Myanmar Society of Oral Implantology collaborates with Myanmar Dental Association ( Yangon Division) and celebrates Yangon Dental Festival. At this event, as the President of MSOI, I present this topic. References list was collected in separate folder.

1. Bone Regeneration and
Substitutes
Professor Dr. Kyaw Tint
B.D.S.(IDM), M.D.Sc.(UDM), Ph.D(TMDU)
Dip.Med.Ed (UOPH) ,Cert. in Higher Education(IIE,USA)
Attached to IADR, JBI, PFA

2. • Bone: constituents and sources
• Bone Healing , remodelling process and
mesenchymal stem cells
• Bone Defect & Critical Size
• Bone graft, Biomaterials and Nano Technology
• Surgical indications & Autotooth graft
• Research on bone substitutes
• How to select, How to check
• Guide line & Policy & Legal Binding

3. Bone
• Organic 30% Ingorganic 70%
• Hydroxyapatite, also called hydroxylapatite
(HA), is a naturally occurring mineral form of
calcium apatite with the formula Ca5(PO4)3(OH),
but it is usually written Ca10(PO4)6(OH)2 to
denote that the crystal unit cell comprises two
entities
• Hydroxyapatite is the hydroxyl endmember of
the complex apatite group

4. • collagen is the building block of the organic
matrix—a triple helix with diameter of 1.5 nm.
• the hydroxyapatite crystals are platelets that
have a diameter of approximately 70– 100 nm
and thickness of 1 nm. They originally nucleate
at the gaps between collagen fibrils.
Bone constituents

9. Imflammation, Repair, Remodelling

10. Healing after tooth extraction

14. It is better to know
Mesenchymal Stem Cells

15. Origin of mesenchymal stemm cells
• While originally identified in the bone marrow
• MSCs have been extracted from numerous
tissues including adipose , heart, dental pulp ,
peripheral blood, and cord blood.
• One of the major properties of MSCs is their
ability to differentiate into various cells:
like adipocytes , chondrocytes, osteoblasts,
neurons, muscles , and hepatocytes in vitro
after treatment with induction agents

16. Migration, adhesion, and proliferation
• stimulated in vitro by many growth factors
including Platelet-derived growth factor
(PDGF) , Epidermal growth factor (EGF) ,
Vascular endothelial growth factor (VEGF) ,
Transforming growth factor (TGF-β) , Bone
morphogenetic protein-2 (BMP-2) and BMP-4
• plasma clot serves as storage to fibrin
molecules and release system for a variety of
bioactive factors

17. Migration, adhesion, and proliferation
• After MSCs recruitment in the injured site,
cells adhere on the local extracellular matrix
as well as on the implant surface beginning an
extensive proliferation in order to build up
new tissue.

19. Differentiation
• Under the influence of these growth factors,
MSCs switch to osteoblastic cells
• In some cases, implants are encapsulated by
fibrous tissue due to the proliferation and
differentiation of MSCs into fibroblastic cells

20. Bone Defect and Critical Size
• Bone defect caused by tooth extraction,
periodontal disease, trauma, cyst, tumor and
infection
• Noncritical defects may heal without planned
reconstruction and secondary surgery
• 2.5cm in Human,1.5cm in rabbit, 8mm in rat

21. The term “bone graft” was defined by
Muschler (Bauer, 2000) as
• “any implanted material that alone or in
combination with other materials
- promotes a bone healing response by
- providing osteogenic, osteoinductive or
osteoconductive properties”

22. What are OSTEOgenesis, induction,
promotion, conduction?
• vital osteoblasts originating from the bone
graft material contribute to new bone growth
• stimulation of osteoprogenitor cells to
differentiate into osteoblasts (BMP)
• enhancement of osteoinduction without the
possession of osteoinductive (DFDBA)
• the bone graft material as a framework

23. What are..
• Osseoinduction is the ability to promote de novo
bone formation remote from the host bone even
within noncalcified tissues
• Osseoconduction is the property of promoting bone
growth from the surrounding host bone onto the
surface of the graft material, using the graft as a
framework

24. • Is Bone grafting possible?
• Yes, because bone tissue has the ability to
regenerate completely

26. Bone Graft and Graft Substitutes
Description Examples Osteo
genic
Osteo
inductive
Osteo
conductive
Autograft + + +
Allograft Allegro, Orthoblast,
Grafton
+ +
Factor based TGF-b,PDGF, FGF, BMP + +
Cell based Mesenchymal Stem Cell + +
Ceramic based Osteograt, Osteoset,
NovaBone
Limited +
Polymer based Cortoss, OPLA, Immix +,
Bioresorbable
Miscellaneous HA granules, block &
Composite, ProOsteon
+,
Bioresorbable

27. Autogenous bone grafts
less risk of graft rejection
Availability
Sterility
Biocompatibility
Osseoinductive potential
Osseoconductive potential
Ease of use
Type: Cancellous and Cortical

28. Autogenous bone graft

29. Autogenous bone graft

30. • If autogenous bone graft is not available,
We have to use Bone Substitutes:
Allograft or Artificial bone
In other words, Biomaterials….

