1. Engineering of Bone Tissue
for augmentation procedures
Requirements
Current solutions
Bi-Phasic Calcium Sulfate
By Dr. Amir Kraitzer

2. Outline
1. Overview
2. Bone and Bone Augmentation
3. Bone graft materials
4. Bi-Phasic calcium sulfate Bone Graft – Bond
Bone

3. Bone Augmentation
• The past decade brought a new era in
bone repair fueled by the latest
technological advances
• Part of the routine surgical spine,
orthopedics and dental care
• New methods and new bone grafts
facilitated grafting procedures
• Bone graft sources:
– The patient itself
– Cadavers
– Animals
– Synthetic
• ~500,000 bone graft procedures performed in US yearly ~ 2.2 million worldwide
• Estimated cost of $2.5 billion per year
• Dental bone graft estimated cost 8% of total bone graft

4. Periodontal disease
• Account for ~60% of tooth loss
• Affect one or more of the
following tissues:
– alveolar bone
– periodontal ligament
– cementum
– gingiva
• Bacteria and plaque cause
toxins eventually lead to
inflammation

5. Outline
1. Overview
2. Bone and Bone Augmentation
3. Bone graft materials
4. Bi-Phasic calcium sulfate Bone Graft – Bond
Bone

6. Bone augmentation
• Following tooth extraction the alveolar ridge resorbes
• Early bone loss can be reduced by socket grafting
• Augmentation replaces missing bone
• Grafting materials are implanted and fused with natural bone over time
• Granular or block type grafts require membrane due to particle
migration
• Grafting procedures repair jaw bone defects:
– periodontal defects
– post extraction defects
– bone reconstruction
– implant placement
– Infections
– cyst or tumor surgery defects
Bone Augmentation:
http://www.toothiq.com/dental-videos/dental-video-bone-resorption.html

7. Augmentation Procedures
• Grafting procedures performed primarily by
periodontists or experienced dentists
• Require wound healing understanding
• Require knowledge of the mechanical, material
and biological properties of the graft
Sinus lift procedure

8. Bone Structure
Bone is a highly ordered structure on the macroscopic,
cellular and molecular levels.
• Mineralized component: 60% • Blood supply:
of the bone is hydroxylapatite – Receives 5 - 10% of cardiac
crystals: Ca10(PO4)6(OH)2 output
• Organic matrix: 40% of the – Arterial supply
bone mostly collagen – Microcirculation
• Cellular components: – Venous return
– Osteoprogenitor cells
– Osteoblast
– Osteocyte
– Osteoclast

9. Bone Biology
Osteoblast
• Bone forming cell
• Responsible for deposition and calcification of bone matrix
• Osteoblasts synthesize collagen and other proteins
Osteocyte
• Mature, fully differentiated osteoblast
• Surrounded by mineralized bone matrix
Osteoclast
• Responsible for the resorptive aspect of bone remodeling
• Elaborates enzymes, acids for resorption of bone matrix
Osteoprogenitor Cells
• Pluripotential cells
• Stem cells
• Bone marrow stromal cells

10. Bone Structure
Bone may be classified on the basis
of its clinical structure
• Compact Bone (cortical) - Dense,
solid bone such as the outer
cortical layer
• Trabecular bone (spongy or
cancellous bone) - non dense
bone located between compact
bone.
Bone anatomy and microstructure
http://www.youtube.com/watch?v=c5zcGv8M
vMc&feature=related
http://www.youtube.com/watch?v=ylmanEGjR
uY&NR=1&feature=fvwp

11. Bone Structure development
Cortical or cancellous bone is of two main types
• Woven (embryonic) Bone
– Immature
– rapidly forming bone
– Randomly distributed oseocytes
– poorly mineralized
– structurally weak
– replaced with lamellar bone
• Lamellar Bone
– Mature bone
– Arranged parallel collagen fibers , HA and bone cells
– Main load bearing component of the bone
– Slowly formed (approximately 0.6 to 1 mm/ day)

