Glenoid bone strain after anatomical total shoulder arthroplasty: In vitro measurements with micro-CT and digital volume correlation.

Glenoid implant loosening remains a major source of failure and concern after anatomical total shoulder arthroplasty (aTSA). It is assumed to be associated with eccentric loading and excessive bone strain, but direct measurement of bone strain after aTSA is not available yet. Therefore, our objective was to develop an in vitro technique for measuring bone strain around a loaded glenoid implant. A custom loading device (1500 N) was designed to fit within a micro-CT scanner, to use digital volume correlation for measuring displacement and calculating strain. Errors were evaluated with three pairs of unloaded scans. The average displacement random error of three pairs of unloaded scans was 6.1 µm. Corresponding systematic and random errors of strain components were less than 806.0 µÎµ and 2039.9 µÎµ, respectively. The average strain accuracy (MAER) and precision (SDER) were 694.3 µÎµ and 440.3 µÎµ, respectively. The loaded minimum principal strain (8738.9 µÎµ) was 12.6 times higher than the MAER (694.3 µÎµ) on average, and was above the MAER for most of the glenoid bone volume (98.1%). Therefore, this technique proves to be accurate and precise enough to eventually compare glenoid implant designs, fixation techniques, or to validate numerical models of specimens under similar loading.

Decellularised tissues obtained by a CO2-philic detergent and supercritical CO2.

Tissue decellularisation has gained much attention in regenerative medicine as an alternative to synthetic materials. In decellularised tissues, biological cues can be maintained and provide cellular environments still unmet by synthetic materials. Supercritical CO2 (scCO2 ) has recently emerged as a promising alternative decellularisation technique to aggressive detergents; in addition, scCO2 provides innate sterilisation. However, to date, decellularisation with scCO2 is limited to only a few tissue types with low cellular density. In the current study, a scCO2 technique to decellularise high density tissues, including articular cartilage, tendon and skin, was developed. Results showed that most of the cellular material was removed, while the sample structure and biocompatibility was preserved. The DNA content was reduced in cartilage, tendon and skin as compared to the native tissue. The treatment did not affect the initial tendon elastic modulus [reduced from 126.35 ± 9.79 MPa to 113.48 ± 8.48 MPa (p 〉 0.05)], while it reduced the cartilage one [from 12.06 ± 2.14 MPa to 1.17 ± 0.34 MPa (p 〈 0.0001)]. Interestingly, cell adhesion molecules such as fibronectin and laminin were still present in the tissues after decellularisation. Bovine chondrocytes were metabolically active and adhered to the surface of all decellularised tissues after 1 week of cell culture. The developed method has the potential to become a cost-effective, one-step procedure for the decellularisation of dense tissues.

Effect of temporal onsets of mechanical loading on bone formation inside a tissue engineering scaffold combined with cell therapy.

Several approaches to combine bone substitutes with biomolecules, cells or mechanical loading have been explored as an alternative to the limitation and risk-related bone auto- and allo-grafts. In particular, human bone progenitor cells seeded in porous poly(L-lactic acid)/tricalcium phosphate scaffolds have shown promising results. Furthermore, the application of mechanical loading has long been known to be a key player in the regulation of bone architecture and mechanical properties. Several in vivo studies have pointed out the importance of its temporal offset. When an early mechanical loading was applied a few days after scaffold implantation, it was ineffective on bone formation, whereas a delayed mechanical loading of several weeks was beneficial for bone tissue regeneration. No information is reported to date on the effectiveness of applying a mechanical loading in vivo on cell-seeded scaffold with respect to bone formation in a bone site. In our study, we were interested in human bone progenitor cells due to their low immunogenicity, sensitivity to mechanical loading and capacity to differentiate into osteogenic human bone progenitor cells. The latest capacity allowed us to test two different bone cell fates originating from the same cell type. Therefore, the general aim of this study was to assess the outcome on bone formation when human bone progenitor cells or pre-differentiated osteogenic human bone progenitor cells are combined with early and delayed mechanical loading inside bone tissue engineering scaffolds. Scaffolds without cells, named cell-free scaffold, were used as control. Surprisingly, we found that (1) the optimal solution for bone formation is the combination of cell-free scaffolds and delayed mechanical loading and that (2) the timing of the mechanical application is crucial and dependent on the cell type inside the implanted scaffolds.

