 6 thoracolumbar vertebrae (Th12) obtained from the female donors were scanned in the non-dissected cadavers under 2 different resolutions – group A: 120 kVp, 100 mAs, with a resolution of 0.29×0.29×1.3 mm. 3. ; group B: 120 kVp, 360 mAs, with a resolution of 0.18×0.18×0.6 mm. 3. A solid calibration phantom (QRM-BDC) was placed beneath the cadavers during the scans. Cuboids with the size of 12.3×12.3×14.3 mm. 3. were cropped from the center of each vertebral body. The FE model was created by converting each image voxel into hexahedron (C3D8). Inhomogeneous material property was defined for the cuboid [4], i.e. the image greyscale value were firstly calibrated into the bone mineral density (BMD), then the Young's modulus and yield stress were calculated from the BMD [5] for each element. Statistical analysis was performed to compare the FE predicted mechanical properties between the groups and the significance level was set to 95% (α=0.05). Results. The trabecular structure is more clearly mimicked in the models from group B than those from group A. The modulus (mean ± SE) in group A is 5.9% higher than that in group B (193.33 ± 31.67 MPa vs. 182.50 ± 27.07 MPa). The yield strength (mean ± SE) in group A is 6.4% higher than that in group B (0.99 ± 0.21MPa vs. 0.93 ± 0.17MPa). However, the paired t-test shows there is no significant difference of the mechanical properties in the two groups (p=0.109 for the modulus and p=0.234 for the yield strength). Discussion. This study shows that there is no influence of the voxel size on the clinical CT derived FE cancellous bone models. This finding can help choose a better, less invasive CT protocol for the patient when creating a clinical CT image based FE model. Acknowledgements. This study is financially supported by the Federal Ministry of Education and Research and the state of Hamburg, Germany

We have tested the axial and torsional stability of femoral components after revision arthroplasty in a cadaver model, using impacted morsellised cancellous graft and cement. Each one of six matched pairs of fresh frozen human femora had either a primary or a revision prosthesis cemented in place. For the ‘revision’ experiments, all cancellous bone was removed from the proximal femur which was then over-reamed to create a smooth-walled cortical shell. An MTS servohydraulic test frame was used to apply axial and torsional loads to each specimen through the prosthetic femoral heads with the femur submerged in isotonic saline solution at 37°C. The mean subsidence was 0.27 ± 0.17 mm for the primary and 0.52 ± 0.30 mm for the revision groups. The difference was statistically significant (p < 0.025), but the mean subsidence was < 1 mm in both groups. The mean maximum torque before failure was 42.9 ± 26.9 N-m for the primary and 34.8± 20.7 N-m for the revision groups. This difference was not statistically significant (p > 0.015). Based on our results we suggest that revision of the femoral component using morsellised cancellous graft followed by cementing with a collarless prosthesis with a polished tapered stem restores the integrity of the proximal femur and provides immediate stability of the implant

Previous studies have shown that low-density, rod-like trabecular structures develop in regions of low stress, whereas high-density, plate-like trabecular structures are found in regions of high stress. This phenomenon suggests that there may be a close relationship between the type of trabecular structure and mechanical properties. In this study, 160 cancellous bone specimens were produced from 40 normal human tibiae aged from 16 to 85 years at post-mortem. The specimens underwent micro-CT and the microstructural properties were calculated using unbiased three-dimensional methods. The specimens were tested to determine the mechanical properties and the physical/compositional properties were evaluated. The type of structure together with anisotropy correlated well with Young’s modulus of human tibial cancellous bone. The plate-like structure reflected high mechanical stress and the rod-like structure low mechanical stress. There was a strong correlation between the type of trabecular structure and the bone-volume fraction. The most effective microstructural properties for predicting the mechanical properties of cancellous bone seem to differ with age

