institute of solid state physics, bulgarian academy of sciences, 1784 sofia, bulgaria, 72...

Institute of Solid State Physics, Bulgarian Academy of Sciences,1784 Sofia, Bulgaria, 72 Tzarigradsko Chaussee blvd.

PRODUCTION OF HIERARCHICALLY ORGANIZED

MICRO- AND NANOMETER SCALE SURFACES :

DEVELOPMENT OF NOVEL TECHNOLOGY FOR

IMPLANT COATINGS AND CELLS GROWTH

PRAMATAROVA Lilyana., Assoc. Prof. Dr.

Institute of Solid State Physics, Bulgarian Academy of Sciences,

72 Tzarigradsko Chaussee, bulv.,1784 Sofia, Bulgaria tel: +359-2-7144265 fax: +359-2-9753632 E-mail: [email protected] Web page: www.issp.bas.bg

mailto:[email protected]

http://www.issp.bas.bg/






PARTICIPANTS

1. Institute of Solid State Physics, Bulgarian Academy of Sciences, Assoc. Prof. Dr. L. Pramatarova, Development of in-vitro systems and production of hydroxyapatite (HA), RTD, Bulgaria; Address: Assoc. Prof. Dr. L. Pramatarova Institute of Solid State Physics, Bulgarian Academy of Sciences72 Tzarigradsko Chaussee blvd., 1784 Sofia, Bulgaria, tel. +359-2-7144265, fax +359-2-9753632 e-mail: [email protected] , web page: www.issp.bas.bg

2. Pulslight Ltd., Bulgaria (MS. I. Kostadinov), Laser systems and laser processing, (SME), Bulgaria Address: Pulslight Ltd., 72 Tzarigradsko Chaussee, blvd., 1784 Sofia, Bulgaria, tel: +359-2-9743002, fax: +359-2- 9743002 e-mail: [email protected], web page: www.pulslight.com

3. Base BIO POSITIONNING, (SME), FranceDr Didier Mauroy, Leader of the Project, Disposable use microchip for the real-time detection of thrombosisAddress: Rue de la Citadelle 11 F-33410 Rions, France tel.: + 33 (0) 556 769 301e-mail: [email protected]






http://www.pulslight.com/








The aim of the proposed project is the development of novel technology based on a process of laser-liquid-solid-interaction (LLSI) in simulated body fluids (SBF) and its

optimisation as a model of in vitro system for the controllable production of samples with hierarchically organized micro and

nanometer scale surfaces, typical for nature. The process of LLSI is based on simultaneously microengineering

of beforehand nanostructured substrate and growth of a layer of hydroxyapatite (HA) on the surface.

The HAP layer will be used as implant coatings as well as a non viral carrier in the gene therapy of certain bone pathologies.

For the implementation of the project the groupe is closely cooperated with a SME (Pulslight LTD, Sofia), ensures the laser system (copper bromide pulsed laser, equipped with a precise scanning system) necessary for the realization

of the LLSI technology.


METHOD FOR HYDROXYAPATITE GROWTH INDUCED BY THE PROCESS OF

LASER-LIQUID-SOLID INTERACTION (LLSI)

• The method of LLSI process employs a deposition system and a process, which allows interaction between a scanning laser beam and a liquid precursor solution (simulated body fluid, SBF), and also simultaneous laser illumination of the substrate during the laser-liquid interaction, thereby stimulating the nucleation and growth of hydroxyapatite (HA).

• Variously modified surfaces serve as substrates for the HA growth, induced by a laser-liquid-solid interaction process.


SCHEME OF AN IN VITRO SYSTEM ON THE BASE ON THE PROCESS OF

LASER-LIQUID-SOLID-INTERACTION (LLSI)


LASER PARAMETERS:

CuBr (copper bromide) laser 1 = 511 nm 2 = 578 nm

P = 4.5 W (average laser power) = 35 ns (pulse duration)d = 50 m (diameter of laser spot)f = 1 – 19000 Hz (repetition rate)N = 1 – 19000 pulses/min v = 1 – 2000 mm/s (velocity of scanner)

In the LLSI processing technique external radiation source is used. It is a pulsedcopper bromide vapor laser in visible wavelengths (with energy of the lasertransition 2.4 eV and 2.1 eV for 511 nm - green and for 578 nm yellow linerespectively).


