explains about bone grafts and growth factors and conclusive statement on usage of both in implantology

1. Bone grafts and
growth factors in
Implantology
Dr Lakkireddy Vasavi reddy
II MDS

2. Contents:
• Introduction
• Definition
• Terminology
• History
• Classification of bone grafts
• Grafting types
• Graft materials
• Growth factors
• Conclusion

3. Introduction:
• Recent advances in biotechnology have provided the
implant surgeon with access to a great variety of bone
grafting materials and the possibility of easier implant
treatment for the patient as well as for the surgeon.

4. Definition:
• GRAFT: Material, especially living tissue or an
organ, surgically attached to or inserted into a
body part to replace a damaged part or
compensate for a defect.

5. Terminology:
• OSTEOGENESIS refers to the
formation or development of new
bone by cells contained in the graft.
• occurs when viable osteoblasts
and precursor osteoblasts are
transplanted
• E.g. Autogenous iliac bone and
marrow grafts.

6. • OSTEOINDUCTION involves new bone formation by differentiation of local uncommitted
connective tissue cells into bone- forming cells under the influence of one or more inducing
agents.
• E.g. Demineralised bone matrix (DMB) or bone morphogenetic proteins (BMP)(Giannobile &
Somerman 2003; Reynolds et al. 2003)
• OSTEOCONDUCTION occurs when non-vital implant or graft material serves as a scaffold for the
ingrowth of precursor osteoblasts into the defect. Usually followed by gradual resorption of the
graft material.
• E.g. Autogenous cortical bone or banked bone allografts , bone derived or synthetic bone
substitutes.
• -if the implanted material is not resorbable (hydroxyapatite) the incorporation is by apposition to
the material surface.

7. History:
Autogenous (Extra oral) – first for periodontal application (Zolton Hegedus, 1923)
Xenografts (Forsberg -1956, Melcher – 1962)
Autogenous (Intra oral)- Nabers & Oleary - 1965
1970s – Allogenic freeze dried bone (James Mellonig & Gerald
Bowers 1976 – FDBA)
1980s – Demineralized allogenic freeze dried bone (Urist)
1990s – Newer Xenografts and alloplastic bone replacement grafts

8. Classification of bone grafts:
ROSE AND MEALEY CLASSIFICATION
BONE AND BONE SUBSTITUTES Periodontology
2000(1999) hishamf. Nasr,maryelizabeth aichelmann-
reidy & raymonda. Yukna

9. BONE DERIVED MATERIAL
Vital bone graft
Autograft
ORAL
Osseous coagulum
Bone blend
Bone harvested from extraction site,
tuberosity, edentulous ridge
EXTRAORAL
Iliac crest
Allograft
Cryopreserved bone
Fresh bone from iliac crest
Nonvital bone graft
Allograft(human bone)
FDBA
DFDBA
Xenograft
Anorganic bovine bone
NON OSSEOUS
MATERIAL
 Organic
Dentin
Cementum
Coral
 Anorganic(alloplasts)
Calcium sulphate
Calcium phosphate- HA
Calcium ceramics
Bioactive glass
Polymers
ROSE &MEALEY

10. Material source: (Periodontology 2000)
BONE SUBSTITUTES
XENOGRAFTS
Bovine derived hydroxyapatite
Coralline calcium carbonate
ALLOPLASTS
Bioceramics
Tricalcium phosphate
Hydroxyapatite
Bioactive glasses
polymers
HUMAN BONE
 1. Autogenous grafts
Extraoral
Intraoral
 Allogenic grafts
Fresh frozen bone
FDBA
DFDBA
Periodontology 2000(1999)

11. Rationale for
use in
implantology:
Placement of implants requires sufficient bone volume
and biologic quality. This is due to the macro design of
the implant, which demands certain dimensional
properties for long-term success.
Other factors which make bone grafting necessary are:
• The resorption of the edentulous ridge post
extraction
• Presence of bony defects due to trauma or infection
• The need to place implants in strategic sites for
functional and esthetic success. In esthetic areas, soft
tissue requires a bony base since “soft tissue follows
hard tissue”