31. The ideal characteristics of a
substitute bone graft material
Sterile
Non-toxic
Non-immunogenic
Osteoinductive or osteoconductive
Favorable clinical handling
Resorption and replacement by host bone e.g
CaC03
Synthetic Available in sufficient quantities
Low in cost

32. Allograft (Allogenic grafts)
• Bone derived from cadavers
• Decalcified freeze-dried bone allograft (DFDBA),
with bone morphogenetic protein
• Or mineralized freeze-dried (FDBA)
• They are osteo inductive/ conductive, providing a
framework for new bone growth
• Available in varying thicknesses of 20–700 μm,
(prion will be inactivated by heat)

33. How to treat Allograft
• Physical debridement- remove soft tissue,
cellular load and ultrasonic washing,
• Ethanol treatment- denaturalize proteins and
viral deactivation
• Antibiotic wash- to kill bacteria
• Sterilization- gamma radiation,
• Ethylene oxide- spore elimination (Khan, 2005)
• Antibiotic- twice for 1hr, frozen -70, dried up
(Kao, 2007)

34. Xenograft
Deproteinized bovine bone mineral
• Similar properties to human cancellous bone
• As a purely mineral(Calcium) graft it is
osseoconductive
• Mixed with the patient’s blood and packed
into the defect
• As a filler to increase the volume of
autogenous graft material

35. How to extract/treat Xenograft
• Thermal and chemical extraction
• 0.25 to 1mm size, 75% porous
• Non resorbable in vivo

36. Biomaterial
• Definition -material exploited in contact with
living tissues, organisms,or microorganisms
- can be derived either from nature or
- synthesized in the laboratory
- using a variety of chemical approaches
- utilizing metallic components, polymers,
ceramics or composite materials

37. • Ideally, a biomaterial
- should be non-toxic, non-irritant, have no
carcinogenic or allergic potential and,
- if used as a filling material, should be
harmless to the pulp

38. Scope
• The field of biomaterials science encompasses
all classes of material, i.e. polymers, ceramics,
glasses and metals,
• and a wide range of branches of surgery:
dental, ophthalmic, orthopaedic, cardiovascular
and so on.

39. Biomaterials are used in:
• Joint replacements
• Bone plates
• Bone cement
• Artificial ligaments and tendons
• Dental implants for tooth fixation
• Blood vessel prostheses
• Heart valves
• Skin repair devices (artificial tissue)
• Cochlear replacements

40. • Contact lenses
• Breast implants
• Drug delivery mechanisms
• Sustainable materials
• Vascular grafts
• Stents
• Nerve conduits
• Surgical sutures, clips, and staples for wound
closure

41. Biocompatibility
• Biocompatibility is related to the behavior of
biomaterials in various environments under
various chemical and physical conditions
• For example, a material may elicit little or no
immune response in a given organism, and
may or may not able to integrate with a
particular cell or tissue.

42. Biocompatibility
• not a property of a material per se; the
material needs to elicit an appropriate
response
• distinct from that of inertness, which would
imply a complete absence of response from
the body (e.g GP points)

43. Biomaterial as scaffold
• When the damage is so extreme that it is
impossible to use the patient’s own cells,
artificial tissue cells are grown. It needs a
scaffold that the cells can grow and organize on
• The characteristics of the scaffold must be that it
is biocompatible, cells can adhere to the
scaffold, mechanically strong and biodegradable.

44. Biopolymers
• Produced by living organisms.
• e.g- Cellulose and starch, proteins and peptides,
and DNA and RNA in which the monomeric units,
respectively, are sugars, amino acids, and
nucleotides.

