Experimental assessment of pelvis slipping during postless traction for orthopaedic applications.

BACKGROUND: The application of lower limb traction during hip arthroscopy and femur fractures osteosynthesis is commonplace in orthopaedic surgeries. Traditional methods utilize a perineal post on a traction table, leading to soft tissue damage and nerve neuropraxia. A postless technique, using high-friction pads, has been considered as a potential damage-free alternative. However, whether these pads sufficiently prevent patient displacement remains unknown. Thus, this study systematically assesses the efficacy of commercial high-friction pads (PinkPad and CarePad) in restraining subject displacement, for progressively increasing traction loads and different Trendelenburg angles. METHODS: Three healthy male subjects were recruited and tested in supine and Trendelenburg positions (5° and 10°), using a customized boot-pulley system. Ten load disks (5 kg) were dropped at 15s intervals, increasing gradually the traction load up to 50 kg. Pelvis displacement along the traction direction was measured with a motion capture system. The displacement at 50 kg of traction load was analyzed and compared across various pads and bed inclinations. Response to varying traction loads was statistically assessed with a quadratic function model. RESULTS: Pelvis displacement at 50 kg traction load was below 60 mm for all conditions. Comparing PinkPad and CarePad, no significant differences in displacement were observed. Finally, similar displacements were observed for the supine and Trendelenburg positions. CONCLUSIONS: Both PinkPad and CarePad exhibited nearly linear behavior under increasing traction loads, limiting displacement to 60 mm at most for 50 kg loads. Contrary to expectations, placing subjects in the Trendelenburg position did not increase adhesion.

Unraveling the transcriptome profile of pulsed electromagnetic field stimulation in bone regeneration using a bioreactor-based investigation platform.

INTRODUCTION: Human mesenchymal stem cells (hMSCs) sense and respond to biomechanical and biophysical stimuli, yet the involved signaling pathways are not fully identified. The clinical application of biophysical stimulation including pulsed electromagnetic field (PEMF) has gained momentum in musculoskeletal disorders and bone tissue engineering. METHODOLOGY: We herein aim to explore the role of PEMF stimulation in bone regeneration by developing trabecular bone-like tissues, and then, culturing them under bone-like mechanical stimulation in an automated perfusion bioreactor combined with a custom-made PEMF stimulator. After selecting the optimal cell seeding and culture conditions for inspecting the effects of PEMF on hMSCs, transcriptomic studies were performed on cells cultured under direct perfusion with and without PEMF stimulation. RESULTS: We were able to identify a set of signaling pathways and upstream regulators associated with PEMF stimulation and to distinguish those linked to bone regeneration. Our findings suggest that PEMF induces the immune potential of hMSCs by activating and inhibiting various immune-related pathways, such as macrophage classical activation and MSP-RON signaling in macrophages, respectively, while promoting angiogenesis and osteogenesis, which mimics the dynamic interplay of biological processes during bone healing. CONCLUSIONS: Overall, the adopted bioreactor-based investigation platform can be used to investigate the impact of PEMF stimulation on bone regeneration.

DXA-based statistical models of shape and intensity outperform aBMD hip fracture prediction: A retrospective study.

Areal bone mineral density (aBMD) currently represents the clinical gold standard for hip fracture risk assessment. Nevertheless, it is characterised by a limited prediction accuracy, as about half of the people experiencing a fracture are not classified as at being at risk by aBMD. In the context of a progressively ageing population, the identification of accurate predictive tools would be pivotal to implement preventive actions. In this study, DXA-based statistical models of the proximal femur shape, intensity (i.e., density) and their combination were developed and employed to predict hip fracture on a retrospective cohort of post-menopausal women. Proximal femur shape and pixel-by-pixel aBMD values were extracted from DXA images and partial least square (PLS) algorithm adopted to extract corresponding modes and components. Subsequently, logistic regression models were built employing the first three shape, intensity and shape-intensity PLS components, and their ability to predict hip fracture tested according to a 10-fold cross-validation procedure. The area under the ROC curves (AUC) for the shape, intensity, and shape-intensity-based predictive models were 0.59 (95%CI 0.47-0.69), 0.80 (95%CI 0.70-0.90) and 0.83 (95%CI 0.73-0.90), with the first being significantly lower than the latter two. aBMD yielded an AUC of 0.72 (95%CI 0.59-0.82), found to be significantly lower than the shape-intensity-based predictive model. In conclusion, a methodology to assess hip fracture risk uniquely based on the clinically available imaging technique, DXA, is proposed. Our study results show that hip fracture risk prediction could be enhanced by taking advantage of the full set of information DXA contains.

