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zahnimplantate
nicht metallischen

Biocompatibility in vitro

The results have been selected for publication in the oral :

SYDNEY MAI 17-21 2004

Biocompatibility Testing

Biocompatibility of the test material was performed according to ISO 10993 « Biological evaluation of medical devices – Part 1 : Evaluation and testing ».

Cytotoxicity (ISO 10993-5)

• in direct contact
• using an extract

Systemic acute toxicity in the mouse (ISO 10993-11)

Intradermal irritation (ISO 10993-10)

Sensitization (ISO 10993-10)

Mutagenicity (ISO 10993-3):

• Ames test (OECD n° 471)
• Chromosome aberrations using human lymphocytes (OECD n° 473)
• Sister chromatide exchanges using CHO cells (OECD n° 479)

In accordance with the norm : ISO 10993

Materials and Methods

Cytocompatibility

Test material : disc (15.5 mm in diameter) of the composite exhibiting a smooth surface, γ-ray sterilized.

Test system : human osteoblasts (3rd passage)

• Arising from trabecular bone
• Checked free from mycoplasma
• Characterised with regard to phenotype expression (PAL, osteocalcin, collagen type I).

Protocol :

• Test material discs are placed on the bottom of 24-well (15.5 mm in diameter) tissue culture plates. - Negative control is polystyrene of culture plates
• Reference material is polished cpTitanium
• Assessed parameters : attachment at 3 and 6 h, proliferation over 27
• days, ALP activity at day 3, 15 and 27, SEM at day 3 and 27.
• Initial cell seeding : 5 000 cells/cm².

Cell Adhesion by SEM

Cytocompatibility

Surface State of PEEK / TCP / TiO2	HOB at 3 days ( x3000 )
BIOPIK® at 27 days
HOB at 27 days ( x300 )	HOB at 27 days ( x1000 )

HOB attachement and Proliferation

Alkaline Phosphatase Activity

For BIOPIK  ® : differencial value 15 to 23 %

Clinical Results

• A CE marked dental implant application is currently in use, based on the PEEK / TCP / TiO2 formulation described.
• 6000 cylindric implants have been implanted over a 10 years period with 96% success
• The material flexibility allows new designs material flexibility

PEI: Post-extractional implant
HBI: Implant after healing
IF: Implant failure

Assay realised on BIOPIK®

Cytotoxicity test

• Protocol : Cytotoxicity test according to ISO 10993-5(or EN 30993-5) “Biological evaluation of medical devices- Tests for cytotoxicity : in vitro methods” (LEMI procedures n° 7.11 and 7.12) - LEMI code : FA 141194-2

Result of the test : The material is not cytotoxic.

Evaluation in the mouse of the systemic responses to the extracts of materials following intravenous (NaCl 0.9%) and intraperitoneal (sesame oil) injections

• Protocol : According to EN 30993-11”Biological evaluation of medical devices-Part 11 : Tests for systemic toxicity” using two types of extracts prepared according to EN 30993-12(COFRAC PPT.10) - LEMI code: FA 141194-3

Result of the test : The test material meets the requirements of this test.

Evaluation on the rabbit of the local responses to the extracts of materials following intracutaneous injection

• Protocol : Intradermal irritation in the rabbit according to EN 30993-10”Biological evaluation of medical devices - Part 10 : irritation and sensitization tests” using two types of extract prepared according to EN 30993-12(COFRAC PPT.10) -  LEMI code : FA 141194-3

Result of the test : The test material meets the requirements of this test.

Evaluation of the sensitizing potential of the extract of a biomaterial: Guinea-Pig Maximization test (G.P.M.T.)

• Protocol : Maximization sensitization test in the Guinea pig according to EN 30993-10 “Biological evaluation of medical devices - Part 10: Irritation and sensitization tests using a polar (physiological saline) extract prepared according to EN 30993-12 (COFRAC PPT.10) - LEMI code : FA 141194-3

Result of the test : The extract is not sensitizing by contact with the skin (class 1).

Genotoxicity test: Salmonella Typhimurium,reverse mutation assay

• Test procedure : Genotoxicity test according to ISO 10993-3”biological evaluation of medical and dental devices - Tests for genotoxicity, carcinogenicity and reproductive toxicity” and the OECD guideline N°471 - LEMI code: FA 141194-2

Result of the test : The material did not induce reverse mutations on TA-98,TA-100,TA-1535,TA-1537,TA-1538. Salmonella typhimurium strains, in presence or absence of metabolic activation.

Genotoxicity test : In vitro mammalian cytogenetic test

• Test procedure : Genotoxicity test according to ISO 10993-3 “Biological evaluation of medical and dental devices –Tests for genotoxicity, carcinogenicity and reproductive toxicity” and the OECD guideline N°473 (LEMI Procedure n° 9.2a) - LEMI code: FA 141194-2

Result of the test : The material did not induce chromosome aberrations in human lymphocytes in culture in the presence or absence of metabolic activation.

Biodegradation test : test material,composite material,BIOPIK ®

• Protocol : Biodegradation test according to ISO, ISO TR 10993-9 “Biological evaluation of medical devices- Part 9: Degradation of materials related to biological testing” (LEMI operating procedure n° MB08/57). - LEMI code FA 141194-1

Result of the test : The’’ in vitro”’ kinetic study of the Titane and Calcium dissolution, over a period of 42 days, using the test meterial, let appear a very low ion dissolution :

• (Ti)<1ng/cm2/day
• (Ca)=0.5µg/cm2/day

Cytocompatibility test : test material, rough and polished BIOPIK®

• rough BIOPIK®(disk):LEMI code FA 141194-1
• polished BIOPIK®(disk) : LEMI code FA 140498
• polished BIOPIK®-implant lame :LEMI code SB 120398

Protocol :

1. Human osteoblast attachement according NF S 91-145.
2. Human osteoblast proliferation according to NF S 91-142.
3. Human osteoblast alkaline phosphatase activity according LEMI operating procedure n°5.4.

Result of the test : Very good cytocompatibility of the polished BIOPIK® (implant lame). On it attachement, spreading outand colonization cells are rapid and perfect with an excellent metabolic activity.

Research pyrogenic substances: Sterile dental implant

• Protocol : European pharmacopee third edition(1997)-2.6.8.pyrogen

Result of the test : The product does meet the requirements.

Bioburden test : non sterile dental implant

• Protocol : Bioburden test according to NF EN 1174  ’’sterilization of medical devices – estimation of the population of micro-organisms on product’’.

Result of the test : The bioburden before sterilization is compatible with a sterilization process.

Comparative biocompatibility

Study N° 2 : performed from an other cell line

PEEK-OPTIMA	TITANIUM	BIOPIK ®

At 27 days , differential value for BIOPIK® material : more than 40% !

BIOPIK ® : biocompatibility qualities

• Extremely biocompatible, graft principle
• Metal free
• No heterogeneity : physic or atomic
• Totally dielectric : no waves problems
• Inert in front of radiotherapy
• No allergy
• Conformable in front of human tissues