1. Calcium sulfate
120 years of research
Dr. Amir Kraitzer
Ph.D, MBA

2. “Simplicity is not an objective in art,
but one achieves simplicity despite one's
self by entering into the real sense
of things”
Constantine Brancusi
Brancusi - The Newborn in
the Museum of Modern Art,
New York

3. Agenda

4. History of Calcium sulfate
Bassanite
9,000 year old traces in Mesopotamia
5,000 year old remnants in ancient
Egyptian pyramids
1700‘s–Henry the 8th, king of France,
orders covering all wooden walls with
plaster

5. Calcium sulfate Applications
Constructions
Art
Agriculture
Food and Beverage
Cosmetics
19th century plasterwork from House
of Borujerdies in Kashan, Iran

6. Calcium sulfate in Medicine
 Pharmaceuticals
 Medical devices
 External Plaster casts
 Internal (Orthopedics, Dental, Spine,
Osteoporosis, tumor, trauma)
Upper Right Mirzayan et al. 2001
Arm (61F)
Implantation At 3 months At 5 months

7. Agenda

8. Bone Healing Mechanisms
 Bone is the only tissue capable of regenerating itself
completely
 The degree of regeneration depends on the
mechanism of bone healing
Repair Regeneration
Formation of a regeneration is
Bone new tissue the preferred of tissue having
Formation mechanism
different than original complete
in terms of bone bone similar structure andto
healing leading
higher volume of new formed bone of original bone
composition
Composition: Composition:
Graft High amount of New
Voids Formed Bone
Fibrotic tissue Blood vessels
Low amount of New
Formed Bone

9. Agenda

10. Bone graft requirements
(1) Osteoconductive
 Mechanical support for cell migration and differentiation
 Interconnected porous system to allow cell and protein infiltration
(2) Bioresorbable
(2) Osteoinductive
 Resorbs completely in the rate of new bone formation
 Contain GF offering stimulation towards osteoblastic differentiation
(3) Bioactive and encourage migration of osteoprogenitor cells
Biologically recruit
(3) Osteogenic the cycle required for new bone formation
Chemically activates
 Contains living cells within the graft to form new bone

11. Bioactive properties
 Platelets are a natural source
of growth factors
 Platelet infiltration is allowed
by the microporosity of the
graft during wound healing
 A Bioactive graft would
activate the platelets
 Activated platelets release GF
such as PDGF, and BMPs
 These GFs stimulate bone
formation and angiogenesis

12. Temporary Scaffolding Properties
Volume
Graft resorption
Week 12
Woven Bone Lamellar Bone
Partial volume
Pores (400 m) allow cell migration
and angiogenesis
First 4 weeks
Entire volume
Pores (100 m) allow growth
Bone Growth
factors infiltration Week 20 further
Complete graft resorption
4 16 Time (weeks)

13. Slow Graft resorption
Volume
Graft resorption
Bone Growth
50%
Mechanically interferes
bone formation
Reduce GF and cell
infiltration
4 16 Time (weeks)

14. Fast Graft resorption
Volume
Graft resorption
50%
Reduce graft stability and
Bone Growth amount of new bone formed
Particle migration increase
inflammation
4 16 Time (weeks)

15. Ideal synthetic graft
Totally replaced by natural bone
Scaffolding properties
• Resorb in a rate equivalent to bone growth
• Micro and macro structure for GF infiltration
and cell migration
Bioactive properties

16. Agenda

17. Calcium Sulfate -Literature
Peltier
Alderman
Peltier 1960 - Rapid healing and lack of significant host
Bell
response. Ebourg & biou Scarano
Shaffer & Apps Ricci Horowitz
Hauptli Pecora Silveira and Mazor
Ricci (2000)
Kovacevic – CS dissolution forms a Intini
Strocchi
mineralised, HA-like latticework an
Pecora (1997) - CS does not act simply asOrsini inert filler, but
Cotzee Kelly
it play a role in osteogenesis
Nielscn Sottosanti Yu
Berner MacNeill
Coetzee (1980) – CS promotes osteogenic Wilkins
Nystrom
Petrova
Edburg
activity, stimulating bone growth in contact with bone or
Kofmann
Nordmann Cunningham
periosteum
Dreesman
Dreesman successfully treated tuberculous bone cavities using CS
1892 1920s 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010

18. CS Material Properties
CS composition
• Dihydrate- CaSO4 · 2H2O
• Hemihydrate- CaSO4 · 0.5H2O
• Anhydrate- CaSO4
Setting
• Hemihydrate sets into Dihydrate in 15-20 Minutes
• Slight exothermic reaction
pH
• 7.3
Mechanical properties
• 10 -20MPa

19. CS Resorption properties
Volume Maintains scaffolding properties
between 4–10 weeks
Woven Bone Lamellar Bone
Graft
Bone Growth
4 10 Time (weeks)

20. CS Resorption mechanism
CS dissolves by surface erosion forming
hydroxyapatite bone like structure
HA
HA
CS
CS CS
time
Three dissolution mechanisms:
 Dissolution by hydrolysis
 Enzymatic lysis by low pH
 Osteoclasts and osteoblasts

21. CS Resorption mechanism
100μm Bar
CS cement implanted in a rabbit
2 weeks post implantation
Apatite precipitate
Rings of precipitated apatite are
formed in morphology and
composition similar to bone

22. CS Biological Properties
Both material and its degradation products
are biocompatible
Cells are able to migrate over CS
Prevents soft tissue in-growth
Human osteoblast over CS in late stage of
mitosisIncrease rates of vital bone growth

23. CS Promotes Bone growth
Stage 1 Stage 2 Stage 3
Infiltration Activation Differentiation
Due to the Calcium ions These GF cause
hygroscopic nature activate platelets to angiogenesis and
of CS, platelets and release GFs osteogenic differentiation
GF infiltrate through including PDGF and from mesenchymal stem
its microstructure BMPs cells

24. Calcium Sulfate in practice
Calcium Sulfate Calcium Sulfate
Hemihydrate Dihydrate
Good handling Has granular
properties
Cementable
Non cementable
Setting is retarded
by proteins, blood
and saliva
Rapid resorption
User sensitive

25. Sub- Optimal setting
Calcium sulfate Hemihydrate Calcium sulfate Dihydrate

26. Crystallinity
and material properties
Optimal setting
Highly crystalline structure
Good material properties
Higher strength Longer Resorption

27. Questions?