DESIGH OF LASER SCANNING

• ARGES scanner head equips the pulsed CBL


e-mail: [email protected]/


Experimental Approach

Substrates: - stainless steel and titan- materials, widely used in orthopedic and

dentistry for medical implants- silicon- widely used material in microelectronics - quartz (or silica glass)- typical piezo-electric material

- polymers- also find different applications as implants

Solution: SBF, supersaturated with respect to calcium and phosphorus aqueous solution resemble the composition, ion-concentrations and pH of human blood plasma


Experimental Approach

Methods for surface modification of the materials

- whole surfase ion implantation; - ion implantation through mask ; - laser irradiation of the surface; - nanostructures; - porous silicon; - poly silicon;

- deposition of extracellular matrix proteins;


Results: SEM images of hydroxyapatite on modified by ion implantation of whole surface of SS, S and SG

substrates

SS S SG


Results: Morphology of HA layer grown on the surfaces iplanted with Ca and P through the

mask

• Substrates:

• Stainless steel (SS)

• Silicon (S)

• Silica glass (SG)

Mask design


Results: Applying of LLSI process on the surfaces, implanted by Ca and P ions through a mask

(с)

900 1200 1500 3000 35000.2

0.4

0.6

0.8

1.0

1.2(a)

(2,4)

(1,3) (4)

(3)

(2)

(1)

(1) SS/CaP_hs_4h(2) SS/CaP_hs_24h(3) SS/CaP_vs_4h(4) SS/CaP_vs_24h

Re

flect

ion

(a

.u.)

Wavenumber (cm-1)900 1200 1500 3000 3500

0.0

0.2

0.4

0.6

0.8

1.0

1.2(b)

(3)

(2)

(1)

Wavenumber (cm-1)

(1) SS/CaP_LLSI_0h(2) SS/CaP_LLSI_4h(3) SS/CaP_LLSI_24h

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

SS

/initi

al_L

LSI_

24h

SS

/initi

al_L

LSI_

4h

SS

/CaP

_vs_

24h

SS

/CaP

_vs_

4h

SS

/CaP

_hs_

24h

SS

/CaP

_hs_

4h

SS

/CaP

_LLS

I_24

h

SS

/CaP

_LLS

I_4h

SS

/CaP

_LLS

I_0h

Opt

ical

den

sity

at 9

62 c

m-1

•FTIR results

•SEM results

Mask design


Results: HRTEM of nanostructured semiconductors such as Si or CdSe nanopaticals

in SiOx material The method includes surface modification of substrates by subsequent physical vapor deposition of SiOx and CdSe at room temperature in two different regimes or thermal Si nanoparticle growth in SiO (x<2) films.


Results: SEM , Raman and FTIR studies of nanostructured CdSe in SiOx thin films after applying of LLSI

SEM

600 1200

30

60

90

120

150

1500900300

CdSe v3 PO

4

v1 PO

4

v4 PO

4v2 PO

4

(d)

S101

S79

S47Inte

nsity

(a.u

.)

Wavenumbers (cm-1)

400 800 1200 1600 20000

3

6

9

12

15

18(e)

S101

S79

S47R

efle

ctio

n (%

)

Wavenumbers (cm-1)

Raman FTIR


Results: SEM and EDX studies: Formation of NaCl crystals and hydroxyapatite layer on nanostructured CdSe in SiOx

thin films after applying LLSI process


Results: SEM of porous Silicon (PS)

PS has been shown to be an excellent candidate biomaterial, following studies establishing its biostability and non-toxicity. These favourable properties, coupled with the ease of its topographical manipulation, make it an ideal material for the growth of hydroxyapatite (HA) for use as an artificial bone material. The method

includes surface modification by electrochemical and laser induced chemical

etching.orientation (111) orientation (100)


Results: Formation of hydroxyapatite layer on Porous Silicon after applying the process of

laser-liquid-solid interaction (LLSI)


Amorphous, nano- and polycrystalline silicon films

The films are deposed by magnetron sputtering and metal induced crystallization at low temperatures (<550oC). Facilities: deposition system

Dion.


