Preventing extrinsic mechanisms of bioprosthetic degeneration using polyphenols.

Objectives: The purpose of this study was to evaluate the impact of a polyphenols-based treatment on the extrinsic mechanisms responsible for early bioprosthetic heart valve (BHV) degeneration. Structural degeneration can be driven by both extrinsic and intrinsic mechanisms. While intrinsic mechanisms have been associated with inherent biocompatibility characteristics of the BHV, the extrinsic ones have been reported to involve external causes, such as chemical, mechanical and hydrodynamic, responsible to facilitate graft damage.

Structural changes of rat mitral valve chordae tendineae during postnatal development.

Background And Aim Of The Study: Mitral valve chordae tendineae are an essential component for correct functioning of the human heart. The microstructural make-up of the chordae is responsible for their tensile properties, and is seen gradually to change with age. However, little is known of the maturation of chordae tendineae and their microstructure.

Transcatheter valves: a brave New World.

Over the past five years, transcatheter valves have stimulated the attention of physicians, engineers, and investors. Transcatheter valve design and implantation techniques depart from the time-proven features of surgical valves, and this has an important impact on the safety and efficacy of prosthetic valve therapy. Herein is reviewed the performance of transcatheter valve procedures in comparison to surgical valves, together with a summary of the specific design features of several emerging transcatheter valves.

Ultrastructure of porcine mitral valve chordae tendineae.

Background And Aim Of The Study: The chordae tendineae, which form an important component of the mitral valve apparatus, experience continuous cyclic loading and are thus well-adapted for effectively storing and dissipating energy. An understanding of their microstructure would be expected to shed light on the mechanism of their remarkable durability.

Methods: In these studies, porcine mitral valve chordae from freshly slaughtered pigs were used.

Direct measurement of nonuniform large deformations in soft tissues during uniaxial extension.

Understanding the complex relationships between microstructural organization and macromechanical function is fundamental to our knowledge of the differences between normal, diseased/injured, and healing connective tissues. The long-term success of functional tissue-engineered constructs or scaffolds may largely depend on our understanding of the structural organization of the original tissue. Although innovative techniques have been used to characterize and measure the microstructural properties of collagen fibers, a large gap remains in our knowledge of the behavior of intermediate scale (i.

Skewness angle of interfibrillar proteoglycan increases with applied load on chordae tendineae.

In highly aligned connective tissues, such as tendon, collagen fibrils are linked together by proteoglycans (PGs). We used transmission electron microscopy to observe the collagen fibril-proteoglycan interactions in porcine mitral valve chordae under loaded conditions. Comparison of fibril-proteoglycan configuration between stressed and load-free states showed that PGs mainly attached to collagen fibrils perpendicularly in the load-free situation, and became skewed when the chordae were loaded.

Novel geometries for tissue-engineered tendonous collagen constructs.

A promising approach to addressing the performance limitations of currently available mechanical and bioprosthetic heart valves lies in tissue engineering. Tissue-engineered valves should incorporate the complex microstructure of the native valves to mimic their unique mechanics. This would include a layered topology, mesh networks, and branched collagen fiber bundles.

Skewness angle of interfibrillar proteoglycans increases with applied load on mitral valve chordae tendineae.

In highly aligned connective tissues, such as tendon, collagen fibrils are linked together by proteoglycans (PGs). Recent mechanical and theoretical studies on tendon micromechanics have implied that PGs mediate mechanical interactions between adjacent collagen fibrils. We used transmission electron microscopy to observe the collagen fibril-PG interactions in porcine mitral valve chordae under variable loading conditions and found that PGs attached to collagen fibrils perpendicularly in the load-free situation, and became skewed when the chordae were loaded.

Inverse parameter fitting of biological tissues: a response surface approach.