12. Bone Modeling and Remodeling
• Bone is capable of self-repair and adapts new loads
(Wolff’s Law)
• When stimulated under load the cortical portion of
bone becomes thicker
• Bone becomes weaker without stimulus
• Two fundamental concepts, modeling and remodeling,
describe the dynamic nature of bone
– Remodeling - Osteoclastic resorption and osteoblastic
formation is balanced
– Modeling – Bone changes its 3D size and shape in
response to stimulus or physical force
Bone formation:
http://www.youtube.com/watch?v=X6E5Rz9tOKE&feature=related

13. BONE TISSUE MECHANICAL PROPERTIES
Tensile Strength (MPa) and % elongation at break of
cortical bone from the human femur as a function of age

14. Ostseoporosis
A disease of bones that leads to an increased risk of fracture.
Remodeling imbalance between bone resorption and bone
formation
Healthy bone Osteoporosis

15. Outline
1. Overview
2. Bone and Bone Augmentation
3. Bone graft materials
4. Bi-Phasic calcium sulfate Bone Graft – Bond
Bone

16. Mechanisms of Graft Healing
An ideal bone graft should possess the properties involved in
bone healing
(1) Osteoconductive
– Matrix providing 3D lattice with interconnected pores
– Allowing cells to migrate for ingrowth of new blood vessels
and osteoprogenitor cells
(2) Osteoinductive
– Recruit and encourage migration of osteoprogenitor cells
– Stimulating factors towards osteoblastic differentiation
(3) Osteogenic
– Formation of new bone from living cells transplanted within
the graft

17. Bone Grafting Materials
Classification of Grafting Materials Based on Source
• Autograft (Autogenous) - Refers to a transplant of viable
cortical or cancellous bone from one location to another
within the same patient
• Allograft- Refers to a transplant within the same species,
such as the human bone sourced from cadavers.
• Xenograft- Refers to a cross-species transplantation such
as the use of anorganic bovine bone or bovine collagen in
human subjects
• Alloplast- Refers to implantation of a synthetic material.
As a group, the alloplasts are synthetic osteoconductive
materials.

18. Bone Grafting Materials
Autograft
• Considered the gold standard
• Osteoinductive, osteoconductive, and osteogenic properties
• The risk of infection is minimal
• Bone is harvested from mouth, hip, iliac crest or chin
Disadvantages
• Low availability of bone volume
• Require a second operative site
• Significant patient morbidity

19. Bone Grafting Materials
Allografts
• Human cadavers source
• Mineralized freeze dried allograft
– Osteoconductive and Osteoinductive
– Low bioavailabilty and activity of bone morphogenetic proteins (BMP)
• Demineralized freeze dried bone
– Osteoinductive
– The process exposes BMP
• BMP cause differentiation of mesenchymal cells into osteoblasts
Disadvantages
• Lack of uniformity in the products of individual banks
• Risk of disease transmission and unpredictability
• Possible infections, and antigenicity risks
Grafton® DBM Gel

20. Bone Grafting Materials
Xenograft
• Naturally derived hydroxylapatite from bovine, coral
• Osteoconductive
• Similar structure, chemistry, and porosity of human bone
Disadvantages
• Risk of disease transmission
• Remains in the defect for years
• Continuous macrophage activity
Histology review:
http://www.youtube.com/watch?v=bTP2hAG0
wcM&feature=channel

21. Alloplast synthetic grafts
Dense Hydroxylapatite
• High density, high crystallinity and no resorption over time
• Particles placed adjacent to bone become surrounded by bone
• Particles placed more than a few millimeters are surrounded by fibrous
connective tissue
Low-Density Hydroxylapatite
• Plasma-sprayed HA applied to implant surfaces
• Amorphous
• Resorbable
Beta-Tricalcium Phosphate
• Granular Matrix type:
– Porous particles (100-300 μm) pore size
– Resorbed and replaced by bone in 9 to 12 months
• Cement Type:
– Injected and hardens in 12 hours