Osteoporosis (OP) results in a reduction in the mechanical competence of the bone tissue of the sufferers. In skeletal sites such as the proximal femur and the vertebrae, OP manifests itself in low trauma fragility fractures which are debilitating for the patient. The relationships between the compressive strength of cancellous tissue and its apparent density are well established in studies of the past. Recently the authors have presented a method able to assess the fracture toughness properties of cancellous bone (1), a challenging cellular material which can exhibit large elasto-plastic deformations. The in-vitro measurement of fracture toughness alongside the customary compressive strength can provide a comprehensive assessment of the mechanical capacity of cancellous bone, which will reflect closer its ability to resist crack initiation. The aims of the present study were: (1) to examine whether the observed fracture toughness deterioration can also be detected by non-invasive quantitative ultrasound (QUS); and (2) to provide rational evidence for the well proven ability of QUS to predict directly ‘risk of fracture’. 20 femoral heads were obtained from donors undergoing emergency surgery for a fractured neck of femur. QUS investigations of the calcaneus, proximal phalanx and distal radius were undertaken within 72 hours of surgery. 128 fracture toughness samples and 20 compression cores were manufactured and tested. Two clinical QUS systems were used to obtain in-vivo scan data and then directly compared those to the density, porosity and the fracture mechanics of tissue extracted from the same individuals. The results demonstrated not only that there was a significant link between in-vivo determined QUS values for the calcaneus and finger to the density of the density of the femoral head; but that there was also a significant link between the QUS results from the calcaneus and the fracture toughness of the cancellous bone from the femoral head. These results point towards a systemic effect of osteoporosis which affects similarly different parts of the skeleton and supports the use of clinical QUS systems as a diagnostic tool for the prediction of fracture risk

Intermittent treatment with parathyroid hormone (PTH) has an anabolic effect on both intact cancellous and cortical bone. Very little is known about the effect of the administration of PTH on the healing of fractures or the incorporation of orthopaedic implants. We have investigated the spontaneous ingrowth of callus and the formation of bone in a titanium chamber implanted at the medioproximal aspect of the tibial metaphysis of the rat. Four groups of ten male rats weighing approximately 350 g were injected with human PTH (1-34) in a dosage of 0, 15, 60 or 240 μg/kg/day, respectively, for 42 days from the day of implantation of the chamber. During the observation period the chamber became only partly filled with callus and bone and no difference in ingrowth distance into the chamber was found between the groups. The cancellous density was increased by 90%, 132% and 173% in the groups given PTH in a dosage of 15, 60 or 240 μg/kg/day, respectively. There was a linear correlation between bone density and the log PTH doses (r. 2. = 0.6). Our findings suggest that treatment with PTH may have a potential for enhancement of the incorporation of orthopaedic implants as well as a beneficial effect on the healing of fractures when it is given in low dosages

Rotator cuff tears are common, with failure rates of up to 94% for large and massive tears. 1. For such tears, reattachment of the musculotendinous unit back to bone is problematic, and any possible tendon-bone repair heals through scar tissue rather than the specially adapted native enthesis. We aim to develop and characterise a novel soft-hard tissue connector device, specific to repairing/bridging the tendon-bone injury in significant rotator cuff tears, employing decellularised animal bone partially demineralised at one end for soft tissue continuation. Optimisation samples of 15×10×5mm. 3. , trialled as separate cancellous and cortical bone samples, were cut from porcine femoral condyles and shafts, respectively. Samples underwent 1-week progressive stepwise decellularisation and a partial demineralisation process of half wax embedding and acid bathing. Characterisations were performed histologically for the presence/absence of cellular staining in both peripheral and central tissue areas (n=3 for each cortical/cancellous, test/PBS control and peripheral/central group), and with BioDent reference point indentation (RPI) for pre- and post-processing mechanical properties. Histology revealed absent cellular staining in peripheral and central cancellous samples, whilst reduced in cortical samples compared to controls. Cancellous samples decreased in wet mass after decellularisation by 45.3% (p<0.001). RPI measurements associated with toughness (total indentation depth, indentation depth increase) and elasticity (1st cycle unloading slope) showed no consistent changes after decellularisation. X-rays confirmed half wax embedding provided predictable control of the mineralised-demineralised interface position. Initial optimisation trials show proof-of-concept of a soft-hard hybrid scaffold as an immune compatible xenograft for irreparable rotator cuff tears. Decellularisation did not appreciably affect mechanical properties, and further biological, structural and chemical characterisations are underway to assess validity before in vivo animal trials and potential clinical translation