In this paper, we present the application of a semi-global inverse method for determining material parameters of biological tissues. The approach is based on the successive response surface method, and is illustrated by fitting constitutive parameters to two nonlinear anisotropic constitutive equations, one for aortic sinus and aortic wall, the other for aortic valve tissue. Material test data for the aortic sinus consisted of two independent orthogonal uniaxial tests.

Mesostructures of the aortic valve.

Background And Aim Of The Study: The aortic valve cusp is commonly described as a three-layered structure containing circumferentially aligned fiber bundles. Little is known, however, regarding fiber bundle sizes, branching patterns, or how they are connected. This is because previous morphological studies relied primarily on histological sectioning and staining techniques, which tend to affect all of the collagen, regardless of structure or orientation.

Heart valve tissue engineering.

Tissue-engineered heart valves have been proposed by physicians and scientists alike to be the ultimate solution for treating valvular heart disease. Rather than replacing a diseased or defective native valve with a mechanical or animal tissue-derived artificial valve, a tissue-engineered valve would be a living organ, able to respond to growth and physiological forces in the same way that the native aortic valve does. Two main approaches have been attempted over the past 10 to 15 years: regeneration and repopulation.

Mitral valve stiffening in end-stage heart failure: evidence of an organic contribution to functional mitral regurgitation.

Objective: Mitral regurgitation is a complication for many patients with congestive heart failure. Although this regurgitation is considered purely functional, we hypothesize that the alterations in cardiac geometry and function induce dysfunctional remodeling of the mitral valve, which can be demonstrated by alterations in the material behavior of the leaflets and chordae.

Methods: Mitral leaflets and chordae from 23 valves from transplant recipient hearts (11 with dilated and 12 with ischemic cardiomyopathy) and from 21 normal valves (from autopsy) were mechanically tested.

Invariant formulation for dispersed transverse isotropy in aortic heart valves: an efficient means for modeling fiber splay.

Most soft tissues possess an oriented architecture of collagen fiber bundles, conferring both anisotropy and nonlinearity to their elastic behavior. Transverse isotropy has often been assumed for a subset of these tissues that have a single macroscopically-identifiable preferred fiber direction. Micro-structural studies, however, suggest that, in some tissues, collagen fibers are approximately normally distributed about a mean preferred fiber direction.

Fractional order viscoelasticity of the aortic valve cusp: an alternative to quasilinear viscoelasticity.

Background: Quasilinear viscoelasticity (QLV) theory has been widely and successfully used to describe the time-dependent response of connective tissues. Difficulties remain, however, particularly in material parameter estimation and sensitivities. In this study, we introduce a new alternative: the fractional order viscoelasticity (FOV) theory, which uses a fractional order integral to describe the relaxation response.

Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements: an extracellular matrix and echocardiographic study.

Objectives: This study assessed apparently normal mitral valves from patients with congestive heart failure (CHF) using biochemical and echocardiographic measures of extracellular matrix (ECM) and anatomy.

Background: Mitral regurgitation (MR) is frequently found in patients with CHF. This MR is considered purely functional, yet animal studies suggest that altered left ventricular (LV) function leads to increased cellularity and fibrosis of the mitral valve.

Relationship between collagen fibrils, glycosaminoglycans, and stress relaxation in mitral valve chordae tendineae.

The tensile properties of mitral valve chordae tendineae derive from their structural make-up. The objectives of this study were to compare the stress relaxation properties of different types of chordae and relate their variation to structural features. Fifty chordae from eight hearts were subjected to stress relaxation tests.

Biomechanical and echocardiographic characterization of flail mitral leaflet due to myxomatous disease: further evidence for early surgical intervention.

Background: Flail mitral leaflet (FML) is a common complication of mitral valve prolapse, often leading to severe mitral regurgitation (MR) and left ventricular dysfunction. In the absence of timely surgical correction, survival is significantly impaired. Early recognition of FML and identification of risk factors is important because early intervention increases the chances of survival.

Stress relaxation preconditioning of porcine aortic valves.

