Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair.

Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 µm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.

Automatic generation of subject-specific finite element models of the spine from magnetic resonance images.

The generation of subject-specific finite element models of the spine is generally a time-consuming process based on computed tomography (CT) images, where scanning exposes subjects to harmful radiation. In this study, a method is presented for the automatic generation of spine finite element models using images from a single magnetic resonance (MR) sequence. The thoracic and lumbar spine of eight adult volunteers was imaged using a 3D multi-echo-gradient-echo sagittal MR sequence. A deep-learning method was used to generate synthetic CT images from the MR images. A pre-trained deep-learning network was used for the automatic segmentation of vertebrae from the synthetic CT images. Another deep-learning network was trained for the automatic segmentation of intervertebral discs from the MR images. The automatic segmentations were validated against manual segmentations for two subjects, one with scoliosis, and another with a spine implant. A template mesh of the spine was registered to the segmentations in three steps using a Bayesian coherent point drift algorithm. First, rigid registration was applied on the complete spine. Second, non-rigid registration was used for the individual discs and vertebrae. Third, the complete spine was non-rigidly registered to the individually registered discs and vertebrae. Comparison of the automatic and manual segmentations led to dice-scores of 0.93-0.96 for all vertebrae and discs. The lowest dice-score was in the disc at the height of the implant where artifacts led to under-segmentation. The mean distance between the morphed meshes and the segmentations was below 1 mm. In conclusion, the presented method can be used to automatically generate accurate subject-specific spine models.

Effectiveness of BMP-2 and PDGF-BB Adsorption onto a Collagen/Collagen-Magnesium-Hydroxyapatite Scaffold in Weight-Bearing and Non-Weight-Bearing Osteochondral Defect Bone Repair: In Vitro, Ex Vivo and In Vivo Evaluation.

Despite promising clinical results in osteochondral defect repair, a recently developed bi-layered collagen/collagen-magnesium-hydroxyapatite scaffold has demonstrated less optimal subchondral bone repair. This study aimed to improve the bone repair potential of this scaffold by adsorbing bone morphogenetic protein 2 (BMP-2) and/or platelet-derived growth factor-BB (PDGF-BB) onto said scaffold. The in vitro release kinetics of BMP-2/PDGF-BB demonstrated that PDGF-BB was burst released from the collagen-only layer, whereas BMP-2 was largely retained in both layers. Cell ingrowth was enhanced by BMP-2/PDFG-BB in a bovine osteochondral defect ex vivo model. In an in vivo semi-orthotopic athymic mouse model, adding BMP-2 or PDGF-BB increased tissue repair after four weeks. After eight weeks, most defects were filled with bone tissue. To further investigate the promising effect of BMP-2, a caprine bilateral stifle osteochondral defect model was used where defects were created in weight-bearing femoral condyle and non-weight-bearing trochlear groove locations. After six months, the adsorption of BMP-2 resulted in significantly less bone repair compared with scaffold-only in the femoral condyle defects and a trend to more bone repair in the trochlear groove. Overall, the adsorption of BMP-2 onto a Col/Col-Mg-HAp scaffold reduced bone formation in weight-bearing osteochondral defects, but not in non-weight-bearing osteochondral defects.

The influence of foramina on femoral neck fractures and strains predicted with finite element analysis.

Hip fractures following a low-impact fall are common in the elderly. Finite element (FE) models of the proximal femur can improve the prediction of fracture risk over current clinical standards. Foramina in the femoral neck may influence its fracture mechanics, albeit the majority of FE modelling approaches do not consider them. This study aimed to show how foramina affect fracture propagation and FE strain predictions in the femoral neck. µCT images were taken of 10 cadaveric proximal femora before and after fracture, following quasi-static mechanical loading representing a sideways fall. The µCT images of the fractured femora were used to determine where the bones fractured in relation to the foramina. FE models were created based on µCT and clinical CT scans of the intact femora. The superolateral side of the femoral neck was modelled with high detail including foramina. Element-specific Young's moduli were assigned and the models were solved quasi-statically. The models predicted high strains inside foramina, agreeing with experimental strain measurements. However, these high strains inside foramina were often not related to the observed fracture location. µCT images also confirmed that the foramina mostly remained intact after fracture. Using a fracture criterion based on local strain averaging improved the accuracy of the predicted fracture location as well as the correlation between the FE predicted fracture forces and the experimentally measured peak forces. To conclude, the presence of foramina can influence the fracture pattern in femoral neck fractures and inclusion of foramina in FE models improves the prediction of local strain concentrations.

The Hydration State of Bone Tissue Affects Contrast in Neutron Tomographic Images.

