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Biomedical subjects

M S Sacks

Publications and source records attributed to M S Sacks.

At least 19 recordsLinked to original sources

Mechanical evaluation and design of a multilayered collagenous repair biomaterial.

One method of fabricating implantable biomaterials is to utilize biologically derived, chemically modified tissues to form constructs that are both biocompatible and remodelable. Rigorous mechanical characterization is a necessary component in material evaluation to ensure that the constructs will withstand in vivo loading. In this study we performed an in-depth biaxial mechanical and quantitative structural analysis of GraftPatch (GP), a biomaterial constructed by assembling chemically treated layers of porcine small intestinal submucosa (SIS). The mechanical behavior of GP was compared to both native SIS and to glutaraldehyde-treated bovine pericardium (GLBP) as a reference biomaterial. Under biaxial loading, GP was found to be stiffer than native SIS and mechanically anisotropic, with the preferred fiber direction demonstrating greater stiffness. Quantitative structural analysis using small-angle light scattering indicated a uniform fiber structure similar to GLBP and SIS. To enable test-protocol-independent quantitative comparisons, the biaxial mechanical data were fit to an orthotropic constitutive model, which indicated a similar degree of mechanical anisotropy between the three groups. We also demonstrate how the constitutive model can be used to design layered biocomposite materials that can undergo large deformations.

Animals↗

Bioprosthetic heart valve leaflet motion monitored by dual camera stereo photogrammetry.

Dual camera stereo photogrammetry (DCSP) was applied to investigate the leaflet motion of bioprosthetic heart valves (BHVs) in a physiologic pulse flow loop (PFL). A 25-mm bovine pericardial valve was installed in the aortic valve position of the PFL, which was operated at a pulse rate of 70 beats/min and a cardiac output of 5 l/min. The systolic/diastolic aortic pressure was maintained at 120/80 mmHg to mimic the physiologic load experienced by the aortic valve. The leaflet of the test valve was marked with 80 India ink dots to form a fan-shaped matrix. From the acquired image sequences, 3-D coordinates of the marker matrix were derived and hence the surface contour, local mean and Gaussian curvatures at each opening and closing phase during one cardiac cycle were reconstructed. It is generally believed that the long-term failure rate of BHV is related to the uneven distribution of mechanical stresses occurring in the leaflet material during opening and closing. Unfortunately, a quantitative analysis of the leaflet motion under physiological conditions has not been reported. The newly developed technique permits frame-by-frame mapping of the leaflet surface, which is essential for dynamic analysis of stress-strain behavior in BHV.

Algorithms↗

How much work is required to puncture dura with Tuohy needles?

The effects of needle bevel orientation and cerebrospinal fluid (CSF) pressure on dural displacement and force required to penetrate cadaveric dura were studied using 40 samples. A constant hydrostatic pressure was applied to the subdural surface, either high or low, simulating the sitting and lateral positions. A 17-gauge Tuohy needle was advanced through the dura with the bevel oriented parallel or perpendicular to dural fibres. Travel distance and peak force at which dural penetration occurred were measured under both pressure conditions. The work required to produce dural penetration was calculated. Greater force and work were required to penetrate dura in the perpendicular orientation (P < 0.05), regardless of the subdural pressure exerted. Dural displacement was similar under both pressure conditions.

Adult↗

Surface geometric analysis of anatomic structures using biquintic finite element interpolation.

The surface geometry of anatomic structures can have a direct impact upon their mechanical behavior in health and disease. Thus, mechanical analysis requires the accurate quantification of three-dimensional in vivo surface geometry. We present a fully generalized surface fitting method for surface geometric analysis that uses finite element based hermite biquintic polynomial interpolation functions. The method generates a contiguous surface of C2 continuity, allowing computation of the finite strain and curvature tensors over the entire surface with respect to a single in-surface coordinate system. The Sobolev norm, which restricts element length and curvature, was utilized to stabilize the interpolating polynomial at boundaries and in regions of sparse data. A major advantage of the current method is its ability to fully quantify surface deformation from an unstructured grid of data points using a single interpolation scheme. The method was validated by computing both the principal curvature distributions for phantoms of known curvatures and the principal stretch and principal change of curvature distributions for a synthetic spherical patch warping into an ellipsoidal shape. To demonstrate the applicability to biomedical problems, the method was applied to quantify surface curvatures of an abdominal aortic aneurysm and the principal strains and change of curvatures of a deforming bioprosthetic heart valve leaflet. The method proved accurate for the computation of surface curvatures, as well as for strains and curvature change for a surface undergoing large deformations.

