Biomedical subjects

Michael S Sacks

Publications and source records attributed to Michael S Sacks.

14 recordsLinked to original sources

PubMed2004

Biodegradable poly(ether ester urethane)urea elastomers based on poly(ether ester) triblock copolymers and putrescine: synthesis, characterization and cytocompatibility.

Polymers with elastomeric mechanical properties, tunable biodegradation properties and cytocompatibility would be desirable for numerous biomedical applications. Toward this end a series of biodegradable poly(ether ester urethane)urea elastomers (PEEUUs) based on poly(ether ester) triblock copolymers were synthesized and characterized. Poly(ether ester) triblock copolymers were synthesized by ring-opening polymerization of epsilon-caprolactone with polyethylene glycol (PEG). PEEUUs were synthesized from these triblock copolymers and butyl diisocyanate, with putrescine as a chain extender. PEEUUs exhibited low glass transition temperatures and possessed tensile strengths ranging from 8 to 20MPa and breaking strains from 325% to 560%. Increasing PEG length or decreasing poly(caprolactone) length in the triblock segment increased PEEUU water absorption and biodegradation rate. Human umbilical vein endothelial cells cultured in a medium supplemented with PEEUU biodegradation solution suggested a lack of degradation product cytotoxicity. Endothelial cell adhesion to PEEUUs was less than 60% of tissue culture polystyrene and was inversely related to PEEUU hydrophilicity. Surface modification of PEEUUs with ammonia gas radio-frequency glow discharge and subsequent immobilization of the cell adhesion peptide Arg-Gly-Asp-Ser increased endothelial adhesion to a level equivalent to tissue culture polystyrene. These biodegradable PEEUUs thus possessed properties that would be amenable to applications where high strength and flexibility would be desirable and exhibited the potential for tuning with appropriate triblock segment selection and surface modification.

Absorbable Implants↗

PubMed2003

Prevention of polyurethane valve cusp calcification with covalently attached bisphosphonate diethylamino moieties.

OBJECTIVE: Calcification of polyurethane prosthetic valve leaflets causes a major functional impairment. Previously we showed that polyurethane heart valves modified with covalently linked bisphosphonate groups were resistant to calcification in vivo. However, we also found that the highly polar anionic bisphosphonate groups on the polyurethane surface attracted sodium counter ion adsorption, and thereby increased the elastomer's water absorption to 20% of total weight. In this study we address the increased water absorption by investigating the hypothesis that covalently attaching cationic diethylamino groups to the bisphosphonate-modified polyurethane will reduce water absorption. Thus we evaluated the mechanical and in vivo anticalcification properties of heart-valve leaflets composed of this modified polymer. METHODS: Diethylamino and bisphosphonate groups (DBP) were appended to the polyurethane Biospan's hard segment using previously published bromoalkylation methodology. Water absorption and biaxial mechanical and uniaxial failure testing were used to determine the mechanical properties of the DBP-modified polymer. Rat subdermal implants (60 days) and extended (150 days) single pulmonary leaflet replacements in juvenile sheep provided in vivo assessments of the bisphosphonate-modified polyurethane. RESULTS: The water absorption properties of the DBP-modified polymers and unmodified polyurethanes were 1.86 and 2.3 %, respectively. Biaxial mechanical tests showed the DBP-modified polymer was more compliant than the unmodified control material, but all polymeric material had similar uniaxial failure properties. In both rat subdermal and sheep circulatory implants, the DBP-modified polyurethane resisted calcification, as assessed by scanning electron microscopy, with complete calcification inhibition in prosthetic sheep valve leaflet replacements. CONCLUSION: DBP polyurethane possesses physical (water absorption) and biomechanical properties comparable to unmodified polyurethane and can resist intrinsic heart-valve leaflet calcification in blood-stream implants.

Animals↗

PubMed2003

Multiaxial mechanical behavior of biological materials.

