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M S Sacks

Publications and source records attributed to M S Sacks.

At least 37 records · Page 2Linked to original sources

Local mechanical anisotropy in human cranial dura mater allografts.

Human cranial dura mater (CDM) allograft's success as a repair biomaterial is partly due to its high mechanical strength, which facilitates its ability to form water-tight barriers and resist high in-vivo mechanical loads. Previous studies on CDM allograft mechanical behavior used large test specimens and concluded that the allograft was mechanically isotropic. However, we have quantified CDM microstructure using small angle light scattering (SALS) and found regions of well-aligned fibers displaying structural symmetry between the right and left halves (Jimenez et al., 1998). The high degree of fiber alignment in these regions suggests that they are mechanically anisotropic. However, identification of these regions using SALS requires irreversible tissue dehydration, which may affect mechanical properties. Instead, we utilized CDM structural symmetry to estimate the fiber architecture of one half of the CDM using computer graphics to flip the SALS fiber architecture map of the corresponding half about the plane of symmetry. Test specimens (20 mm x 4 mm) were selected parallel and perpendicular to the preferred fiber directions and subjected to uniaxial mechanical failure testing. CDM allografts were found to be locally anisotropic, having an ultimate tensile strength (UTS) parallel to the fibers of 12.76 +/- 1.65 MPa, and perpendicular to the fibers of 5.21 +/- 1.01 MPa (mean +/- sem). These results indicate that uniaxial mechanical tests on large samples used in previous studies tended to mask the local anisotropic nature of the smaller constituent sections. The testing methods established in this study can be used in the evaluation of new CDM processing methods and post-implant allograft mechanical integrity.

Aged↗

A method to quantify the fiber kinematics of planar tissues under biaxial stretch.

We have developed a method for measuring fiber kinematics in two-dimensional soft collagenous tissues. The technique combines small-angle light scattering (SALS) and biaxial stretch controlled by simultaneous optical strain measurement. Preliminary findings on porcine aortic valve leaflets and bovine pericardium indicate that fiber kinematics are highly tissue specific and are generally non-affine. The mobility of the fibers within each tissue seems to be specialized to perform a distinct physiological function. Quantitative knowledge of a tissue's angular fiber distribution and its transformation during biaxial stretch is critical for microstructural modeling of planar tissues. Our results underscore the importance of measuring fiber kinematics for each specific tissue type that is to be modeled.

Animals↗

Collagen fiber architecture of a cultured dermal tissue.

Advances in tissue engineering have led to the development of artificially grown dermal tissues for use in burn and ulcer treatments. An example of such an engineered tissue is Dermagraft, which is grown using human neonatal fibroblasts on rectangular sheets of biodegradable mesh. Using small angle light scattering (SALS), we quantified the collagen fiber architecture of Dermagraft with the mesh scaffold contributions removed through the use of a structurally based optical model. Dermagraft collagen fibers were found to have a preferred direction nearly parallel to the long dimension of the kite-shaped mesh opening with small spatial variations over the mesh. This study demonstrated the utility of SALS as a rapid and inexpensive technique for the evaluation of gross collagen fiber architecture in engineered tissues.

Cells, Cultured↗

High-resolution magnetic resonance imaging to characterize the geometry of fatigued porcine bioprosthetic heart valves.

BACKGROUND AND AIMS OF THE STUDY: Porcine bioprosthetic heart valves (PBHV) continue to suffer from limited long-term durability. Failure of PBHV occurs mainly in the cusps and is characterized by mechanical damage, usually in conjunction with calcification. Mechanisms underlying calcification have received considerable attention, yet mechanical damage phenomena remain poorly understood. The structural response of PBHV cusps to in-vivo cyclic loading involves three primary factors: (i) mechanical properties; (ii) fiber architecture; and (iii) 3D geometry. Previous finite element studies have shown cuspal stress distribution to be highly sensitive to subtle changes in geometry, yet to date, cusp geometry has been largely ignored in studies of PBHV durability. METHODS: A non-destructive method was developed to quantify PBHV 3D geometry using high-resolution magnetic resonance (MR) imaging. Images were obtained in three orthogonal planes from virgin and accelerated tested (50 x 10(6) and 200 x 10(6) cycles) PBHVs to fully capture 3D cuspal geometry. Surface curvatures were computed using a local biquadric surface patch approach. RESULTS: Results indicated a tendency for cusps to permanently deform with accelerated testing, manifesting primarily as sagging of the cusp. This sagging induced areas of high curvature from the central belly region upwards to the nodulus of Aranti, corresponding to known locations of tissue failure. CONCLUSIONS: It is likely that the observed changes in cuspal geometry induce deleterious alterations in the stress distribution, independent of those related to mechanical properties and fiber structure, and contribute to valve failure. Our results suggest that PBHV designers should attempt to compensate for the deleterious geometric changes that occur post-implantation.

