Hemocompatibility of Surface

Modified Diamond-like Carbon

CoatingsR. K. Roy, M.-W. Moon, K.-R. Lee

Future Technology Research Laboratories, KIST, Seoul, Korea

D.K. HanBiomaterials Research Center, KIST, Seoul, Korea

J.-H. ShinDepartment of Radiology, Asan Medical Center, Universtiy of Ulsan, Korea

A. KamijoUniv. Tokyo Hospital, Tokyo, Japan

T. HasebeTachikawa Hospital, Keio University, Tokyo, Japan

ABMC 2007, Tsukuba, 2007. 12. 6.

Requirements for Bioimplants1. Should not cause infections2. Prevent uncontrolled cell growth3. Maintain their integrity inside the body4. Interact in a controllable way with the

biological environment5. Avoid formation of debris

Requirements for Bioimplants1. Should not cause infections2. Prevent uncontrolled cell growth3. Maintain their integrity inside the body4. Interact in a controllable way with the

biological environment5. Avoid formation of debris

Surface PropertiesSurface Properties

Bioimplant Materials

Required Surface Properties

• Biological Compatibility– Nontoxic, Noncarcinogenic, Noninflammatory

• Chemical Compatibility– Corrosion Resistance

• Mechanical Compatibility– Surface Hardness, Wear Resistance

Diamond-like Carbon :Diamond-like Carbon :as a Strong Candidate Coating as a Strong Candidate Coating

Vascular Stents

• Formation of blood clots Restenosis• Release of metal ions

Hemocompatible and Hermetic CoatingHemocompatible and Hermetic Coating

Clotted Artery

DLC Coated Blood Contacting Implants

CarbofilmTM by Sorin Biomedica, Inc.

DLC is sufficiently hemocompatible?

• DLC film is not a specific material but a group of amorphous carbon thin films. For each application, we need to optimize the property.

Understanding of hemocompatibilityof various DLC surfaces

Si incorporated DLC films with modified surface

Si-DLC Film

10-14 10-13 10-12 10-11 10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-3 10-2 10-1 100 101

-600

-400

-200

0

200

400

600

800

1000

1200

1400

1600

Po

ten

tial (

mV

vs

SC

E)

Current Density (A/cm2)

Substrate Si-C:H, Bias voltage = -400V a-C:H, Bias voltage = -800V a-C:H, Bias voltage = -400V

Potentiodynamic Polarization in Saline Solution

Thin Solid Films, 475, 291-397 (2005).J. Biomed. Mater. Res. A in press (2007).

Schematic diagram of RF PACVD system.

Film Preparation

• Film Deposition– C6H6 + SiH4

– Pressure : 1.33 Pa– Bias voltage : -400V– Film thickness : ~500nm – Si Concentration in the

film : 2 at.%

• Surface Treatment– O2, N2, H2, CF4

– Pressure : 1.33 Pa– Bias voltage : -400V– 10min

Surface modification of Si-DLC

20

40

60

80

100W

ater

co

nta

ct a

ng

le (

in d

egre

e)

SiDLC( O2treated)

SiDLC(N2treated)

SiDLC(H2treated)

SiDLC(CF4treated)

SiDLCSi Nitinol

Energetics of Surface

(cos ) lv sv sl

22ll

pl

dllv

22ss

ps

dssv

)(2

cos1

)(2)(2cos1

lslslv

lv

pl

ps

lv

dl

ds

Liquid αl βl

γlv

(ergs/cm2)

Water 4.67 7.14 72.8

Formamide 6.28 4.32 58.2

2 : Fowkes' Eq.d dsl sv lv s l

Surface Energy

Polar component

0

10

20

30

40

50

60

SiDLC SiDLC (O

2

treated)

SiDLC (N

2

treated)

SiDLC (H

2

treated)

SiDLC (CF4

treated)

Sur

face

ene

rgy

(dyn

e/cm

)

Dispersive component

Polar Component and Wetting

0 10 20 30 40 50 600

20

40

60

80

100W

ater

co

nta

ct a

ng

le (

deg

ree)

Polar component of surface energy (dyne/cm)

CF4 plasma

N2 plasma

As depositedH2 plasma

O2 plasma

Si wafer

Interfacial Tension with Human Blood

α (dyne/cm)1/2

β (dyne/cm)1/2

Human Blood

3.3 6.0

221

22112 )()(

0

5

10

15

20

25

SiDLC(O2

treated)

