TREATMENT OF MITRAL VALVE INSUFFICIENCY BY SHAPE

MEMORY POLYMER BASED ACTIVE ANNULOPLASTY

Pilar Lafont Morgado, Andrés Díaz Lantada, Héctor Lorenzo-Yustos, Julio Muñoz-García

División de Ingeniería de Máquinas – E.T.S.I. Industriales – Universidad Politécnica de Madrid

C/ José Gutiérrez Abascal, nº 2. 28006 – Madrid, Spain

Ignacio Rada Martínez, Antonio Jiménez Ramos, José Luis Hernández Riesco

Hospital Gómez Ulla

Glorieta del Ejército s.n. 28047 – Madrid, Spain

Keywords: Shape Memory Polymers (SMP), Mitral valve Insufficiency, Annuloplasty ring, Laser Stereolithography,

Silicone mould vacuum casting, Biomaterials.

Abstract: Active materials are capable of responding in a controlled way to different external physical or chemical

stimuli by changing some of their properties. These materials can be used to design and develop sensors,

actuators and multifunctional systems with a large number of applications for developing medical devices.

(for both surgery and implants).

Shape memory polymers are active materials with thermo-mechanical coupling (changes in temperature

induce shape changes) and a capacity to recover from high levels of distortion, (much greater than that

shown by shape memory alloys), which combined with a lower density and cost has favoured the

appearance of numerous applications. In many cases, these materials are of medical grade, which increases

the chances of obtaining biocompatible devices.

This paper presents the design, manufacture, “shape memory” programming process and in vitro trials of an

active annuloplasty ring for the treatment of mitral valve insufficiency, developed by using shape memory

polymers. This has been done with the collaboration betweeen researchers from Universidad Politécnica de

Madrid and doctors from the Hospital General Central de la Defensa.

1 MITRAL INSUFFICIENCY AND

POSSIBLE IMPROVEMENTS

IN ANNULOPLASTY

TREATMENT

1.1 Mitral Valve Insufficiency

The mitral valve is made up of two components

whose mission is to channel the blood from the left

auricle to the left ventricle. Firstly, there is the so-

called “mitral valve complex” comprising the mitral

annulus, the valve leaflets, and the commissures

joining both valves. Apart from the mitral valve

complex itself, this valve has the so-called “tensor

complex”, which in turn comprises the chordae

tendineae which continue with the papillary muscles

attached to the left ventricle.

A failure of any of these elements leads to

functional changes in the mitral apparatus, such as

mitral insufficiency, explained below, and

hemodynamic repercussions.

Mitral insufficiency (or regurgitation) is defined

as the systolic regurgitation of blood from the left

ventricle to the left auricle, due to incompetence in

mitral valve closing. This can arise for three main

reasons: a) primary disease of the mitral valve; b) an

anatomic or functional alteration in the chordae

tendineae or in the papillary muscles, and c) a

disorder in the correct function of the left auricle and

the left ventricle (Díaz Rubio, 1994).

Valve reconstruction is currently the preferred

treatment for mitral insufficiency provided this is

possible. With the aid of preoperative transesophagic

echocardiography lesions can be located and their

extent seen, so a surgeon can evaluate if valve repair

is possible and thus design an exact plan for any

Lafont Morgado P., Díaz Lantada A., Lorenzo-Yustos H., Muñoz-García J., Rada Martínez I., Jiménez Ramos A. and Luis Hernández Riesco J. (2008).

TREATMENT OF MITRAL VALVE INSUFFICIENCY BY SHAPE MEMORY POLYMER BASED ACTIVE ANNULOPLASTY.

In Proceedings of the First International Conference on Biomedical Electronics and Devices, pages 17-22

DOI: 10.5220/0001046400170022

 SciTePress

operation required. Nowadays, the object of this

surgery is not simply limited to eliminating mitral

insufficiency but in many cases to reconstructing the

geometry of the entire mitral valve apparatus to

ensure a durable repair.

Surgically restoring the geometry to normal

conditions consists in: a) augmenting or reducing the

abnormal leaflets; b) replacing broken or short

chordae tendineae using “Goretex” type sutures, and

c) annuloplasty.