45. Alloplastic graft materials
• no risk of cross-infection
• but may still give rise to an antigenic response
• as a framework for bone formation on their
surface and are therefore osseoconductive
• They include:
- Hydroxyapatite , Calcium Phosphate
- Tricalcium Phosphate (TCP), Bioactive Glasses
- Calcium Carbonate

48. Coral system: limestone skeletons of marine polyps oEWmausmuf

49. 1 : 1.67

50. TCP Granules
Micropores
Size

51. Involvement of Nanotechnology
in bone substitute production

52. Nanotechnology
• “Nano” is derived from the Greek word for “dwarf.”
• American Physicist and Nobel Laureate Dr. Richard
Phillips Feynman who presented
• a paper called “There is plenty of room at the
bottom” in December 29, 1959, at the annual
meeting of the American Physical Society at
California Institute of Technology

53. History of nanotechnology
In 1959 Richrad Feynman
presented ideas for creating
Nano scale machines
Norio Taniguchi
introduced the term
‘nanotechnology’
1980s, development in this field was
greatly enhanced with advances in
electron microscopy

55. A nanometer is
• one billionth of a meter, or 3 to 5 atoms in
width.
• 40,000 nanometers lined up in a row to equal
the width of a human hair.
• Nanotechnology can be approached in two
ways: “top-down” and “bottom-up”
approaches

56. Approaches in nanotechnology
Top-down Approach
Creating Nano-scale materials
by physically or chemically
breaking down larger materials
Bottom-up Approach
Assembling Nano materials
atom-by-atom or molecule-by
molecule (self assembling)

57. Top-down Bottom-up
Method miniaturization agglomeration
From macroscopic Atoms or
molecules
To Micro/nanoscale Macromolecular
Tech Machining/etching Self-organize/
self-assemble
e.g Semi-conductor
Cochlear
replacements
polymer
Two ways approaches

58. Dip-pen nanolithography ( DPN)

59. Bioactive glass in dentistry
• use as bone grafts, implant coatings, bone
cements, toothpaste, and various other
applications in dentistry.
• e.g-Bioglass, Perioglass
• Bioactive glasses are known for
osteoconductivity and bonding to bone
through the release of ions and formation of a
layer of apatite

60. Composition and synthesis of
bioactive glass nanoparticles
• The sol-gel-derived bioactive glasses, the
composition of 60% SiO2, 36% CaO, and
4% P2O5 (by weight) has a high level of
bioactivity, (phosphorus pentoxide)
• The synthesis of bioactive glass uses typical
precursors like tetraethyl orthosilicate (TEOS),
calcium nitrate (CN), and triethylphosphate
(TEP).

62. Surgical procedures that require the
use of bone substitutes
• Sinus lift
• Alveolar ridge augmentation
Onlay bone grafts
Guided bone regeneration and
titanium mesh

63. Sinus Lift

64. Alveolar ridge augmentation
• Onlay bone graft
- Fixing a biomaterial in the shape of a block
directly onto the bone surface of the
alveolar ridge, and covered with the
periosteum and oral mucosa

65. GBR and titanium mesh

66. ABB using Ti mesh

67. Autotooth Bonegraft

68. Teeth as a bone substitute
• a composite of organic and inorganic :minerals
of the calcium phosphate range, collagen, and
other organic elements.
• 5phases (hydroxyapatite, tricalcium phosphate,
octacalcium phos-phate, amorphous calcium
phosphate [TCP], and brushite)
• Good bony remodeling can be made when
calcium phosphate is put into a living system.

69. The chemical compositions of teeth
and bone are very similar
• Enamel is 96% inorganic ingredients and 4%
organic ingredients and water.
• Dentin has a 65% : 35% ratio,
• Cementum has the ratio of 45-50% : 50-55%
• Alveolar bone is made up of 65% inorganic
ingredients and 35% organic ingredients.

70. • Tooth dentin and cementum contain a number
of bone growth factors including type I
collagen and bone morphogenic protein
(BMP)
• Type I collagen accounts for 90%, with the
rest consisting of noncollagenous proteins,
biopolymer, lipid, citrate, lactate, etc

71. • Noncollagenous proteins are phosphophoryn,
sialoprotein, glycoprotein, proteoglycan, BMP,
etc
• They can perform the role of promoting bone
resorption and bone formation
• Therefore, bone graft materials using teeth are
considered to be potentially useful in clinics3-5

72. Autotooth bone graft
Maxillary 3rd
molar was extracted

73. Root portion was prepared for bone substitute

74. Dentin particles of size 300-1200 microns
were obtained
Dentin cleanser was added for 7 min.
Dentin particles were dried and
treated using PBS solution for 3 min.
(phosphate buffered saline)