SiDLC(N2

treated)

SiDLC(H2

treated)

Blo

od B

iom

ater

ial i

nter

faci

al t

ensi

on

(dyn

e/cm

)

SiDLC SiDLC(CF4

treated)

α β

Si-DLC 5.4 ± 0.5 3.3 ± 0.6

Si-DLC (CF4 treated) 5.0 ± 0.4 2.0 ± 0.5

Si-DLC (N2 treated) 5.1 ± 0.2 5.5 ± 0.3

Si-DLC (O2 treated) 4.2 ± 0.1 7.3 ± 0.1

Si-DLC (H2 treated) 5.5 ± 0.3 3.5 ± 0.4

100 102 104 106

4

8

12

16

Inte

nsi

ty (

x1

0 )

Binding energy (eV)

Si-C

Si 2pSiDLC

Si2O3

SiO2

(b)

280 284 288 2920

10

20

30

40

50

Inte

nsi

ty (

x1

0 2

)

Binding energy (eV)

C=C

C-C

Si-DLC

C 1s(a)

280 284 288 2920

10

20

30

40

Inte

nsity

( x

10

2 )

Binding energy (eV)

C=C

C-CC-OH

H2-Si-DLC

C 1s(c)

100 102 104 106

4

8

12

16In

tens

ity (

x10

)

Binding energy (eV)

Si-C

Si-Si

Si2O3

Si 2pH2-Si-DLC(d)

XPS Anaysis

280 284 288 2920

5

10

15

20

25

Inte

nsity

( x

10 2 )

Binding energy (eV)

C-CFn

CF-CFn

CF2 CF3

1

2

C 1sCF4-Si-DLC(e)

100 102 104 106

4

6

8

10

Inte

nsi

ty (

x 1

0 )

Binding energy (eV)

Si-C

Si2O3

SiO2

Si-Si

Si 2pCF4-Si-DLC(f)

684 688 692

10

20

30

40

Inte

nsity

( x

10 2

)

Binding energy (eV)

F 1s

CF4-Si-DLCCFn(g)

_

_

100 102 104 106

5

10

15

20

25

Inte

nsity

(x1

0)

Binding energy (eV)

Si-N

Si-CSiO2

Si 2pN2-Si-DLC(i)

280 284 288 2920

5

10

15

20

25In

tens

ity (

x 1

0 2

)

Binding energy (eV)

C 1sN2-Si-DLCC=C

C=N

C=N

C-C

C-N

(h)

394 396 398 400 402 4044

8

12

16

Inte

nsity

( x

10

2 )

Binding energy (eV)

N 1s

N2-Si-DLC

C-N

C=N

N1

N2

(j)

N1 : Si-NN2 : C=N

280 284 288 2920

4

8

12

16

Inte

nsity

( x

10 2

)

Binding energy (eV)

C=C

C-C C-O C=O

C 1sO2-Si-DLC(k)

100 102 104

20

40

60

80

Inte

nsi

ty (

x10

)

Binding energy (eV)

Si 2pO2-Si-DLC

Si2O3

SiO2

Si-C

(l)

528 530 532 534 536

10

20

30

40

50

Inte

nsi

ty (

x1

0 2

)

Binding energy (eV)

O 1sO2-Si-DLC

Si=O

C=O

(m)

_

_

100 102 104 106

4

8

12

16

Inte

nsi

ty (

x1

0 )

Binding energy (eV)

Si-C

Si 2pSiDLC

Si2O3

SiO2

(b)

280 284 288 2920

10

20

30

40

50

Inte

nsi

ty (

x1

0 2

)

Binding energy (eV)

C=C

C-C

Si-DLC

C 1s(a)

XPS Anaysis

280 284 288 2920

4

8

12

16

Inte

nsity

( x

10 2

)

Binding energy (eV)

C=C

C-C C-O C=O

C 1sO2-Si-DLC(k)

100 102 104

20

40

60

80

Inte

nsity

(x1

0)

Binding energy (eV)

Si 2pO2-Si-DLC

Si2O3

SiO2

Si-C

(l)

XPS Analysis

FilmsChemical bonds present on surface

(XPS analysis)

Si-DLC or Si-DLC (H plasma

treated)C=C, C-C, Si-C, Si-O

Si-DLC(CF4 plasma treated)

C=C, C-C, C-CFn, Si-C, Si-O

Si-DLC(N plasma treated)

C=C, C-C, C-N, Si-N, Si-O

Si-DLC(O plasma treated)

C=C, C-C, C-O, Si-O

aPTT Measurement

• Activated partial thromboplastin time (aPTT) determines the ability of blood to coagulate through the intrinsic coagulation mechanism.