1.2 Treating Mitral Insufficiency with

Annuloplasty

Carpentier’s description of a rigid prosthetic ring to

allow a selective reduction of the entire mitral

annulus opened the way to modern mitral repair.

Annuloplasty consists in inserting the said ring-

shaped device into the coronary sinus and after

applying traction, retraction or heat, it reduces its

perimeter, thereby reducing the mitral annulus and

improving the contact between the valve leaflets,

which leads to a reduction in the patient’s degree of

mitral insufficiency (Hernández, 2005).

Since then, a series of implants have been

developed that can be basically classified as rigid or

flexible and total or partial. Rigid monoplane

implants have been displaced due to the large

number of experimental and clinical works showing

that the perimeter of the mitral annulus constantly

changes in size and shape during the heart cycle.

The recent findings showing that these changes are

produced in a three-dimensional way with a

hyperbolic paraboloid shaped ring has given rise to

new rigid three-dimensional prosthesis. Duran

proposes replacing the most conventional devices

for other flexible or semi-rigid designs that

reproduce the three-dimensional shape, such as the

one marketed by Medtronic Inc..

1.3 Desirable Improvements

Employing Progressive Procedures

However, inserting a device to close the mitral valve

means making additional demands on the heart that

may lead to postoperatory problems. It would be

ideal to insert a ring with the same shape as the

patient’s mitral annulus and, when they have

recovered from the operation, progressively act on

this ring (in several stages) and remotely. This seeks

to maintain a balanced situation and not excessively

overload the patient’s heart during the operation.

In this way, the progressive closing of the

patient’s mitral annulus can be controlled and, by

using non-invasive inspection technologies, the

improvement in the patient’s mitral insufficiency

can be evaluated after each stage of the ring

actuation.

2 SOLVING MECHANICAL

OPERATION USING SHAPE

MEMORY POLYMER BASED

DEVICES

2.1 Shape Memory Polymers in

Medical Devices

Shape memory polymers (SMPs) are materials that

give a mechanical response to temperature changes.

When these materials are heated above their

“activation” temperature, there is a radical change

from rigid polymer to an elastic state that will allow

deformations of up to 300%. If the material is cooled

after manipulation it retains the imposed shape; it

“freezes”, the said structure returning to a rigid but

“non-equilibrium” state. When the material is heated

above its activation temperature, it recovers its

initial undeformed state.

The cycle can be repeated numerous times

without degrading the polymer and most suppliers

can formulate different materials with activation

temperatures ranging between –30 ºC and 260 ºC,

depending on the application required.

They are therefore active materials that present

thermomechanical coupling and

a capacity to recover

from high levels of distortion

, (much greater than

shown by shape memory alloys), which combined

with a lower density and cost has favoured the

appearance of numerous applications. Their

properties allow applications for manufacturing

sensors and actuators, especially for the aeronautic,

automobile and medical industry (Lendlein, Kelch,

2002).

The main problem associated with the use of

shape memory polymers is the lack of structured

processes for developing devices based on these

materials. The design process for these devices and

the transformation processes for these materials need

to be more thoroughly investigated.

The main advantages of shape memory polymers

are:

• They are new materials with the ability to

change their geometry from an initial

deformed shape to a second shape

predetermined during the manufacturing

process.

BIODEVICES 2008 - International Conference on Biomedical Electronics and Devices

• They are more economical than shape

memory alloys.

• Different additives can be used to change

their properties “a la carte”, to better adapt

them to the end application.

• The levels of deformation are much greater

than those obtainable using shape memory

alloys.

• They can also be more easily processed and

allow the use of “Rapid Prototyping

Technologies”, which speeds up the

production of devices.

• More complex geometries and actuators

can be obtained than with developments

based on shape memory alloy.

However, due to their recent appearance, in

many cases their mechanical and thermomechanical

properties are still not completely typified, which

gives rise to doubts concerning how devices based

on these materials will react. One of the basic aims

of current research is to increase knowledge of the

properties of these polymers by improving

characterization processes.

Regarding the development of medical devices,

both surgical and implantable ones, they have

additional advantages to those mentioned above:

• They are frequently medical grade

materials which increases the chances of

obtaining biocompatible devices.

