Publications by authors named "Pasquale Vena"

21 Publications

  • Page 1 of 1

AFM and Fluorescence Microscopy of Single Cells with Simultaneous Mechanical Stimulation via Electrically Stretchable Substrates.

Materials (Basel) 2021 Jul 24;14(15). Epub 2021 Jul 24.

Department of Informatics, Bioengineering, Robotics, and System Engineering (DIBRIS), University of Genova, 16145 Genova, Italy.

We have developed a novel experimental set-up that simultaneously, (i) applies static and dynamic deformations to adherent cells in culture, (ii) allows the visualization of cells under fluorescence microscopy, and (iii) allows atomic force microscopy nanoindentation measurements of the mechanical properties of the cells. The cell stretcher device relies on a dielectric elastomer film that can be electro-actuated and acts as the cell culture substrate. The shape and position of the electrodes actuating the film can be controlled by design in order to obtain specific deformations across the cell culture chamber. By using optical markers we characterized the strain fields under different electrode configurations and applied potentials. The combined setup, which includes the cell stretcher device, an atomic force microscope, and an inverted optical microscope, can assess in situ and with sub-micron spatial resolution single cell topography and elasticity, as well as ion fluxes, during the application of static deformations. Proof of performance on fibroblasts shows a reproducible increase in the average cell elastic modulus as a response to applied uniaxial stretch of just 4%. Additionally, high resolution topography and elasticity maps on a single fibroblast can be acquired while the cell is deformed, providing evidence of long-term instrumental stability. This study provides a proof-of-concept of a novel platform that allows in situ and real time investigation of single cell mechano-transduction phenomena with sub-cellular spatial resolution.
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http://dx.doi.org/10.3390/ma14154131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347060PMC
July 2021

Development of a micro-scale method to assess the effect of corrosion on the mechanical properties of a biodegradable Fe-316L stent material.

J Mech Behav Biomed Mater 2021 02 1;114:104173. Epub 2020 Nov 1.

Department of Mechanical Engineering, 817 Sherbrooke St. West, Room 270, McGill University, Montreal, Quebec, H3A 0C3, Canada; Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, H1T 1C8, Canada. Electronic address:

The application of biodegradable materials to stent design has the potential to transform coronary artery disease treatment. It is critical that biodegradable stents have sustained strength during degradation and vessel healing to prevent re-occlusion. Proper assessment of the impact of corrosion on the mechanical behaviour of potential biomaterials is important. Investigations within literature frequently implement simplified testing conditions to understand this behaviour and fail to consider size effects associated with strut thickness, or the increase in corrosion due to blood flow, both of which can impact material properties. A protocol was developed that utilizes micro-scale specimens, in conjunction with dynamic degradation, to assess the effect of corrosion on the mechanical properties of a novel Fe-316L material. Dynamic degradation led to increased specimen corrosion, resulting in a greater reduction in strength after 48 h of degradation in comparison to samples statically corroded. It was found that thicker micro-tensile samples (h > 200 μm) had a greater loss of strength in comparison to its thinner counterpart (h < 200 μm), due to increased corrosion of the thicker samples (203 MPa versus 260 MPa after 48 h, p = 0.0017). This investigation emphasizes the necessity of implementing physiologically relevant testing conditions, including dynamic corrosion and stent strut thickness, when evaluating potential biomaterials for biodegradable stent application.
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http://dx.doi.org/10.1016/j.jmbbm.2020.104173DOI Listing
February 2021

An experimental procedure to perform mechanical characterization of small-sized bone specimens from thin femoral cortical wall.

J Mech Behav Biomed Mater 2020 12 1;112:104046. Epub 2020 Sep 1.

