Need for Heart Valves With Improved Functionality

7/29/2019 Need for Heart Valves With Improved Functionality

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Need for heart valves with

improved functionality

Though primitive measures to engineer heart valves

promise to improve survival period, they come with

disadvantages :

1. Coagulation

2. Mechanical instability ( to match and withstand

pressure)

3. Failure to function and support cell grow

4. ECM production and organisation5. Appropriate degrading nature of scaffold.

Need for heart valves with

improved functionality

Though primitive measures to engineer heart valves

promise to improve survival period, they come with

disadvantages :

1. Coagulation

2. Mechanical instability ( to match and withstand

pressure)

3. Failure to function and support cell grow

4. ECM production and organisation5. Appropriate degrading nature of scaffold.


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Topics to be discussed

Structure and function of heart valves:

Cell types

Prosthetic heart valves

Mechanical valve prosthesis:

Bio prosthetic Valves:

Dynamic loading of heart valves Loading on natural heart valve

Modelling of flow dynamics


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Introduction

Applications of tissue engineering in regenerative medicine range from structural

tissue (eg: cartilage, bone) to complex organs (e.g., heart, liver, kidney and

pancreas) .

Cardiovascular tissue engineering has primarily considered blood vessels,

myocardium and heart valves.

This review focuses on the application of tissue engineering technology to heart

valves.

Conventional surgical procedures and artificial synthetic prosthetic devices offerserious complications in heart valve replacements. Each of the following, even

though they offer increased survival life, has its own set of limitations .

The disadvantages of mechanical heart valves include thromboemolic

complication . However, a tissue-engineered valve has the ability to function as a

living implant like the natural heart valves, growing and lasting a lifetime .

This article focus mainly on the types of bio prosthetic valves and the methods to

seed and culture cells on them.


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Extra cellular matrix

It has also been emphasized that the extracellular matrix plays a critical

role in the effective functioning of the valves.

Its production, composition, along with the remodelling processes

is critical.

So, the ECM should be stimulated in such a way that they result in a valveorganization similar to the native valve .

It has been hypothesized that the physical strain inside the leaflets has a

more dominant effect on their development than the flow over them .


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Heart valves

The efficiency of the heart as a pump depends not only on the force of its

contractions but also on the correct functioning of its four valves.

The heart has four valves.

Two of them are situated between the upper and lower chambers (atrium and

ventricle) on each side of the heart, the tricuspid valve on the right and the mitral

valve on the left.

The other two lie at the exit of each ventricle into the two large arteries carrying

blood from the heart, the pulmonary valve at the exit from the right ventricle intothe pulmonary artery, and the aortic valve at the exit from the left ventricle into

the aorta.


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Structure of Heart valves

Together collagen, elastin, and GAGs comprise the valvular ECM.

Important structures in the aortic and pulmonary valves are the cusps,

commissures, and the supporting structures in the aortic and pulmonary roots. The key components of the mitral and tricuspid valves , are the leaflets,

commissures, annulus, chordate tendineae, papillary muscles, and atrial and

ventricular myocardium.

Cusps are cupped, or bowl shaped, segments . When blood is moving in the

right direction the cusps separate widely; when blood tries to move in the

opposite direction the cusps close tightly and form a watertight seal direction.

Valve cusps and leaflets are sufficiently thin to be nourished predominantly by

diffusion from the hearts blood hence they have only focal blood vessels and

nerves .

Microscopically, the heart valves have same structure and composed of three

layers,(1) Ventricularis - closest to the inflow surface and rich in radially aligned

elastin fibres

(2) Fibrosa - closest to the outflow layer, containing predominantly

circumferentially aligned, macroscopically crimped, densely packed collagen.

(3) Spongiosa - located in the central part and rich in glycosoaminoglycans(GAGs) and loosely packed collagen


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Structure of Heart valve


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Mechanical Stress:

During every cardiac cycle the leaflets undergo complex mechanical stresses

(1) sheer stress due to blood flow (open valve)

(2) flexture - opening and closing of valve

(3) tension (closed valve).

Forces acting on the wall on the macroscopic level are translated into biochemical

responses at the tissue level which are transduced into VIC( Vascular Interstitial

cells) response on cellular level.


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Function of heart valves

The valves allow blood to pass into and out of the heart chambers in one directiononly, with no backflow of blood

The aortic valve allows the flow of blood from the left ventricle to the aortaduring left ventricular contraction. It also prevents backward flow of bloodduring its relaxation.