• Soaking for 60min in platelet poor plasma (PPP: 7x103/l) using human whole blood from healthy volunteer.

25

26

27

28

29

30

SiDLC(O2

treated)

SiDLC(N2

treated)

SiDLC(H2

treated)

SiDLC(CF4

treated)

aPT

T (

sec)

1 hour

Plasma Protein Adsorption

• ELISA analysis after treating the samples with albumin (3mg/ml) and fibrinogen (0.2mg/ml) solution.

• Better hemocompatibility can be expected on the surface with higher ratio of albumin/fibrinogen adsorption.

0.0

0.5

1.0

1.5

2.0

SiDLC (H2

treated)

SiDLC(O2

treated)

SiDLC(N2

treated)

SiDLC (CF4

treated)

SiDLC

Alb

umin

/ f

ibri

noge

n ra

tio

5 mins

60 mins

Platelet Adhesion Measurement

• Soaked for 60 min in PRP (1.5x1015/ml) from human whole blood from healthy volunteer.

• Adherent platelet are fixed and dehydrated for observation under OM and SEM.

Si-DLC Si-DLC(CF4) Si-DLC(N2) Si-DLC(O2)0

10

20

30

40

50

60

70

80

90

100

Pla

tele

t Ad

he

sio

n A

rea

Ra

tio (

%)

Specimen

Platelet Activation

Goodman and Allen et al.

On a-C:H surface

Lose discoid shape

Develope thin pseudopodia

Become large, spiny sphere covered by Pseudopodia

Fully spread

Platelets on Si-DLC

Platelets on Si-DLC (N2)

Platelet on Si-DLC (O2)

Nitrogen or Oxygen Plasma Treatment

25

26

27

28

29

30

SiDLC(O2

treated)

SiDLC(N2

treated)

SiDLC(H2

treated)

SiDLC(CF4

treated)

aPT

T (

sec)

1 hour

0.0

0.5

1.0

1.5

2.0

SiDLC (H2

treated)

SiDLC(O2

treated)

SiDLC(N2

treated)

SiDLC (CF4

treated)

SiDLC

Alb

umin

/ fib

rinog

en r

atio

5 mins

60 mins

Si-DLC Si-DLC(CF4) Si-DLC(N2) Si-DLC(O2)0

10

20

30

40

50

60

70

80

90

100

Pla

tele

t A

dh

esi

on

Are

a R

atio

(%

)

Specimen

Sl.No.

ReferencesHemocompatibility

Improves by

1Baier,

Academic Press,New York, 1970.

Critical surface tension of materials ~ 20-30dyne/cm

2Akers,

J.Colloid Interface Sci. 59 (1977) 461.

Zone of biocompatibility

3Ruckensten & Gourisanker,J. Colloid Interface Sci. 101

(1984) 436.

Blood biomaterial interfacial tension of

the order of 1-3 dyne/cm

4

Callow,International

Biodeterioration & degradation, 34 (1994) 333.

Surfaces having initial surface tension

20-30 dyne/cm

5Yu,

Surf. Coat. Technol.128-129 (2000) 484.

Low blood biomaterial interfacial tension

(8.5 dyne/cm)

6Kwok,

Diam. Rel. Mater. 14 (2005) 78.

interfacial tension of about the same magnitude as cell-medium interfacial

tension (1-3 dyne/cm)

Hemocompatibility and the Surface

0

5

10

15

20

25

SiDLC(O2 treated)

SiDLC(N2 treated)

SiDLC(H2 treated)

Blo

od

Bio

ma

teri

al i

nte

rfa

cia

l te

nsi

on

(d

yne

/cm

)

SiDLC SiDLC(CF4 treated)

Conclusions

• Hemocompatibility of Si-DLC film would be improved by surface treatment using nitrogen and oxygen plasma.– Large surface energy (large polar component)– Low interfacial energy with blood

• Aging of the surface with large surface energy should be carefully considered in characterizing their surface properties. Characterization should be done within 12 hours after the treatment.

Acknowledgement

Financial Support from 'Center for Nanostructured Materials Technology' under '21st Century Frontier R&D Programs' of the Ministry of Science and Technology of Korea (code #: 06K1501-01610), and Taewoong Medical Co. Ltd.