1. MACROPOROUS SCAFFOLDS FOR BONE REPLACEMENT

2. SCAFFOLD is, as in house building, a structure meant to support the growing edifice: bone regeneration Simulates the features of trabecular (cancellous, spongy) bone

3. Cancellous Bone Porous and interconnected structure: Resistance to compression 2-12 MPa, porosity 60- 70% vol.

4. Requirements for a SCAFFOLD  Pore Dimension > 100µm-150µm  Pore volume Percentage > 50% vol.  High interconnection degree  Suitable mechanical properties  Workability  Bioactivity  Good surface-cell interaction (to favor cell proliferation and growth)

5. Preparation Techniques  Solid Freeform Fabrication  Foams Method  Starch consolidation (*)  Gel-casting  Dual phase mixing  Burn-out of organic phases (*)  Polymeric sponge method (*) * Used at our Dept.

6. Preparation Techniques  Solid Freeform Fabrication  Foams Method  Starch consolidation (*)  Gel-casting  Dual phase mixing  Burn-out of organic phases (*)  Polymeric sponge method (*) * Used at our Dept.

7. Solid Freeform Fabrication: a very expensive technique for reproducing 3D objects

9. Preparation Techniques  Solid Freeform Fabrication  Foams Method  Starch consolidation (*)  Gel-casting  Dual phase mixing  Burn-out of organic phases (*)  Polymeric sponge method (*) * Used at our Dept.

10. Several ways of introducing porosity into the systems: from suspensions from sol-gel

11. Several ways of introducing porosity into the systems: from suspensions from sol-gel

12.  Foams with H 2 O 2 glass powder suspensions are foamed with a dilute solution of H 2 O 2 at 60°C. The release of O 2 generates the porous structure, then the substrate is sintered Navarro, Biomaterials 25 (2004) 4233–4241 phosphate glass P 2 O 5 –CaO– Na 2 O–TiO 2 Scaffold 3D

13. 40% H 2 O 2 60% H 2 O 2

14.  Foams with in situ polymerization Sepulveda, J Eur Cer Soc 1999

15. Different Microstructures as a function of foaming degree

16. Garrn J Eur Cer Soc 24(2004)579-587 Other possibility: Albumin as foam former in water sospension Anfiphylic proprieties, (both polar and apolar aminoacids) albumin

17. Several ways of introducing porosity into the systems: from suspensions from sol-gel

18. FOAMING SOL-GEL Jones, J mat Sci 38(2003)3783-3790 Sol-gel glasses: more expensive, but more bioactive and bio-reabsorbable because of a mesotexture (pores 2-50 nm) Reactions o Hydrolysis of reactant o alcohol condensation o Water condensation Factors pH Temperature and duration of reaction Concentration of reagents Ratio H 2 O/Si Ageing Drying

19. General scheme for sol-gel procedure

20. Sol-gel method Solution: dispersion at the molecular level Sol: suspension of microscopic particles (colloids). Light scattering (Tyndall effect) Gel: a suspension keeping its form. Reticulation among particles Gels come from sols

21. Use of alcoxides R-O-Me TEOS: tetraetoxysilane (C 2 H 5 O) 4 Si, ma also Me = Ti, etc. Steps: 1. hydrolysis 2. monomer condensation 3. formation of particles (sol) 4. agglomeration of particles to form the gel

22. Hydrolysis (EtO) 4 Si + 4 H2O  H 4 SiO 4 + 4 EtOH acid (and base) catalyzed: H - protonation of TEOS I (EtO) 3 Si- O-Et + H+  (EtO) 3 Si- O-Et + -attack of water on Si atom (as shown by measurements with H 2 18 O) - release of EtOH with formation of + (EtO) 3 Si-O-H I H - distacco di H + che ritorna in circolo

24. Silicic acid condenses to silica

25. To obtain massive sol-gel glasses

28. 600°C700°C 800°C1000°C

29. Mesopores distribution as obtained from nitrogen adsorption (BJH method) Macropores as obtained from mercury porosimeter (described below)

30. Sintering: from glass to vetroceramics Wollastonite present

31. 8h 3 days Different bioactivity of samples sintered at different temperatures: Low-tp samples favor the formation of HAp

32. Compression behavior of scaffolds I Linear region (max resistance) II Collapse of the pores III Res. to compression of the solid