Neutron tomography has emerged as a promising imaging technique for specific applications in bone research. Neutrons have a strong interaction with hydrogen, which is abundant in biological tissues, and they can penetrate through dense materials such as metallic implants. However, in addition to long imaging times, two factors have led to challenges in running in situ mechanical characterization experiments on bone tissue using neutron tomography: 1) the high water content in specimens reduces the visibility of internal trabecular structures; 2) the mechanical properties of bone are dependent on the hydration state of the tissue, with drying being reported to cause increased stiffness and brittleness. This study investigates the possibility of improving image quality in terms of neutron transmission and contrast between material phases by drying and rehydrating in heavy water. Rat tibiae and trabecular bovine bone plugs were imaged with neutron tomography at different hydration states and mechanical testing of the bone plugs was carried out to assess effects of drying and rehydration on the mechanical properties of bone. From analysis of image histograms, it was found that drying reduced the contrast between bone and soft tissue, but the contrast was restored with rehydration. Contrast-to-noise ratios and line profiles revealed that the contrast between bone tissue and background was reduced with increasing rehydration duration but remained sufficient for identifying internal structures as long as no free liquid was present inside the specimen. The mechanical analysis indicated that the proposed fluid exchange protocol had no adverse effects on the mechanical properties.

Fracture behavior of a composite of bone and calcium sulfate/hydroxyapatite.

Calcium sulfate/hydroxyapatite (CaS/HA) biomaterials have been investigated for use in several orthopedic applications. However, the mechanical interactions between the composite of CaS/HA and bone at the microscale are still unknown. The aim of this study was to determine if and how augmentation with CaS/HA alters the fracture behavior of bone. Eleven cylinders of trabecular bone were drilled from human femoral heads and cleaned from bone marrow. Among them, five cylinders were injected with CaS/HA to generate composite specimens, while the others were kept intact. One extra specimen of pure CaS/HA was prepared. All specimens were compressed in situ using synchrotron X-ray tomography and imaged at ∼2% strain intervals. Structural properties were calculated from the images in unloaded state and mechanical properties were determined from the load-curves. CaS/HA alone displayed the highest peak force and stiffness and the lowest strain at fracture. All composite specimens had a higher peak force than the pure bone specimens and the composite specimens had higher toughness than the pure CaS/HA specimen. Furthermore, the fracture behavior was analyzed further to characterize the local deformations. The pure bone specimens presented damage in multiple trabeculae and the CaS/HA specimen displayed sharp transition in strains, with low strain in one load step and large cracks in the next. The composite specimens deformed uniformly, with the CaS/HA preventing tissue damage and the bone preventing cracks in the CaS/HA from propagating through the specimen. In conclusion, using tomography with in situ loading, it was possible to show how CaS/HA can help prevent bone tissue damage before global failure.

A New Augmentation Method for Improved Screw Fixation in Fragile Bone.

Pertrochanteric fractures (TF) due to osteoporosis constitute nearly half of all proximal femur fractures. TFs are treated with a surgical approach and fracture fixation is achieved using metallic fixation devices. Poor quality cancellous bone in osteoporotic patients makes anchorage of a fixation device challenging, which can lead to failure of the fracture fixation. Methods to reinforce the bone-implant interface using bone cement (PMMA) and other calcium phosphate cements in TFs have been described earlier but a clear evidence on the advantage of using such biomaterials for augmentation is weak. Furthermore, there is no standardized technique for delivering these biomaterials at the bone-implant interface. In this study, we firstly describe a method to deliver a calcium sulphate/hydroxyapatite (CaS/HA) based biomaterial for the augmentation of a lag-screw commonly used for TF fixation. We then used an osteoporotic Sawbones model to study the consequence of CaS/HA augmentation on the immediate mechanical anchorage of the lag-screw to osteoporotic bone. Finally, as a proof-of-concept, the method of delivering the CaS/HA biomaterial at the bone-implant interface as well as spreading of the CaS/HA material at this interface was tested in patients undergoing treatment for TF as well as in donated femoral heads. The mechanical testing results indicated that the CaS/HA based biomaterial increased the peak extraction force of the lag-screw by 4 times compared with un-augmented lag-screws and the results were at par with PMMA. The X-ray images from the patient series showed that it was possible to inject the CaS/HA material at the bone-implant interface without applying additional pressure and the CaS/HA material spreading was observed at the interface of the lag-screw threads and the bone. Finally, the spreading of the CaS/HA material was also verified on donated femoral heads and micro-CT imaging indicated that the entire length of the lag-screw threads was covered with the CaS/HA biomaterial. In conclusion, we present a novel method for augmenting a lag-screw in TFs, which could potentially reduce the risk of fracture fixation failure and reoperation in fragile osteoporotic patients.

Augmenting a dynamic hip screw with a calcium sulfate/hydroxyapatite biomaterial.

