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

Agenda

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Section 1 – Introduction

Section 2 – Background

Bone Regeneration

Bone Graft Requirements

Section 3 – The value of Calcium Sulfate (CS)

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

Calcium sulfate ApplicationsConstructionsArtAgricultureFood and BeverageCosmetics

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19th century plasterwork from House of Borujerdies in Kashan, Iran

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

Agenda

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Section 1 – Introduction

Section 2 – Background

Bone Regeneration

Bone Graft Requirements

Section 3 – The value of Calcium Sulfate (CS)

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

Agenda

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Section 1 – Introduction

Section 2 – Background

Bone Regeneration

Bone Graft Requirements

Section 3 – The value of Calcium Sulfate (CS)

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

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

Slow Graft resorption

Bone Growth

Graft resorption

Volume

164 Time (weeks)

50%

Mechanically interferes bone formationReduce GF and cell infiltration

Bone Growth

Graft resorption

Volume

164 Time (weeks)

Fast Graft resorption

50%

Reduce graft stability and amount of new bone formedParticle migration increase inflammation

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

Agenda

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Section 1 – Introduction

Section 2 – Background

Bone Regeneration

Bone Graft Requirements

Section 3 – The value of Calcium Sulfate (CS)

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

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

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

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

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

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

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

Optimal setting

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Calcium sulfate Hemihydrate Calcium sulfate Dihydrate

Sub-

Crystallinity and material properties

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Good material propertiesHigher strength Longer Resorption

Highly crystalline structure

Optimal setting

Questions?

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