12. Indications:
• In alveolar sockets post extraction
• To refill a local bony defect due to
trauma or infection
• To refill a peri-implant defect due to peri-
implantitis
• For vertical augmentation of the
mandible and maxilla
• For horizontal augmentation of the
mandible and maxilla

13. Decision making:

16. Ideal
requirement of
bone graft:
• Nontoxic
• Nonantigenic
• Resistant to infection
• No root resorption or
ankylosis
• Strong and resilient
• Predictability
• Induce new attachment
• Easily adaptable
• Readily and sufficiently
available
• Minimal surgical
procedure
• Stimulates new
attachment
• minimal post-operative
sequelae
• Completely replaced by
host bone of the same
quality – quantity

17. For a bone
graft to be
successful:
1. Osteoblasts must be present at the site
2. Blood supply must be sufficient for
nourishment
3. The graft must be stabilized during
healing
4. The soft tissue must not be under
tension

18. DECISION MAKING FOR GRAFT
SELECTION
AUTOGENOUS
CORE OR BLOCKS
NON-AUTOGENOUS GRAFTS
PARTICULATE OR
BONE GRAFT
PASTE PARTICULATE
OR BONE
PUTTY GRAFT
BONE PUTTY
GRAFT
Autogenous
graft available at
primary site
Autogenous graft
not available at
primary site
Intact extraction
socket
Moderately
compromised
extraction
socket
Onlay /
severely
compromised
extraction
socket
THUMB RULE:
MAXIMIZE
AUTOGENOUS
GRAFTS

20. Monocortical block graft:
• Horizontal alveolar deficiencies
can easily be reconstructed with a
monocortical block bone graft.
• The technique uses a cortical
block of bone harvested from a
remote site and used to increase
the width of bone.
• The block graft taken from an
intraoral (e.g., mandibular
symphysis or ramus) or extraoral
(e.g., iliac crest or tibia) site is
fixated to the prepared recipient
site with screws.
• The graft can be separated from
overlying soft tissues with a
barrier membrane or simply
covered with the mucoperiosteal
flap.

21. • Fixation hardware (i.e., screws and
plates) should be removed after an
adequate period of healing
(approximately 6 months).
• The disadvantage of this technique is
the biologic limitation of
revascularizing large bone blocks.
• It therefore is crucial to have
sufficient osteogenic cells in the
residual surface of the surrounding
bone and to limit this technique to
horizontal augmentation and only
minimal vertical defects.

22. Particulate graft:
• Advantages of particulate bone grafts (or bone chips) are
that the smaller pieces of bone demonstrate more rapid
ingrowth of blood vessels (revascularization), larger
osteoconduction surface, more exposure of
osteoconductive growth factors, and easier biologic
remodeling when compared with a bone block.
• If the bone has been harvested in block size, a bone mill
is necessary to particulate the bone and prepare the
bone to be transplanted into the bone defect.

23. • Particulate grafts are indicated in
defects with multiple osseous
walls or single bone walls and
when implants are placed
simultaneously with the bone
augmentation procedure.
• If a bone defect does not have
sufficient osseous walls to contain
the graft and if an implant is
placed simultaneously, a barrier
membrane is secured along the
periphery with tacks or screws.

24. Autografts:
• The autogenous graft (where tissue is
transferred from one location to
another in the same individual) is
considered to be the gold standard.
• It is osteogenic, osteoinductive and
osteoconductive.
• There is biological activity due to vital
cells and growth factors.
• There is also no risk of disease
transmission.
• However, there is an increased risk of
pain, infection, donor site morbidity,
complexity in the surgical procedure,
and a limited supply of bone.