For native and engineered biological tissues, there exist many physiological, surgical, and medical device applications where multiaxial material characterization and modeling is required. Because biological tissues and many biocompatible elastomers are incompressible, planar biaxial testing allows for a two-dimensional (2-D) stress-state that can be used to fully characterize their three-dimensional (3-D) mechanical properties. Biological tissues exhibit complex mechanical behaviors not easily accounted for in classic elastomeric constitutive models. Accounting for these behaviors by careful experimental evaluation and formulation of constitutive models continues to be a challenging area in biomechanical modeling and simulation. The focus of this review is to describe the application of multiaxial testing techniques to soft tissues and their relation to modern biomechanical constitutive theories.

Anisotropy↗

PubMed2003

A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials.

Dynamic flexure is a major mode of deformation in the native heart valve cusp, and may effect the mechanical and biological development of tissue engineered heart valves (TEHV). To explore this hypothesis, a novel bioreactor was developed to study the effect of dynamic flexural stimulation on TEHV biomaterials. It was implemented in a study to compare the effect of uni-directional cyclic flexure on the effective stiffness of two candidate TEHV scaffolds: a non-woven mesh of polyglycolic acid (PGA) fibers, and a non-woven mesh of PGA and poly L-lactic acid (PLLA) fibers, both coated with poly 4-hydroxybutyrate (P4HB). The bioreactor has the capacity to dynamically flex 12 rectangular samples (25 x 7.5 x 2mm) under sterile conditions in a cell culture incubator. Sterility was maintained in the bioreactor for at least 5 weeks of incubation. Flexure tests to measure the effective stiffness in the "with-flexure" (WF) and opposing "against-flexure" (AF) directions indicated that dynamically flexed PGA/PLLA/P4HB scaffolds were approximately 72% (3 weeks) and 76% (5 weeks) less stiff than static controls (p<0.01), and that they developed directional anisotropy by 3 weeks of incubation (stiffer AF, p<0.01). In contrast, both dynamically flexed and static PGA/P4HB scaffolds exhibited a trend of decreased stiffness with incubation, with no development of directional anisotropy. Dynamically flexed PGA/P4HB scaffolds were significantly less stiff than static controls at 3 weeks (p<0.05). Scanning electron microscopy revealed signs of heterogeneous P4HB coating and fiber disruption, suggesting possible explanations for the observed mechanical properties. These results indicate that dynamic flexure can produce quantitative and qualitative changes in the mechanical properties of TEHV scaffolds, and suggest that these differences need to be accounted for when comparing the effects of mechanical stimulation on the development of cell-seeded TEHV constructs.

Absorbable Implants↗

PubMed2003

Experimentally tractable, pseudo-elastic constitutive law for biomembranes: I. Theory.

Although visco-elastic in general, the stress-strain relation of biomembranes is one-to-one or pseudo-elastic when being loaded after preconditioning. This pseudo-elastic relation is hypoelastic (i.e., it is not hyperelastic), yet much of the stress response can be characterized by a scalar function omega that represents the work done (per unit reference volume) on the specimen during loading. (Since a pseudo-strain-energy function W is optimized to fit the test data and not the work done, omega is not equal to W in general.) The remaining part tR of the stress response does no work during loading. With biaxial testing, omega can be definitively determined from data. Moreover, for tests with the stretch directions coaxial to the axes of anisotropy, tR can be accurately characterized by a scalar function omega that depends on the strain. This paper is part 1 of 2 with "I. Theory" and "II. Application."

Animals↗

PubMed2003

Experimentally tractable, pseudo-elastic constitutive law for biomembranes: II. Application.

This is the second paper of a 2 part series. In the first, a theoretical framework is developed that provides 3 enhancements for the constitutive theory of biomembranes. 1) Covariance amongst response terms is minimized, 2) the pseudo-strain-energy potential is redefined so as to be measurable, and 3) the stress response is decomposed into 2 parts--a hyperelastic part plus a hypoelastic-stress-residual. This paper illustrates the experimental advantages of this novel constitutive theory via analysis of biaxial test data obtained from chemically treated bovine pericardium.