Animals↗

Biaxial mechanical properties of the native and glutaraldehyde-treated aortic valve cusp: Part II--A structural constitutive model.

We have formulated the first constitutive model to describe the complete measured planar biaxial stress-strain relationship of the native and glutaraldehyde-treated aortic valve cusp using a structurally guided approach. When applied to native, zero-pressure fixed, and low-pressure fixed cusps, only three parameters were needed to simulate fully the highly anisotropic, and nonlinear in-plane biaxial mechanical behavior. Differences in the behavior of the native and zero- and low-pressure fixed cusps were found to be primarily due to changes in the effective fiber stress-strain behavior. Further, the model was able to account for the effects of small (< 10 deg) misalignments in the cuspal specimens with respect to the biaxial test axes that increased the accuracy of the model material parameters. Although based upon a simplified cuspal structure, the model underscored the role of the angular orientation of the fibers that completely accounted for extreme mechanical anisotropy and pronounced axial coupling. Knowledge of the mechanics of the aortic cusp derived from this model may aid in the understanding of fatigue damage in bioprosthetic heart valves and, potentially, lay the groundwork for the design of tissue-engineered scaffolds for replacement heart valves.

Animals↗

Biaxial mechanical properties of the natural and glutaraldehyde treated aortic valve cusp--Part I: Experimental results.

To date, there are no constitutive models for either the natural or bioprosthetic aortic valve (AV), in part due to experimental complications related to the AV's small size and heterogeneous fibrous structure. In this study, we developed specialized biaxial testing techniques for the AV cusp, including a method to determine the local structure-strain relationship to assess the effects of boundary tethering forces. Natural and glutaraldehyde (GL) treated cusps were subjected to an extensive biaxial testing protocol in which the ratios of the axial tensions were held at constant values. Results indicated that the local fiber architecture clearly dominated cuspal deformation, and that the tethering effects at the specimen boundaries were negligible. Due to unique aspects of cuspal fiber architecture, the most uniform region of deformation was found at the lower portion as opposed to the center of the cuspal specimen. In general, the circumferential strains were much smaller than the radial strains, indicating a profound degree of mechanical anisotropy, and that natural cusps were significantly more extensible than the GL treated cusps. Strong mechanical coupling between biaxial stretch axes produced negative circumferential strains under equibiaxial tension. Further, the large radial strains observed could not be explained by uncrimping of the collagen fibers, but may be due to large rotations of the highly aligned, circumferential-oriented collagen fibers in the fibrosa. In conclusion, this study provides new insights into the AV cusp's structure-function relationship in addition to requisite data for constitutive modeling.

Animals↗

Quantification of the fiber architecture and biaxial mechanical behavior of porcine intestinal submucosa.

Porcine small intestinal submucosa (SIS) has been shown to serve as a remodelable tissue scaffold in a wide range of applications. Despite the large number of experimental studies, there is a lack of fundamental information on SIS anisotropic mechanical behavior and how this behavior changes postimplantation. As a first step in our study of remodeling biomaterials, we performed biaxial mechanical testing to quantify the anisotropic mechanical behavior and used small-angle light scattering (SALS) to quantify the gross fiber structure of fresh, unimplanted SIS. Structural results indicate that SIS displays primarily a single, continuous preferred fiber direction oriented parallel to the long axis of the intestine. Occasionally, two distinct fiber populations oriented at approximately +/-28 degrees with respect to the longitudinal axis could be distinguished. Consistent with this structure, SIS exhibited a nonlinear, anisotropic mechanical response with higher stresses along the longitudinal axis. Further, the circumferential stress-strain response was strongly affected by the maximum longitudinal strain level, but the maximum circumferential strain level only weakly affected the longitudinal stress-strain response. This asymmetric mechanical coupling suggests strong mechanical interactions on a fiber level. SIS stress-strain response also was similar to glutaraldehyde-treated bovine pericardium, attesting to the substantial strength of SIS in the fresh, untreated state. The results of this study will provide a basis for a future analysis of the structural and mechanical changes during the remodeling process.