Development and validation of cryopreserved or freeze-dried decellularized human dermis for transplantation.

For decades, dermal tissue grafts have been used in various regenerative, reconstructive, and augmentative procedures across the body. To eliminate antigenicity and immunogenic response while still preserving the individual components and collective structural integrity of the extracellular matrix (ECM), dermis can be decellularized. Acellular dermal matrix (ADM) products like such are produced to accurately serve diverse clinical purposes. The aim of the present study is to evaluate the efficacy of a novel decellularization protocol of the human dermis, which eliminates residual human genetic material without compromising the biomechanical integrity and collagenous content of the tissue. Moreover, a freeze-drying protocol was validated. The results showed that though our decellularization protocol, human dermis can be decellularized obtaining a biocompatible matrix. The procedure is completely realized in GMP aseptic condition, avoiding tissue terminal sterilization.

Cross-link augmentation enhances CFR-PEEK short fixation in lumbar metastasis stabilization.

Introduction: Spinal stability plays a crucial role in the success of the surgical treatment of lumbar vertebral metastasis and, in current practice, less invasive approaches such as short constructs have been considered. Concurrently, carbon fiber-reinforced (CFR) poly-ether-ether-ketone (PEEK) fixation devices are expanding in oncologic spinal surgery thanks to their radiotransparency and valid mechanical properties. This study attempts to provide an exhaustive biomechanical comparison of different CFR-PEEK surgical stabilizations through a highly reproducible experimental setup. Methods: A Sawbones biomimetic phantom (T12-S1) was tested in flexion, extension, lateral bending, and axial rotation. An hemisome lesion on L3 vertebral body was mimicked and different pedicle screw posterior fixations were realized with implants from CarboFix Orthopedics Ltd: a long construct involving two spinal levels above and below the lesion, and a short construct involving only the levels adjacent to L3, with and without the addition of a transverse rod-rod cross-link; to provide additional insights on its long-term applicability, the event of a pedicle screw loosening was also accounted. Results: Short construct reduced the overloading onset caused by long stabilization. Particularly, the segmental motion contribution less deviated from the physiologic pattern and also the long-chain stiffness was reduced with respect to the prevalent long construct. The use of the cross-link enhanced the short stabilization by making it significantly stiffer in lateral bending and axial rotation, and by limiting mobiliza-tion in case of pedicle screw loosening. Discussion: The present study proved in vitro the biomechanical benefits of cross-link augmentation in short CFR-PEEK fixation, demonstrating it to be a potential alternative to standard long fixation in the surgical management of lumbar metastasis.

Novel Load Systems for In Vitro Testing of Biomaterials and Medical Devices.

In the mechanical characterization of materials or devices, the real load conditions to which they will be subjected in their operational environment must often be simulated by starting from the availability of universal testing machines [...].

Decellularized cryopreserved human pericardium: a validation study towards tissue bank practice.