• The combined use of preoperative

inspection technologies and CAD-CAE-

CAM technologies means that prostheses

and customised devices can be tailored for

patients.

• Their activation temperature and properties

can be adapted to the application, thanks to

the amount of copolymers employed and

the use of additives.

Among the medical devices developed that take

benefit from the advantages of these polymers, the

most notable are self-expanding stents, drug release

devices, thrombectomy devices, intelligent sutures

and active catheters (Lendlein, 2002, 2005, Wilson,

2006).

2.2 Shape Memory Polymers for Active

Annuloplasty

Commercial annuloplasty rings based on shape

memory polymers have been patented but not yet

developed.

The Sorin Group’s Memo 3D manages to reduce

its shape by using a shape memory alloy (Nitinol

type, similar to those used in the manufacture of

self-expanding stents). However, the change of

shape is produced during the operation itself on

making contact with human body temperature,

which means that no postoperative measures are

possible.

Besides, the capacity of shape memory polymers

to recover their shape against efforts of up to around

7 MPa means that a 3 mm thick annuloplasty ring,

similar to devices currently in use, manufactured

with these materials will be able to overcome a

circumferential force of between 4 N to 12 N that is

imposed by the patient’s mitral annulus.

In accordance with the above, what is proposed

is a ring made of shape memory polymer and

electrical resistances or heaters distributed inside to

activate the “shape memory effect” and therefore the

required shape change.

Firstly, the ring adapts to the end size required

(that needed to eliminate the mitral insufficiency)

and with the resistances already in place. The ring is

then uniformly heated to a temperature higher than

the transition temperature (situated for the end

product between 41 ºC and 43 ºC) and is forced to

take on the expanded transitory shape (to do this

cone-shaped tools can be used with a cross section

similar to that of the mitral annulus), letting it cool

down to room temperature. The device also consists

of a battery to power the resistances and heat them.

The rise in temperature of the resistances causes a

local rise in temperature, which, if suitably

controlled leads to a change in phase of the SMP and

the associated size reduction.

Using an associated electronic control enables

the resistances to be operated in pairs and at

different times, in order to carryout the progressive

or “step by step” operation required on the ring.

Figure 1 shows a preliminary design.

Figure 1: Preliminary active annuloplasty ring design.

SMP with internal resistances for heating.

A patent for this device was applied for by the

authors under the title of “Active annuloplasty

system for the progressive treatment of valve

insufficiencies and other cardiovascular pathologies”

TREATMENT OF MITRAL VALVE INSUFFICIENCY BY SHAPE MEMORY POLYMER BASED ACTIVE

ANNULOPLASTY

on 13 December 2006 with Application Number

P200603149 and is currently being evaluated by the

Spanish Patents and Trade Marks Office.

The following sections present the design

alternatives and the prototypes obtained, as well as

the first “in vitro” trials performed, the results, and

future recommendations for optimising the results.

The development has been carried out in

collaboration between researchers from from

Universidad Politécnica de Madrid and doctors from

the Hospital General Central de la Defensa.

3 DESIGN AND MANUFACTURE

OF PROTOTYPES

Computer aided design and calculation technologies,

(CAD – Computer Aided Design and CAE –

Computer Aided Engineering), have become an

essential tool for developing medical devices. They

enable alternative shapes and designs to be obtained

quickly, as well as making it easier to evaluate their

advantages by being able to analyse stress,

deformations, ergonomics or dynamic response.

They are also highly valuable for comparing and

selecting the different materials that can be used. In

addition, when combined with preoperative

inspection techniques, they serve to design

implantable devices tailored for the patient

measurements and simulate their implantation.

Figure 2 shows alternative designs for

annuloplasty rings made by using the “Solid Edge

v.18” computer design package. With the help of

these programmes it is very simple to change the

parameters of a design, which enables a shape to be

adapted to the size of a particular patient’s mitral

annulus or change the thickness of rings depending

on how long the device is required to last.

Figure 2: Alternative designs for annuloplasty rings

produced with CAD technologies.

Bellow is explained how prototypes are

manufactured from the designs shown and the

advantages of using rapid prototyping and rapid

tooling technologies.