22. Alloplast synthetic grafts/more
Bioglass
• Amorphous
• Composed of calcium phosphate, sodium, and silicon
• Bioactive layer for bone cell attraction to form a HA
layer
Bioplant HTR®
• Polymethyl methacrylate (PMMA) beads with a calcium
hydroxide (CH) coating
• Porous (350 μm) to facilitate bone ingrowth
• Partially resorbable (CH)

23. Ideal Synthetic bone graft
• Materials – HA or HA forming materials
• Pore size, distribution, and porosity (matrix graft)
– Pores of 100 m form bone (Pores of 15-40 m produce fibrous tissue)
– Pore of 300-500 m permit vascular in-growth
– Interconnected pores
• Granule size (granular graft)
– Grains larger than 10 m prevent stimulation of macrophage phgocytosis
• Crystalline structure
– Affect the surface adsorption of osteogenic cells
– Affects mechanical and resorption profile
• Mechanical properties
– Should be in close proximity to the mechanical properties of bone

24. Stress Shielding
• Reduced bone density due to removal of
stress by an implant
• Stimulus for remodeling is required to
maintain bone mass (Wolff's law)
• We must select materials which are in close
proximity to bone’s mechanical properties

25. Density Elastic Yield strength Tensile %
(g/cm3) modulus (MPa) Strength Elongation
(GPa)* (MPa) at break
SS 316L 7.9 190 690 860 12%
30% cold worked
Ti-6Al-4V or 4.5 114 830 900 14 %
ASTM F136
annealed
PLLA 1.3 2.7 -- 50 5 -10%
Density Elastic Compressive Tensile %
(g/cm3) modulus Strength Strength Elongation
(GPa)* (MPa) (MPa) at break
Cortical Bone ~2 17 - 24 100-230 90-130 1-3%
Cancellous ~1 0.1 - 4.5 2-12 10-20 5-7%
Bone
*In tension

26. Resorption rate
• In the early phase of healing material should remain stable
• Resorbtion rate should correlate the rate of bone formation
– Fast resorption compromise the osteocoductivity
– Slow resorption may block bone in-growth
• Homogenous solubility
– Prevent premature microparticles separation
ActifuseReduce macrophage phagocytosis
– (Ca-Po with silicate
ions replaced phosphate
– Assist bone-forming metabolism
groups in the calcium
phosphate• ionic lattice)
constant physiological concentration of calcium and phosphate ions
Actifuse compared to β-TCP
(VitossTM) and calcium
sulfate (Osteoset TM) in the
distal femoral condyle of
the New Zealand white
rabbit

27. Novel Bi-Phasic Calcium
sulfate bone graft

28. Calcium Sulfate (CS)
• Long history of use as a void filler Alderman, 1969;
• First used in 1892 by Dreesmann in
orthopedics Bahn, 1966;
• Highly biocompatible
Bell, 1964;
• Osteoconductive
• Fully resorbed over a period of 5–7 weeks Coetzee, 1980;
• New bone formed in a normal morphology
Edberg, 1930;
Gitelis et al., 2001;
Kelly et al., 2001;

29. The Bi Phasic Calcium Sulfate Concept
Hemihydrate Dihydrate
CaSO4 · 0.5H2O CaSO4 · 2H2O
Advantages Disadvantages Advantages Disadvantages
• Moldable • Does not set in presence of • High strength • Non-moldable
• Cementable blood/saliva • Resorption rate • Non- cementable
• Low strength equivalent to bone
• Fast resorption growth
• Is not affected by
blood and saliva

30. CS Hemihydrate
+ CS Dihydrate
Bi–Phasic Calcium Sulfate

31. Bi – Phasic CS Advantages
 Fast and efficient setting under blood and saliva (2-5 min)
 High crystalline percentage
 Resorbtion rate equivalent to bone growth (4-10 weeks)
 Moldable
 Average reaction temperature - 30°C
 Neutral pH
 Preserves the 3D space
 Mechanical properties equivalent to bone

32. Future of Bone Grafts
• Facilitate treatment
• Enhanced resorption rate
– Composite bone graft with various rates of resorption
– Osteoconductive only when required
• Effective and safe biological activity
– Promotion of osteoblastic proliferation, differentiation and function
Thank you