Algorithms↗

A method for planar biaxial mechanical testing that includes in-plane shear.

A limitation in virtually all planar biaxial studies of soft tissues has been the inability to include the effects of in-plane shear. This is due to the inability of current mechanical testing devices to induce a state of in-plane shear, due to the added cost and complexity. In the current study, a straightforward method is presented for planar biaxial testing that induces a combined state of in-plane shear and normal strains. The method relies on rotation of the test specimen's material axes with respect to the device axes and on rotating carriages to allow the specimen to undergo in-plane shear freely. To demonstrate the method, five glutaraldehyde treated bovine pericardium specimens were prepared with their preferred fiber directions (defining the material axes) oriented at 45 deg to the device axes to induce a maximum shear state. The test protocol included a wide range of biaxial strain states, and the resulting biaxial data re-expressed in material axes coordinate system. The resulting biaxial data was then fit to the following strain energy function W: [equation: see text] where E'ij is the Green's strain tensor in the material axes coordinate system and c and Ai are constants. While W was able to fit the data very well, the constants A5 and A6 were found not to contribute significantly to the fit and were considered unnecessary to model the shear strain response. In conclusion, while not able to control the amount of shear strain independently or induce a state of pure shear, the method presented readily produces a state of simultaneous in-plane shear and normal strains. Further, the method is very general and can be applied to any anisotropic planar tissue that has identifiable material axes.

Animals↗

Fatigue-induced changes in bioprosthetic heart valve three-dimensional geometry and the relation to tissue damage.

BACKGROUND AND AIM OF THE STUDY: In a previous study, we used magnetic resonance (MR) imaging to reconstruct, three-dimensionally, porcine bioprosthetic heart valve (PBHV) cusp geometry. Initial results using three valves indicated that accelerated testing induced changes in cuspal shape, including focal regions of high curvature. Since for thin-walled shell structures, such as the PBHV cusp, curvature changes can affect the stress distribution independently from changes to mechanical properties, shape changes might have adverse effects on PBHV durability. METHODS: The MR technique was applied to an expanded valve database to explore more fully shape change with fatigue. The spatial curvature distribution was compared across valves subjected to a range of accelerated test times. RESULTS: Results confirmed our initial findings that PBHV cusps undergo a continuous, non-recoverable deformation with accelerated testing. This deformation resulted in an increase in the portion of cuspal surface exhibiting high curvature values. In one cusp we mapped structural information obtained by small-angle light scattering back to the three-dimensional cuspal surface using an interpolation technique. Results from the mapped cusp demonstrated a strong spatial correlation between elevated curvatures and structural damage. CONCLUSIONS: The observed changes in cuspal shape accelerate PBHV damage due to an increase in flexural strains induced by an increase in curvature reversal during operation, rather than an increase in tension during closure.

Bioprosthesis↗

Effects of epidural steroids on lumbar dura material properties.

Epidural steroid injections are commonly used in the treatment of low back pain and radiculopathy based on their antiinflammatory and analgesic benefits. However, steroids are known to affect collagen synthesis, material strength, and tissue healing. The purpose of this study was to assess the effects of serial epidural steroid injections on the material properties of the lumbar dura mater. Serial epidural steroid injections of saline or methylprednisolone at 2-week intervals were performed in three paired groups of canines; a separate noninjected group was used as controls. Postmortem, dural sample testing to failure and histologic analysis was performed. Mechanical failure testing revealed no clinically significant change in the transverse dorsal dura tensile strength between all saline-injected, steroid-injected, or noninjected controls. Histologic analysis demonstrated no overt disruption of collagen matrix organization; however, electron microscopy demonstrated a significant decrease in the number of intracytoplasmic mitochondria of dural fibroblasts in steroid-injected animals, suggesting a metabolic inhibitory effect within steroid-injected dura mater. In the clinical time frame of this study, serial epidural steroid injections appeared to produce no significant material or matrix changes in the lumbar dura.