Department of Chemistry, Materials and Chemical Engineering Giulio Natta, Laboratory of Biological Structure Mechanics (LaBS) - Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133, Milano, Italy. Electronic address:

The cortical shell of the femoral neck plays a role in determining the overall neck strength. However, there is a lack of knowledge about the mechanical properties of cortical tissue of the femoral neck due to challenges in implementing accurate testing protocols for the thin shell. Indeed, mechanical properties are commonly derived from mechanical testing performed on tissue samples extracted from the femoral diaphysis, i.e. assuming tissue homogeneity along the femur. The aim of this work was to set up a reliable methodology to determine mechanical properties of bone samples extracted from thin cortical shell of the femoral neck. A three-point bending test was used to determine elastic and post-elastic properties of cortical bone samples extracted from the inferior and superior femoral neck. An optical system was used to monitor the sample deflection. Accuracy was preliminarily evaluated by determining the elastic modulus of an aluminium alloy. A good intra- and inter-sample variability was found on determining aluminium elastic modulus: 1.6% and 3.6%, respectively. Additionally, aluminium elastic modulus value was underestimated by less than 1%. A pilot trial was performed on a human femoral neck to assess the procedure feasibility. A total of 22 samples were extracted from the inferior and superior femoral neck and successfully tested. Preliminary results suggest that mechanical properties of cortical bone tissue extracted from human femoral neck might be side dependent, the superior tissue seems to exhibit better mechanical properties than the inferior one, at least in terms of yield stress and maximum strain. This supposedly different mechanical competence must be further investigated. The proposed procedure makes it feasible to carry out such studies.
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http://dx.doi.org/10.1016/j.jmbbm.2020.104046DOI Listing
December 2020

Dilatational and shear waves in poro-vioscoelastic media.

J Mech Behav Biomed Mater 2019 09 4;97:99-107. Epub 2019 May 4.

University of Illinois at Chicago, Department of Bioengineering, Chicago, USA. Electronic address:

Dynamic elastography methods are being developed for quantitatively and noninvasively mapping the viscoelastic properties of biological tissue that are often altered by disease and injury, as well as response to treatment. This involves inducing mechanical wave motion that also can be affected by the multiphase porous nature of the tissue, whether it be consideration of blood perfusion in the vascular network found in many regions of interest, or consideration of air movement in the complex bronchial tree within the lungs. Elastographic mapping requires reconstructing material properties based on interpretation of the measured wave motion. Reconstruction methods that explicitly incorporate poroelastic behavior are an active area of development. In the present article the equivalence of two theoretical approaches to modeling poroelastic behavior is demonstrated specifically in the frequency domain using parameter values that span the range expected in vivo for analysis of blood and air-infused regions. The two methods are known as (1) the mixture or biphasic formulation and (2) the poroelastic approach. The case of acoustic wave propagation in the lungs is specifically addressed by comparison of analytical predictions to recently reported experimental measurements. Establishing and validating this equivalence of theoretical approaches not only strengthens our fundamental understanding of the relevant physics, but also may lead to improved numerical methods for simulation and elastography reconstruction.
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http://dx.doi.org/10.1016/j.jmbbm.2019.04.039DOI Listing
September 2019

Anisotropic composite material phantom to improve skeletal muscle characterization using magnetic resonance elastography.

J Mech Behav Biomed Mater 2019 01 25;89:199-208. Epub 2018 Sep 25.

Richard and Loan Hill Department of Bioengineering, University of Illinois at Chicago, 851 South Mogan Street, 212 SEO, Chicago, IL 60607-7052, USA. Electronic address:

