Anisotropic Mechanical Response of Bovine Pericardium Membrane Through Bulge Test and In-Situ Confocal-Laser Scanning.

In this work, we present a new experimental setup for the assessment of the anisotropic properties of Bovine Pericardium (BP) membranes. The chemically fixed BP samples have been subjected to a bulge test with in situ confocal laser scanning at increasing applied pressure. The high resolution topography provided by the confocal laser scanning has allowed to obtain a quantitative measure of the bulge displacement; after polynomial fitting, principal curvatures have been obtained and a degree of anisotropy (DA) has been defined as the normalized difference between the maximum and minimum principal curvatures. The experiments performed on the BP membranes have allowed us to obtain pressure-displacement data which clearly exhibit distinct principal curvatures indicating an anisotropic response. A comparison with curvatures data obtained on isotropic Nitrile Buthadiene Rubber (NBR) samples has confirmed the effectiveness of the experimental setup for this specific purpose. Numerical simulations of the bulge tests have been performed with the purpose of identifying a range of constitutive parameters which well describes the obtained range of DA on the BP membranes. The DA values have been partially validated with biaxial tests available in literature and with suitably performed uni-axial tensile tests.

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

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.

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

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.

Computational models for the simulation of the elastic and fracture properties of highly porous 3D-printed hydroxyapatite scaffolds.

Bone scaffolding is a promising approach for the treatment of critical-size bone defects. Hydroxyapatite can be used to produce highly porous scaffolds as it mimics the mineralized part of bone tissue, but its intrinsic brittleness limits its usage. Among 3D printing techniques, vat photopolymerization allows for the best printing resolution for ceramic materials. In this study, we implemented a Computed micro-Tomography based Finite Element Model of a hydroxyapatite porous scaffold fabricated by vat photopolymerization. We used the model in order to predict the elastic and fracture properties of the scaffold. From the stress-strain diagram of a simulated compression test, we computed the stiffness and the strength of the scaffolds. We found that three morphometric features substantially affect the crack pattern. In particular, the crack propagation is not only dependent on the trabecular thickness but also depends on the slenderness and orientation of the trabeculae with respect to the load. The results found in this study can be used for the design of ceramic scaffolds with heterogeneous pore distribution in order to tailor and predict the compressive strength.

Micro-CT imaging and finite element models reveal how sintering temperature affects the microstructure and strength of bioactive glass-derived scaffolds.

This study focuses on the finite element simulation and micromechanical characterization of bioactive glass-ceramic scaffolds using Computed micro Tomography ([Formula: see text]CT) imaging. The main purpose of this work is to quantify the effect of sintering temperature on the morphometry and mechanical performance of the scaffolds. In particular, the scaffolds were produced using a novel bioactive glass material (47.5B) through foam replication, applying six different sintering temperatures. Through [Formula: see text]CT imaging, detailed three-dimensional images of the scaffold's internal structure are obtained, enabling the extraction of important geometric features and how these features change with sintering temperature. A finite element model is then developed based on the [Formula: see text]CT images to simulate the fracture process under uniaxial compression loading. The model incorporates scaffold heterogeneity and material properties-also depending on sintering temperature-to capture the mechanical response, including crack initiation, propagation, and failure. Scaffolds sintered at temperatures equal to or higher than 700 [Formula: see text]C exhibit two-scale porosity, with micro and macro pores. Finite element analyses revealed that the dual porosity significantly affects fracture mechanisms, as micro-pores attract cracks and weaken strength. Interestingly, scaffolds sintered at high temperatures, the overall strength of which is higher due to greater intrinsic strength, showed lower normalized strength compared to low-temperature scaffolds. By using a combined strategy of finite element simulation and [Formula: see text]CT-based characterization, bioactive glass-ceramic scaffolds can be optimized for bone tissue engineering applications by learning more about their micromechanical characteristics and fracture response.

Mechanical characterization of miniaturized 3D-printed hydroxyapatite parts obtained through vat photopolymerization: an experimental study.