Zone-dependent mechanical properties of human articular cartilage obtained by indentation measurements.

Emerging 3D printing technology permits innovative approaches to manufacture cartilage scaffolds associated with layer-by-layer mechanical property adaptation. However, information about gradients of mechanical properties in human articular cartilage is limited. In this study, we quantified a zone-dependent change of local elastic modulus of human femoral condyle cartilage by using an instrumented indentation technique. From the cartilage superficial zone towards the calcified layer, a gradient of elastic modulus values between 0.020 ± 0.003 MPa and 6.44 ± 1.02 MPa was measured. To validate the tissue quality, the histological tissue composition was visualized by glycosaminoglycan and collagen staining. This work aims to introduce a new protocol to investigate the zone-dependent mechanical properties of graded structures, such as human articular cartilage. From this knowledge, better cartilage repair strategies could be tailored in the future.

Importance of trabecular anisotropy in finite element predictions of patellar strain after Total Knee Arthroplasty.

Patellar fracture and anterior knee pain remain major complications after Total Knee Arthroplasty (TKA). Patient-specific finite element (FE) models should help improve understanding of these complications through estimation of joint and bone mechanics. However, sensitivity of predictions on modeling techniques and approaches is not fully investigated. In particular, the importance of patellar bone anisotropy, usually omitted in FE models, on strain prediction is still unknown. The objective of this study was thus to estimate the influence of modeling patellar trabecular anisotropy on prediction of patellar strain in TKA models. We compared FE-derived strain predictions with isotopic and anisotropic material properties using 17 validated FE models of the patella after TKA. We considered both non-resurfaced and resurfaced patellae, in a load-bearing TKA joint. We evaluated and compared the bone volume above a strain threshold and, in addition, estimated if the difference in isotopic and anisotropic predictions was consistent between patellae of different average bone volume fraction. Compared to the anisotropic reference, the isotropic prediction of strained volume was 3.7±1.8 times higher for non-resurfaced patellae and 1.5±0.4 times for resurfaced patellae. This difference was higher for patellae with lower average bone volume fraction. This study indicates that strain predictions acquired via isotropic patellar FE models should be interpreted with caution, especially when patellae of different average bone volume fraction are compared.

Stability Enhancement Using Hyaluronic Acid Gels for Delivery of Human Fetal Progenitor Tenocytes.

Tendon afflictions are very common, and their negative impact is high both at the workplace and in leisure activities. Tendinopathies are increasing in prevalence and can lead to tendon ruptures, where healing is a long process with outcomes that are often disappointing. Human fetal progenitor tenocytes (hFPTs) have been recently tested in vitro as a potential cell source to stimulate tendon regeneration. The aim of the present study was to compare different commercial hyaluronic acid (HA) gels, which could be used to resuspend hFPTs in a formulation that would allow for good delivery of the cells. No medium or growth supplement was used in the formulation in order to make it therapeutically dispensable. These conditions are stringent for cells, but surprisingly, we found that different formulations could allow a good survival for up to 3 days when stored at 4°C (refrigerator stable). The gels must allow a good survival of the cells in parallel with a good stability of the preparation over time and sufficient viscosity to remain in place if deposited on a wounded location. Moreover, the cells must conserve their ability to attach and to proliferate. hFPTs were able to survive and to recover from all of the tested gels, but some products showed some advantages over others in terms of survival and viscosity. Finally, the Ostenil Tendon HA gel fulfilled all of the requirements and presented the best compromise between a good survival and sufficient rheological characteristics to create an interesting cell delivery system.

Full-field measurement of micromotion around a cementless femoral stem using micro-CT imaging and radiopaque markers.