Animals↗

Matrix macromolecules that affect the viscoelasticity of calfskin.

The chemical basis of viscoelasticity of bovine skin was explored by mechanical relaxation spectroscopy after selective enzymatic degradation. Measurements covered a wide range of time scales because water was replaced in the tissue with aqueous mixtures of ethylene glycol, which maintained a water-like electrical environment for the charged macromolecules down to -50 degrees C. Macromolecular components that couple the fibrils to the interfibrillar matrix contribute about half the values of the resultant storage and loss moduli, while removal of components that are readily extractable, so perhaps free in the matrix, did not alter these mechanical quantities or their relaxations. The precision of the method reveals the effects of fibril-attached matrix, when conventional methods of mechanical testing fail.

Animals↗

A constitutive relation for passive right-ventricular free wall myocardium.

We applied the pseudostrain energy function of Humphrey et al. [J. biomech. Engng 112, 333-346 (1990a, b)] to characterize the passive biaxial mechanical properties of the right ventricle free wall myocardium [Sacks and Chuong, J. biomech. Engng 115, 202-205 (1993)]. The myocardium was assumed to be incompressible, pseudoelastic, and transversely isotropic, with transmural variations in fiber orientation within test specimens accounted for by the strain energy function. Using nonlinear regression, material constants were determined for the right ventricle free wall myocardium from the sinus and conus regions. The pseudostrain energy function was found to model the biaxial mechanical data well (r2 > 0.99). Transmural variations in Cauchy stresses, as well as the magnitude of the in-plane shear stress, were found to be small. Although comparisons with the left ventricle midwall myocardium data [Humphrey et al., J. biomech. Engng 112, 340-346 (1990b)] show clear quantitative differences, there is an overall qualitative similarity in the mechanical behavior of ventricular myocardium.

Animals↗

Biaxial mechanical properties of passive right ventricular free wall myocardium.

The biaxial mechanical properties of right ventricular free wall (RVFW) myocardium were studied. Tissue specimens were obtained from the sub-epicardium of potassium-arrested hearts and different stretch protocols were used to characterize the myocardium's mechanical response. To assess regional differences, we excised tissue specimens from the conus and sinus regions. The RVFW myocardium was found to be consistently anisotropic, with a greater stiffness along the preferred (or averaged) fiber direction. The anisotropy in the conus region was more pronounced than in the sinus region. A comparison with studies of left ventricle (LV) midwall myocardium revealed that, 1) the fiber direction stiffnesses are greater in the RVFW than in the LV, 2) the degree of anisotropy is greater in the RVFW than in the LV.

Animals↗

Characterization of collagen fiber architecture in the canine diaphragmatic central tendon.

The diaphragmatic central tendon (DCT), a collagenous soft tissue membrane, acts as a mechanical buffer between the costal and crural muscles. Its direction of mechanical anisotropy has been shown to correspond to the collagen fiber preferred directions. These preferred directions were determined by gross histological examination, and were thus qualitative. In this work we quantified the collagen fiber architecture throughout the DCT using small angle light scattering (SALS). Helium-Neon laser light was passed through tendon specimens and the resultant scattered light distribution, which characterized the local collagen fiber architecture, was recorded with a linear array of five photodiodes. Throughout the DCT two distinct collagen fiber populations were consistently found. For each population three parameters were determined: 1) the preferred directions of collagen fibers, 2) the volume fraction (Vf) of fibers, 3) OI, an orientation index, which ranges from 0 percent for a random network to 100 percent for a perfectly oriented network. Vector maps were used to display results from 1) and 2), and showed a primary group (G1) going from the crural to costal muscles and a secondary one (G2) running perpendicular to G1. Comparisons of Vf between G1 and G2 showed that G1 contained about three times as many fibers as G2, a ratio similar to that found for the degree of mechanical anisotropy. OI were found to be about 60 percent, indicating a high degree of orientation, with no significant regional or population differences (p less than 0.05). These quantitative results suggest that throughout the DCT the degree of mechanical anisotropy is controlled exclusively by Vf.