75. Bone graft placed
Suturing done
Periodontal dressing given.

76. Research on bone substitutes
•Although first studies regarding bone
substitutes dates from 1920 by Albee
(Albee, 1920), until 1980´s
there are very few studies in reference
this issue

77. Physicochemical Characterization
of Biomaterials Commonly
Used in Dentistry as Bone Substitutes
—Comparison
with Human Bone
Margarida Figueiredo,1 Jose Henriques,2 Gabriela Martins,1
Fernando Guerra,2
Fernando Judas,3 Helena Figueiredo4

78. Bovine
BioOss,(cancellous
PepGen P-15 (cortical)
Porcine
OsteoBiol
Coraline
Biocoral
Human
SEM
Particle size
Analysis
250–1000, 250–420 250–1000 640- 1000
Mercury
Intrusion
+ + +
Density
G cm-3
3.21, 3.20 2.43 2.92 2.3 (Nat)
3.1 (Cal)
Surface Area
m2 g-1
59.7, 1.72 42.4 0.26
FTIR spectrum
(Fourier transform
infrared
spectroscopy
Collagen
bundles
XRD (chemical )
(resolution X-ray
diffractometry)

79. Three-dimensional bone tissue substitute based on a
human mesenchymal stem cell
culture on a nanofiber carrier and inorganic matrix
Martin Krbec1, Lukáš Plíštil2, Eva Matoušková2, Václav Mandys3, Jakub Ježek1,
Markéta Sedlinská4, Valér Džupa1
University Hospital Královské Vinohrady,
1Department of Orthopaedics and Traumatology,
2Centre for Applied Bioimplantology,
3Institute of Pathology, Prague, Czech Republic
4University of Veterinary and Pharmaceutical Sciences Brno, Faculty of
Veterinary Medicine,
Equine Clinic, Department of Reproduction, Brno, Czech Republic
Received December 4, 2015
Accepted February 10, 2016

80. Bone Substitutes in Netherland

81. • How about MYANMAR?.....
• When we want to use…they will order…
• FDA ????

82. Some Clinical evidences
Multicenters….

86. Let us to use Bone Substitutes

87. When you have to use BS, Check …
Name Content Particle Size Pore Size & % Resorption Rate
Ceros TCP
C:P= 1:1.5
Tricalcium
Phosphate
100-500um 10um, 60% 24W
Product Name Osteogenic Osteoinductive Osteoconductive Biodegradable
Product
Name
Company Origin Chemical
Composition
Form Ceramic/Cement
Biomet etc Synthetic/
Bovine
Solid/paste

88. Property of BS depends on
• Power to bone formation: Genesis, induction,
promotion, conduction
• Biodegradability, active by OC and/or
macrophage, passive by degradation and
dissolution
• Porosity, surface geometry, surface chemistry
• Host factor- bone quality, vascularity of graft
bed, tobacco addiction

89. How much you have to use..?
Root apex resection (1 g)
Sinus lift (2.0-3.0 g)
Periodontal defect (1.0-2.0 g)
Alveolar defect (2.0-3.0 g)

90. Important considerations for application
- Mix with patient own blood, cancellous bone or
bone marrow
-Direct contact with the vital bone
-Inflamed and nercrotic tissue must be removed
and the bone freshly exposed
-Granule size is determined by the size of the bone
defect

91. Important considerations for application
• Ensure tension-free wound closure, avoid
overfilling and pressure sores to nerve and
vessels
• Membrane is recommended in the area of
mastication forces or facial muscle movements
• 4 to 6 months for defect-filling cases, 6-12
months for sinus lift cases
• In large defect, mix with autograft (50:50)

92. LEGAL BINDINGs

93. Why?
• The Centers for Disease Control and Prevention
(CDC) gave an update: allograft-associated
bacterial infections — United States, 2002.
• Tissue allografts are commonly used in
orthopedic surgical procedures; in 1999,
approximately 650,000 musculoskeletal
allografts were distributed by tissue
processors.

94. • After the reported death of a recipient of an
allograft contaminated with Clostridium spp.
(an anaerobic spore and toxin-forming
organism),,,,,,,
• CDC investigated this case and solicited
additional reports of allograft-associated
infections; 26 cases have been identified

96. • Bone: constituents, sources
• Bone Healing , remodelling process and
mesenchymal stem cells
• Bone Defect & Critical Size
• Bone graft, Biomaterials and Nano Technology
• Surgical indications & Autotooth graft
• Research on bone substitutes
• How to select, How to check
• Guide line & Policy & Legal Binding

97. References Folder

98. Thanks for your kind attention