The mitral valve allows the flow of blood from the left atrium into the leftventricle during left ventricular relaxation. It also prevents leaking of bloodfrom the left ventricle to the left atrium during left ventricular contraction.

The tricuspid valve allows the flow of blood from the right atrium into the rightventricle during right ventricular relaxation. It also prevents leaking of bloodfrom the right ventricle to the right atrium during left ventricular contraction.

The pulmonary valve allows the flow of blood from the right ventricle tothe pulmonary artery during right ventricular contraction. It also preventsbackward flow during its relaxation.

Properties of Heart valves:

Viability

Sufficient strength to withstand repetitive and substantial mechanical stress

Ability to adapt and repair injury by connective tissue remodelling.


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Prosthetic heart valvesCurrently used heart valve prostheses can be divided into two basic groups,

Mechanical prostheses

Biological prostheses

Mechanical valve prosthesis:

It provide good structural durability but also have the risk of prosthetic valve

endocarditic and high rates of thromboemolic complication caused by their non-physiological surface and flow abnormalities.

Anticoagulation therapy is needed for those patients for entire life which causes

spontaneous bleeding and embolism; particularly patients aged 70 years .

Hence bio prosthetic heart valves came into existence.


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Bio prosthetic Valves:

There are three types of bio prosthetic valves are available:

Porcine xenograft valves and bovine pericardial valves ( implants derived

from species other than human ), Allograft valves ( homograft- derived from humans other than patients ),

Auto graft (derived from autologous patients tissue ).

The advantages : Xenograft are chemically crosslinked which inhibitsautolysis, enhances mechanical stability, creating possibility of havingvalves of different sizes, risk of thromboemboliccomplication is muchlower. Due to chemical pre treatment they differ from native valves intheir closing and opening behaviour that is xenografts were stiffer inradial manner whereas less stiff in circumferential manner compared tonative porcine valves.

The disadvantages : The durability of the valve is much lower, structural

failure is strongly age limited that is xenografts are suitable for eldersmore than children and young adults.


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Examples of heart valve prostheses:

(A) Mechanical heart valve

(Medtronic) including sewing ring

(B) Biological heart valve (non-living

fixed tissue) surrounded by a sewing

ring.

(C) Living, tissue engineered tri-

leafletheart valve based on human

marrow stromal cells .


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Dynamic loading on Heart

Valves


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EFFECT OF BLOOD FLOW

Systolic and diastolic pressures lead to tensile and compressive

stress development on the valves.

Change in bending nature of the valve.

This is due to change in shear stress and pressure load

Blood flow also varies on the inward and outward sides of the heartvalves

Blood flow on the ventricularis side UNIDIRECTIONAL AND

PULSATILE

Blood flow on the fibrosa side SLOWER AND OSCILLATORY

DATAS : SYSTOLE VALVE OPEN ZERO PRESSURE GRADIENT

DIASTOLE VALVE CLOSED 80 mmHg PRESSURE GRADIENT

SHEAR STRESS ACTING ON VALVE SURFACE l 30-1500 dynes/cm sq.


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EFFECT ON ENDOTHELIAL

CELLS OF HEART VALVE

Valvular Endothelial Cells

Valvular Interstitial Cells

Dynamic loading induces the formation of ECM by

VICs.During this process there will be deposition of :

1.Collagen

2. GAGs.

This was confirmed with the execution of RossOperation.

Alignment of VECsperpendicular to flow direction


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VORTEX FORMATION Sinus of

Valsalva vortex formation harmony with

the aortic sinus and its curved

geometry provides a closure

mechanism for the aortic

Valve. NOTE:

Velocity profile, time course of blood

flow and magnitude of the peak

velocity


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Vortex formationEddying motion

deceleration of blood flow stimuli for

vave closure


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Modelling of Flow Dynamics

Flow based deformation measurement

Local tissue strains volumetric changes ofheart valves


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Flow based deformation measurement - Apparatus

Fluid injected inside upper chamber valves deform

signal recorded fluid enters lower chamber valves

return to original shape corresponding signal recorded


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Mechanism of valve closure


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Scaling levels

A single scaling level promises bulkproperties but effective functioning notproved.

Various levels:1. Molecular level laser focusing on collagen

2. Cellular level* continuum * fluid and solid

3. Tissue level

Anisotropic, non-linearproperties of tissues.

4. Organ level physiclal examinations

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Need for Heart Valves With Improved Functionality