-
7/29/2019 Need for Heart Valves With Improved Functionality
1/24
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
2/24
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
-
7/29/2019 Need for Heart Valves With Improved Functionality
3/24
3
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
4/24
4
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 .
-
7/29/2019 Need for Heart Valves With Improved Functionality
5/24
5
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
6/24
6
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
-
7/29/2019 Need for Heart Valves With Improved Functionality
7/24
7
Structure of Heart valve
-
7/29/2019 Need for Heart Valves With Improved Functionality
8/24
8
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
9/24
9
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
10/24
-
7/29/2019 Need for Heart Valves With Improved Functionality
11/24
11
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
12/24
12
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
13/24
13
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 .
-
7/29/2019 Need for Heart Valves With Improved Functionality
14/24
14
-
7/29/2019 Need for Heart Valves With Improved Functionality
15/24
Dynamic loading on Heart
Valves
-
7/29/2019 Need for Heart Valves With Improved Functionality
16/24
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.
-
7/29/2019 Need for Heart Valves With Improved Functionality
17/24
-
7/29/2019 Need for Heart Valves With Improved Functionality
18/24
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
-
7/29/2019 Need for Heart Valves With Improved Functionality
19/24
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
-
7/29/2019 Need for Heart Valves With Improved Functionality
20/24
Vortex formationEddying motion
deceleration of blood flow stimuli for
vave closure
-
7/29/2019 Need for Heart Valves With Improved Functionality
21/24
Modelling of Flow Dynamics
Flow based deformation measurement
Local tissue strains volumetric changes ofheart valves
-
7/29/2019 Need for Heart Valves With Improved Functionality
22/24
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
-
7/29/2019 Need for Heart Valves With Improved Functionality
23/24
Mechanism of valve closure
-
7/29/2019 Need for Heart Valves With Improved Functionality
24/24
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