Animals↗

PubMed2003

Incorporation of experimentally-derived fiber orientation into a structural constitutive model for planar collagenous tissues.

Structural constitutive models integrate information on tissue composition and structure, avoiding ambiguities in material characterization. However, critical structural information (such as fiber orientation) must be modeled using assumed statistical distributions, with the distribution parameters estimated from fits to the mechanical test data. Thus, full realization of structural approaches continues to be limited without direct quantitative structural information for direct implementation or to validate model predictions. In the present study, fiber orientation information obtained using small angle light scattering (SALS) was directly incorporated into a structural constitutive model based on work by Lanir (J. Biomech., v. 16, pp. 1-12, 1983). Demonstration of the model was performed using existing biaxial mechanical and fiber orientation data for native bovine pericardium (Sacks and Chuong, ABME, v.26, pp. 892-902, 1998). The structural constitutive model accurately predicted the complete measured biaxial mechanical response. An important aspect of this approach is that only a single equibiaxial test to determine the effective fiber stress-strain response and the SALS-derived fiber orientation distribution were required to determine the complete planar biaxial mechanical response. Changes in collagen fiber crimp under equibiaxial strain suggest that, at the meso-scale, fiber deformations follow the global tissue strains. This result supports the assumption of affine strain to estimate the fiber strains. However, future evaluations will have to be performed for tissue subjected to a wider range of strain to more fully validate the current approach.

Animals↗

PubMed2003

Biaxial mechanical response of bioprosthetic heart valve biomaterials to high in-plane shear.

Utilization of novel biologically-derived biomaterials in bioprosthetic heart valves (BHV) requires robust constitutive models to predict the mechanical behavior under generalized loading states. Thus, it is necessary to perform rigorous experimentation involving all functional deformations to obtain both the form and material constants of a strain-energy density function. In this study, we generated a comprehensive experimental biaxial mechanical dataset that included high in-plane shear stresses using glutaraldehyde treated bovine pericardium (GLBP) as the representative BHV biomaterial. Compared to our previous study (Sacks, JBME, v.121, pp. 551-555, 1999), GLBP demonstrated a substantially different response under high shear strains. This finding was underscored by the inability of the standard Fung model, applied successfully in our previous GLBP study, to fit the high-shear data. To develop an appropriate constitutive model, we utilized an interpolation technique for the pseudo-elastic response to guide modification of the final model form. An eight parameter modified Fung model utilizing additional quartic terms was developed, which fitted the complete dataset well. Model parameters were also constrained to satisfy physical plausibility of the strain energy function. The results of this study underscore the limited predictive ability of current soft tissue models, and the need to collect experimental data for soft tissue simulations over the complete functional range.

Animals↗

PubMed2003

Effects of papillary muscle position on in-vitro dynamic strain on the porcine mitral valve.

BACKGROUND AND AIM OF THE STUDY: Improved knowledge of mitral valve (MV) mechanics is essential to understand normal MV function and design and evaluate new surgical repair procedures. Initially, the dynamic deformation of the central region of the porcine MV anterior leaflet was quantified under simulated physiological conditions to explore the effects of varying papillary muscle (PM) position. METHODS: Fresh porcine MVs were mounted in an in-vitro physiological flow loop. The PM positions were set to normal, taut, and slack states to simulate physiological and pathological PM positions. Leaflet deformation was measured by tracking the displacement of 16 markers (approximately 250 microm diameter) placed in a 5 x 5 mm section of the central region of the anterior leaflet, approximately 5 mm from the annulus and coaptation line. Local leaflet tissue strain and strain rates were calculated from measured displacements under dynamic loading conditions. A total of 11 mitral valves was studied. RESULTS: Under the normal PM positional state, the average areal strain rate during valve closure was typically approximately 620% per second. While not measurably altering the maximal areal strain rate, the slack PM position led to a delay in complete valve closure and more rapid leaflet loading (defined as delta transvalvular pressure/delta areal strain) in late systole compared to the other two PM positions. CONCLUSION: It was shown that PM position influenced the MV loading process in the central area of the anterior leaflet. The slack PM position led to a delay in complete valve closure and more rapid leaflet loading in late systole. This increase in loading rate may have long-term consequences in MV function.

