3. RATIONALE AND CLASSIFICATION OF BONE GRAFTS.

Since the aim of using bone graft materials is to reconstruct and regenerate lost

periodontal tissues mainly the alveolar bone it is important to understand. The

basic bone physiology, which is discussed in the following sections.

BONE BIOLOGY AND BONE PHYSIOLOGY

Bone defined as hard, strong calcified connective tissue. Its shape and volume

changes markedly in response to functional and physiologic influences. Bone is

composed of two types of osseous tissues:

I. Cortical (Compact bone)- This is dense and makes up the exterior

surfaces of bones.
 II. Cancellous bone – This is spongy in consistency, made up of a
latticework of trabeculae.

Bone tissue is made of various types of cells:-

I. Osteoblasts

II. Bone Lining Cells

III. Osteocytes

IV. Osteoclasts

OSTEOBLASTS CELLS
Osteoblasts are cuboidal cells that are located along the bone surface comprising

4–6% of the total resident bone cells and are largely known for their “bone

forming function”. They have been differentiated from the Osteoprogenitor cells

of mesenchymal origin. They secrete osteoid, the un-mineralized organic matrix

that subsequently undergoes mineralization thus giving the bone its strength and
rigidity. Various factors like the transforming growth factor, bone

morphogenetic protein, fibroblast growth factor, platelet derived growth factor

induce the differentiation of Osteoprogenitor cells just before bone formation. 31

BONE LINING CELLS

Bone lining cells are quiescent flat-shaped osteoblasts that cover the bone

surfaces, where neither bone resorption nor bone formation occurs. These cells

exhibit a thin and flat nuclear profile; its cytoplasm extends along the bone

surface and displays few cytoplasmic organelles such as profiles of rough

endoplasmic reticulum and Golgi apparatus. Some of these cells show processes

extending into canaliculi, and gap junctions are also observed between adjacent

bone lining cells and between these cells and osteocytes32

OSTEOCYTES

Osteocytes, which comprise 90–95% of the total bone cells, are the most

abundant and long-lived cells, with a lifespan of up to 25 years. Different from

osteoblasts and osteoclasts, which have been defined by their respective

functions during bone formation and bone resorption, osteocytes were earlier

defined by their morphology and location. For decades, due to difficulties in

isolating osteocytes from bone matrix led to the erroneous notion that these cells

would be passive cells, and their functions were misinterpreted .33

OSTEOCLASTS

Osteoclasts are terminally differentiated multinucleated cells, which originate

from mononuclear cells of the hematopoietic stem cell lineage, under the

influence of several factors. Among these factors the macrophage colony-

stimulating factor (M-CSF), secreted by Osteoprogenitor mesenchymal cells

and osteoblasts, and RANK ligand, secreted by osteoblasts, osteocytes, and

stromal cells, are included Together, these factors promote the activation of

transcription factors and gene expression in osteoclasts.34

BONE REMODELLING - ROLE OF OSTEOBLASTS AND OSTEOCLAST

Bone remolding is an active and dynamic process relies on the correct balance

between bone resorption by osteoclast and bone deposition by osteoblast.

Bone mass is maintained by a balance between the activity of osteoblasts

(right), which form bone, and osteoclasts (left), which break it down. Normally,

bone formation and bone resorption are closely coupled processes involved in

the normal remodeling of bone. Osteoblasts make bone by producing a matrix

that then becomes mineralized. Osteoblasts also regulate osteoclast activity

through expression of cytokines such as receptor activator of nuclear factor-κB

ligand (RANKL), which activates osteoclast differentiation, and osteoprotegerin

(OPG), which inhibits RANKL. Factors that are known to stimulate osteoblast

proliferation or differentiation are bone morphogenetic protein (BMP),

transforming growth factor-β (TGFβ), insulin-like growth factor (IGF),

fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular

endothelial growth factor (VEGF) and WNT. The WNT antagonist DKK blocks

osteoblast proliferation. Osteoclasts are large multinucleate cells that break

down bone and are responsible for bone resorption.35

PHYSIOLOGY

The incorporation of a bone graft is defined as the "process of envelopment and

inter-digitation of the donor bone tissue with new bone deposited by the

recipient." this process follows a typical multistep cascade that is briefly

introduced here and defined in greater detail later. Initially, the bone graft

produces a response leading to the accumulation of inflammatory cells,

followed by the chemotaxis of host mesenchymal cells to the graft site.