25. Bone trephined
from within the jaw
without damaging
the roots
8-12week
postextraction
healing sites
Bone removed
during osteoplasty
and ostectomy
Tori or exostoses Edentulous ridges Maxillary tuberosity
Mental and
mandibular
retromolar areas
INTRAORAL
SOURCES
EXTRAORAL
SOURCES
Iliac crest grafts

26. Cortical bone shavings:
• Shavings of cortical bone removed by hand chisels during
osteoplasty and ostectomy were used to treat one, two wall
defects(Nabers & O’Leary 1965)
• Due to large particle size(1559.6 X 183µm), and potential for
sequestration, they were replaced by osseous coagulum and bone
blend

27. Osseous coagulum:
• Mixture of bone dust and blood
• This technique used small particles ground from cortical
bone
• Sources are lingual ridge on the mandible, exostosis,
edentulous ridges, bone distal to a terminal tooth or
bone removed by osteoplasty or ostectomy.
• The advantage is the ease of obtaining bone from already
exposed surgical sites
• Disadvantage is inability to procure from large defect
sites.

28. Bone blend:
• The bone blend technique uses an autoclaved
plastic capsule and pestle.
• Bone is removed from a predetermined site,
triturated in the capsule to a workable plastic like
mass, and packed into bony defects.
• Froum and co-workers have found osseous
coagulum – bone blend procedures to be at least as
effective as iliac auto grafts and open curettage.

29. Cancellous
bone marrow
transplants:
SOURCES
• Maxillary tuberosity especially if the third
molars are not present
• Healing sites – allowed to heal for 8-12 weeks
and apical portion is used as donor material
• Edentulous ridges can be approached with a
flap and cancellous bone and marrow are
removed with curettes

30. Bone swaging:
• This technique requires the existence of an edentulous area
adjacent to the defect from which the bone is pushed into
contact with the root surface without fracturing the bone
at its base.
• Bone swaging is technically difficult, and its usefulness is
limited

31. Extra oral (Iliac autografts):
• The use of fresh or preserved iliac cancellous
marrow bone has been extensively investigated.
• iliac bone and marrow have the most
osteogenic and regenerative potential and are
one of the two graft materials with reported
ability to regenerate periodontium horizontally
or with “zero wall” defects, meaning actual
crestal apposition of bone

32. Allografts:
• Allografts are bone taken from one human
for transplantation to another..
• There are various types of allografts
available, including
1. Freeze-dried bone allograft (FDBA)
2. Demineralized freeze-dried bone
allograft (DFDBA).
• Both allografts and xenografts are foreign
to the organism and therefore have the
potential to provoke an immune response

33. • AAP recommends the use of cortical
rather than cancellous bone
allografts since cancellous bone is
more antigenic and there is more
bone matrix and consequently more
inductive components in cortical
bone(AAP 1994)

35. UNDECALCIFIED FREEZE-DRIED
BONE ALLOGRAFT (FDBA):
• Several clinical studies by Mellonig, Bowers, and co-
workers reported bone fill exceed 50% in 67% of the
defects grafted with FDBA and in 78% of the defects
grafted with FDBA plus autogenous bone.
• FDBA, however, is considered an osteoconductive
material, whereas decalcified FDBA (DFDBA) is
considered an osteoinductive graft. Laboratory
studies have found that DFDBA has a higher
osteogenic potential than FDBA and is therefore
preferred.

36. DECALCIFIED FREEZE-
DRIED BONE ALLOGRAFTS
• Experiments by urist and co-workers have
established the osteogenic potential of DFDBA.
• Demineralization in cold, diluted hydrochloric acid
exposes the components of bone matrix, closely
associated with collagen fibrils that have been
termed bone morphogenetic protein.
• DFDBA is believed to induce bone formation due to
the influence of bone-inductive proteins called bone
morphogenetic proteins (BMPs) exposed during the
demineralization process.

37. Xenografts:
2 sources of xenograft are,
• Bovine bone &Natural coral
1. Bovine-derived hydroxyapatite
2. Coralline calcium carbonate
3. Calf bone (Boplant)
4. Kiel bone
It provides long- term volume stability.
Porous natural hydroxyapatite can be
obtained from animal bones.