In uniaxial tensile testing, load preconditioning is used to generate repeatable load/elongation curves and set a "reference state" for subsequent tensile tests. We have observed however, that for porcine aortic valve (PAV) tissues, preconditioning does not lead to repeatable stress relaxation curves. We thus investigated possible experimental protocols that could be used to generate repeatable load/elongation and stress relaxation curves.

Cell viability mapping within long-term heart valve organ cultures.

Background And Aim Of The Study: Organ cultures maintain cells within their native microstructural environment, and thus offer greater potential for studying tissue disease and remodeling than do monolayer cell cultures or pathological examinations of diseased tissue. To validate an in-vitro heart valve organ culture model, cell viability was examined within valve tissues over sustained culture periods.

Methods: Following culture of blocks of valve tissue for 1 to 49 days, cross-sections were cut with a vibratome, stained with a LIVE/DEAD kit, and imaged with confocal microscopy to quantify the number of live and dead cells present.

Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading.

This study was designed to identify the specific proteoglycans and glycosaminoglycans (GAGs) in the leaflets and chordae of the mitral valve and to interpret their presence in relation to the tensile and compressive loads borne by these tissues. Leaflets and chordae from normal human mitral valves (n = 31, obtained at autopsy) were weighed and selected portions digested using proteinase K, hyaluronidase, and chondroitinases. After fluorescent derivatization, fluorophore-assisted carbohydrate electrophoresis was used to separate and quantify the derivatized saccharides specific for each GAG type.

The effect of strain rate on the viscoelastic response of aortic valve tissue: a direct-fit approach.

Knowledge of strain-rate sensitivity of soft tissue viscoelastic and nonlinear elastic properties is important for accurate predictions of biomechanical behavior and for quantitative assessment of the effects of disease or surgical/pharmaceutical intervention. Soft tissues are known to exhibit mild rate sensitivity, but experimental artifacts related to testing system control can confound estimation of these effects. "Perfect" ramp-and-hold stress-relaxation tests become difficult at high strain rates because of problems related to undershoot/overshoot error and vibrations.

Characterization of statically loaded tissue-engineered mitral valve chordae tendineae.

Chordae tendineae are essential to the proper function of the mitral valve. Native chordae contain a dense collagenous core and an outer elastin sheath. We have been using the principle of directed collagen gel shrinkage to fabricate tissue-engineered mitral valve chordae.

Fabrication of mitral valve chordae by directed collagen gel shrinkage.

The principles of tissue engineering are being used to explore numerous applications in reconstructive surgery. Mitral valve chordae are one such potential area, as mitral valve repair is increasing in popularity and synthetic materials have not been used widely. The use of cells, combined with reconstituted type I collagen, is an attractive option for fabricating materials for the replacement of thin tendonous structures such as mitral valve chordae.

Ultraviolet light-induced modification of crosslinked hyaluronan gels.

Hyaluronan (HA) gels (hylans) crosslinked with divinyl sulfone (DVS) are highly biocompatible and can be structurally modified to obtain desired mechanical properties that are attractive for their use as tissue-engineering scaffolds. However, unmodified hylan gels are not good substrates for cell attachment or infiltration, likely as a result of their smooth surface and the highly anionic nature of HA. This study investigated whether the cell-adhering characteristics of hylan gels could be enhanced by irradiation with ultraviolet (UV) light, with or without prior dehydration.

Glycosaminoglycan profiles of myxomatous mitral leaflets and chordae parallel the severity of mechanical alterations.

Objectives: This biochemical study compared the extracellular matrix of normal mitral valves and myxomatous mitral valves with either unileaflet prolapse (ULP) or bileaflet prolapse (BLP).

Background: Myxomatous mitral valves are weaker and more extensible than normal valves, and myxomatous chordae are more mechanically compromised than leaflets. Despite histological evidence that glycosaminoglycans (GAGs) accumulate in myxomatous valves, previous biochemical analyses have not adequately examined the different GAG classes.