Pericardial patches are currently used as reconstructive material in cardiac surgery for surgical treatment of cardiac septal defects. Autologous pericardial patches, either treated with glutaraldehyde or not, can be used as an alternative to synthetic materials or xenograft in congenital septal defects repair. The availability of an allogenic decellularized pericardium could reduce complication during and after surgery and could be a valid alternative. Decellularization of allogenic tissues aims at reducing the immunogenic reaction that might trigger inflammation and tissue calcification over time. The ideal graft for congenital heart disease repair should be biocompatible, mechanically resistant, non-immunogenic, and should have the ability to growth with the patients. The aim of the present study is the evaluation of the efficacy of a new decellularization protocol of homologous pericardium, even after cryopreservation. The technique has proven to be suitable as a tissue bank procedure and highly successful in the removal of cells and nucleic acids content, but also in the preservation of collagen and biomechanical properties of the human pericardium.

An automated 3D-printed perfusion bioreactor combinable with pulsed electromagnetic field stimulators for bone tissue investigations.

In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulations.

Are the forearm muscles excited equally in different, professional piano players?

BACKGROUND AND OBJECTIVES: Professional pianists tend to develop playing-related musculoskeletal disorders mostly in the forearm. These injuries are often due to overuse, suggesting the existence of a common forearm region where muscles are often excited during piano playing across subjects. Here we use a grid of electrodes to test this hypothesis, assessing where EMGs with greatest amplitude are more likely to be detected when expert pianists perform different excerpts. METHODS: Tasks were separated into two groups: classical excerpts and octaves, performed by eight, healthy, professional pianists. Monopolar electromyograms (EMGs) were sampled with a grid of 96 electrodes, covering the forearm region where hand and wrist muscles reside. Regions providing consistently high EMG amplitude across subjects were assessed with a non-parametric permutation test, designed for the statistical analysis of neuroimaging experiments. Spatial consistency across trials was assessed with the Binomial test. RESULTS: Spatial consistency of muscle excitation was found across subjects but not across tasks, confining at most 20% of the electrodes in the grid. These local groups of electrodes providing high EMG amplitude were found at the ventral forearm region during classical excerpts and at the dorsal region during octaves, when performed both at preferred and at high, playing speeds. DISCUSSION: Our results revealed that professional pianists consistently load a specific forearm region, depending on whether performing octaves or classical excerpts. This spatial consistency may help furthering our understanding on the incidence of playing-related muscular disorders and provide an anatomical reference for the study of active muscle loading in piano players using surface EMG.

Kinematics and kinetics comparison of ultra-congruent versus medial-pivot designs for total knee arthroplasty by multibody analysis.

Nowadays, several configurations of total knee arthroplasty (TKA) implants are commercially available whose designs resulted from clinical and biomechanical considerations. Previous research activities led to the development of the so-called medial-pivot (MP) design. However, the actual benefits of the MP, with respect to other prosthesis designs, are still not well understood. The present work compares the impact of two insert geometries, namely the ultra-congruent (UC) and medial-pivot (MP), on the biomechanical behaviour of a bicondylar total knee endoprosthesis. For this purpose, a multibody model of a lower limb was created alternatively integrating the two implants having the insert geometry discretized. Joint dynamics and contact pressure distributions were evaluated by simulating a squat motion. Results showed a similar tibial internal rotation range of about 3.5°, but an early rotation occurs for the MP design. Furthermore, the discretization of the insert geometry allowed to efficiently derive the contact pressure distributions, directly within the multibody simulation framework, reporting peak pressure values of 33 MPa and 20 MPa for the UC and MP, respectively. Clinically, the presented findings confirm the possibility, through a MP design, to achieve a more natural joint kinematics, consequently improving the post-operative patient satisfaction and potentially reducing the occurrence of phenomena leading to the insert loosening.

Personalised 3D Assessment of Trochanteric Soft Tissues Improves HIP Fracture Classification Accuracy.