The presence and progression of neuromuscular pathology, including spasticity, Duchenne's muscular dystrophy and hyperthyroidism, has been correlated with changes in the intrinsic mechanical properties of skeletal muscle tissue. Tools for noninvasively measuring and monitoring these properties, such as Magnetic Resonance Elastography (MRE), could benefit basic research into understanding neuromuscular pathologies, as well as translational research to develop therapies, by providing a means of assessing and tracking their efficacy. Dynamic elastography methods for noninvasive measurement of tissue mechanical properties have been under development for nearly three decades. Much of the technological development to date, for both Ultrasound (US)-based and Magnetic Resonance Imaging (MRI)-based strategies, has been grounded in assumptions of local homogeneity and isotropy. Striated skeletal and cardiac muscle, as well as brain white matter and soft tissue in some other organ regions, exhibit a fibrous microstructure which entails heterogeneity and anisotropic response; as one seeks to improve the accuracy and resolution in mechanical property assessment, heterogeneity and anisotropy need to be accounted for in order to optimize both the dynamic elastography experimental protocol and the interpretation of the measurements. Advances in elastography methodology at every step have been aided by the use of tissue-mimicking phantoms. The aim of the present study was to develop and characterize a heterogeneous composite phantom design with uniform controllable anisotropic properties meant to be comparable to the frequency-dependent anisotropic properties of skeletal muscle. MRE experiments and computational finite element (FE) studies were conducted on a novel 3D-printed composite phantom design. The displacement maps obtained from simulation and experiment show the same elliptical shaped wavefronts elongated in the plane where the structure presents higher shear modulus. The model exhibits a degree of anisotropy in line with literature data from skeletal muscle tissue MRE experiments. FE simulations of the MRE experiments provide insight into proper interpretation of experimental measurements, and help to quantify the importance of heterogeneity in the anisotropic material at different scales.
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http://dx.doi.org/10.1016/j.jmbbm.2018.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211788PMC
January 2019

Biomimetic engineering of the cardiac tissue through processing, functionalization, and biological characterization of polyester urethanes.

Biomed Mater 2018 07 3;13(5):055006. Epub 2018 Jul 3.

Institute of Clinical Physiology, IFC-CNR, Via Moruzzi 1, I-56124 Pisa, Italy.

Three-dimensional (3D) tissue models offer new tools in the study of diseases. In the case of the engineering of cardiac muscle, a realistic goal would be the design of a scaffold able to replicate the tissue-specific architecture, mechanical properties, and chemical composition, so that it recapitulates the main functions of the tissue. This work is focused on the design and preliminary biological validation of an innovative polyester urethane (PUR) scaffold mimicking cardiac tissue properties. The porous scaffold was fabricated by thermally induced phase separation (TIPS) from poly(ε-caprolactone) diol, 1,4-butanediisocyanate, and l-lysine ethyl ester. Morphological and mechanical scaffolds characterization was accomplished by confocal microscopy, and micro-tensile and compression techniques. Scaffolds were then functionalized with fibronectin by plasma treatment, and the surface treatment was studied by x-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared spectra, and contact angle measurements. Primary rat neonatal cardiomyocytes were seeded on scaffolds, and their colonization, survival, and beating activity were analyzed for 14 days. Signal transduction pathways and apoptosis involved in cells, the structural development of the heart, and its metabolism were analyzed. PUR scaffolds showed a porous-aligned structure and mechanical properties consistent with that of the myocardial tissue. Cardiomyocytes plated on the scaffolds showed a high survival rate and a stable beating activity. Serine/threonine kinase (AKT) and extracellular signal-regulated kinases (ERK) phosphorylation was higher in cardiomyocytes cultured on the PUR scaffold compared to those on tissue culture plates. Real-time polymerase chain reaction analysis showed a significant modulation at 14 days of cardiac muscle (MYH7, prepro-ET-1), hypertrophy-specific (CTGF), and metabolism-related (SLC2a1, PFKL) genes in PUR scaffolds.
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http://dx.doi.org/10.1088/1748-605X/aaca5bDOI Listing
July 2018

Micro-CT based finite element models for elastic properties of glass-ceramic scaffolds.

J Mech Behav Biomed Mater 2017 01 23;65:248-255. Epub 2016 Aug 23.

Department of Chemistry, Materials and Chemical Engineering, Laboratory of Biological Structure Mechanics (LaBS) - Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy; I.R.C.C.S., Via R. Galeazzi 4, 20161 Milano, Italy. Electronic address:

