J Jan Neggers

Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling

UNLABELLED In order to create tissue-engineered heart valves with long-term functionality, it is essential to fully understand collagen remodeling during neo-tissue formation. Collagen remodeling is thought to maintain mechanical tissue homeostasis. Yet, the driving factor of collagen remodeling remains unidentified. In this study, we determined the collagen architecture and the geometric and mechanical properties of human native semilunar heart valves of fetal to adult age using confocal microscopy, micro-indentation and inverse finite element analysis. The outcomes were used to predict age-dependent changes in stress and stretch in the heart valves via finite element modeling. The results indicated that the circumferential stresses are different between the aortic and pulmonary valve, and, moreover, that the stress increases considerably over time in the aortic valve. Strikingly, relatively small differences were found in stretch with time and between the aortic and pulmonary valve, particularly in the circumferential direction, which is the main determinant of the collagen fiber stretch. Therefore, we suggest that collagen remodeling in the human heart valve maintains a stretch-driven homeostasis. Next to these novel insights, the unique human data set created in this study provides valuable input for the development of numerical models of collagen remodeling and optimization of tissue engineering. STATEMENT OF SIGNIFICANCE Annually, over 280,000 heart valve replacements are performed worldwide. Tissue engineering has the potential to provide valvular disease patients with living valve substitutes that can last a lifetime. Valve functionality is mainly determined by the collagen architecture. Hence, understanding collagen remodeling is crucial for creating tissue-engineered valves with long-term functionality. In this study, we determined the structural and material properties of human native heart valves of fetal to adult age to gain insight into the mechanical stimuli responsible for collagen remodeling. The age-dependent evolutionary changes in mechanical state of the native valve suggest that collagen remodeling in heart valves is a stretch-driven process.

Indentation response of human patella with elastic modulus correlation to localized fractal dimension and bone mineral density.

The goal of this study was to determine material properties for the anterior cortex and subcortical regions of human patellae and relate those properties to mineral density and fractal dimension of the bone. Ten human patellae were obtained from eight fresh frozen human cadavers and subjected to anteriorly-directed spherical indentation-relaxation experiments using two different sized indenters to two different indentation depths. Response data were fit to a three-mode viscoelastic model obtained through elastic-viscoelastic correspondence of the Hertzian contact relation for spherical indentation. A location-specific effective bone density measurement that more heavily weighted bone material close to the indentation site (by von Mises stress distribution) was determined from micro-computed tomography (38µm resolution) data captured for each specimen. The same imagery data were used to compute location specific fractal dimension estimates for each indentation site. Individual and averaged patella material models verified the hypothesis that when the larger indenter and greater indentation depth is used to engage the surface and deeper (trabecular) bone, the bone exhibits a more compliant response than when only the surface (cortical) bone was engaged (instantaneous elastic modulus was 325MPa vs. 207MPa, p<0.05). Effective bone mineral density was shown to be a significant predictor of the elastic modulus for both small and large indentation types (p<0.05) despite relatively low correlations. Exponential regressions of fractal dimension on elastic modulus showed significant relationships with high correlation for both the small (R(2)=0.93) and large (R(2)=0.97) indentations.

Enhanced Global Digital Image Correlation for Accurate Measurement of Microbeam Bending

Microbeams are simple on-chip test structures used for thin film and MEMS materials characterization. Profilometry can be combined with Euler-Bernoulli (EB) beam theory to extract material parameters, like the E-modulus. Characterization of time-dependent microbeam bending is required, though non-trivial, as it involves long term sub-microscale measurements. Here we propose an enhanced global digital image correlation (GDIC) procedure to analyze time-dependent microbeam bending. Using GDIC we extract the full-field curvature profile from optical profilometry data of thin metal microbeam bending experiments, whilst simultaneously correcting for rigid body motion resulting from drift. This work focusses on the implementation of this GDIC procedure and evaluation of its accuracy through a numerical assessment of the proposed methodology.

Global Digital Image Correlation for Pressure Deflected Membranes

Bulge testing is known for its ability to quantify the mechanical behavior of homogeneous thin membranes. In this method the measured quantities are related to the averaged stress and strain using bulge equations that only exist for a very limited set of membrane geometries. A novel 3D Digital Image Correlation (DIC) method is proposed to directly measure the strain and curvature fields without using any closed form approximation of the deformation kinematics. Importantly, for membranes under pressure, the stress is directly related to the curvature.

Interface Integrity in Stretchable Electronics

Stretchable electronic devices enable numerous futuristic applications. Typically, these devices consist of a (metal) interconnect system embedded in a stretchable (rubber) matrix. This invokes an apparent stretchability conflict between the interconnect system and the matrix. This conflict is addressed by shaping the interconnects in mechanistic patterns that bend and twist to facilitate global stretchability. Metal-rubber type stretchable electronic systems exhibit catastrophic interface delamination, which is investigated in this research. The fibrillation process occurring at the delamination front of the metal-rubber interface is investigated through in-situ SEM imaging of the progressing delamination front of peel tests of rubber on copper samples. Results show that the interface strength is dependent on the delamination rate and the interface roughness. Additionally, the fibril geometry seems highly dependent on the interface roughness, while being remarkably independent on the delamination- rate.

Advances in Delamination Modeling of Metal/Polymer Systems: Continuum Aspects

Adhesion and delamination have been pervasive problems hampering the performance and reliability of micro- and nano-electronic devices. In order to understand, predict, and ultimately prevent interface failure in electronic devices, development of accurate, robust, and efficient delamination testing and prediction methods is crucial. Adhesion is essentially a multi-scale phenomenon: at the smallest scale possible, it is defined by the thermodynamic work of adhesion. At larger scales, additional dissipative mechanisms may be active which results in enhanced adhesion at the macroscopic scale and are the main cause for the mode angle dependency of the interface toughness. Undoubtedly, the macroscopic adhesion properties are a complex function of all dissipation mechanisms across the scales. Thorough understanding of the significance of each of these dissipative mechanisms is of utmost importance in order to establish physically correct, unambiguous values of the adhesion properties, which can only be achieved by proper multi-scale techniques.

A Generic, Time-Resolved, Integrated Digital Image Correlation, Identification Approach

A generic one-step Integrated Digital Image Correlation (I-DIC) inverse parameter identification approach is introduced that enables direct identification of constitutive model parameters by intimately integrating a Finite Elements Method (FEM) with Digital Image Correlation (DIC), directly connecting the complete time sequence of experimental images to the sought model parameters. The problem is cast into a transparent single-minimization formulation with explicit expression of the unknowns, being the material properties and, optionally, experimental uncertainties such as misalignments. The tight integration between FEM and DIC creates an information dialogue that yields accurate material parameters while providing necessary regularization to the DIC problem, making the method robust and noise insensitive. Through this method the versatility of the FEM method is translated to the experimental realm, simplifying the existing experiments and creating new experimental possibilities.

Full-Field Bulge Testing Using Global Digital Image Correlation

The miniature bulge test is an acknowledged method for characterizing freestanding thin films. Nevertheless, some discrepancies in the quantitative results from such tests can be found in literature, explained in part by erroneous assumptions in the analytical description used to compute the global stress and strain from the membrane pressure and deflection. In this research, a new method is presented which renders the analytical description obsolete. A specialized Global Digital Image Correlation technique on high resolution, confocal microscopy, surface height maps of bulged membranes, has been developed. This method is able to capture full-field continuous deformation maps, from which local strain maps are computed. Additionally, local stress maps are derived from full-field curvature maps and the applied pressure. The local stress-strain maps allow the method to be used on inhomogeneous, anisotropic membranes as well as on exotic membrane shapes.