Figure 3 shows the physical models obtained in

epoxy resin by laser stereolithography using an

SLA-350 machine available at the Product

Development Laboratory of Universidad Politécnica

de Madrid, from the designs shown in Figure 2.

Together with the annuloplasty designs, also shown

is a 3 mm thick, 30 mm outer diameter toroidal ring

to give the image an idea of scale.

Figure 3: Models obtained by laser stereolithography from

files containing the 3D part geometry.

The parts obtained by stereolithography are

particularly suitable for checking sizes, shapes and

appearance. They can also be used as models for

obtaining silicone moulds, which are subsequently

used to obtain polyurethane resin replicas, more

resistant and suited to working trials, and which also

possess shape memory properties. With the vacuum

casting process different types of bicomponent

resins can be used, with a wide range of properties,

and the prototypes obtained reproduce the mould

cavities with great precision (roughnesses of up to

50 μm) (Lafont, 2000).

The chosen material is a polyurethane resin from

MCP Iberia company with reference 3174 which is

supplied in bicomponent form, which means it can

be cast (after mixing the two components) in

silicone moulds to obtain the prototype shape

required.

It must be pointed out that shape change

temperature of the polyurethane resin used is not

suited to the “in vivo” end trials, nor fits the initial

specifications which required a range of 41 to 43 ºC

to activate the shape memory effect.

However, this polyurethane resin has been used

because it is easies to manipulate and cast in silicone

moulds, which enables prototypes to be made in less

than 5 days from computer file to end material.

Other mould manufacture technologies are

currently being used for casting alternative shape

memory polymers which do not attack the silicone

moulds and whose transition temperature can be set

from 4 to 6 ºC above that of the human body, suited

to the “in vivo”.

BIODEVICES 2008 - International Conference on Biomedical Electronics and Devices

Figure 4 shows silicone moulds obtained from

the physical epoxy resin models displayed in Figure

3. These moulds enable prototypes to be obtained

from the material with shape memory properties.

Figure 4: Silicone moulds obtained from laser

stereolithographic models.

Enhanced design models have led to the

construction of new silicone moulds and the

obtaining of improved prototype annuloplasty rings,

both solid ones and with circumferential grooves for

housing the heating resistances. These are shown in

Figure 5.

Figure 5: Different polyurethane resin prototypes obtained

under vacuum casting in silicone moulds. Both open and

closed rings were made to analyse alternative

performances.

4 PROGRAMMING PROCESS OF

THE SHAPE MEMORY

When the annuloplasty rings have been shaped to

ensure the mitral valve closes properly, they need to

undergo heat deformation at 80 ºC in the case of

polyurethane resin, (higher temperature than that

needed to activate the shape memory effect), to

increase their cross section until it coincides with the

patient’s mitral valve annulus in the initial state of

insufficiency.

By doing this, a temporary shape is obtained and

the ring can be implanted without submitting the

patient’s heart to an additional overload due to a

sudden reduction in the section of the mitral valve.

After the surgical operation the recovery effect

of the original shape is activated, which produces a

gradual, controllable closure of the valve and a

controlled recovery of mitral regurgitation.

To perform this “shape memory programming

process”, tools were used that were obtained by laser

stereolithography in the form of a cone base with a

similar cross section to that of the patient´s mitral

annulus.

Figures 6 shows the tool and deformations

caused to ring prototypes thanks to the use of a

counter-shape that acts as a press on the tool and the

prototype.

Figure 6: Design and prototype of a tool for programming

shape memory effect. Deformation caused at 80 ºC to

obtain a temporary shape.

Figure 7 shows an annuloplasty ring with the

temporary shape already applied and prepared for

implant and the first “in vitro” trials. With the aid of

a cone base a 15% increase in cross section was

produced (maximum inner diameter ring size pass

from 26 to 28 mm), which will be used to evaluate

the subsequent shape memory recovery in “in vitro”

trials.

Figure 7: Active ring with heating resistances with the

temporary shape already applied. It is ready to be

implanted and subsequently activated.

5 RESULTS OF “IN VITRO”

TRIALS

For performing the first “in vitro trials” two pig

hearts were used because of their similarity to

human ones, as is demonstrated by their being used

for biological valve replacement operations.