Animals↗

On the anisotropy of the canine diaphragmatic central tendon.

We studied the mechanical and anatomical anisotropy of the canine diaphragmatic central tendon (CT). Dumb-bell-shaped strips with effective dimensions of 10 x 2 mm (length x width) were cut from different regions of the canine diaphragmatic CT in two different orientations relative to the direction of neighboring muscle fibers. Specimens sampled with their long axial dimension oriented parallel to the neighboring muscle fibers were named Group-1 and those sampled with an orientation perpendicular to the neighboring muscle fibers were named Group-2. Results from one-dimensional stress-strain and tensile failure strength tests revealed that the CT is a nonlinear, inelastic, and anisotropic material. Group-1 specimens were found to have a higher stiffness, higher failure strength and higher strain energy density at failure than Group-2 specimens. Polarized microscopy showed that multiple sheets of collagen fiber bundles formed an orthogonal network in the tendon. Collagen fiber bundles along Group-1 direction formed parallel trajectory lines connecting the neighboring costal and crural muscles; bundles along Group-2 direction were observed to orient 90 degrees away. At the central apex region of the CT, collagen bundles of Group-1 formed a fan-like trajectory pattern. This collagen network architecture was compared favorably to the trajectories of an approximated principal stress field in the CT due to simulated contractile forces from its adjacent costal and crural muscles. These combined results suggest a structure-function relationship for the anatomical and mechanical anisotropy in the canine diaphragmatic CT.

Animals↗

Regional deformation and contractile function in canine right ventricular free wall.

We used biplane cinefluorgraphy to study the regional deformation and local contractile function of the canine right ventricular free wall (RVFW) among the inflow, midventricular, and outflow regions. For a region delimited by three neighboring markers, under the assumption of homogeneous deformation, we identified the magnitudes and directions of principal shortening or elongation and changes in area every 16.7 ms. Furthermore, we extended this approach to study the alterations of these parameters during RV afterload increase by applying pulmonary artery (PA) occlusion. Results show that, at both control and PA occlusion states, the outflow region was subjected to maximal fractional area reduction (AR) and maximal time rate of fractional area reduction (ARR) during systole, with no differences between inflow and midventricular regions (P less than 0.05). At the control state, the percent AR and the corresponding value for ARR were 27% and 179%/s at the outflow, 19% and 112%/s at the midventricular, and 15% and 107%/s at the inflow region, respectively. During PA occlusion, they became 21% and 115%/s at the outflow, 14% and 97%/s at the midventricular, and 15% and 102%/s at the inflow region, respectively. Statistically, only the outflow region deformation was affected by PA occlusion (P less than 0.05). For the control state, we also compared the direction of regional principal shortening at end systole to the local transmural myocardial fiber orientations. The directions were found to correspond closely to the mean of all local transmural fiber orientations. This suggests that the regional RVFW deformation we measured is the combined deformation behavior from all the local participating myofibers.

Animals↗

Quantification of vertical-fiber defect in cattle hide by small-angle light scattering.

Vertical-fiber defect (VFD), an abnormal arrangement of collagen fibers in hides of certain cattle breeds, is still not fully understood. Prior work has been limited to subjective histological examinations from hide biopsies. A device using small angle light scattering (SALS) was used to quantify the collagen fiber orientation of sections taken from hide biopsies. Sections were chosen from the Hereford cattle breed and classified by conventional observation as belonging to either the normal, intermediate, or vertical phenotypes. The vertical fibers occur only in the upper reticular dermis, with the fibers in the lower reticular dermis lying parallel to the plane of the hide in all phenotypes. By SALS the vertical phenotype was found to be significantly different from the normal phenotype, whilst the intermediate phenotype was found to be structurally indistinguishable from the vertical one. No evidence was found for the existence of other phenotypes.

Animals↗

In vivo 3-D reconstruction and geometric characterization of the right ventricular free wall.