Analgesia, Epidural↗

Imposed state of deformation determines local collagen fibre orientation but not apparent mechanical properties.

In a previous study, we have shown that the observed biaxial material behaviour of planar connective tissues is influenced by the sample gripping method. Commonly used suture attachments produced an apparently more compliant and extensible material compared to the same sample with clamped edges. We hypothesized that these differences were due to the imposed collagen fibre constraint under each method. In this study, we have directly compared the collagen fibre orientations which result under both gripping schemes. Small angle light scattering (SALS) was used to determine collagen fibre orientations in square bovine pericardial samples, before and after a 10% equibiaxial stretch. Local fibre distributions were determined at the sample centre and at the grip-sample interface. Resulting scattering patterns were statistically compared using repeated measures ANOVA. After stretch, collagen fibre distributions were identical at the sample centre where deformation is measured--but not at the sample boundaries. Therefore, the central fibre orientation distribution appears to be exclusively determined by the imposed deformation state. However, it is important to note that the loads necessary to achieve a given deformation depended strongly on gripping method. The resulting apparent differences in mechanical properties must be due to the method of load transmission. Indeed, fibres were observed to arc around suture attachment points, suggesting a discontinuous load transfer to the specimen which produced an apparent increase in extensibility and compliance. By contrast, only smooth transitions were observed at the clamped edges. Direct transmission of load from grip-to-grip in clamped samples (away from the sample centre) increased apparent stiffness.

Animals↗

Optimal bovine pericardial tissue selection sites. I. Fiber architecture and tissue thickness measurements.

Use of bovine pericardium as an engineered biomaterial in the fabrication of bioprosthetic heart valves is limited, in part, by substantial intra- and intersac variations in its fibrous structure. To quantitatively assess this variability, we determined the fiber architecture of 20 whole BP sacs. Each sac was mounted on a prolate spheroidal mold, cleared and preserved in 100% glycerol, then sectioned into four equisized quadrants. This preparation method allowed for accurate intersac comparisons and minimized tissue distortions. The fiber architecture was evaluated by small-angle light scattering (SALS) using a 2.54-mm rectilinear grid resulting in approximately 1200 SALS measurements per quadrant, along with tissue thickness measured at 55 locations per quadrant. The fiber architecture was described in terms of fiber preferred directions, degree of orientation, and asymmetry of the fiber angular distribution. The BP sac fiber architecture demonstrated substantial intra- and intersac variability, with local fiber preferred directions changing by as much as 90 degrees within approximately 5 mm. Overall, most sacs revealed potential selection areas in the apex region characterized by a high degree of orientation, high uniformity in fiber preferred directions, and uniform tissue thickness. However, the size, location, and fiber orientation of these potential selection areas varied sufficiently from sac-to-sac to question whether anatomic location alone is sufficient for consistent localization of regions of high structural uniformity suitable for improved BHV design.

Animals↗

Optimal bovine pericardial tissue selection sites. II. Cartographic analysis.

In Part I of this work we used small-angle light scattering (SALS) to quantify the fiber architecture of 20 bovine pericardial sacs, along with corresponding tissue-thickness measurements, to determine optimal material selection sites. In order to determine the anatomic consistency of these sites, the fiber architecture and thickness data from all 20 sacs were averaged together using a cartographic analysis method that took advantage of the geometry of the prolate spheroid mold used to process the sacs. Optimal selection sites were determined based on a local criteria where all fiber preferred directions within a 2.54-cm circular area were within +/- 10 degrees. The largest contiguous area (LCA) for the entire BP sac was 20.54 cm2, located in the vicinity of the left ventricle of the heart. The LCA tissue thicknesses were also relatively uniform, further supporting the use of these areas. However, even within these optimal areas there was a +/- 20 degrees standard deviation in local fiber preferred directions, resulting in at best a 40 degrees spread in local preferred directions. The observed structural variability may be due to regionally heterogeneous physiologic loadings induced by the ligamentous attachments. These attachments may alter the regional fiber preferred orientation to support local mechanical loadings. Overall, given the inherent structural variability of the BP sac, we conclude that use of anatomic location alone will not consistently guarantee the selection of tissue specimens with a highly homogeneous and predictable fibrous structure. It is thus suggested that a direct fiber measurement presorting method be employed when selecting BP specimens for bioprosthetic applications where tissue structural homogeneity and uniformity is critical.