Figure 8 shows the process for activating the

shape memory process in the ring and reducing the

associated mitral ring cross section.

The 4,7 Ω resistances (a total of 7 resistances

with serial connection) were supplied with power by

a 12 V transformer. Thus an intensity of 364 mA

was obtained, similar to what can be supplied by

TREATMENT OF MITRAL VALVE INSUFFICIENCY BY SHAPE MEMORY POLYMER BASED ACTIVE

ANNULOPLASTY

implantable commercial devices. The images (left to

right) show a 10.7% reduction in cross section

during an operating period of 150 seconds. This

means a 71%, recovery compared to effort since the

increase in cross section induced was 15%.

By interrupting heating the temperature

decreases and the recovery process is halted, which

means the required effect can be obtained step by

step. By recommencing the heating process the

recovery will continue, although in these first “in

vitro” trials heating was done continuously in order

to evaluate the maximum recovery that could be

obtained and the duration of the entire process.

Temperature was continuoustly measured using a

thermocouple.

Error!

Figure 8: Activating the shape memory effect using

heating resistances.

Despite it being desirable a cross section

reduction of 15% to 20%, it is very important to

point out the material’s capacity for recovery while

overcoming the forces imposed by the mitral

annulus of the hearts used.

6 FUTURE IMPROVEMENTS

AND CONCLUSIONS

For the postoperative and progressive treatment of

mitral insufficiency the use of an annuloplasty

device made of shape memory polymer has been

proposed. It has electrical resistances distributed

inside it to activate the “shape memory” effect, so

that the required change in shape to reduce mitral

regurgitation can be progressively induced. This

provides an alternative to current devices, that do not

permit any change of shape after implantation, and

therefore any errors committed during the operation

cannot be corrected.

The design, manufacturing, “shape memory”

effect programming and “in vitro” trials of such an

annuloplasty ring for treating mitral insufficiency,

developed by using shape memory polymers, have

been presented.

This has been done in collaboration between

researchers from from Universidad Politécnica de

Madrid and doctors from the Hospital General

Central de la Defensa.

Using computer aided manufacture and design

technologies has enabled different designs and

prototypes to be produced in parallel, as well as

rapid improvements to obtain the devices that were

used in the in vitro trials.

Future actions regarding improvements in the

shape memory programming process should lead to

optimising the reduction in mitral ring cross section

up to the required 15% to 20%. Using alternative

shape memory polymers with a lower activation

temperature will also result in more suitable devices,

since they will require a smaller size heating system

and will be easier to manufacture.

However, it is very important to point out the

material’s capacity for recovery against the forces

imposed by the mitral annulus of the hearts used,

which shows the feasibility of developing an active

annuloplasty system based on the use of shape

memory polymers.

REFERENCES

Díaz Rubio, M., Espinós, D., 1994. Tratado de Medicina

Interna. Editorial Médica Panamericana.

Carpentier, A., 1983. Cardiac Valve Surgery – The French

Correction. Journal of Thoracic and Cardiovascular

Surgery.

Duran, C., 1992. Duran Flexible Annuloplasty Repair of

the Mitral and Tricuspid Valves: Indications, Patient

Selection, and Surgical Techniques Using the Duran

Flexible Annuloplasty Ring. Medtronic Inc..

Hernández, J.M., 2005. Manual de Cardiología

Intervencionista. Sociedad Española de Cardiología.

Sección de Hemodinámica y Cardiología

Intervencionista.

Lendlein, A., S. Kelch, 2002. Shape-Memory Polymers.

Angewandte Chemie International.

Lendlein, A., Langer, R., 2002. Biodegradable, elastic

shape-memory polymers for potential biomedical

applications. Science.

Lendlein, et al., 2005. Light-induced shape-memory

polymers. Nature.

Wilson,T., et al., 2006. Shape Memory Polymer

Therapeutic Devices for Stroke. Lawrence Livermore

National Laboratory.

Lafont, P., Lorenzo, H. et al., 2000. Rapid Tooling:

moldes rápidos a partir de estereolitografía. Revista de

plásticos modernos.

BIODEVICES 2008 - International Conference on Biomedical Electronics and Devices