Results: Formation of hydroxyapatite on polycrystalline silicon films


Results: Extracellular matrix (ECM) proteins

20 30 40 50 60 700

10

20

30

40

Sample HA grain size, nm HA/ECM/SS 46 ± 10 HA/ECM/SG 36 ± 7 HA/ECM/S 23 ± 5

ECM/S

ECM/SG

HAaustenite

2 Theta ( 0 )

ECM/SS

Inte

nsity

(cp

s)

500 1000 1500 2000 2500 3000 3500 40000

10

20

30

40

50

60

70

80

400 800 1200

50

100

150

200

250

300

350HA/ECM/SS,Raman spectrum

Inte

nsi

ty (

a.u

.)

Wavenumber (cm-1)6001635

980-1066

1415

872

560

HA/ECM/SS, FTIR spectrum

Re

fle

ctio

n (

%)

Wavenumber (cm-1)

The method includes surface modification of the substrates by their coating with ECM proteins - to promote interactions with bone-forming cells. ECM was observed to act as a matrix for the growth of HA and leads to more homogeneous layer distribution on the surface and a better arranged structure.


List of recent publications 1. L. Pramatarova, E. Pecheva, D. Nesheva, Z. Levi, Z. Aneva, R. Pramatarova, U. Bismayer, T. Petrov, Study of modified solid surfaces by nanostructured CdSe in SiOx thin films, physica status solidi c, v. 0(3) (2003) 1070-1074 2.E. Pecheva, L. Pramatarova, M. F. Maitz, M. T. Pham, Study of the calcium phosphate layer grown on AISI 316 stainless steel from simulated body fluid, Journal of Materials Science: Materials in Electronics 14 (2003) 775-776 3.L. Pramatarova, E. Pecheva, T. Petrov, N. Minkovski, A. Kondyurin, R. Pramatarova, Ion beam modified surfaces as substrates for hydroxyapatite growth induced by laser-liquid-solid interaction, Proceedings of SPIE, v. 5449 (2004) 41-45 4.L. Pramatarova, E. Pecheva, T. Petrov, N. Minkovski, A. Kondyurin, R. Pramatarova, Enhancement of hydroxyapatite formation by laser-liquid-solid interaction, Proceedings of SPIE, v. 5449 (2004) 46-50 5.L. Pramatarova, E. Pecheva, M. F. Maitz, M. T. Pham, A. Kondyurin, Ion beam patterning of solid surfaces for hydroxyapatite deposition, Vacuum, Vol 76/2-3 pp 335-338 (2004) 6.L. Pramatarova, E. Pecheva, T. Petrov, A. Kondyurin, R. Pramatarova, N. Minkovski, Ion beam and laser processing for hydroxyapatite formation, Vacuum, Vol 76/2-3 pp 339-342 (2004) 7.L. Pramatarova, E. Pecheva, D. Dimova-Malinovska, R. Pramatarova, U. Bismayer, M. Kamenova, T. Petrov, N. Minkovski, Porous silicon as a substrate for hydroxyapatite growth, Vacuum, Vol 76/2-3 pp 135-138 (2004) 8.E. Pecheva, L. Pramatarova, M. F. Maitz, M. T. Pham, A. Kondyurin, Extracellular matrix used in an in-vitro model system for hydroxyapatite formation, Annals of Transplantation 9 (1A) (2004) 58-60 9.L. Pramatarova, E. Pecheva, M. F. Maitz, M. T. Pham, A. Kondyurin, Growth of hydroxyapatite layers on solid surfaces patterned by ion implantation, Annals of Transplantation 9 (1A) (2004) 40-42 10.E. Pecheva, L. Pramatarova, M. F. Maitz, M. T. Pham, A. Kondyuirin, Kinetics of hydroxyapatite deposition on solid substrates modified by sequential dual implantation of Ca and P ions. Part I. FTIR and Raman spectroscopy study, Applied Surface Science 235 (1-2) (2004) 176-181 11.E. Pecheva, L. Pramatarova, M. F. Maitz, M. T. Pham, A. Kondyuirin, Kinetics of hydroxyapatite deposition on solid substrates modified by sequential dual implantation of Ca and P ions. Part II. Morphological, composition and structure study, Applied Surface Science 235 (1-2) (2004) 170-175 12.L. Pramatarova, E. Pecheva, , M. F. Maitz, M. T. Pham, A. Kondyurin, R. Pramatarova, P. Montgomery, Analysis of hydroxyapatite films grown on whole-surface ion implanted substrates for studying the process of biomineralization, Nanoscience and Nanotechnology, eds. E. Balabanova, I. Dragieva. Heron Press, Sofia, issue 4 (2004) 295-298 13.L. Pramatarova, E. Pecheva, R. Presker, M. Stutzmann, M. Hanzlik, Patterned surfaces for hydroxyapatite in vitro growth, Journal of Optoelectronics and Advanced Materials, Vol. 7, No. 1, June 2005, p 469-472