Thereafter, the primitive host cells differentiate into chondroblasts and

osteoblasts, a process under the influence of various osteoinductive factors. The

additional processes of bone graft revascularization and necrotic graft resorption

occur concurrently. Finally, bone production from the osteoblasts onto the
graft's three-dimensional framework occurs, followed by bone remodeling in

response to mechanical stress36.

An ideal bone graft would provide all elements required during these phases of

graft incorporation and lend structural support during the process. This ideal

graft would possess the following:

(A)OSTEOCONDUCTION

It is the physical property of the bone to serve as a scaffold for

viable bone healing. Osteoconduction also allows for the in growth of neo-

vasculature and the infiltration of osteogenic precursor cells into the graft site.

Osteoblasts from the margin of defect that is being grafted, utilize the bone graft

material as a framework upon which to spread and generate new bone. These

properties are found in cancellous autografts, allografts, demineralized bone

matrix, hydroxyapatite, collagen and calcium phosphate.

(B). OSTEOGENESIS

It is the property of the graft to produce new bone and this

depends on the presence of live bone cells in the graft. Osteogenic graft

materials contain viable cells with the ability to form bone or the potential to

differentiate into bone forming cells. These cells which participate in the early

stages of the healing process to unite the graft with the host bone must be

protected during the grafting procedure to ensure viability.

(C). OSTEOINDUCTION

It is the ability of the graft to induce the stem cells to differentiate into

mature bone cells. This process is associated with the presence of bone

growth factors within the graft material as a supplement to the bone graft.

Bone morphogenetic proteins and demineralized bone matrix are the principal

osteoinductive materials37.

CLASSIFICATION OF BONE GRAFTS

Multiple classification systems have been used to organize bone replacement

grafts,

I.
According to Reynolds et al. 201038

Bone grafting material is dependent primarily on its chemical composition,

structure, and physical properties.

1. Ceramic-based bone grafting materials. used for bone and periodontal

regeneration, and function primarily through osteoconduction.

Commercially available ceramic-based materials include calcium

phosphates (e.g., tricalcium phosphate and hydroxyapatite), calcium

sulfate, and bioactive glass.

2. Polymers can be classified based on source: natural and synthetic.

i. Natural polymers- Natural polymers that have been used in the

fabrication of bone grafting materials include polysaccharides (e.g.,

 agarose, alginate, hyaluronic acid, chitosan) and polypeptides (e.g.,

collagen, gelatin, Bio-Oss Collagen).

ii. Synthetic polymers - (poly(glycolic acid), poly(L-lactic acid),

polyorthoester, polyanhydride)

II. According to David L. Hoexter,200239.

There are four basic divisions of bone grafts:

i. Autogenous bone- Autologous or autogenous bone grafting involve

utilizing bone obtained from same individual receiving the graft. Bone

can be harvested from nonessential bones, such as from iliac crest,

mandibular symphysis (chin area), and anterior mandibular ramus

(coronoid process).

ii. Allographic bone- Allograft is derived from humans. The difference is

that allograft is harvested from an individual other than the one receiving

the graft.

iii. Alloplastic bone- Alloplastic grafts may be made from hydroxyapatite, a

naturally occurring mineral (main mineral component of bone), made

from bioactive glass. Hydroxyapatite is a synthetic bone graft, which is

the most used now due to its osteoconduction, hardness, and acceptability

by bone.

iv. Xenographic bone - Xenogratfs are bone grafts from a species other than

human, such as bovine and are used as a calcified matrix.