A prerequisite to biomedical analyses of the right ventricular free wall (RVFW) is the characterization of its in vivo geometry and instantaneous wall thickness (WT). We present a method to reconstruct and mathematically model the in vivo RVFW surface geometry using ECG-gated magnetic resonance imaging (MRI). From digitized contours we reconstructed the endo- and epicardial surfaces of the entire heart, and approximated the RVFW surface geometry by local biquadric surface patches. An insurface coordinate system was developed, with respect to which the metric tensor, curvature tensor, major (k2), and minor (k1) principal curvatures were computed. The method was evaluated using MRI data from one dog, which showed that k2 was about 10 times k1, with k2 and k1 approximately perpendicular and parallel to the RV long axis, respectively. During systole, k1 and both principal curvature directions remained essentially unchanged, while k2 revealed only a 7% decrease (rho < 0.05) in the sinus region. These results suggest that while the RVFW undergoes small changes in surface geometry during systole, its overall curvature remained constant. The WT/mean radius of curvature ratio was less than 0.1 during systole throughout the RVFW, indicating it can be idealized as a thin shell.

Animals↗

A small angle light scattering device for planar connective tissue microstructural analysis.

The planar fibrous connective tissues of the body are composed of a dense extracellular network of collagen and elastin fibers embedded in a ground matrix, and thus can be thought of as biocomposites. Thus, the quantification of fiber architecture is an important step in developing an understanding of the mechanics of planar tissues in health and disease. We have used small angle light scattering (SALS) to map the gross fiber orientation of several soft membrane connective tissues. However, the device and analysis methods used in these studies required extensive manual intervention and were unsuitable for large-scale fiber architectural mapping studies. We have developed an improved SALS device that allows for rapid data acquisition, automated high spatial resolution specimen positioning, and new analysis methods suitable for large-scale mapping studies. Extensive validation experiments revealed that the SALS device can accurately measure fiber orientation for up to a tissue thickness of at least 500 microns to an angular resolution of approximately 1 degree and a spatial resolution of +/-254 microns. To demonstrate the new device's capabilities, structural measurements from porcine aortic valve leaflets are presented. Results indicate that the new SALS device provides an accurate method for rapid quantification of the gross fiber structure of planar connective tissues.

Animals↗

Collagen fiber orientation as quantified by small angle light scattering in wounds treated with transforming growth factor-beta2 and its neutalizing antibody.

The purpose of this study was determine quantitative differences in collagen fiber orientation in a wound healing model in the presence of transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 antibody. Full-thickness wounds were made in the paravertebral area of two young pigs. Wounds were treated once, topically, with either transforming growth factor-beta2 or anti-transforming growth factor-beta2 antibody, or with methylcellulose gel. Control wounds were left untreated. Tissue biopsies were obtained from each wound on days 7, 14 and 46 post wounding. Tissue sections were stained with hematoxylin and eosin, and collagen fiber preferred orientation was quantified using small angle light scattering. Our results indicated that wounds treated with transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 antibody had a significantly higher degree of orientation of collagen fibers than normal unwounded skin on days 7, 14 and 46 (p < 0.001). Transforming growth factor-beta2- treated wounds had a higher degree of orientation of collagen fibers than control wounds on days 7 and 14 (p < 0.001), and control wounds displayed a higher degree of orientation than wounds treated with anti-transforming growth factor-beta2,3 and normal unwounded skin at all time points (p < 0.001). These results suggest that differences in the dermal collagen degree of orientation correlate with scarring, and show that small angle light scattering can be used quantitatively to assess differences in the collagen fiber architecture of dermal wounds.

Administration, Topical↗

Collagen fiber architecture of bovine pericardium.

Small-angle light scattering (SALS) was used to quantify the collagen fiber architecture of 12 bovine pericardium (BP) specimens overlying the right and left anterior surfaces of the heart. The collagen fiber architecture was described in terms of preferred collagen fiber directions, volume fractions (Vf), and degree of orientation. To explore the relationship between BP collagen architecture and mechanical anisotropy, biaxial mechanical tests were performed on two specimens chosen for their extremes of collagen fiber architecture. About 38% of the SALS test locations showed the occurrence of two distinct collagen fiber populations, with the primary population Vf typically 90%. Structurally, the left anterior specimens appeared to be the most homogeneous, with an overall preferred direction close to the circumferential direction of the heart. The right side specimens were inconsistent, with a broad range of fiber orientations. The direction of greatest stiffness was consistent with the underlying collagen fiber architecture. Overall, these results suggest that 1) the mechanical behavior of BP is quantitatively consistent with its collagen fiber architecture; 2) the variability of BP mechanical anisotropy is caused by variations in collagen fiber preferred directions; and 3) the left anterior side of the bovine pericardial sac might be a good material selection site for bioprosthesis fabrication.