Passive soft tissues surrounding the trochanteric region attenuate fall impact forces and thereby control hip fracture risk. The degree of attenuation is related to Soft Tissue Thickness (STT). STT at the neutral hip impact orientation, estimated using a regression relation in body mass index (BMI), was previously shown to influence the current absolute risk of hip fracture (ARF0) and its fracture classification accuracy. The present study investigates whether fracture classification using ARF0 improves when STT is determined from the subject's Computed-Tomography (CT) scans (i.e. personalised) in an orientation-specific (i.e. 3D) manner. STT is calculated as the shortest distance along any impact orientation between a semi-automatically segmented femur surface and an automatically segmented soft tissue/air boundary. For any subject, STT along any of the 33 impact orientations analysed always exceeds the value estimated using BMI. Accuracy of fracture classification using ARF0 improves when using personalised 3D STT estimates (AUC = 0.87) instead of the BMI-based STT estimate (AUC = 0.85). The improvement is smaller (AUC = 0.86) when orientation-specificity of CT-based STT is suppressed and is nil when personalisation is suppressed instead. Thus, fracture classification using ARF0 improves when CT is used to personalise STT estimates and improves further when, in addition, the estimates are orientation specific.

Improving the Hip Fracture Risk Prediction with a Statistical Shape-and-Intensity Model of the Proximal Femur.

Severe predictions have been made regarding osteoporotic fracture incidence for the next years, with major economic and social impacts in a worldwide greying society. However, the performance of the currently adopted gold standard for fracture risk prediction, the areal Bone Mineral Density (aBMD), remains moderate. To overcome current limitations, the construction of statistical models of the proximal femur, based on three-dimensional shape and intensity (a hallmark of bone density), is here proposed for predicting hip fracture in a Caucasian postmenopausal cohort. Partial Least Square (PLS)-based statistical models of the shape, intensity and their combination were developed, and the corresponding modes and components were identified. Logistic regression models using the first two shape, intensity and shape-intensity PLS components were implemented and tested within a 10-fold cross-validation procedure as predictors of hip fracture. It emerged that (1) intensity components were superior to shape components in stratifying patients according to their fracture status, and that (2) a combination of intensity and shape improved patients risk stratification. The area under the ROC curve was 0.64, 0.85 and 0.92 for the models based on shape, intensity and shape-intensity combination respectively, against a 0.72 value for the aBMD standard approach. Based on these findings, the presented methodology turns out to be promising in tackling the need for an enhanced fracture risk assessment.

Could light-curing time, post-space region and cyclic fatigue affect the nanomechanical behavior of a dual-curing cement for fiber post luting?

OBJECTIVE: To evaluate the effects of curing time, post-space region and cyclic fatigue on the micromechanical properties of a fiber-post luting cement. The null hypotheses were that (1) curing time, (2) fatigue and (3) post-space region does not affect the nanoindentation modulus and hardness of the dual-curing cement. MATERIALS AND METHODS: 48 premolars were endodontically treated and a class I cavity and 8 mm deep post space was prepared. Fiber posts were luted with a universal, dualized adhesive system and a dual-curing cement following manufacturer's instructions. Specimens were divided into three groups (16 specimens for each group) according to light-curing time (no light-curing, 20 s light-curing and 120 s light-curing), which was performed with a LED lamp at 1000 mW/cm 2. The coronal part of the cavity was restored using a nano-filled resin composite. After 24 h, 8 specimens for each group were randomly extract in order to undergo to fatigue test in wet condition through a chewing simulator, while the other specimens were kept in distilled water as benchmark. All the restored teeth were then sectioned in 1 mm thick slices perpendicularly to the fiber post axis. Specimen slices were classified in coronal and apical to be tested through a nanoindenter. Data were analyzed through Kruskal-Wallis test with a significance level of 1%, in order to evaluate the influence of treatments (i.e., curing time and cyclic loading) on the micromechanical properties of the tested luting cement. RESULTS: Both fatigue and curing time significantly influenced nanoindentation modulus and hardness of dual-curing cement (p < 0.01). No significant differences were reported for post space region. A significant interaction was found among the analyzed factors (p < 0.01). SIGNIFICANCE: 120 s light-curing time is recommended in order to achieve optimal mechanical proprieties, independently from post space region and cyclic fatigue. As matter of fact, 120 s light-curing allowed to prevent strain hardening induced by the fatigue simulation.