Conference Participation 2004

1. E. Pecheva, L. Pramatarova, George Altankov, Investigation of the fibroblast behavior on different material surfaces, abstract presented at the 9th Ceramics, Cells and Tissues Meeting, 28 September– 1 October 2004, Faenza, Italy. 2. L. Pramatarova, E. Pecheva, T. Petrov, R. Presker, M. Stutzmann, Hydroxyapatite kinetic deposition on solid substrates induced by laser-liquid-solid interaction, paper presented at the XIII ISQE 2004 International School on Quantum Electronics Laser Physics and Applications, 20-24 September 2004, Bourgas, Bulgaria3. L. Pramatarova, E. Pecheva, D. Dimova-Malinovska, R. Presker, M. Stutzmann, U. Schwarz, R. Kniep, A novel laser-liquid-solid interaction process for hydroxyapatite formation on porous silicon, paper presented at the XIII ISQE 2004 International School on Quantum Electronics Laser Physics and Applications, 20-24 September 2004, Bourgas, Bulgaria. 4. L. Pramatarova, E. Pecheva, D. Nesheva, Z. Aneva, A. L. Toth, E. Horvath, F. Riesz, Hydroxyapatite growth on glass/CdSe/SiOx nanostructures, paper presented at the European Material Research Society Fall Meeting 06 – 10 September 2004, Warsaw, Poland. 5. L. Pramatarova, E. Pecheva, R. Presker, U. Schwarz, R. Kniep, Natural opal as a model system for studying the process of biomineralization, paper presented at the European Material Research Society Fall Meeting 06 – 10 September 2004, Warsaw, Poland. 6. L. Pramatarova, E. Pecheva, R. Presker, M. Stutzmann, M. Maitz, M. Pham, Patterned surfaces for hydroxyapatite in vitro growth, abstract presented at NATO Advanced Study Institute: Nanostructured and advanced materials for applications in sensor, optoelectronic and photovoltaic technology, 6-17 September 2004, Sozopol, Bulgaria. 7. L. Pramatarova, E. Pecheva, D. Dimova-Malinovska, R. Presker, M. Stutzmann, U. Schwarz, R. Kniep, Mechanism of hydroxyapatite formation on porous silicon in simulated body fluid, abstract presented at NATO Advanced Study Institute: Nanostructured and advanced materials for applications in sensor, optoelectronic and photovoltaic technology, 6-17 September 2004, Sozopol, Bulgaria. 8. L. Pramatarova, E. Pecheva, R. Presker, M. Stutzmann, M. Maitz and M. Pham, Patterned surfaces for hydroxyapatite in vitro growth, paper presented at the 13th International School on Condensed Matter Physics, 30 August-3 September 2004, Varna, Bulgaria. 9. L. Pramatarova, E. Pecheva, R. Presker, M.T. Pham, M.F. Maitz, M. Stutzmann, Hydroxyapatite growth induced by native extra cellular matrix deposition on solid surfaces, paper presented at the European Cells and Materials Conference, 28-30 June 2004, Davos, Switzerland. 10. E. Pecheva, L. Pramatarova, G. Altankov, Fibroblast interaction with different material surfaces, extended abstract presented at the European Cells and Materials Conference, 28-30 June 2004, Davos, Switzerland. 11. L. D. Pramatarova E. Pecheva, R. Presker, Novel processing technology for production and use of hydroxyapatite nanostructures, Sixth Workshop on NANOSCIENCE & NANOTECHNOLOGY - November 24-27, 2004, Sofia, Bulgaria .