A good primary stability of cementless femoral stems is essential for the long-term success of total hip arthroplasty. Experimental measurement of implant micromotion with linear variable differential transformers is commonly used to assess implant primary stability in pre-clinical testing. But these measurements are often limited to a few distinct points at the interface. New techniques based on micro-computed tomography (micro-CT) have recently been introduced, such as Digital Volume Correlation (DVC) or markers-based approaches. DVC is however limited to measurement around non-metallic implants due to metal-induced imaging artifacts, and markers-based techniques are confined to a small portion of the implant. In this paper, we present a technique based on micro-CT imaging and radiopaque markers to provide the first full-field micromotion measurement at the entire bone-implant interface of a cementless femoral stem implanted in a cadaveric femur. Micromotion was measured during compression and torsion. Over 300 simultaneous measurement points were obtained. Micromotion amplitude ranged from 0 to 24µm in compression and from 0 to 49µm in torsion. Peak micromotion was distal in compression and proximal in torsion. The technique bias was 5.1µm and its repeatability standard deviation was 4µm. The method was thus highly reliable and compared well with results obtained with linear variable differential transformers (LVDTs) reported in the literature. These results indicate that this micro-CT based technique is perfectly relevant to observe local variations in primary stability around metallic implants. Possible applications include pre-clinical testing of implants and validation of patient-specific models for pre-operative planning.

Variability of the pullout strength of cancellous bone screws with cement augmentation.

BACKGROUND: Orthopaedic surgeons often face clinical situations where improved screw holding power in cancellous bone is needed. Injectable calcium phosphate cements are one option to enhance fixation. METHODS: Paired screw pullout tests were undertaken in which human cadaver bone was augmented with calcium phosphate cement. A finite element model was used to investigate sensitivity to screw positional placement. FINDINGS: Statistical analysis of the data concluded that the pullout strength was generally increased by cement augmentation in the in vitro human cadaver tests. However, when comparing the individual paired samples there were surprising results with lower strength than anticipated after augmentation, in apparent contradiction to the generally expected conclusion. Investigation using the finite element model showed that these strength reductions could be accounted for by small screw positional changes. A change of 0.5mm might result in predicted pullout force changes of up to 28%. INTERPRETATION: Small changes in screw position might lead to significant changes in pullout strength sufficient to explain the lower than expected individual pullout values in augmented cancellous bone. Consequently whilst the addition of cement at a position of low strength would increase the pullout strength at that point, it might not reach the pullout strength of the un-augmented paired test site. However, the overall effect of cement augmentation produces a significant improvement at whatever point in the bone the screw is placed. The use of polymeric bone-substitute materials for tests may not reveal the natural variation encountered in tests using real bone structures.

Translation of biomechanical concepts in bone tissue engineering: from animal study to revision knee arthroplasty.

Bone defects in revision knee arthroplasty are often located in load-bearing regions. The goal of this study was to determine whether a physiologic load could be used as an in situ osteogenic signal to the scaffolds filling the bone defects. In order to answer this question, we proposed a novel translation procedure having four steps: (1) determining the mechanical stimulus using finite element method, (2) designing an animal study to measure bone formation spatially and temporally using micro-CT imaging in the scaffold subjected to the estimated mechanical stimulus, (3) identifying bone formation parameters for the loaded and non-loaded cases appearing in a recently developed mathematical model for bone formation in the scaffold and (4) estimating the stiffness and the bone formation in the bone-scaffold construct. With this procedure, we estimated that after 3 years mechanical stimulation increases the bone volume fraction and the stiffness of scaffold by 1.5- and 2.7-fold, respectively, compared to a non-loaded situation.

Importance of the subscapularis muscle after total shoulder arthroplasty.