Hydroxyapatite is one of the materials of choice for tissue engineering bone scaffolds manufacturing. Vat photopolymerization (VPP) is a promising Additive Manufacturing (AM) technology capable of producing scaffolds with high resolution micro-architecture and complex shapes. However, mechanical reliability of ceramic scaffolds can be achieved if a high fidelity printing process is obtained and if knowledge of the intrinsic mechanical properties of the constituent material is available. As the hydroxyapatite (HAP) obtained from VPP is subjected to a sintering process, the mechanical properties of the material should be assessed with specific reference to the process parameters (e.g. sintering temperature) and to the specific characteristic size of the microscopic features in the scaffolds. In order to tackle this challenge the HAP solid matrix of the scaffold was mimicked in the form of miniaturized samples suitable for ad hoc mechanical characterization, which is an unprecedented approach. To this purpose small scale HAP samples, having a simple geometry and size similar to that of the scaffolds, were produced through VPP. The samples were subjected to geometric characterization and to mechanical laboratory tests. Confocal laser scanning and Computed micro-Tomography (micro-CT) were used for geometric characterization; while, micro-bending and nanoindentation were used for mechanical testing. Micro-CT analyses have shown a highly dense material with negligible intrinsic micro-porosity. The imaging process allowed quantifying the variation of geometry with respect to the nominal size showing high accuracy of the printing process and identifying printing defects on one specific sample type, depending on the printing direction. The mechanical tests have shown that the VPP produces HAP with an elastic modulus as high as approximately 100GPa and flexural strength of approximately 100MPa. The results of this study have shown that vat photopolymerization is a promising technology capable of producing high quality HAP with reliable geometric fidelity.

Mechanical Properties of Robocast Glass Scaffolds Assessed through Micro-CT-Based Finite Element Models.

In this study, the mechanical properties of two classes of robocast glass scaffolds are obtained through Computed micro-Tomography (micro-CT) based Finite Element Modeling (FEM) with the specific purpose to explicitly account for the geometrical defects introduced during manufacturing. Both classes demonstrate a fiber distribution along two perpendicular directions on parallel layers with a 90∘ tilting between two adjacent layers. The crack pattern identified upon compression loading is consistent with that found in experimental studies available in literature. The finite element models have demonstrated that the effect of imperfections on elastic and strength properties may be substantial, depending on the specific type of defect identified in the scaffolds. In particular, micro-porosity, fiber length interruption and fiber detaching were found as key factors. The micro-pores act as stress concentrators promoting fracture initiation and propagation, while fiber detachment reduces the scaffold properties substantially along the direction perpendicular to the fiber plane.

Silk Vascular Grafts with Optimized Mechanical Properties for the Repair and Regeneration of Small Caliber Blood Vessels.

As the incidence of cardiovascular diseases has been growing in recent years, the need for small-diameter vascular grafts is increasing. Considering the limited success of synthetic grafts, vascular tissue engineering/repair/regeneration aim to find novel solutions. Silk fibroin (SF) has been widely investigated for the development of vascular grafts, due to its good biocompatibility, tailorable biodegradability, excellent mechanical properties, and minimal inflammatory reactions. In this study, a new generation of three-layered SF vascular scaffolds has been produced and optimized. Four designs of the SILKGraft vascular prosthesis have been developed with the aim of improving kink resistance and mechanical strength, without compromising the compliance with native vessels and the proven biocompatibility. A more compact arrangement of the textile layer allowed for the increase in the mechanical properties along the longitudinal and circumferential directions and the improvement of the compliance value, which approached that reported for the saphenous and umbilical veins. The higher braid density slightly affected the grafts' morphology, increasing surface roughness, but the novel design mimicked the corrugation approach used for synthetic grafts, causing significant improvements in kink resistance.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Dilatational and shear waves in poro-vioscoelastic media.

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.

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

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.

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

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.

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

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.

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

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.