Animals↗

The aortic valve microstructure: effects of transvalvular pressure.

We undertook this study to establish a more quantitative understanding of the microstructural response of the aortic valve cusp to pressure loading. Fresh porcine aortic valves were fixed at transvalvular pressures ranging from 0 mmHg to 90 mmHg, and small-angle light scattering (SALS) was used to quantify the gross fiber structure of the valve cusps. At all pressures the fiber-preferred directions coursed along the circumferential direction. Increasing transvalvular pressure induced the greatest changes in fiber alignment between 0 and 1 mmHg, with no detectable change past 4 mmHg. When the fibrosa and ventricularis layers of the cusps were re-scanned separately, the fibrosa layer revealed a higher degree of orientation while the ventricularis was more randomly oriented. The degree of fiber orientation for both layers became more similar once the transvalvular pressure exceeded 4 mmHg, and the layers were almost indistinguishable by 60 mmHg. It is possible that, in addition to retracting the aortic cusp during systole, the ventricularis mechanically may contribute to the diastolic cuspal stiffness at high transvalvular pressures, which may help to prevent over distention of the cusp. Our results suggest a complex, highly heterogeneous structural response to transvalvular pressure on a fiber level that will have to be duplicated in future bioprosthetic heart valve designs.

Animals↗

Effects of accelerated testing on porcine bioprosthetic heart valve fiber architecture.

We undertook the following study to quantitatively assess the changes in porcine bioprosthetic heart valve (PBHV) fiber architecture to increasing levels of fatigue damage using an in vitro accelerated test model. PBHVs were subjected to 0-500 million test cycles at 16 Hz, and small-angle light scattering (SALS) was used to quantify the gross fiber structure of the cusps. The degree of gross fiber alignment remained essentially constant from 0 to 500 million cycles over the entire cusp. Increasing fiber orientation randomness, indicative of local damage, was observed only in the vicinity of the nodulus of Arantii after 50 million cycles. The SALS data from the damaged regions suggested shearing between fiber layers, which may be part of the failure process and accelerates valve failure. Histological analysis revealed a relatively intact gross fiber structure with the collagen fiber crimp remaining, although delamination and de-registration of the crimp was also observed. Accelerated tested PBHVs also demonstrated a pronounced 'sagging', which began at the earliest cycle number tested (1.4 million cycles) and whose rate decreased logarithmically with cycle number. Results of this study suggest that PBHV cusps can alter their shape without any visually apparent material yielding or fiber failure under continual cyclic loading. Further, while most of the 4 mmHg pressure fixed PBHV's gross fiber architecture remains unchanged after 500 million cycles of accelerated testing, localized accumulated fiber damage can occur on a sub-visual structural level as early as 50 million cycles.

Animals↗

Quantification of the collagen fibre architecture of human cranial dura mater.

The purpose of this study was to quantify and map the gross fibre architecture of the cranial dura mater (CDM) using small angle light scattering (SALS). In SALS, HeNe laser light is passed through the tissue, and the resultant scattering pattern is analysed to determine the preferred fibre direction and degree of orientation. The dura mater was found to be a complex structure with fibre orientations ranging from highly aligned to nearly random. In the temporal region, 80% of the samples (n = 20) were found to have regions composed of highly oriented fibres with a mean fibre direction of 6.3 degrees +/- 0.8 degree with respect to the sagittal plane (i.e. almost parallel to the superior sagittal sinus). These highly aligned regions were found in symmetric anatomical locations about the median sagittal sinus and had similar fibre orientations over both hemispheres. Although our sample size was small, we found that the size of the symmetric regions, which covered 14.4 +/- 1.6% of the total CDM area, was not influenced by subject's age or sex. The presence of these highly oriented fibre regions in CDM may be due to mechanical forces exerted on dura mater during its development. These forces may have induced realignment of the collagen fibres in the direction of tensile pull, although the exact basis for the unique gross fibre architecture of CDM remains unknown.

Brain↗

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↗