BACKGROUND: The rotator cuff muscles are the main stabilizer of the glenohumeral joint. After total shoulder arthroplasty using anterior approaches, a dysfunction of the subscapularis muscle has been reported. In the present paper we tested the hypothesis that a deficient subscapularis following total shoulder arthroplasty can induce joint instability. METHODS: To test this hypothesis we have developed an EMG-driven musculoskeletal model of the glenohumeral joint. The model was based on an algorithm that minimizes the difference between measured and predicted muscular activities, while satisfying the mechanical equilibrium of the glenohumeral joint. A movement of abduction in the scapular plane was simulated. We compared a normal and deficient subscapularis. Muscle forces, joint force, contact pattern and humeral head translation were evaluated. FINDINGS: To satisfy the mechanical equilibrium, a deficient subscapularis induced a decrease of the force of the infraspinatus muscle. This force decrease was balanced by an increase of the supraspinatus and middle deltoid. As a consequence, the deficient subscapularis induced an upward migration of the humeral head, an eccentric contact pattern and higher stress within the cement. INTERPRETATION: These results confirm the importance of the suscapularis for the long-term stability of total shoulder arthroplasty.

Injectable calcium phosphate cement for augmentation around cancellous bone screws. In vivo biomechanical studies.

In lower cancellous apparent bone density, it can be difficult to achieve adequate screw fixation and hence stable fracture fixation. Different strategies have been proposed, one of them is through augmentation using calcium phosphate cement in the region at or close to the screw thread itself. To support the hypothesis of an improved screw fixation technique by augmentation of the bone surrounding the implanted screw, in vivo biomechanical and densitometric studies are performed on rabbit specimen where normal and simulated weak bone quality are considered. In particular, the evolution of screw stability till 12 weeks following the implantation is quantified. A statistical significance in the pull out force for augmented versus non-augmented screws was found for the shorter time periods tested of ≤ 5 days whilst the pull out force was found to increase with time for both augmented and non-augmented screws during the 12 week course of the study. The results of the study demonstrate that the use of an injectable calcium phosphate cement which sets in vivo can significantly improve screw pull out strength at and after implantation for normal and simulated weak bone quality.

Biomechanics and tissue engineering.

Development of artificial scaffold for musculo-skeletal applications, especially in load-bearing situations, requires the consideration of biomechanical aspects for its integrity and its function. However, the biomechanical loading could also be used to favour tissue formation through mechano-transduction phenomena. Design of scaffold could take advantages of this intrinsic mechanical loading.

Combined effects of zoledronate and mechanical stimulation on bone adaptation in an axially loaded mouse tibia.

BACKGROUND: local bisphosphonate delivery may be a solution to prevent periprosthetic bone loss and improve orthopedic implants fixation. In load-bearing implants, periprosthetic bone is exposed to high mechanical demands, which in normal conditions induce an adaptation of bone. In this specific mechanical situation, the modulation of the bone response by bisphosphonate remains uncertain. METHODS: we assessed the combined effects of zoledronate and mechanical loading on bone adaptation using an in-vivo axial compression model of the mouse tibia and injections of zoledronate. Bone structure was quantified with in-vivo microCT before and after the period of stimulation and the mechanical properties of the tibias were evaluated with 3 point-bending tests after sacrifice. FINDINGS: axial loading induced a localized increase of cortical thickness and bone area. Zoledronate increased cortical thickness, bone perimeter, and bone area. At the most loaded site of the tibia, the combined effect of zoledronate and mechanical stimulation was significantly smaller than the sum of the individual effects measured at the same site in the control groups. INTERPRETATIONS: the results of this study suggested that a negative interaction between zoledronate and mechanical loading might exist at high level of strain.

Bone regeneration and stem cells.

This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.

Tightening force and torque of nonlocking screws in a reverse shoulder prosthesis.

BACKGROUND: Reversed shoulder arthroplasty is an accepted treatment for glenohumeral arthritis associated to rotator cuff deficiency. For most reversed shoulder prostheses, the baseplate of the glenoid component is uncemented and its primary stability is provided by a central peg and peripheral screws. Because of the importance of the primary stability for a good osteo-integration of the baseplate, the optimal fixation of the screws is crucial. In particular, the amplitude of the tightening force of the nonlocking screws is clearly associated to this stability. Since this force is unknown, it is currently not accounted for in experimental or numerical analyses. Thus, the primary goal of this work is to measure this tightening force experimentally. In addition, the tightening torque was also measured, to estimate an optimal surgical value. METHODS: An experimental setup with an instrumented baseplate was developed to measure simultaneously the tightening force, tightening torque and screwing angle, of the nonlocking screws of the Aquealis reversed prosthesis. In addition, the amount of bone volume around each screw was measured with a micro-CT. Measurements were performed on 6 human cadaveric scapulae. FINDINGS: A statistically correlated relationship (p<0.05, R=0.83) was obtained between the maximal tightening force and the bone volume. The relationship between the tightening torque and the bone volume was not statistically significant. INTERPRETATION: The experimental relationship presented in this paper can be used in numerical analyses to improve the baseplate fixation in the glenoid bone.

Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep.

Previous studies support resorbable biocomposites made of poly(L-lactic acid) (PLA) and beta-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used beta-TCP bone substitute (ChronOS, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point.

Mechanical interaction between cells and fluid for bone tissue engineering scaffold: modulation of the interfacial shear stress.

An analytical model of the fluid/cell mechanical interaction was developed. The interfacial shear stress, due to the coupling between the fluid and the cell deformation, was characterized by a new dimensionless number N(fs). For N(fs) above a critical value, the fluid/cell interaction had a damping effect on the interfacial shear stress. Conversely, for N(fs) below this critical value, interfacial shear stress was amplified. As illustration, the role of the dynamic fluid/cell mechanical coupling was studied in a specific biological situation involving cells seeded in a bone scaffold. For the particular bone scaffold chosen, the dimensionless number N(fs) was higher than the critical value. In this case, the dynamic shear stress at the fluid/cell interface is damped for increasing excitation frequency. Interestingly, this damping effect is correlated to the pore diameter of the scaffold, furnishing thus target values in the design of the scaffold. Correspondingly, an efficient cell stimulation might be achieved with a scaffold of pore size larger than 300 microm as no dynamic damping effect is likely to take place. The analytical model proposed in this study, while being a simplification of a fluid/cell mechanical interaction, brings complementary insights to numerical studies by analyzing the effect of different physical parameters.

Comparison of polyethylene wear in anatomical and reversed shoulder prostheses.

Wear of polyethylene is associated with aseptic loosening of orthopaedic implants and has been observed in hip and knee prostheses and anatomical implants for the shoulder. The reversed shoulder prostheses have not been assessed as yet. We investigated the volumetric polyethylene wear of the reversed and anatomical Aequalis shoulder prostheses using a mathematical musculoskeletal model. Movement and joint stability were achieved by EMG-controlled activation of the muscles. A non-constant wear factor was considered. Simulated activities of daily living were estimated from in vivo recorded data. After one year of use, the volumetric wear was 8.4 mm(3) for the anatomical prosthesis, but 44.6 mm(3) for the reversed version. For the anatomical prosthesis the predictions for contact pressure and wear were consistent with biomechanical and clinical data. The abrasive wear of the polyethylene in reversed prostheses should not be underestimated, and further analysis, both experimental and clinical, is required.

Targeted mechanical properties for optimal fluid motion inside artificial bone substitutes.

Our goal was to develop a method to identify the optimal elastic modulus, Poisson's ratio, porosity, and permeability values for a mechanically stressed bone substitute. We hypothesized that a porous bone substitute that favors the transport of nutriments, wastes, biochemical signals, and cells, while keeping the fluid-induced shear stress within a range that stimulates osteoblasts, would likely promote osteointegration. Two optimization criteria were used: (i) the fluid volume exchange between the artificial bone substitute and its environment must be maximal and (ii) the fluid-induced shear stress must be between 0.03 and 3 Pa. Biot's poroelastic theory was used to compute the fluid motion due to mechanical stresses. The impact of the elastic modulus, Poisson's ratio, porosity, and permeability on the fluid motion were determined in general and for three different bone substitute sizes used in high tibial osteotomy. We found that fluid motion was optimized in two independent steps. First, fluid transport was maximized by minimizing the elastic modulus, Poisson's ratio, and porosity. Second, the fluid-induced shear stress could be adjusted by tuning the bone substitute permeability so that it stayed within the favorable range of 0.03 to 3 Pa. Such method provides clear guidelines to bone substitute developers and to orthopedic surgeons for using bone substitute materials according to their mechanical environment.