In this study, the mechanical properties of porous glass-ceramic scaffolds are investigated by means of three-dimensional finite element models based on micro-computed tomography (micro-CT) scan data. In particular, the quantitative relationship between the morpho-architectural features of the obtained scaffolds, such as macroscopic porosity and strut thickness, and elastic properties, is sought. The macroscopic elastic properties of the scaffolds have been obtained through numerical homogenization approaches using the mechanical characteristics of the solid walls of the scaffolds (assessed through nanoindentation) as input parameters for the numerical simulations. Anisotropic mechanical properties of the produced scaffolds have also been investigated by defining a suitable anisotropy index. A comparison with morphological data obtained through the micro-CT scans is also presented. The proposed study shows that the produced glass-ceramic scaffolds exhibited a macroscopic porosity ranging between 29% and 97% which corresponds to an average stiffness ranging between 42.4GPa and 36MPa. A quantitative estimation of the isotropy of the macroscopic elastic properties has been performed showing that the samples with higher solid fractions were those closest to an isotropic material.
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http://dx.doi.org/10.1016/j.jmbbm.2016.08.020DOI Listing
January 2017

Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c) Using Differential Pulse Voltammetry (DPV).

Sensors (Basel) 2016 Jul 1;16(7). Epub 2016 Jul 1.

Department of Chemical & Biomolecular Engineering and Electronics Design Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.

A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV) was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET) substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor. This was a roll-to-roll cost-effective manufacturing process making the single-use disposable in vitro HbA1c biosensor a reality. Self-assembled monolayers of 3-Mercaptopropionic acid (MPA) were employed to covalently immobilize anti-HbA1c on the surface of gold electrodes. Electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) confirmed the excellent coverage of MPA-SAM and the upward orientation of carboxylic groups. The hindering effect of HbA1c on the ferricyanide/ferrocyanide electron transfer reaction was exploited as the HbA1c detection mechanism. The biosensor showed a linear range of 7.5-20 µg/mL of HbA1c in 0.1 M PBS. Using undiluted human serum as the test medium, the biosensor presented an excellent linear behavior (R² = 0.999) in the range of 0.1-0.25 mg/mL of HbA1c. The potential application of this biosensor for in vitro measurement of HbA1c for diabetic management was demonstrated.
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http://dx.doi.org/10.3390/s16071024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970074PMC
July 2016

Special issue: multiscale biomechanics.

J Biomech Eng 2015 Jul 2;137(7). Epub 2015 Jun 2.

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http://dx.doi.org/10.1115/1.4030529DOI Listing
July 2015

Repair of osteochondral defects in the minipig model by OPF hydrogel loaded with adipose-derived mesenchymal stem cells.

Regen Med 2015 ;10(2):135-51

IRCCS Istituto Ortopedico Galeazzi; Via R. Galeazzi 4, 20161 Milano, Italy.

Aim: Critical knee osteochondral defects in seven adult minipigs were treated with oligo(polyethylene glycol)fumarate (OPF) hydrogel combined with autologous or human adipose-derived stem cells (ASCs), and evaluated after 6 months.

Methods: Four defects were made on the peripheral part of right trochleas (n = 28), and treated with OPF scaffold alone or pre-seeded with ASCs.

Results: A better quality cartilage tissue characterized by improved biomechanical properties and higher collagen type II expression was observed in the defects treated by autologous or human ASC-loaded OPF; similarly this approach induced the regeneration of more mature bone with upregulation of collagen type I expression.

Conclusion: This study provides the evidence that both porcine and human adipose-derived stem cells associated to OPF hydrogel allow improving osteochondral defect regeneration in a minipig model.
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http://dx.doi.org/10.2217/rme.14.77DOI Listing
January 2016

A quantitative interpretation of the response of articular cartilage to atomic force microscopy-based dynamic nanoindentation tests.

J Biomech Eng 2015 Jul 2;137(7). Epub 2015 Jun 2.