Internal fixation failure in hip fractures can lead to reoperation. Calcium sulfate/hydroxyapatite (CaS/HA) is a biomaterial that can be used for augmenting fracture fixation. We aimed to determine whether an injection of 2 ml CaS/HA increases the fixation of a dynamic hip screw inserted in synthetic and human trabecular bone. The study consists of two parts: 1) synthetic bone blocks (n = 74), with three subgroups: empty (cannulated screw, no injection), cannulated, and fenestrated; and 2) osteoporotic human femoral heads (n = 29), with the same subgroups. The heads were imaged using µCT. Bone volume fraction, insertion angle, and head diameter were measured. Pullout tests were performed and peak force, stiffness, and work were measured. The fenestrated group showed increases in pullout strength compared to no injection in the synthetic blocks. The cannulated group showed a higher pullout strength in low-density blocks. In the femoral heads, the variation was larger and there were no significant differences between groups. The bone volume fraction correlated with the peak force and work, and the insertion angle correlated with the stiffness. CaS/HA can improve the fixation of a dynamic hip screw. For clinical use, spreading of the material around the threads of the screw must be ensured.

Femoral strength and strains in sideways fall: Validation of finite element models against bilateral strain measurements.

Low impact falls to the side are the main cause of hip fractures in elderly. Finite element (FE) models of the proximal femur may help in the assessment of patients at high risk for a hip fracture. However, extensive validation is essential before these models can be used in a clinical setting. This study aims to use strain measurements from bilateral digital image correlation to validate an FE model against ex vivo experimental data of proximal femora under a sideways fall loading condition. For twelve subjects, full-field strain measurements were available on the medial and lateral side of the femoral neck. In this study, subject-specific FE models were generated based on a consolidated procedure previously validated for stance loading. The material description included strain rate dependency and separate yield and fracture strain limits in tension and compression. FE predicted fracture force and experimentally measured peak forces showed a strong correlation (R2 = 0.92). The FE simulations predicted the fracture initiation within 3 mm distance of the experimental fracture line for 8/12 subjects. The predicted and measured strains correlated well on both the medial side (R2 = 0.87) and the lateral side (R2 = 0.74). The lower correlation on the lateral side is attributed to the irregularity of the cortex and presence of vessel holes in this region. The combined validation against bilateral full-field strain measurements and peak forces has opened the door for a more elaborate qualitative and quantitative validation of FE models of femora under sideways fall loading.

Elucidating failure mechanisms in human femurs during a fall to the side using bilateral digital image correlation.

An improved understanding of the mechanical properties of human femurs is a milestone towards a more accurate assessment of fracture risk. Digital image correlation (DIC) has recently been adopted to provide full-field strain measurements during mechanical testing of femurs. However, it has typically been used to measure strains on the anterior side of the femur, whereas in both single-leg-stance and sideways fall loading conditions, the highest deformations result on the medial and lateral sides of the femoral neck. The goal of this study was to measure full-field deformations simultaneously on the medial and lateral side of the femoral neck in a configuration resembling a fall to the side. Twelve female cadaver femurs were prepared for DIC measurements and tested in sideways fall at 5 mm/s displacement rate. Two pairs of cameras recorded the medial and lateral side of the femoral neck, and deformations were calculated using DIC. The samples exhibited a two-stage failure: first, a compressive collapse on the superolateral side of the femoral neck in conjunction with peak force, followed by complete femoral neck fracture at the force drop following the post-elastic phase. DIC measurements corroborated this observation by reporting no tensile strains above yield limit for the medial side of the neck up to peak force. DIC measurements registered onto the bone micro-architecture showed strain localizations in proximity of cortical pores due to, for instance, blood vessels. This could explain previously reported discrepancies between simulations and experiments in regions rich with large pores, like the superolateral femoral neck.

Fracture strength of the proximal femur injected with a calcium sulfate/hydroxyapatite bone substitute.

BACKGROUND: Available interventions for preventing fragility hip fractures show limited efficacy. Injection of a biomaterial as bone substitute could increase the fracture strength of the hip. This study aimed to show the feasibility of injecting a calcium sulfate/hydroxyapatite based biomaterial in the femoral neck and to calculate the consequent change in strength using the finite element method. METHODS: Five patients were injected with 10 ml calcium sulfate/hydroxyapatite in their femoral neck. Quantitative CT scans were taken before and after injection. Five additional patients with fragility hip fractures were also scanned and the images from the non-fractured contralateral sides were used. Finite element models were created for all proximal femora with and without injection and the models were tested under stance and sideways fall loading until fracture. The change in fracture strength caused by the injection was calculated. Additionally, perturbations in volume, location, and stiffness of the injected material were created to investigate their contribution to the fracture strength increase. FINDINGS: The 10 ml injection succeeded in all patients. Baseline simulations showed theoretical fracture strength increases of 0-9%. Volume increase, change in location and increase in stiffness of the material led to increases in fracture strength of 1-27%, -8-26% and 0-17%, respectively. Altering the location of the injection to a more lateral position and increasing the stiffness of the material led to increases in fracture strength of up to 42%. INTERPRETATION: This study shows that an injection of calcium sulfate/hydroxyapatite is feasible and can theoretically increase the hip's fracture strength.