To analyse bone stresses in humerus-megaprosthesis construct in response to axial loading under varying implant lengths in proximal humeral replacement following tumour excision. CT scans of 10 cadaveric humeri were processed in 3D Slicer to obtain three-dimensional (3D) models of the cortical and cancellous bone. Megaprostheses of varying body lengths (L) were modelled in FreeCAD to obtain the 3D geometry. Four FE models: group A consisting of intact bone; groups B (L=40mm), C (L=100mm) and D (L=120mm) comprising of humerus-megaprosthesis constructs were created. Isotropic linear elastic behaviour was assigned for all materials. A tensile load of 200N was applied to the elbow joint surface with the glenohumeral joint fixed with fully bonded contact interfaces. Static analysis was performed in Abaqus. The bone was divided at every 5% bone length beginning distally. Statistical analysis was performed on maximum von Mises stresses in cortical and cancellous bone across each slice using one-way ANOVA (0-45% bone length) and paired t-tests (45-70% bone length). To quantify extent of stress shielding, average percentage change in stress from intact bone was also computed. Maximum stress was seen to occur distally and anteriorly above the coronoid fossa. Results indicated statistically significant differences between intact state and shorter megaprostheses relative to longer megaprostheses and proximally between intact and implanted bones. Varying levels of stress shielding were recorded across multiple slices for all megaprosthesis lengths. The degree of stress shielding increased with implant lengthening being 2-4 times in C and D compared to B. Axial loading of the humerus can occur with direct loading on outstretched upper limbs or indirectly through the elbow. Resultant stress shielding effect predicted in longer megaprosthesis models may become clinically relevant in repetitive axial loading during activities of daily living. It is recommended to use shorter megaprosthesis to prevent failure

Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios. Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration. Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 μg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 μg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 μg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08). We conclude that administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release

Objectives. Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Methods. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays. Results. After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm. 2. , . sd. 14660 versus 9421 μm. 2. , . sd. 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion. We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73–81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1

Treatment of large bone defects represents a great challenge for orthopedic surgeons. The main causes are congenital abnormalities, traumas, osteomyelitis and bone resection due to cancer. Each surgical method for bone reconstruction leads its own burden of complications. The gold standard is considered the autologous bone graft, either of cancellous or cortical origin, but due to graft resorption and a limitation for large defect, allograft techniques have been identified. In the bone defect, these include the placement of cadaver bone or cement spacer to create the ‘Biological Chamber’ to restore bone regeneration, according to the Masquelet technique. We report eight patients, with large bone defect (for various etiologies and with an average size defect of 13.3 cm) in the lower and upper limbs, who underwent surgery at our Traumatology Department, between January 2019 and October 2020. Three patients were treated with both cortical and cancellous autologous bone grafts, while five received cortical or cement spacer allografts from donors. They underwent pre and postoperative radiographs and complete osseointegration was observed in all patients already undergoing monthly radiographic checks, with a restoration of length and range of motion. In our study, both the two stage-Masquelet and the cortical bone graft from a cadaver donor proved to be valid techniques in patients with very extensive defects to reconstruct the defect, restore the length, minimize implant left in situ and achieve complete functional recovery

To quantify bone-nail fit in response to varying nail placements by entry point translation in straight antegrade humeral nailing using three-dimensional (3D) computational analysis. CT scans of ten cadaveric humeri were processed in 3D Slicer to obtain 3D models of the cortical and cancellous bone. The bone was divided into individual slices each consisting of 2% humeral length (L) with the centroid of each slice determined. To represent straight antegrade humeral nail, a rod consisting of two cylinders with diameters of 9.5mm and 8.5mm and length of 0.22L mm and 0.44L mm respectively joined at one end was modelled. The humeral head apex (surgical entry point) was translated by 1mm in both anterior-posterior and medio-lateral directions to generate eight entry points. Total nail protrusion surface area, maximum nail protrusion distance into cortical shell and top, middle, bottom deviation between nail and intramedullary cavity centre were investigated. Statistical analysis between the apex and translated entry points was conducted using paired t-test. A posterior-lateral translation was considered as the optimal entry point with minimum protrusion in comparison to the anterior-medial translation experiencing twice the level of protrusion. Statistically significant differences in cortical protrusion were found in anterior-medial and posterior-lateral directions producing increased and decreased level of protrusion respectively compared to the apex. The bottom anterior-posterior deviation distance appeared to be a key predictor of cortical breach with the distal nail being more susceptible. Furthermore, nails with anterior translation generated higher anterior-posterior deviation (>4mm) compared to posterior translation (<3mm). Aside from slight posterolateral translation of the entry point from the apex, inclusion of a distal posterior-lateral bend into current straight nail design could improve nail fitting within the curved humeral bone, potentially improving distal working length within the flat and narrow medullary canal of the distal humeral shaft