III. According to Nasr HF in 1965, 40
I) Human bone
1. Autografts or autogenous grafts.

i. Extraoral- Extraoral autografts from iliac cancellous bone and marrow

provide a great osteogenic potential, being able to induce

cementogenesis, bone regeneration and Sharpey’s fibers reattachment.

ii. Intraoral- Intraoral autogenous bone grafts harvested from the maxillary

tuberosity, edentulous alveolar areas, healing bony wound, extraction

sites and mental and retromolar areas.

a. Blend of cortical and cancellous intraoral bone.

b. Cortical bone chip.

c. Osseous coagulum.

2. Allografts or allogenic grafts.

i. Fresh frozen bone
ii. Freeze-dried bone allografts (FDBA)
iii. Demineralized freeze-dried bone allografts (DFDBA)

II) Bone substitutes

3. Xenografts or xenogenic grafts
i. Bovine-derived hydroxyapatite
ii. Coralline calcium carbonate
4. Alloplasts or alloplastic grafts
i. Absorbable
ii. Nanoabsorber

CURRENTLY AVAILABLE BONE GRAFTS

Graft Material Biologic Source Commercially available
mechanism form.
Freeze –dried Bone Osteoconduction Allograft  Grafton
graft
(FDBA)
Demineralized Osteoinductive Allograft  GraftonR DBM
freeze Dried  Grafton PlusR
Bone DBM Paste,
graft.(DFDBA)  Accell
ConnexusTM,
 DBXR,
 Demineralized
Bone Matrix ,
  Dynagraft putty
 Osteofil allograft
bone paste
RegenafilR,
 Altiva DBM
Paste, BioSetTM,
RTI Allograft
Paste and
 OsteofilR contain
human
demineralized
freeze-dried bone
allograft
Anorganic Bovine – Osteoconductive Xenograft  Bio-Oss
Derived Bone graft  Bio-Oss Collagen,
(BDX)  OsteoGraf/N ,
 and PepGen P-15.

Anorganic porcine- Osteoconductive Xenograft  OsteoBiol Gen-Os

Derived bone graft
Coralline Calcium Osteoconductive Xenograft  Bicoral
Corbonate
Polymethylmetacryl Osteogenic Alloplast  HTR synthetic
ate and (Alloplastic Bone –Bioplant
Polyhydroxylethyl Synthetic  Poly –HEMA
methacrylate Graft) Hydron
Polymers (PMMA-
PHEMA)
Demineralized Osteoinduction Alloplast  Solvent retention
Dentin Matrix (Alloplastic of contemporary
(DDM) Synthetic commercial dentin
Graft) bonding agent
Hydroxyapatite Osteoconductive Alloplast  Polycrystalline
(Alloplastic ceramic form of
Synthetic pure densely
Graft sintered HA,
 Coralline porous
non–resorbable
hydroxylapatite,
 Resorbable
 nonceramic
hydroxylapatite
 Nanocrystalline
hydroxyapatite

Calcium Phosphate Osteoconductive Alloplast  Embare

cement (CPC) (Alloplastic  Biobon
Synthetic  Biopex
Graft  Callos

Beta-Tricalcium Osteoconductive Alloplast  Sybo graf plu-

Phosphate (TCP) (Alloplastic HAP and
Synthetic BetaTCP
Graft
Calcium Sulphate Osteoconductive Alloplast  Capset
(Alloplastic
Synthetic
Graft
Bioactive Glasses Osteoconductive Alloplast  Bioglass
(Alloplastic  periglass
Synthetic
Graft
Oily CaOH2 Osteoinduction Alloplast  OCHS;
Suspension (Alloplastic Osteoinductal
Synthetic
Graft
Porous Titanium Osteoconductive Alloplast  Tigran™ PTG
Granules (Alloplastic
Synthetic
Graft
Composite Grafts Osteoconductive Alloplast  HealosR
Osteoinductive (Alloplastic  Tricos
Osteogenesis Synthetic  ceramics
Graft