In this paper, a quantitative interpretation for atomic force microscopy-based dynamic nanoindentation (AFM-DN) tests on the superficial layers of bovine articular cartilage (AC) is provided. The relevant constitutive parameters of the tissue are estimated by fitting experimental results with a finite element model in the frequency domain. Such model comprises a poroelastic stress-strain relationship for a fibril reinforced tissue constitution, assuming a continuous distribution of the collagen network orientations. The identification procedure was first validated using a simplified transversely isotropic constitutive relationship; then, the experimental data were manually fitted by using the continuous distribution fibril model. Tissue permeability is derived from the maximum value of the phase shift between the input harmonic loading and the harmonic tissue response. Tissue parameters related to the stiffness are obtained from the frequency response of the experimental storage modulus and phase shift. With this procedure, an axial to transverse stiffness ratio (anisotropy ratio) of about 0.15 is estimated.
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http://dx.doi.org/10.1115/1.4030175DOI Listing
July 2015

Orientation and size-dependent mechanical modulation within individual secondary osteons in cortical bone tissue.

J R Soc Interface 2013 Apr 6;10(81):20120953. Epub 2013 Feb 6.

Department of Structural Engineering, LaBS-Laboratory of Biological Structure Mechanics, Politecnico di Milano, P.zza L. da Vinci 32, 20133 Milan, Italy.

Anisotropy is one of the most peculiar aspects of cortical bone mechanics; however, its anisotropic mechanical behaviour should be treated only with strict relationship to the length scale of investigation. In this study, we focus on quantifying the orientation and size dependence of the spatial mechanical modulation in individual secondary osteons of bovine cortical bone using nanoindentation. Tests were performed on the same osteonal structure in the axial (along the long bone axis) and transverse (normal to the long bone axis) directions along arrays going radially out from the Haversian canal at four different maximum depths on three secondary osteons. Results clearly show a periodic pattern of stiffness with spatial distance across the osteon. The effect of length scale on lamellar bone anisotropy and the critical length at which homogenization of the mechanical properties occurs were determined. Further, a laminate-composite-based analytical model was applied to the stiffness trends obtained at the highest spatial resolution to evaluate the elastic constants for a sub-layer of mineralized collagen fibrils within an osteonal lamella on the basis of the spatial arrangement of the fibrils. The hierarchical arrangement of lamellar bone is found to be a major determinant for modulation of mechanical properties and anisotropic mechanical behaviour of the tissue.
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http://dx.doi.org/10.1098/rsif.2012.0953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627101PMC
April 2013

Integrating qPLM and biomechanical test data with an anisotropic fiber distribution model and predictions of TGF-β1 and IGF-1 regulation of articular cartilage fiber modulus.

Biomech Model Mechanobiol 2013 Nov 25;12(6):1073-88. Epub 2012 Dec 25.

Mechanical Engineering Department, California Polytechnic State University, San Luis Obispo, CA, USA.

A continuum mixture model with distinct collagen (COL) and glycosaminoglycan elastic constituents was developed for the solid matrix of immature bovine articular cartilage. A continuous COL fiber volume fraction distribution function and a true COL fiber elastic modulus ([Formula: see text] were used. Quantitative polarized light microscopy (qPLM) methods were developed to account for the relatively high cell density of immature articular cartilage and used with a novel algorithm that constructs a 3D distribution function from 2D qPLM data. For specimens untreated and cultured in vitro, most model parameters were specified from qPLM analysis and biochemical assay results; consequently, [Formula: see text] was predicted using an optimization to measured mechanical properties in uniaxial tension and unconfined compression. Analysis of qPLM data revealed a highly anisotropic fiber distribution, with principal fiber orientation parallel to the surface layer. For untreated samples, predicted [Formula: see text] values were 175 and 422 MPa for superficial (S) and middle (M) zone layers, respectively. TGF-[Formula: see text]1 treatment was predicted to increase and decrease [Formula: see text] values for the S and M layers to 281 and 309 MPa, respectively. IGF-1 treatment was predicted to decrease [Formula: see text] values for the S and M layers to 22 and 26 MPa, respectively. A novel finding was that distinct native depth-dependent fiber modulus properties were modulated to nearly homogeneous values by TGF-[Formula: see text]1 and IGF-1 treatments, with modulated values strongly dependent on treatment.
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http://dx.doi.org/10.1007/s10237-012-0463-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637957PMC
November 2013

Role of damage mechanics in nanoindentation of lamellar bone at multiple sizes: experiments and numerical modeling.