Surgeons treating fractures with many small osteochondral fragments have often expressed the clinical need for an adhesive to join such fragments, as an adjunct to standard implants. If an adhesive would maintain alignment of the articular surfaces and subsequently heal it could result in improved clinical outcomes. However, there are no bone adhesives available for clinical indications and few pre-clinical models to assess safety and efficacy of adhesive biomaterial candidates. A bone adhesive candidate based on water, α-TCP and an amino acid phosphoserine was evaluated in-vivo in a novel murine bone core model (preliminary results presented EORS 2019) in which excised bone cores were glued back in place and harvested @ 0, 3, 7, 14, 28 and 42days. Adhesive pull-out strength was demonstrated 0–28 days, with a dip at 14 days increasing to 11.3N maximum. Histology 0–42 days showed the adhesive progressively remodelling to bone in both cancellous and cortical compartments with no signs of either undesirable inflammation or peripheral ectopic bone formation. These favourable results suggested translation to a large animal model. A porcine dental extraction socket model was subsequently developed where dental implants were affixed only with the adhesive. Biomechanical data was collected @ 1, 14, 28 and 56 days, and histology at 1,14,28 and 56 days. Adhesive strength assessed by implant pull-out force increased out to 28 days and maintained out to 56 days (282N maximum) with failure only occurring at the adhesive bone interface. Histology confirmed the adhesive's biocompatibility and osteoconductive behavior. Additionally, remodelling was demonstrated at the adhesive-bone interface with resorption by osteoclast-like cells and followed by new bone apposition and substitution by bone. Whilst the in-vivo dental implant data is encouraging, a large animal preclinical model is needed (under development) to confirm the adhesive is capable of healing, for example, loaded osteochondral bone fragments. Acknowledgements: The murine study was supported, in part, by the Swedish Foundation for Strategic Research (#RMA15-0110)

The success of cementless orthopaedic implants relies on bony ingrowth and active bone remodelling. Much research effort is invested to develop implants with controllable surface roughness and internal porous architectures that encourage these biological processes. Evaluation of these implants requires long-term and costly animal studies, which do not always yield the desired outcome requiring iteration. The aim of our study is to develop a cost-effective method to prescreen design parameters prior to animal trials to streamline implant development and reduce live animal testing burden. Ex vivo porcine cancellous bone cylinders (n=6, Ø20×12mm) were extracted from porcine knee joints with a computer-numerically-controlled milling machine under sterile conditions within 4 hours of animal sacrifice. The bone discs were implanted with Ø6×12mm additive manufactured porous titanium implants and were then cultured for 21days. Half underwent static culture in medium (DMEM, 10% FBS, 1% antibiotics) at 37°C and 5% CO. 2. The rest were cultured in novel high-throughput stacked configuration in a bioreactor that simulated physiological conditions after surgery: the fluid flow and cyclic compression force were set at 10ml/min and 10–150 N (1Hz,5000 cycles/day) respectively. Stains were administered at days 7 and 14. Samples were evaluated with widefield microscopy, scanning electron microscopy (SEM) and with histology. More bone remodelling was observed on the samples cultured within the bioreactor: widefield imaging showed more remodelling at the boundaries between the implant-bone interface, while SEM revealed immature bone tissue integration within the pores of the implant. Histological analysis confirmed these results, with many more trabecular struts with new osteoid formation on the samples cultured dynamically compared to static ones. Ex vivo bone can be used to analyse new implant technologies with lower cost and ethical impact than animal trial. Physiological conditions (load and fluid flow) promoted bone ingrowth and remodelling

Introduction and Objective. Curative resection of proximal humerus tumours is now possible in this era of limb salvage with endoprosthetic replacement considered as the preferred reconstructive option. However, it has also been linked with mechanical and non-mechanical failures such as stem fracture and aseptic loosening. One of the challenges is to ensure that implants will endure the mechanical strain under physiological loading conditions, especially crucial in long surviving patients. The objective is to investigate the effect of varying prosthesis length on the bone and implant stresses in a reconstructed humerus-prosthesis assembly after tumour resection using finite element (FE) modelling. Methods. Computed tomography (CT) scans of 10 humeri were processed in Mimics 17 to create three-dimensional (3D) cortical and cancellous solid bone models. Endoprostheses of different lengths manufactured by Stryker were modelled using Solidworks 2020. The FE models were divided into four groups namely group A consisting of the intact humerus and groups B, C and D composed of humerus-prosthesis assemblies with a body length of 40, 100 and 120 mm respectively and were meshed using linear 4-noded tetrahedral elements in 3matic 13. The models were then imported into Abaqus CAE 6.14. Isotropic linear elastic behaviour with an elastic modulus of 13400, 2000 and 208 000 MPa were assigned to the cortical bone, cancellous bone and prosthesis respectively and a Poisson's ratio of 0.3 was assumed for each material. To represent the lifting of heavy objects and twisting motion, a tensile load of 200 N for axial loading and a 5 Nm torsional load for torsional loading was applied separately to the elbow joint surface with the glenohumeral joint fixed and with all contact interfaces defined as fully bonded. A comparative analysis against literature was performed to validate the intact model. Statistical analysis of the peak von Mises stress values collected from predicted stress contour plots was performed using a one-way repeated measure of analysis of variance (with a Bonferroni post hoc test) using SPSS Statistics 26. The average change in stress of the resected models from the intact state were then determined. Results. The validation of the intact humerus displayed a good agreement with literature values. The peak bone stress occurred distally above the coronoid and olecranon fossa closer to the load application region in the intact and resected bone models with a significant amount of loading borne by the cortical bone, while the peak implant stress occurred at the bone-prosthesis contact interface under both loading conditions. Based on the results obtained, a statistically significant difference (p =.013) in implant stress was only seen to occur between groups B and C under tension. Results illustrate initiation of stress shielding with the bone bearing lesser stress with increasing resection length which may eventually lead to implant failure by causing bone resorption according to Wolff's law. The peak implant stress under torsion was 3–5 times the stress under tension. The best biomechanical behaviour was exhibited in Group D, having the least average change in stress from the intact model, 5% and 3.8% under tension and torsion respectively. It can be deduced that the shorter the prosthesis length, the more pronounced the effect on cortical bone remodelling. With the maximum bone and implant stresses obtained being less than their yield strength, it can be concluded that the bone-implant construct is safe from failure. Conclusions. The developed FE models verified the influence of varying the prosthesis length on the bone and implant stresses and predicted signs of stress shielding in longer endoprostheses. By allowing for 2 cm shortening in the upper extremity and post-surgical scarring, it is beneficial to err towards a shorter endoprosthesis