Physical Characterization of Bismuth Oxide Nanoparticle Based Ceramic Composite for Future Biomedical Application.

Employment and the effect of eco-friendly bismuth oxide nanoparticles (BiONPs) in bio-cement were studied. The standard method was adopted to prepare BiONPs-composite. Water was adopted for dispersing BiONPs in the composite. A representative batch (2 wt. % of BiONPs) was prepared without water to study the impact of water on composite properties. For each batch, 10 samples were prepared and tested. TGA (thermogravimetric analysis) performed on composite showed 0.8 wt. % losses in samples prepared without water whereas, maximum 2 wt. % weight losses observed in the water-based composite. Presence of BiONPs resulted in a decrease in depth of curing. Three-point bending flexural strength decreased for increasing BiONPs content. Comparative study between 2 wt. % samples with and without water showed 10.40 (±0.91) MPa and 28.45 (±2.50) MPa flexural strength values, respectively, indicating a significant (p < 0.05) increase of the mechanical properties at the macroscale. Nanoindentation revealed that 2 wt. % without water composites showed significant (p < 0.05) highest nanoindentation modulus 26.4 (±1.28) GPa and hardness 0.46 (±0.013) GPa. Usage of water as dispersion media was found to be deleterious for the overall characteristics of the composite but, at the same time, the BiONPs acted as a very promising filler that can be used in this class of composites.

Erratum to "Design of Additively Manufactured Lattice Structures for Biomedical Applications".

[This corrects the article DOI: 10.1155/2020/2707560.].

Comprehensive assessment of bioactive glass and glass-ceramic scaffold permeability: experimental measurements by pressure wave drop, modelling and computed tomography-based analysis.

Proper microstructural and transport properties are fundamental requirements for a suitable scaffold design and realization in tissue engineering applications. Scaffold microstructure (i.e. pore size, shape and distribution) and transport properties (i.e. intrinsic permeability), are commonly recognized as the key parameters related to the biological performance, such as cell attachment, penetration depth and tissue vascularization. While pore characteristics are relatively easy to asses, accurate and reliable evaluation of permeability still remains a challenge. In the present study, the microstructural properties of foam-replicated bioactive glass-derived scaffolds (basic composition 47.5SiO2-2.5P2O5-20CaO-10MgO-10Na2O-10K2O mol.%) were determined as function of the sintering temperature within the range 600-850°C, identified on the basis of thermal analyses that were previously performed on the material. Scaffolds with total porosity between 55 and 84 vol.% and trabecular-like architecture were obtained, with pore morphological features varying according to the sintering temperature. Mathematical modelling, supported by micro-computed tomography (µ-CT) imaging, was implemented to selectively investigate the effect of different pore features on intrinsic permeability, which was determined by laminar airflow alternating pressure wave drop measurements and found to be within 0.051-2.811·10-10 m2. The calculated effective porosity of the scaffolds was in the range of 46 to 66 vol.%, while the average pore diameter assessed by µ-CT varied between 220 and 780 µm, where the values in the lower range were observed for higher sintering temperatures (750-850°C). Experimental results were critically discussed by means of a robust statistical analysis. Finally, the complete microstructural characterization of the scaffolds was achieved by applying the general constitutive equation based on Forchheimer's theory.

Combining shape and intensity dxa-based statistical approaches for osteoporotic HIP fracture risk assessment.

