Edoardo Mazza

Modeling and Simulation of Dielectric Elastomer Actuators

Dielectric elastomers are used as base material for so-called electroactive polymer (EAP) actuators. A procedure and a specific constitutive model (for the acrylic elastomer VHB 4910) are presented in this work for finite element modeling and simulation of dielectric elastomer actuators of general shape and set-up. The Yeoh strain energy potential and the Prony series are used for describing the large strain time-dependent mechanical response of the dielectric elastomer. Material parameters were determined from uniaxial experiments (relaxation tests and tensile tests). Thereby the inverse problem was solved using iterative finite element calculations. A pre-strained circular actuator was built and activated with a predefined voltage. A three-dimensional finite element model of the circular actuator was created and the electromechanical activation process simulated. Simulation and actual measurements agree to a great extent, thus leading to a validation of both the constitutive model and the actuator simulation procedure proposed in this work.

Dynamic measurement of soft tissue viscoelastic properties with a torsional resonator device

A new method for measuring the mechanical properties of soft biological tissues is presented. Dynamic testing is performed using a torsional resonator, whose free extremity is in contact with a tissue sample. An analytical model of a semi-infinite, homogenous, isotropic medium is used to model the shear wave propagation in the material sample and allows determining the complex shear modulus of the soft tissue. By controlling the vibration amplitude, shear strains of less than 0.2% are induced in the tissue so that the material response can be considered as linear viscoelastic. Experiments are performed at different eigenfrequencies of the torsional oscillator and the complex shear modulus is characterized in the range 1-10 kHz. In vitro experiments on bovine and porcine liver are presented in order to demonstrate the sensitivity of the proposed technique, and the reliability of the measurements is confirmed with comparative tests on synthetic material. The experiment does not damage the soft tissue and allows a fast and local measurement, these being prerequisites for future applications in vivo during open surgery.

Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation

Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials.

The mechanical role of the cervix in pregnancy

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy.

Determination of the Mechanical Properties of Soft Human Tissues through Aspiration Experiments

Mechanical models for soft human organs are necessary for a variety of medical applications, such as surgical planning, virtual reality surgery simulators, and for diagnostic purposes. An adequate quantitative description of the mechanical behaviour of human organs requires high quality experimental data to be acquired and analyzed. We present a novel technique for the acquisition of such data from soft tissues and its post processing to determine some parameters of the tissue’s mechanical properties. A small tube is applied to the target organ and a weak vacuum is generated inside the tube according to a predefined pressure history. A video camera grabs images of the deformation profile of the aspirated tissue, and a pressure sensor measures the correspondent vacuum level. The images are processed and used to inform the fitting of uniaxial and continuum mechanics models. Whilst the aspiration test device has been designed to fulfill the requirements for in-vivo applications, for measurements obtained during open surgery, initial experiments performed on human cadaveric tissues demonstrate the ability to both differentiate between different organs and also between normal and diseased organs on the basis of the derived mechanical properties.

Mussel-mimetic tissue adhesive for fetal membrane repair: a standardized ex vivo evaluation using elastomeric membranes

Iatrogenic preterm premature rupture of membranes (iPPROM), the main complication of invasive interventions in the prenatal period, seriously limits the benefit of diagnostic or surgical prenatal procedures. This study aimed to evaluate preventive plugging of punctured fetal membranes in an ex vivo situation using a new mussel‐mimetic tissue adhesive (mussel glue) to inhibit leakage.

Mechanical characterization of the liver capsule and parenchyma

Internal organs are heterogeneous structures, both on the macro- and on the micro-scale. However, they are often modeled as homogeneous solids with uniform material properties. In this light, this work investigates the impact of the liver capsule on the integral behavior of the organ by means of in vitro tests and computer simulations. The stiffness of bovine liver obtained in tissue aspiration experiments differed by a factor of 2 to 3 when the capsule was removed. As a first step, the capsule was implemented as separate structure in a finite element model of the organ undergoing tissue aspiration. The finite element simulations are in good agreement with the experimental results

Relation between mechanical properties and microstructure of human fetal membranes: An attempt towards a quantitative analysis