Animals↗

PubMed2002

Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves.

The durability of bioprosthetic heart valves (BHV) is severely limited by tissue deterioration, manifested as calcification and mechanical damage to the extracellular matrix. Extensive research on mineralization mechanisms has led to prevention strategies, but little work has been done on understanding the mechanisms of noncalcific matrix damage. The present study tested the hypothesis that calcification-independent damage to the valvular structural matrix mediated by mechanical factors occurs in clinical implants and could contribute to porcine aortic BHV structural failure. We correlated quantitative assessment of collagen fiber orientation and structural integrity by small angle light scattering (SALS) with morphologic analysis in 14 porcine aortic valve bioprostheses removed from patients for structural deterioration following 5-20 years of function. Calcification of the explants varied from 0 (none) to 1+ (minimal) to 4+ (extensive), as assessed radiographically. SALS tests were performed over entire excised cusps using a 0.254-mm spaced grid, and the resultant structural information used to generate maps of the local collagen fiber damage that were compared with sites of calcific deposits. All 42 cusps showed clear evidence of substantial noncalcific structural damage. In 29 cusps that were calcified, structural damage was consistently spatially distinct from the calcification deposits, generally in a distribution similar to that noted in porcine BHV subjected to in vitro durability testing. Our results suggest a mechanism of noncalcific degradation dependent on cuspal mechanics that could contribute to porcine aortic BHV failure.

Animals↗

PubMed2002

Synthesis, characterization, and cytocompatibility of elastomeric, biodegradable poly(ester-urethane)ureas based on poly(caprolactone) and putrescine.

The engineering of tissue for mechanically demanding applications in the cardiovascular system is likely to require mechanical conditioning of cell-scaffold constructs prior to their implantation. Scaffold properties amenable to such an application include high elasticity and strength coupled with controllable biodegradative and cell-adhesive properties. To fulfill such design criteria, we have synthesized a family of poly(ester-urethane)ureas (PEUUs) from polycaprolactone and 1,4-diisocyanatobutane. Lysine ethyl ester (Lys) or putrescine was used as chain extenders. To encourage cell adhesion, PEUUs were surface modified with radio-frequency glow discharge followed by coupling of Arg-Gly-Asp-Ser (RGDS). The synthesized PEUUs were highly flexible, with breaking strains of 660-895% and tensile strengths from 9.2-29 MPa. Incubation in aqueous buffer for 8 weeks resulted in mass loss, from >50% (Lys chain extender) to 10% (putrescine chain extender). Human endothelial cells cultured for 4 days with medium containing the degradation products from PEUUs with either the Lys or putrescine chain extender showed no toxic effects. Cell adhesion was 85% of that measured on tissue-culture polystyrene for unmodified PEUU surfaces (p < 0.01) and >160% (p < 0.001) of polystyrene on RGDS-modified PEUUs. These biodegradable PEUUs demonstrate potential for future application as cell scaffolds in cardiovascular tissue-engineering or other soft-tissue applications.

Absorbable Implants↗

PubMed2002

Effects of fixation pressure on the biaxial mechanical behavior of porcine bioprosthetic heart valves with long-term cyclic loading.