Aiming to improve osteoporotic hip fracture risk detection, factors other than the largely adopted Bone Mineral Density (BMD) have been investigated as potential risk predictors. In particular Hip Structural Analysis (HSA)-derived parameters accounting for femur geometry, extracted from Dual-energy X-ray Absorptiometry (DXA) images, have been largely considered as geometric risk factors. However, HSA-derived parameters represent discrete and cross-correlated quantities, unable to describe proximal femur geometry as a whole and tightly related to BMD. Focusing on a post-menopausal cohort (N = 28), in this study statistical models of bone shape and BMD distribution have been developed to investigate their possible role in fracture risk. Due to unavailable retrospective patient-specific fracture risk information, here a surrogate fracture risk based on 3D computer simulations has been employed for the statistical framework construction. When considered separately, BMD distribution performed better than shape in explaining the surrogate fracture risk variability for the analysed cohort. However, the combination of BMD and femur shape quantities in a unique statistical model yielded better results. In detail, the first shape-intensity combined mode identified using a Partial Least Square (PLS) algorithm was able to explain 70% of the surrogate fracture risk variability, thus suggesting that a more effective patients stratification can be obtained applying a shape-intensity combination approach, compared to T-score. The findings of this study strongly advocate future research on the role of a combined shape-BMD statistical framework in fracture risk determination.

Corrigendum: Surgical Treatments for Canine Anterior Cruciate Ligament Rupture: Assessing Functional Recovery Through Multibody Comparative Analysis.

[This corrects the article DOI: 10.3389/fbioe.2019.00180.].

Compact and tunable stretch bioreactor advancing tissue engineering implementation. Application to engineered cardiac constructs.

Physical stimuli are crucial for the structural and functional maturation of tissues both in vivo and in vitro. In tissue engineering applications, bioreactors have become fundamental and effective tools for providing biomimetic culture conditions that recapitulate the native physical stimuli. In addition, bioreactors play a key role in assuring strict control, automation, and standardization in the production process of cell-based products for future clinical application. In this study, a compact, easy-to-use, tunable stretch bioreactor is proposed. Based on customizable and low-cost technological solutions, the bioreactor was designed for providing tunable mechanical stretch for biomimetic dynamic culture of different engineered tissues. In-house validation tests demonstrated the accuracy and repeatability of the imposed mechanical stimulation. Proof of concepts biological tests performed on engineered cardiac constructs, based on decellularized human skin scaffolds seeded with human cardiac progenitor cells, confirmed the bioreactor Good Laboratory Practice compliance and ease of use, and the effectiveness of the delivered cyclic stretch stimulation on the cardiac construct maturation.

Bioreactor Platform for Biomimetic Culture and in situ Monitoring of the Mechanical Response of in vitro Engineered Models of Cardiac Tissue.

In the past two decades, relevant advances have been made in the generation of engineered cardiac constructs to be used as functional in vitro models for cardiac research or drug testing, and with the ultimate but still challenging goal of repairing the damaged myocardium. To support cardiac tissue generation and maturation in vitro, the application of biomimetic physical stimuli within dedicated bioreactors is crucial. In particular, cardiac-like mechanical stimulation has been demonstrated to promote development and maturation of cardiac tissue models. Here, we developed an automated bioreactor platform for tunable cyclic stretch and in situ monitoring of the mechanical response of in vitro engineered cardiac tissues. To demonstrate the bioreactor platform performance and to investigate the effects of cyclic stretch on construct maturation and contractility, we developed 3D annular cardiac tissue models based on neonatal rat cardiac cells embedded in fibrin hydrogel. The constructs were statically pre-cultured for 5 days and then exposed to 4 days of uniaxial cyclic stretch (sinusoidal waveform, 10% strain, 1 Hz) within the bioreactor. Explanatory biological tests showed that cyclic stretch promoted cardiomyocyte alignment, maintenance, and maturation, with enhanced expression of typical mature cardiac markers compared to static controls. Moreover, in situ monitoring showed increasing passive force of the constructs along the dynamic culture. Finally, only the stretched constructs were responsive to external electrical pacing with synchronous and regular contractile activity, further confirming that cyclic stretching was instrumental for their functional maturation. This study shows that the proposed bioreactor platform is a reliable device for cyclic stretch culture and in situ monitoring of the passive mechanical response of the cultured constructs. The innovative feature of acquiring passive force measurements in situ and along the culture allows monitoring the construct maturation trend without interrupting the culture, making the proposed device a powerful tool for in vitro investigation and ultimately production of functional engineered cardiac constructs.