J Mech Behav Biomed Mater 2011 Nov 12;4(8):1852-63. Epub 2011 Jun 12.

Laboratory of Biological Structure Mechanics (LaBS), Department of Structural Engineering, Politecnico di Milano, Milan, Italy.

The aim of this paper is to show that damage mechanisms can account for the response of lamellar bone to nanoindentation tests, with particular regards to the decrease of indentation stiffness with increasing penetration depth and to the loss of contact stiffness during the unloading phase of the test. For this purpose, indentation experiments on bovine cortical bone samples along axial and transverse directions have been carried out at five penetration depths from 50 to 450 nm; furthermore, a continuum damage model has been implemented into finite element analyses, which are able to simulate indentation experiments. Experiments along the axial direction have shown a decrease of about 20% of the indentation modulus with indentation depth; a similar trend was found along the transverse direction. All unloading branches of the force-displacement indentation curves exhibited relevant stiffness loss (curve concavity). The numerical model with damage was able to correctly predict the indentation stiffness and hardness at 300 nm penetration depth along both axial and transverse directions. Furthermore, stiffness loss during unloading was simulated with both qualitative and quantitative agreement with experiments. A final validation has been provided by simulating axial indentation experiments at the remaining penetration depths using the same set of constitutive parameters as those used to simulate the experiments at 300 nm depth. These results support the hypothesis that damage plays a relevant role in the mechanics of lamellar bone and should be taken into account when studying bone mechanical properties at multiple scales.
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http://dx.doi.org/10.1016/j.jmbbm.2011.06.002DOI Listing
November 2011

Trends in biomedical engineering: focus on Smart Bio-Materials and Drug Delivery.

J Appl Biomater Biomech 2011 May-Aug;9(2):87-97

Bioengineering Department, Politecnico di Milano, Milano, Italy.

The present article reviews on different research lines, namely: drug and gene delivery, surface modification/modeling, design of advanced materials (shape memory polymers and biodegradable stents), presently developed at Politecnico di Milano, Italy. For gene delivery, non-viral polycationic-branched polyethylenimine (b-PEI) polyplexes are coated with pectin, an anionic polysaccharide, to enhance the polyplex stability and decrease b-PEI cytotoxicity. Perfluorinated materials, specifically perfluoroether, and perfluoro-polyether fluids are proposed as ultrasound contrast agents and smart agents for drug delivery. Non-fouling, self-assembled PEG-based monolayers are developed on titanium surfaces with the aim of drastically reducing cariogenic bacteria adhesion on dental implants. Femtosecond laser microfabrication is used for selectively and spatially tuning the wettability of polymeric biomaterials and the effects of femtosecond laser ablation on the surface properties of polymethylmethacrylate are studied. Innovative functionally graded Alumina-Ti coatings for wear resistant articulating surfaces are deposited with PLD and characterized by means of a combined experimental and computational approach. Protein adsorption on biomaterials surfaces with an unlike wettability and surface-modification induced by pre-adsorbed proteins are studied by atomistic computer simulations. A study was performed on the fabrication of porous Shape Memory Polymeric structures and on the assessment of their potential application in minimally invasive surgical procedures. A model of magnesium (alloys) degradation, in a finite element framework analysis, and a bottom-up multiscale analysis for modeling the degradation mechanism of PLA matrices was developed, with the aim of providing valuable tools for the design of bioresorbable stents.
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http://dx.doi.org/10.5301/JABB.2011.8563DOI Listing
March 2013

Modeling the collagen fibril network of biological tissues as a nonlinearly elastic material using a continuous volume fraction distribution function.

Math Mech Solids 2011 Sep;16(7):706-715

Mechanical Engineering Department, California Polytechnic State University, San Luis Obispo, CA 93407, USA.