Zero transvalvular pressure fixation is thought to improve porcine bioprosthetic heart valve (BHV) durability by preserving the collagen fiber architecture of the native tissue, and thereby native mechanical properties. However, it is not known if the native mechanical properties are stable during long-term valve operation and thus provide additional durability. To address this question, we examined the biaxial mechanical properties of porcine BHV fixed at 0 and 4mmHg transvalvular pressure following 0, 1 x 10(6), 50 x 10(6), and 200 x 10(6) in vitro accelerated test cycles. At 0 cycles, the extensibility and degree of axial cross-coupling of the zero-pressure-fixed cusps were higher than those of the low-pressure-fixed cusps. Furthermore, extensibility of the zero-pressure-fixed tissue decreased between 1 x 10(6) and 50 x 10(6) cycles, approaching that of the low-pressure-fixed tissue, whose extensibility was unchanged over 0-200 x 10(6) cycles. The decrease in extensibility of the zero-pressure-fixed tissue between 1 x 10(6) and 50 x 10(6) cycles may be attributable to the ability of its collagen fibers to undergo larger changes in orientation and crimp with cyclic loading. These observations suggest that the collagen fiber architecture of the 0-mmHg-fixed porcine BHV, although locked in place by chemical fixation, may not be maintained over a sufficient number of cycles to be clinically beneficial. This study further underscores that chemically treated collagen fibers can undergo conformational changes under long-term cyclic loading not associated with damage.

Animals↗

PubMed2002

Passive biaxial mechanical properties of the rat bladder wall after spinal cord injury.

PURPOSE: Changes in the mechanical properties of the bladder wall after spinal cord injury can alter bladder compliance and wall tension, leading to changes in afferent nerve activity and to abnormal reflex mechanisms. To our knowledge we report the first application of biaxial mechanical testing to the normal bladder wall and demonstrate how these properties change after spinal cord injury. MATERIALS AND METHODS: Whole bladders were harvested from mature female Sprague-Dawley rats weighing 250 to 300 gm. Test group animals underwent complete spinal cord transection at the T9 to T10 level and normal animals comprised the control group. The bladders were cut open longitudinally, the trigone and apex were removed and the remaining tissue was trimmed to a square of 9 to 13 mm. per side. Mechanical properties of the tissue sample were tested using planar biaxial testing, in which a stress was applied in the circumferential and longitudinal (base-apex) directions, and resulting axial strains were measured. RESULTS: In normal and spinal cord injured rats bladder wall tissue demonstrated isotropic mechanical behavior when equal stress levels were applied in anatomical directions. However, under nonequi-biaxial loading bladder specimens were not truly isotropic but displayed anisotropic-like behavior. Spinal cord injured tissues were consistently more compliant than normal controls. CONCLUSIONS: Biaxial mechanical testing can detect differences in normal control and hypertrophied rat bladders 10 and 14 days after spinal cord injury. These changes represent an important component of the bladder response to spinal cord injury.

Animals↗

PubMedDate not supplied

The collagen fibers of the anteroinferior capsulolabrum have multiaxial orientation to resist shoulder dislocation.

Instability of the glenohumeral joint can be associated with anteroinferior capsulolabral rupture. To understand its static stabilizing effect better, the collagen fiber orientation of the inferior glenohumeral ligament (IGHL), a component of the anteroinferior capsulolabrum, was studied with a small angle light scattering technique. Three rectangular samples (approximately 11 x 6 mm) were excised from the axillary pouch, one from the anterior band (AB) of the IGHL and one control sample from the long head of the biceps tendon of 7 cadaveric shoulders. The small angle light scattering technique scans the tissue with a helium-neon laser beam and quantifies the fiber alignment based on the resultant scattering pattern. The fiber orientation was quantified by an orientation index, defined as the angle within which 50% of the fibers lie. The axillary pouch had a random orientation, whereas the AB-IGHL was random with some regions of localized alignment. The percentage of tissue with an orientation index range of 25 degrees to 45 degrees was 23.2% +/- 8.5% and 29.0% +/- 13.1% for the axillary pouch and the AB-IGHL, respectively, whereas that for the long head of the biceps tendon was 61.6% +/- 15.2%. This suggests that the collagen fibers in the IGHL are not highly aligned and the anteroinferior capsulolabrum can be modeled as a continuous sheet. Moreover, a biomechanical evaluation of the anteroinferior capsulolabrum that investigates the possibility that the mechanical properties may be directionally independent should be conducted.

Adult↗