Profile of the Pulslight LTD, Laser systems and laser processing, SME, Bulgaria

• MS. I. Kostadinov, President • Address: • 72 Tzarigradsko chaussee bulv., 1784 Sofia, Bulgaria • tel.: +359 2 9743002• fax: +359 2 9743002• e-mail: [email protected]

• http://www.pulslight.com

Abstract : Pulslight Ltd. is interested in the development and manufacturing of Copper Bromide (CuBr) lasers, which are high power devices that generate pulses of radiation at two wavelengths in the visible region of the spectrum, at 511 and 578 nanometers (nm) as well as in a scientific research and development. Pulslight has scientific collaboration with the Metal Vapor Laser Group at the ISSP, BAS. (Academic N. Sabotinov) and as a result company has high expertise, well developed technology and a good market realization. Pulslight is a partner in two R&D projects (EC funded COPERNICUS Project and NATO funded SCIENCE FOR PEACE Project). The last two years Pulslight Ltd has scientific collaboration with the Assoc. Prof. Dr L. Pramatarova at the ISSP, BAS, leader of the project “Development of in vitro system for growing of hydroxyapatite as an implant coating”.

• The interest for EU project is:.

Application of a CuBr laser MOPA (master-oscillator-power amplifier) system for precision processing of

various hard materials, drilling of micro-holes, and for the marking and cutting of materials.

Application of a CuBr laser in a novel method of laser-liquid-solid-interaction (LLSI) for production of

hydroxyapatite coatings on variously modified surfaces of implants.


Profile of the Base BIO POSITIONNING

Disposable use microchip for the real-time detection of thrombosis• Dr Didier Mauroy, Leade of the Project

• Address: • Rue de la Citadelle 11 , F-33410 Rions, FRANCE • tel.: + 33 (0) 556 769 301 • e-mail: [email protected]

• Abstract : A small French firm has created a new bioelectronic technology able to identify with precision the risk of thrombosis from three electrochemical components: a consumable made of a microchip equipped with silicon sensors and a container (capacity equal to a few milliliters), a microchip reader, and a data processing unit (software + computer). The firm is also specializes in bioelectronic techniques for aqueous environment.

• Base is a start-up developing a biochip (microsystem technology) for the plasma measurement. The methodology consist in the simultaneous measurement of tree essential electro-chemical parameters to give a fine position on 3 axes or 3D of the biological field. The use of the future biochip will give real time measurement at low cost.

• The interest for EU project is: quality control for each plasma like batch; biocompatibility between in vitro and in vivo conditions; adequation between in vitro bio resorbable condition and recipient biological field; position of the plasma like with human thrombosis risk;






Acknowledgements

This research is supported * by Marie Curie grant No HPMT-CT-2000-00182 of the EC and

* by the Bulgarian National Scientific Research Fund through Grant L1213.

* Assistance provided by the staff of PULSSVET Ltd, Sofia and * FZR, Dresden, Germany

In cooperation with * U. Bismayer, Hamburg University, Germany

* M. Stutzmann, Radina Presker, TU-Munich, Walter Schottky Institute * F. Riesz, Hungarian Academy of Sciences, Hungary,

* A. Medvids, Latvian Academy of Sciences, Latvia * D. Nesheva and T. Petrov- ISSP, BAS, Bulgaria;

* D. Dimova-Malinovska, CLSENE, BAS, Bulgaria

* Special thanks to my PhD student E. Pecheva


• Workingprogramme area(s): • (FP6-2003-NMP-TI-3-main) Nanotechnologies and Nanosciences • Priority 3 - NMP • Type of Instruments: • Specific Targeted Research Project (STREP) • Integrated project dedicated to SMEs (IPs-SMEs) • Property Rights: Submitted for Bulgarian patent • Stage of Development: Experimental development stage (laboratory prototype) • Subject Description: Health economics, Medicine, Technology, Coatings, Cells, Inspection, Testing • Subject Index Codes: Medicine, Health, Processing, Information, Technological Systems, Measurement Methods• Subject Class: Medicine, Physics, Materials, Industrial manufacturing technologies • Market Applications: Orthopedic implants, Production of lasers, Diagnostic reagents• Research Interest: Biomineralization, Biomaterials, Material technology, Hydroxyapatite, Growth, Simulated body

fluids, Thin films (coatings), Surface modification (patterning), Micro- and Nanostructured surfaces, Laser interaction. • Country: Any Country • Experts:

We are seeking partners having an experience in following fields: chemistry and online testing of the solutions, growth of thin films and coatings, modification and functionalization of the surfaces, biomaterials, surface engineering, especially partners with well established methodologies for chemical/physical analysis.

We are seeking partners with existing projects or new projects that are still looking for suitable eastern partners.

institute of solid state physics, bulgarian academy of sciences, 1784 sofia, bulgaria, 72...

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