38. Bio-oss:
• It has been successfully used for
both periodontal defects and
implant dentistry.
• It is an osteconductive, porous
bone mineral matrix from bovine
cancellous or cortical bone.
• The trabecular architecture with
interconnecting pores allows for
optimal in- growth of new
vascularity.
• Guided osseous integration rather
than rapid resorption leads to
excellent volume stability of the
graft with the formation of new
bone on the highly structured
bovine bone surface
Bio-oss:

39. The bi-modal pore structure of Bio-Oss is similar to natural
bone
*Pores in the nanometer range: Penetration of Bio-Oss with
tissue fluid.
**Pores in the micrometer range: Enables cell adhesion.
Measurement: Research Analysis Department, F&E
Geistlich Biomaterials, Wolhusen, Switzerland 2006

40. Alloplasts or non bone graft materials:
In addition to bone
graft materials,
many nonbone
graft materials
have been tried for
restoration of the
periodontium.
• Sclera,
• Dura,
• Cartilage,
• Cementum,
• Dentin,
• Plaster of Paris,
• plastic materials,
• Bioceramics – HA & TCP
• Bioactive glasses
• Polymers
• Coral-derived materials.

41. Calcium
phosphate
grafts:
• Two types of calcium phosphate ceramics have been
used:
1. Hydroxyapatite(HA has a calcium-to-phosphate
ratio of 1.67, similar to that found in bone
material. HA is generally nonbioresorbable.
2. Tricalcium phosphate (TCP), with a calcium-to-
phosphate ratio of 1.5, is mineralogically B-
whitlockite. TCP is at least partially bioresorbable.
• The basic principle of using HA and TCP in
combination is a balance between the stable HA
which can be found years after implantation, and
the fast resorbing TCP.
• A ratio between 65:35 and 55:45 of HA to TCP has
been proven particularly suitable in many studies.

42. BIPHASIC CALCIUM PHOSPHATE
βTCP
HA
BIPHASIC
CALCIUM
PHOSPHATE
•Advantage of rapid resorption of βTCP & inert scaffold of HA
•Resorption of βTCP triggers macrophages, which facilitates
differentiation of soft tissue cells in to osteoblasts

43. Bioactive glass:
• When this material comes into
contact with tissue fluids,
• the surface of the particles
becomes coated with
hydroxycarbonateapatite,
• Incorporates organic ground
proteins such as chondroitin
sulfate and glycosaminoglycans,
• attracts osteoblasts that rapidly
form bone.
P2O5 2.5 mol
%
Na2O 24.4 mol
%
CaO 26.9 mol %
SiO2 46.1 mol
%
OSTEOINTEGRATIVE OSTEOCONDUCTIVE

45. Healing after monoblock graft:
Block Graft
transfer
Osteoclast
resorption
begins
Fibroblast
ingrowth
occurs
Matrix
creation for
vascularization
Osteoclasts
create voids in
the graft
Voids are filled
with osteoid
from
osteoblasts
Osteoid is
then
mineralized
Majority of
graft material
is completely
resorbed
New bone
formed

46. Healing after particulate graft:
Particulate
Graft transfer
Scaffold
creation for
ingrowth
Ingrowth of
osetoblasts
and precursor
cells
Matrix
creation for
vascularization
Osteoid is then
mineralized¸
New bone
formed
Majority of
graft material
is completely
resorbed

47. Healing time:
As a general rule,
4-6 months for a graft
volumes less than 5mm in
dimension
Upto 6-10 months for a
graft volume greater than
5mm in dimension

48. Growth factors:
Growth factors are polypeptide hormones that stimulate a wide variety of cellular
events, including chemotaxis, proliferation, differentiation and production of
extracellular matrix proteins.
Growth factors are present at low concentrations in bone matrix and plasma but
execute important biologic functions.
Growth factors bind to transmembrane receptor molecules on mammalian cells and
induce cytoplasmic cascade reactions, which give rise to transcription of mRNA and
intracellular and extracellular protein release.