Despite distinct mechanical functions, biological soft tissues have a common microstructure in which a ground matrix is reinforced by a collagen fibril network. The microstructural properties of the collagen network contribute to continuum mechanical tissue properties that are strongly anisotropic with tensile-compressive asymmetry. In this study, a novel approach based on a continuous distribution of collagen fibril volume fractions is developed to model fibril reinforced soft tissues as a nonlinearly elastic and anisotropic material. Compared with other approaches that use a normalized number of fibrils for the definition of the distribution function, this representation is based on a distribution parameter (i.e. volume fraction) that is commonly measured experimentally while also incorporating pre-stress of the collagen fibril network in a tissue natural configuration. After motivating the form of the collagen strain energy function, examples are provided for two volume fraction distribution functions. Consequently, collagen second-Piola Kirchhoff stress and elasticity tensors are derived, first in general form and then specifically for a model that may be used for immature bovine articular cartilage. It is shown that the proposed strain energy is a convex function of the deformation gradient tensor and, thus, is suitable for the formation of a polyconvex tissue strain energy function.
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http://dx.doi.org/10.1177/1081286510387866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563300PMC
September 2011

Nanoindentation testing and finite element simulations of cortical bone allowing for anisotropic elastic and inelastic mechanical response.

J Biomech 2011 Jul 12;44(10):1852-8. Epub 2011 May 12.

Laboratory of Biological Structure Mechanics, Department of Structural Engineering, Politecnico di Milano, Milan, Italy.

Anisotropy is one of the most peculiar aspects of cortical bone mechanical behaviour, and the numerical approach can be successfully used to investigate aspects of bone tissue mechanics that analytical methods solve in approximate way or do not cover. In this work, nanoindentation experimental tests and finite element simulations were employed to investigate the elastic-inelastic anisotropic mechanical properties of cortical bone. The model allows for anisotropic elastic and post-yield behaviour of the tissue. A tension-compression mismatch and direction-dependent yield stresses are allowed for. Indentation experiments along the axial and transverse directions were simulated with the purpose to predict the indentation moduli and hardnesses along multiple orientations. Results showed that the experimental transverse-to-axial ratio of indentation moduli, equal to 0.74, is predicted with a ∼3% discrepancy regardless the post-yield material behaviour; whereas, the transverse-to-axial hardness ratio, equal to 0.86, can be correctly simulated (discrepancy ∼6% w.r.t. the experimental results) only employing an anisotropic post-elastic constitutive model. Further, direct comparison between the experimental and simulated indentation tests evidenced a good agreement in the loading branch of the indentation curves and in the peak loads for a transverse-to-axial yield stress ratio comparable to the experimentally obtained transverse-to-axial hardness ratio. In perspective, the present work results strongly support the coupling between indentation experiments and FEM simulations to get a deeper knowledge of bone tissue mechanical behaviour at the microstructural level. The present model could be used to assess the effect of variations of constitutive parameters due to age, injury, and/or disease on bone mechanical performance in the context of indentation testing.
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http://dx.doi.org/10.1016/j.jbiomech.2011.04.020DOI Listing
July 2011

A nonlinear constituent based viscoelastic model for articular cartilage and analysis of tissue remodeling due to altered glycosaminoglycan-collagen interactions.

J Biomech Eng 2009 Oct;131(10):101002

Department of Mechanical Engineering, California Polytechnic State University, San Luis Obispo, 93407, USA.

A constituent based nonlinear viscoelastic (VE) model was modified from a previous study (Vena, et al., 2006, "A Constituent-Based Model for the Nonlinear Viscoelastic Behavior of Ligaments," J. Biomech. Eng., 128, pp. 449-457) to incorporate a glycosaminoglycan (GAG)-collagen (COL) stress balance using compressible elastic stress constitutive equations specific to articular cartilage (AC). For uniaxial loading of a mixture of quasilinear VE constituents, time constant and relaxation ratio equations are derived to highlight how a mixture of constituents with distinct quasilinear VE properties is one mechanism that produces a nonlinear VE tissue. Uniaxial tension experiments were performed with newborn bovine AC specimens before and after approximately 55% and approximately 85% GAG depletion treatment with guanidine. Experimental tissue VE parameters were calculated directly from stress relaxation data, while intrinsic COL VE parameters were calculated by curve fitting the data with the nonlinear VE model with intrinsic GAG viscoelasticity neglected. Select tissue and intrinsic COL VE parameters were significantly different from control and experimental groups and correlated with GAG content, suggesting that GAG-COL interactions exist to modulate tissue and COL mechanical properties. Comparison of the results from this and other studies that subjected more mature AC tissue to GAG depletion treatment suggests that the GAGs interact with the COL network in a manner that may be beneficial for rapid volumetric expansion during developmental growth while protecting cells from excessive matrix strains. Furthermore, the underlying GAG-COL interactions appear to diminish as the tissue matures, indicating a distinctive remodeling response during developmental growth.
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http://dx.doi.org/10.1115/1.3192139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966345PMC
October 2009