OBJECTIVE We sought to measure the mechanical baseline behavior of fetal membranes in order to determine constitutive mechanical model parameters for fetal membranes, and to examine their relation to molecular correlates for mechanical function, i.e. collagen and elastin. STUDY DESIGN The uniaxial stress-strain response of nine human term fetal membranes was measured. Methods of nonlinear continuum mechanics were applied for the analysis of the stress-strain curves. Thickness of amnion and chorion were determined from histologic sections for each fetal membrane sample. Complementary biochemical analysis was performed to quantify the soluble collagen and soluble elastin components for each sample. RESULTS We report a straightforward histologic modality for measurements of amnion and chorion thickness. Average thickness of the amnion and chorion layers were 111+/-78 microm, and 431+/-113 microm, respectively, which are about twice larger than previously reported. The average content of acid-soluble elastin was 2.1% of wet weight and the one of pepsin/acetic acid-soluble collagen was 10.5% of dry weight. Our data show an inverse proportionality between soluble elastin and soluble collagen content. The low strain elastic modulus ranged between 10 and 25 kPa. Correlations were found between biochemical data and mechanical parameters: there is clearly a direct proportionality between small strain elastic modulus and elastin content. Further, a (less pronounced) direct correlation was observed also between soluble collagen content and the parameter governing the increase in stiffness at larger strains in the nonlinear mechanical model. The mechanical tests revealed a relatively low variability for samples from the same membrane but a large variation between donors. The proposed nonlinear model provides a good fit of the experimental data, with a coefficient of determination, R(2), typically in the range of 0.94. Membranes failure originated at the clamping points thus impairing the quantification of ultimate stress and strain. Thus, no correlation was found between maximum stress and collagen or elastin content. CONCLUSIONS This study provides a starting point for comprehensive quantitative analysis of the relationship between fetal membranes microstructure and their nonlinear deformation behavior. These insights could become useful in identifying potential medical interventions to prevent membranes rupture.

Assessment of the in vivo biomechanical properties of the human uterine cervix in pregnancy using the aspiration test A feasibility study

OBJECTIVE To date no diagnostic tool is yet available to objectively assess the in vivo biomechanical properties of the uterine cervix during gestation. METHODS We show the first clinical application of an aspiration device to assess the in vivo biomechanical properties of the cervix in pregnancy with the aim to describe the physiological biomechanical changes throughout gestation in order to eventually detect pregnant women at risk for cervical insufficiency (CI). RESULTS Out of 15 aspiration measurements, 12 produced valid results. The stiffness values were in the range between 0.013 and 0.068 bar/mm. The results showed a good reproducibility of the aspiration test. In our previous test series on non-pregnant cervices our repetitive measurements showed a standard deviation of >20% compared to <+/-10% to our data on pregnant cervices. Stiffness values are decreasing with gestational age which indicates a progressive softening of cervical tissue towards the end of pregnancy. Three pregnant women had two subsequent measurements within a time interval of four weeks. Decreasing stiffness values in the range of 20% were recorded. DISCUSSION This preliminary study on the clinical practicability of aspiration tests showed promising results in terms of reproducibility (reliability) and clinical use (feasibility). Ongoing studies will provide further insights on its usefulness in clinical practice and in the detection of substantial changes of the cervix in pregnancy indicative for threatened preterm birth or cervical insufficiency.

Mussel-mimetic tissue adhesive for fetal membrane repair: an ex vivo evaluation.

Iatrogenic preterm prelabor rupture of membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. Here, the proteolytic stability of mussel-mimetic tissue adhesive (mussel glue) and its sealing behavior on punctured fetal membranes are evaluated. The proteolytic degradation of mussel glue and fibrin glue were compared in vitro. Critical pressures of punctured and sealed fetal membranes were determined under close to physiological conditions using a custom-made inflation device. An inverse finite element procedure was applied to estimate mechanical parameters of mussel glue. Mussel glue was insensitive whereas fibrin glue was sensitive towards proteolytic degradation. Mussel glue sealed 3.7mm fetal membrane defect up to 60mbar (45mmHg) when applied under wet conditions, whereas fibrin glue needed dry membrane surfaces for reliable sealing. The mussel glue can be represented by a neo-Hookean material model with elastic coefficient C(1)=9.63kPa. Ex-vivo-tested mussel glue sealed fetal membranes and resisted pressures achieved during uterine contractions. Together with good stability in proteolytic environments, this makes mussel glue a promising sealing material for future applications.