49. PRP( platelet rich plasma):

50. Transforming growth factor:
Transforming growth factor (3 is a member of a large family of biologically active
protein hormones that are structurally related but differ markedly in their function.
TGF- ß consists of 2 subunits held together by covalent bonds.
Most of the cells express at least one of the TGF- ß genes. It is found in high con-
centrations in platelets and in bone.

51. Functions of TGF-β
TGF- ß appears to be a
major regulator of cell
replication and
differentiation.
It can stimulate or
inhibit cell growth.
It can modulate other
growth factors such as
PDGF, EGF, and FGF.
It inhibits epithelial cell
proliferation and
stimulates
mesenchymal cells.
It stimulates fibroblast
chemotaxis and
proliferation and
induces extracellular
matrix production.
It has stimulatory and
inhibitory effects on
osteoblast proliferation

52. Fibroblast growth factor:
There are 7 forms of fibroblast growth factors (FGF). Two are well
described, one is basic (p-FGF), the other acidic (a-FGF).The two
fibroblast growth factors are products of different genes but are
similar in structure and function.
FGF binds tightly to heparan, a major constituent of the extracellular
matrix. a-FGF and p-FGF are stored in the bone matrix (Hauschka et
al., 1986) and may be important factors for the regulation of
osteoblastic cells.

53. Platelet derived growth factor:
Platelet-derived growth factor is a well-characterized protein.
There are two different PDGF polypeptides that are 56% homologous and encoded by different genes. It has
been found to exist in homo-dimer forms (PDGF-AA, PDGF-BB) as well as in heterodimer form (PDGF-AB).
There are two different PDGF receptors: the PDGF- receptor (binds PDGF-AA, PDGF-BB and PDGF-AB) and the
PDGF-ß receptor (binds PDGF-BB and PDGF-AB).
PDGF-BB is the most potent stimulator of mitogenesis, followed by PDGF-AA and -AB. PDGF-BB is twice as
potent as PDGF-AA as a chemoattractant for connective tissue cells, and PDGF-AB increases collagen synthesis

54. Insulin like growth factor:
The insulin-like growth factors (IGF) are a family of single-chain serum proteins that share 49% homology
in sequence with proinsulin.
IGF-I and IGF-II are two poly-peptides from this group that have been well described.
They are synthesised by multiple tissues, including liver, smooth muscle and placenta, and are carried in
plasma as a complex with specific binding proteins.
IGF have been shown to stimulate bone formation and to have an effect on periodontal ligament cells.
It is believed that PDGF and IGF-I have a synergistic effect and that IGF-I alone does not enhance bone
repair.

55. Bone
morphogentic
proteins:
Bone morphogenetic proteins form a subgroup of the
transforming growth factor-b superfamily, which is a large
group of proteins that affect cell growth, migration and
differentiation, and play a regulatory role in tissue
homeostasis and repair.
Bone morphogenetic proteins can induce a local immediate
action, bind to extracellular antagonists at the site of
secretion, or interact with extracellular matrix proteins and
subsequently target cells.
Bone morphogenetic protein-9 may be highly osteogenic
because it is unable to bind to these regulatory molecules
(i.e. noggin). Osteoblasts secrete bone morphogenetic
proteins as well as their antagonists by a delicate regulatory
mechanism during bone formation and remodeling

56. Conclusive statements of bone grafts with
growth factors augmentation: (Misch)
The PRP collected from the patient’s blood many benefit the bone
formation process and/or laid on top of graft and membrane to promote
soft tissue healing.
The use of autologous bone in graft site can increase PDGF, FGF, TGF-β,
IGF and BMP’s, as all are stored in the bone and released during the
augmentation process. The BMP in an autograft primarily has an effect
on providing growth factors at 2 weeks and with a peek at 6 weeks.

57. A third method to introduce growth factors
at a bone graft site is to use an allograft in
the graft site. The DFDB from cortical bone
contains a higher percent of BMP than
trabecular bone, and therefore is a method
of choice. However, the amount of BMP in
commercial bone blank allografts is very
small (0.001mg) and is not a very significant
factor.
A fourth method to increase the growth
factors in graft site is by the RAP process,
which triggers a release of growth factors
into the site.