Dr. Al-Sheikhly Dr. Bigio Dr. Briber Dr. Bonenberger Dr. Ethridge Dr. Fourney Dr. Kofinas Dr. Phaneuf Dr. Seog Mr. John Abrahams Mr. Michael Kasser Mr. Tom Loughran Mr. Xin Zhang

Background Motivation Intellectual merit & impact Technical approach

› Fabrication› Testing› Simulations

Problems Encountered Schedule Future Work Conclusions References

Stents reduce restenosis rates to 10-40% following angioplasty

Desirable stent properties include:› High radial strength› Good compliance matching with arterial walls› Biocompatible› Radio-opacity for visualization during X-ray, MRI, etc.› Contain drugs and/or genes for additional therapy

Stoeckel D, Bonsignore C, Duda S. A survey of stent designs. Min Invas Ther & Allied Technol 2002;11:137-147.

Shape memory polymers are based upon different conformations of polymer chains at different temperatures

Because shape memory effect is not due to a phase change, strains up to 400% are recoverable

Ratna et al. Recent advances in shape memory polymers and composites. J Mat Sci 43 (2008) 254.

http://my.clevelandclinic.org/PublishingImages/heart/stent_smart.jpg

All stents currently approved for use by FDA are metallic

Disadvantages:› Rapid expansion rates› Compliance mismatching› High manufacturing costs› Limited areas available for drug loading

Aim is to improve upon current stent technology through the use of a reinforced shape memory polymer with unique advantages

We hoped to gain an increased understanding of the strengthening mechanisms within a shape memory polymer

A reinforced shape memory polymer stent may be a safer and more biomedically friendly device

Stronger shape memory polymers will have applications in many fields, not just stents

Reinforced SMP stent designed through:

› Fabrication of prototype reinforced SMP material

› Mechanical testing of prototype material

› Computer simulations of reinforced SMP stent response

Materials:› Monomer: tert-butylacrylate (tBA)› Crosslinker: Poly(ethylene glycol)n

dimethacrylate (PEGDMA)› Photoinitiator: 2,2-Dimethoxy-2-

phenylacetophenone (DMPA)› Reinforcement: Montmorillonite clay platelets

(Cloisite®) Samples made with 0%, 0.5%, 1%, 2%, 3%

reinforcement (by weight) at both 20% & 40% crosslinking

tBA & PEGDMA distilled with hydroquinone/methyl-ester remover

tBA, PEGDMA, DMPA (0.1 wt%), & Cloisite® mixed and injected into mold made of 1/16” viton gasket between two glass slides coated with Rain-X® as a releasing agent

UV broad-spectrum light used in photopolymerization

Post-bake performed for 3hrs at 70°C

Cost:› Group spent $910.63 in researching › Materials $0.23/stent, total cost $3.05/stent

Tg determined using DSC› Only non-reinforced samples had obvious

transition› 20% - 38°C, 40% - 27°C

20% & 40% non-reinforced samples 40% cross-linked samples

27.39°C(H)

23.89°C

30.84°C

37.25°C(H)

35.17°C

39.33°C

-0.6

-0.5

-0.4

-0.3

-0.2

Hea

t Flo

w

(W/g

)

-20 0 20 40 60 80

Temperature (°C)

40-NR.001––––––– 20-NR.001– – – –

Exo Up Universal V4.1D TA Instruments

-0.7

-0.5

-0.3

-0.1

0.1

0.3

Hea

t Flo

w

(W/g

)

-20 0 20 40 60 80

Temperature (°C)

40P-3C––––––– 40P-2C– – – – 40P-1C––––– · 40P-0.5C––– – – 40P-NR––– –––

Exo Up Universal V4.1D TA Instruments

Compressive modulus calculated from tensile & flexural tests using method of Mujika et al

Flexural modulus determined using TMA

12

f

t

tc

E

E

EE

t3

3

fsbh4

FLE

Tensile modulus determined using tensile tester

Tensile test specimen Tensile test apparatus & furnace

Tensile modulus at body temperature

Compressive modulus calculation results

Direct measurements were also performed

Two simulation categories:› Reinforced SMP modulus determination› Buckling analysis

Stent designed as non-perforated cylinder

Modulus determination simulated using small block of SMP material

Buckling analysis based on constant, uniform pressure on exterior of stent wall

Max pressure from Agrawal et al› 300mmHg (40KPa) differential pressure across

stent› Use 80KPa for a safety factor of 2

Analyze for wall thickness when collapse occurs› Buckling theory:

3

o2 D

t

1

E2*P

Timoshenko SA, Gere JM. Theory of elastic stability. McGraw Hill, New York, New York 1961.

Unfamiliarity with bioengineering issues ANSYS

› Buckling Fabrication

› Bubbles, high wt% samples Tensile testing at body temperature

› Oven, heat gradients Communication between committees Underestimated time for many processes

Biocompatibility testing› Cytotoxicity, thrombosis, platelet adhesion

Further environmental tests› Creep, erosion, wet strength

More detailed simulations› Uneven plaque distribution, non-cylindrical arteries

Shape memory effect testing› Strain recovery rates & recovery times

Collapse press tests Drug & gene loading investigations Sterilization techniques Clinical trials

Testing revealed much lower than expected moduli for the reinforced SMP material at body temperature due to its lower than expected Tg

› Must control Tg with two cross-linkers & maintain above body temp

The low modulus of the prototype material resulted in a necessary stent wall thickness of 480µm, about twice as large as is practical› 480µm wall thickness reduces flow rate to 58% original flow rate

Simulations as performed were sufficient to show general trends in the behavior of the material but accuracy could be improved with more advanced version of software› Difficulties due to unfamiliarity with software

Yakacki CM, Shandas R, Lanning C, Rech B, Eckstein A, Gall K. Unconstrained recovery characterization of shape-memory polymer networks for cardiovascular applications. Biomaterials 2007;28:2255-2263.

Stoeckel D, Bonsignore C, Duda S. A survey of stent designs. Min Invas Ther & Allied Technol 2002;11:137-147.

Timoshenko SA, Gere JM. Theory of elastic stability. McGraw Hill, New York, New York 1961.

Agrawal CM, Haas KF, Leopold DA, Clark HG. Evaluation of poly(l-lactic acid) as a material for intravascular polymeric stents. Biomaterials 1992;13:176-182.

PEGDMA DMPAtBA

Images from: www.sigmaaldrich.com

Tensile test at body temperature

Tensile test at room temperature

Displacement in x-direction

Displacement in y-direction

Displacement in z-direction

Typical failed buckling analysis resulting displacement