Animals↗

Effects of mechanical fatigue on the bending properties of the porcine bioprosthetic heart valve.

The mechanisms underlying the failure of porcine bioprosthetic aortic heart valves are not well understood. One possible explanation is that delaminations of the layered leaflet structure occur through flexion, leading to calcification and further delaminations, and finally resulting in valve failure. We investigated the changes in flexural rigidity of the belly of aortic valve cusps subjected to accelerated durability testing. We used three-point bending wherein a load was applied to the center of each specimen by a thin stainless steel bar calibrated to a known load-displacement relationship. Ten circumferential and 15 radial specimens from valves fatigued to 0, 50, 100, and 200 million cycles were flexed both with and against the curvature of the cusp. Linear beam theory was applied as a means to compare the relative bending stiffness between groups. Although specimens aligned to the circumferential direction were stiffer when bent against the cuspal curvature, the radial oriented specimens exhibited no bending directional dependence. Both the radial and circumferential specimens experienced a significant decrease in the bending stiffness with an increased number of accelerated test cycles. Overall, our results suggest that it is the fibrosa that experiences the greatest loss of stiffness with mechanically induced fatigue damage.

Animals↗

Orthotropic mechanical properties of chemically treated bovine pericardium.

To facilitate bioprosthetic heart valve design, especially in the use of novel antimineralization chemical technologies, a thorough understanding of the multiaxial mechanical properties of chemically treated bovine pericardium (BP) is needed. In this study, we utilized a small angle light scattering based tissue pre-sorting procedure to select BP specimens with a high degree of structural uniformity. Both conventional glutaraldehyde (GL) and photo-oxidation (PO) chemical treatment groups were studied, with untreated tissue used as the control group. A second set of GL and PO groups was prepared by prestretching them along the preferred fiber direction during the chemical treatment. An extensive biaxial test protocol was used and the resulting stress-strain data fitted to an exponential strain energy function. The high structural uniformity resulted in both a consistent mechanical response and low variability in the material constants. For free fixed tissues, the strain energy per unit volume for GL treated BP was approximately 2.8 times that of PO treated BP at an equibiaxial Green's strain level of 0.16. Pre-stretched tissues exhibited a profound increase in both stiffness and the degree of anisotropy, with the GL treatment demonstrating a greater effect. Thus, structural control leads to an improved understanding of chemically treated BP mechanical properties. Judicious use of this knowledge can facilitate the design and enhanced long-term performance of bioprosthetic heart valves.

Animals↗

Surface strains in the anterior leaflet of the functioning mitral valve.

Abstract-The mitral valve (MV) is a complex anatomical structure whose function involves a delicate force balance and synchronized function of each of its components. Elucidation of the role of each component and their interactions is critical to improving our understanding of MV function, and to form the basis for rational surgical repair. In the present study, we present the first known detailed study of the surface strains in the anterior leaflet in the functioning MV. The three-dimensional spatial positions of markers placed in the central region of the MV anterior leaflet in a left ventricle-simulating flow loop over the cardiac cycle were determined. The resulting two-dimensional in-surface strain tensor was computed from the marker positions using a C0 Lagrangian quadratic finite element. Results demonstrated that during valve closure the anterior leaflet experienced large, anisotropic strains with peak stretch rates of 500%-1,000%/s. This rapid stretching was followed by a plateau phase characterized by relatively constant strain state. We hypothesized that the presence of this plateau phase was a result of full straightening of the leaflet collagen fibers upon valve closure. This hypothesis suggests that the MV collagen fibers are designed to allow leaflet coaptation followed by a dramatic increase in stiffness to prevent further leaflet deformation, which would lead to valvular regurgitation. These studies represent a first step in improving our understanding of normal MV function and to help establish the principles for repair and replacement.

Animals↗