Tourniquet is widely used in orthopedic surgery to reduce intraoperative bleeding and improve visualization. We evaluated the effect of tourniquet application on both peri- and postoperative cefuroxime concentrations in subcutaneous tissue, skeletal muscle, calcaneal cancellous bone, and plasma. The primary endpoint was the time for which the free drug concentration of cefuroxime was maintained above the clinical breakpoint minimal inhibitory concentration (T>MIC) forStaphylococcus aureus (4 µg/mL). Ten patients scheduled for hallux valgus or hallux rigidus surgery were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in subcutaneous tissue, skeletal muscle, and calcaneal cancellous bone. A tourniquet was applied on the thigh of the leg scheduled for surgery. Cefuroxime (1.5 g) was administered intravenously as a bolus 15 minutes prior to tourniquet inflation, followed by a second dose 6 hours later. The mean tourniquet duration (range) was 65 (58; 77) minutes. Dialysates and venous blood samples were collected for 12 hours. For cefuroxime the T>MIC (4 μg/mL) ranged between 4.8–5.4 hours across compartments, with similar results for the tourniquet and non-tourniquet leg. Comparable T>MIC and penetration ratios were found for the first and second dosing intervals. We concluded that administration of cefuroxime (1.5 g) 15 minutes prior to tourniquet inflation is safe in order to achieve tissue concentrations above 4 µg/mL throughout surgery. A tourniquet application time of approximately 1 hour did not affect the cefuroxime tissue penetration in the following dosing interval

Introduction. Cancellous and cortical bone used as a delivery vehicle for antibiotics. Recent studies with cancellous bone as an antibiotic carrier in vitro and in vivo showed high initial peak concentrations of antibiotics in the surrounding medium. However, high concentrations of antibiotics can substantially reduce osteoblast replication and even cause cell death. Objectives. To determine whether impregnation with gentamycine impair the incorporation of bone allografts, as compared to allografts without antibiotic. Materials and method. Seventy two healthy rabbits (24 rabbits in each group) were used for this study. Bone defects (3-mm diameter, 10-mm depth) were created in the femur. Human femoral head prepared according to the Marburg bone bank system was used as bone allograft. In the experimental groups, in 1 group - the defects were filled with bone allografts, in 2 group – Perforated Gentamycin-impregnated bone allografts. The control group did not receive any filling. The animals were killed after 14, 30 and 60 days. Evaluations consisted of X-ray plain radiography, histology at 14-, 30- and 60-days post-surgery. Results. Active osteoblast activity and active formation of new bones were detected around the defect area in all groups, but the amount of new bone formation was greater in the experimental groups than the control group. We found no statistically significant differences in the rate of bone formation between 1 and 2 groups at 14, 30 and 60 days in any of the parameters studied. X-ray results showed no significant difference in bony callus formation around allografts in 1 and 2 groups. In contrast, no significant callus formation was observed in the control group. Conclusion. The use of gentamycin-impregnated bone allografts may be of value in procedures performed at the site of osteomyelitis which require a second stage reconstruction with impacted bone grafting techniques