Poroelastic numerical modelling of natural and engineered cartilage based on in vitro tests.

Biorheology 2006;43(3,4):235-47

Laboratory of Biological Structure Mechanics, Department of Structural Engineering, Politecnico di Milano, Italy.

The mechanisms underlying the ability of articular cartilage to withstand and distribute the loads applied across diarthrodial joints have been widely studied. Experimental tests have been done under several configurations to reveal the tissue response to mechanical stimuli, and theoretical models have been developed for the interpretation of the experimental results. The experiments demonstrated that the tissue is non-linear with strain, both in tension and in compression, non-linear with direction of stimulus, anisotropic in tension and compression, non-homogeneous with depth, resulting in depth dependent mechanical properties, and presents fluid dependent and fluid independent viscoelasticity. None of the models up to now developed is able to describe the whole set of responses of such a complex tissue. The purpose of this study was to develop a combined experimental-numerical approach for the proper description of the cartilage response under confined and unconfined compression. We defined a series of experimental tests to be performed on disks of natural and engineered cartilage and we developed a numerical model for cartilage, based on the biphasic theory, which potentially includes the tension-compression non-linearity, the strain non-linearity and the fluid independent viscoelasticity. The model successfully simulated the confined and unconfined compression experiments performed on disks of natural and engineered cartilage, and was also used to identify parameters of difficult experimental evaluation, such as the collagen stiffness and the permeability. In conclusion, the use of our model in combination with biomechanical experimental testing seems a valuable tool to analyze the mechanical properties of natural cartilage and the biofunctionality of tissue engineered cartilage.
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November 2006

Skin metastases from anaplastic thyroid carcinoma.

Thyroid 2006 May;16(5):513-4

Unit of Endocrinology, Hospital of Tinchi-Pisticci, Matera, Italy.

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http://dx.doi.org/10.1089/thy.2006.16.513DOI Listing
May 2006

A finite element model of the L4-L5 spinal motion segment: biomechanical compatibility of an interspinous device.

Comput Methods Biomech Biomed Engin 2005 Feb;8(1):7-16

Laboratory of Biological Structure Mechanics, Department of Structural Engineering, Politecnico di Milano, 32-20133 Milano, Italy.

The biomechanical compatibility of an interspinous device, used for the "dynamic stabilization" of a diseased spinal motion segment, was investigated. The behaviour of an implant made of titanium based alloy (Ti6Al4V) and that of an implant made of a super-elastic alloy (Ni-Ti) have been compared. The assessment of the biomechanical compatibility was achieved by means of the finite element method, in which suitable constitutive laws have been adopted for the annulus fibrosus and for the metal alloys. The model was aimed at simulating the healthy, the nucleotomized and the treated L4-L5 lumbar segment, subjected to compressive force and flexion-extension as well as lateral flexion moments. The computational model has shown that both the implants were able to achieve their main design purpose, which is to diminish the forces acting on the apophyseal joints. Nevertheless, the Ni-Ti implant has shown a more physiological flexural stiffness with respect to the Ti6Al4V implant, which exhibited an excessive stiffness and permanent strains (plastic strains), even under physiological loads. The computational models presented in this paper seems to be a promising tool able to predict the effectiveness of a biomedical device and to select the materials to be used for the implant manufacturing, within an engineering approach to the clinical problem of the spinal diseases.
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http://dx.doi.org/10.1080/10255840500062914DOI Listing
February 2005
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