FIRST CLINICAL AND RADIOLOGICAL RESULTS OF A NEW CALCIUM VIIth BIOMATERIALS Sydney, May, 2004 FIRST CLINICAL AND RADIOLOGICAL RESULTS OF A NEW CALCIUM PHOSPHATE INJECTABLE CEMENT USED AS A COMPLEMENT IN BONE REPAIR IN 25 CASES OF COMPACTED FRACTURES C SCHWARTZ, Colmar. D MAINARD, Nancy FRANCE.

I) Physical, chemical and biological characteristics VIIth BIOMATERIALS Sydney, May, 2004 A NEW CALCIUM PHOSPHATE CEMENT I) Physical, chemical and biological characteristics C SCHWARTZ, Colmar. D MAINARD, Nancy. J AMEDEE (Bordeaux) P FRAYSSINET (Toulouse) A LERCH (Toulouse)

For us PHOSPHOCALCIUM CEMENTS are: a new form, complementary to calcium phosphate ceramics which - must be injectable to have a - better fill of bone cavities - better fit with the bone tissue - and permit mini-invasive approaches - setting and hardening must be possible in vivo (in a humid environment) with a setting time of +/- 10 mn and some mechanical stability and strength - idealy must be absorbable

According to the nature of cements, this cement is a DCPD Cement (DiHydrated DiCalcic Phosphate) - magnesian calcium phosphate cements - octocalcic phosphate cements - apatite cements

Ca3(PO4)2 + H3PO4 + 6 H2O  3 CaHPO4 , 2 H2O DCPD cement - acid-base reaction - mixing of a liquid phase and a solid phase solid phase : essentially tricalcium phosphate  (> 97%) + sodium pyrophosphate liquid phase : orthophosphoric acid 4 M + sulphuric acid 0,1 M react with water DCPD Ca3(PO4)2 + H3PO4 + 6 H2O  3 CaHPO4 , 2 H2O

- the setting is a very fast reaction dissolution of TCP  and cristallisation of DCPD - the setting is a very fast reaction which leads to a paste (injectability) addition of PPNa brings a better control of setting time addition of H2SO4 improves the mechanical properties Powder / liquid ratio = 2

very sensitive to temperature IMPORTANT +++ FOR SURGEON Maximal injectable time curve Minimal injectable time curve Setting time curve Hardening time Waiting time Injectable time Time of filling the syringe Mixing time Setting speed is very sensitive to temperature

The result: Micropores # 1 m Porosity : 40 % SEM - DCPD = 55 % < 5 m platelet-shaped grains - remaining TCP = 45 % particles between 2 and 50 m Micropores # 1 m Porosity : 40 % SEM Impurities < 1% Traces elements Cd, Pb, As, Hg

Reaction temperature = 45°C Time (min) Température (°C) 10.2 45 °C 14.3 Reaction temperature = 45°C not dangerous to cells or proteins Exothermic reaction

compression strength : 37 MPa We asked for some mechanical stability and strength The compression pressure resistance was tested Cylinder 12 x10 mm compression strength : 37 MPa (ambient air, not in vivo) Young’s Modulus : 900 MPa

It is a acid-base reaction: acidity? It was checked by…

was deposited in culture medium 1) DCPD cement was deposited in culture medium : pH changes of DCPD deposited in culture medium - IMDM medium - Dilution : 1, 5, 10, 25% t : 30 s, 1, 5, 10, 15, 20, 60 min - pH of medium : 7.70 - t° : 18.5°C Time pH remains in physiological limits

2) Kinetic study : 10% DCPD cement and 50% of medium renewed at each 5 minutes and pH measurement (to simulate buffer-effect, as we find in the human body) pH changes kinetics of DCPD (10%) mixed with culture medium IMDM medium - pH of medium: 7,70 - dilution : 10 % t : 5, 10, 15, 20, 30 and 60 mn - t° : 18,5°C 15 mn pH return in physiological limits in

After 4 to 6 days the proliferation curve resumes with the same speed. 3) Study of cytocompatibility: cells growth on DCPD cement MG63 bone cells IMDM + SVF medium - t : 1, 3, 6, 9 days at 37°C - MTT test After 4 to 6 days the proliferation curve resumes with the same speed. MG63 cells proliferation on the cement plastic wet DCPD dry Time in days

9 NZ rabbits (6-7 months, 3,7-5, 1 kg) IN VIVO STUDY Short-term implantation effects of a DCPD-based calcium phosphate cement Frayssinet P and All, Biomaterials, 1998 9 NZ rabbits (6-7 months, 3,7-5, 1 kg) DCPD : 95% -TCP : 4% density 1,43 ; porosity 45% ; pores diameter 7m Model: lesions 4x5 mm on femoral lateral condyle R = injected L = control sacrificed at 2, 6 and 18 weeks

At 2 weeks was noticed : coming from the adjacent bone formation of thin bone trabeculae coming from the adjacent bone This bone was apposed at the cement and coated with osteoid tissue lined with osteoblasts 300 100

At 6 weeks were noticed : and surrounded by immature bone The cement was fragmented, and surrounded by immature bone - a gradual dissolution of the cement - Grains loosened from the cement are phagocytosed  by macrophages and giant cells As in a foreign body reaction 250

Cement breakdown and bone growth are different / phosphocalcic ceramics - no creeping substitution - no osteoblasts directly on cement surface - trabeculae are formed from adjacent bone - quick dissolution of DCPD - bone incorporation and cell degradation of remaining -TCP particles

A NEW CALCIUM PHOSPHATE CEMENT VIIth BIOMATERIALS Sydney, May, 2004 A NEW CALCIUM PHOSPHATE CEMENT II) Clinical aspects C Schwartz, Colmar. D Mainard, Nancy. C Cuny , Metz. P Laffargue, Lille. L Obert, Besançon. P Simon,Strasbourg

« Instructions for use » What MUST be done! Compacted bone 1) Reduce the fracture BONE LOSS

Pour all the liquid in the bowl EUROBONE® Kasios, FH Orthopedics 23° C Pour all the liquid in the bowl T = 0 Add all the powder T = 30 - 40 s Mix with stirrer Fill in the syringe T = 1mn Allow to stand Inject the cement T = 4mn - 5mn Final setting T = 10 mn

4) Cement injection Inject under visual control … to prevent leaks

Indications Post- or non post-traumatic cancellous bone defects As a supplement to a conventional osteosynthesis

FRACTURE of the distal RADIUS Mrs PER. 43 year-old PO C Schwartz, Colmar

Mid-term result…

absorption seen to be species dependant 1 year follow-up C Schwartz, Colmar absorption seen to be species dependant perhaps even individual dependant?

Tibial Plateau fracture JUL.F. pre-operative P Laffargue, Lille

post-operative

after 4 months P Laffargue, Lille

Calcaneum fracture Mr BEGA, 23 year-old PO C Schwartz, Colmar

6 M After 6 M

Fractures of the proximal humerus C Cuny, Metz

BENIGN TUMORS Mini-invasive P Simon, Strasbourg

CONCLUSION: What’s about absorption? No adverse effect in this series + Mechanical benefit + Less invasive approach What’s about absorption?

Thank you for your attention