calcium sulfate bone grafts - 120 years of research
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Calcium sulfate 120 years of research
Dr. Amir KraitzerPh.D, MBA
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“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
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Brancusi - The Newborn in the Museum of Modern Art, New York
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Agenda
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Section 1 – Introduction
Section 2 – Background
Bone Regeneration
Bone Graft Requirements
Section 3 – The value of Calcium Sulfate (CS)
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History of Calcium sulfate
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
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Gypsum
Plaster of paris
Bassanite
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Calcium sulfate ApplicationsConstructionsArtAgricultureFood and BeverageCosmetics
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19th century plasterwork from House of Borujerdies in Kashan, Iran
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Calcium sulfate in Medicine
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Pharmaceuticals Medical devices
External Plaster casts Internal (Orthopedics, Dental, Spine,
Osteoporosis, tumor, trauma)Upper Right Arm (61F)
Implantation At 3 months At 5 months
Mirzayan et al. 2001
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Agenda
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Section 1 – Introduction
Section 2 – Background
Bone Regeneration
Bone Graft Requirements
Section 3 – The value of Calcium Sulfate (CS)
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Bone Healing Mechanisms Bone is the only tissue capable of regenerating itself
completely The degree of regeneration depends on the
mechanism of bone healing
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RepairFormation of a new tissue different than original bone
RegenerationFormation of tissue having similar structure and composition of original bone
Bone regeneration is the preferred mechanism in terms of complete bone healing leading to higher volume of new formed bone
Composition:GraftVoidsFibrotic tissueLow amount of New Formed Bone
Composition:High amount of New Formed BoneBlood vessels
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Agenda
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Section 1 – Introduction
Section 2 – Background
Bone Regeneration
Bone Graft Requirements
Section 3 – The value of Calcium Sulfate (CS)
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Bone graft requirements (1) Osteoconductive
Mechanical support for cell migration and differentiation Interconnected porous system to allow cell and protein infiltration
(2) Bioresorbable Resorbs completely in the rate of new bone formation
(3) Bioactive Chemically activates the cycle required for new bone formation
(2) Osteoinductive Contain GF offering stimulation towards osteoblastic differentiation Biologically recruit and encourage migration of osteoprogenitor cells
(3) Osteogenic Contains living cells within the graft to form new bone
Temporary scaffolding properties
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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
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Temporary Scaffolding Properties
Bone Growth
Graft resorption
Volume
164 Time (weeks)
Woven Bone Lamellar BoneWeek 12Partial volumePores (400mm) allow cell migration and angiogenesis
First 4 weeksEntire volumePores (100mm) allow growth factors infiltration Week 20 further
Complete graft resorption
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Slow Graft resorption
Bone Growth
Graft resorption
Volume
164 Time (weeks)
50%
Mechanically interferes bone formationReduce GF and cell infiltration
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Bone Growth
Graft resorption
Volume
164 Time (weeks)
Fast Graft resorption
50%
Reduce graft stability and amount of new bone formedParticle migration increase inflammation
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Ideal synthetic graftTotally 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
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Avialable using calcium
sulfate as a bone graft
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Agenda
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Section 1 – Introduction
Section 2 – Background
Bone Regeneration
Bone Graft Requirements
Section 3 – The value of Calcium Sulfate (CS)
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1920s 1892 1960s 1970s 2010 2000s 1990s 1980s 1930s 1940s 1950s
Dreesman
Peltier Alderman
Bell Ebourg & biou
Nystrom Petrova
Kofmann
Cotzee
Pecora Strocchi
Orsini Sottosanti
MacNeill Wilkins
Cunningham
Shaffer & Apps Ricci Silveira
Intini Kelly
Yu
Scarano Horowitz
and Mazor
Edburg Nordmann
Nielscn Berner
Hauptli Kovacevic
Calcium Sulfate -Literature
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Dreesman successfully treated tuberculous bone cavities using CS
Peltier 1960 - Rapid healing and lack of significant host response.
Coetzee (1980) – CS promotes osteogenic activity, stimulating bone growth in contact with bone or periosteum
Ricci (2000) – CS dissolution forms a mineralised, HA-like latticeworkPecora (1997) - CS does not act simply as an inert filler, but it
play a role in osteogenesis
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CS Material PropertiesCS 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
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CS Resorption properties
Bone Growth
Volume
104 Time (weeks)
Graft
Woven Bone Lamellar Bone
Maintains scaffolding properties between 4–10 weeks
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CS dissolves by surface erosion forming hydroxyapatite bone like structure
CS Resorption mechanism
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time
CSCS CS
HAHA
Three dissolution mechanisms: Dissolution by hydrolysis Enzymatic lysis by low pH Osteoclasts and osteoblasts
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CS Resorption mechanism
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100μm BarCS cement implanted in a rabbit 2 weeks post implantation
Apatite precipitate
Rings of precipitated apatite are formed in morphology and composition similar to bone
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CS Biological PropertiesBoth material and its degradation products are biocompatible
Cells are able to migrate over CS
Prevents soft tissue in-growth
Increase rates of vital bone growth
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Human osteoblast over CS in late stage of mitosis
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CS Promotes Bone growth
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Stage 1 Infiltration
Stage 2Activation
Stage 3Differentiation
Calcium ions activate platelets to release GFs including PDGF and BMPs
Due to the hygroscopic nature of CS, platelets and GF infiltrate through its microstructure
These GF cause angiogenesis and osteogenic differentiation from mesenchymal stem cells
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Calcium Sulfate in practice
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Calcium Sulfate Hemihydrate
Good handling
Cementable
Setting is retarded by proteins, blood
and saliva
Rapid resorption
User sensitive
Calcium Sulfate Dihydrate
Has granular properties
Non cementable
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Optimal setting
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Calcium sulfate Hemihydrate Calcium sulfate Dihydrate
Sub-
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Crystallinity and material properties
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Good material propertiesHigher strength Longer Resorption
Highly crystalline structure
Optimal setting
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Questions?
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