Dept. of Orthopaedics K.M.C.

Mangalore
Brief Discussion On

Bone Graft Substitutes

Moderators:
Prof. R.M.Shenoy
Dr.Vivek Mahajan

Presenter:
Dr.Neeraj
Date:01/12/09

INTRODUCTION : Although autogenous material , such as iliac crest bone remains the Gold
Standard for filling bony defects, its use increases the morbidity of the surgical procedure, increases
the anaesthesia time and blood loss, and often causes significant post operative donor site
complications. The amount of autogenous bone available for graft is also limited. Cancellous Allograft
has been used successfully but problems of slow incorporation and risk of viral transmission limits its
usefulness. Because of these difficulties and large no. of surgeries that requires bone grafting,
alternative substances for filling bone defects have been developed.
CRITERIA OF A SUCCESSFUL GRAFT : There are 2 basic criteria osteoconduction and
osteoinduction.
An osteoconductive material is one that acts as a scaffold, supporting ingrowth of capillaries,
perivascular tissue and osteoprogenitor cells from the recipient bed
Osteoinductive material is one that can induce nondifferentiated stem cells or osteoprogenitor cells to
differentiate into osteoblasts
An ideal bone graft substitute should provide scaffolding for osteoconduction and growth factors for
osteoinduction.
BONE GRAFT CLASSIFICATION SYSTEM : Laurencin et al (2006) have suggested a
classification scheme of material-based groups,

Type

Description

Examples

Allograft
based

Allograft bone, used alone or in combination with other

materials

Allogro, OrthoBlast, Opteform,

Grafton

Factor
based

Natural and recombinant growth factors, used alone or in

combination with other materials

TGF-beta, PDGF, FGF, BMP

Cell based

Cells used to generate new tissue alone or seeded onto a

support matrix

Mesenchymal stem cells

Ceramic
based

Includes calcium phosphate, calcium sulfate, and bioglass,

used alone or in combination

Osteograf, Norian SRS,

ProOsteon, Osteoset

Polymer
based

Both degradable and nondegradable polymers, used alone or

in combination with other materials

Cortoss, OPLA, Immix

ALLOGRAFT BASED SUBSTITUTES :

Advantages of allograft bone include ready availability in various shapes and sizes and avoidance of
donor-site morbidity. Concerns about the transmission of blood-borne diseases through the
transplantation of allogenic tissue largely have been eliminated through tissue processing and
sterilization procedures. However, both freezing and irradiation affect the process of graft incorporation
and structural strength. Allogeneic bone, with variable biologic properties, is available in many
preparations: demineralized bone matrix, morselized and cancellous chips, corticocancellous and
cortical grafs, and osteochondral and whole- bone segments.

DEMINERALIZED BONE MATRIX : The desired factors and proteins are removed from the allograft
by using a demineralizing agent such as hydrochloric acid. Demineralized bone matrix has been used
in the treatment of long-bone nonunions, acute bone defects caused by fractures, and skeletal defects
resulting from tumor resection. It acts as an osteoconductive and possibly osteoinductive material but
does not provide structural support. Composite grafts of demineralized bone matrix and autologous
bone marrow form a sandlike material that can be injected percutaneously.
FACTOR BASED BONE GRAFT SUBSTITUTES :
Numerous growth factors that have been shown to influence cellular proliferation, differentiation,
chemotaxis, and protein synthesis. These include Bone morphogenic protein(BMP- esp. BMP
2&7),TGF beta, Fibroblast Growth Factor, Platelet-derived Growth Factor,Insulin like growth factor .
The combination of an absorbable collagen sponge soaked with rhBMP-2 and ceramic granules resulted
in trends toward improvements in clinical outcomes and toward a higher rate of radiographic fusion.
This combination of an osteoinductive agent with an osteoconductive matrix may be an effective
replacement for autograft.
CELL BASED BONE GRAFT SUBSTITUTES :
Bone marrow has been used to stimulate bone formation in skeletal defects and nonunions. The major
advantage of this technique is that it can be performed percutaneously, without almost any patient
morbidity. The bone marrow is aspirated with a large bore needle from the iliac crest and injected
percutaneously with fluoroscopic guidance into the nonunion site. Approximately one of every 100,000
nucleated cells aspirated from bone marrow is a stem cell. Centrifugation of aspirated bone marrow at
400 times gravity for ten minutes separates the marrow cells from plasma and preserves the osteogenic
potential of the cells, decreasing the volume of material injected
With current techniques, in vitro differentiation of mesenchymal stem cells toward the osteoblast
lineage is possible. Stem cells are cultured in the presence of various additives such as dexamethasone,
ascorbic acid to direct the undifferentiated cell toward the osteoblast lineage.
Mesenchymal stem cells have also been seeded onto bioactive ceramics conditioned to induce
differentiation to osteoblasts. These have been proposed for use in bone repair prosthetic coatings.
CERAMIC BASED BONE GRAFT SUBSTITUTES :
Osteoconductive bone-graft substitutes include collagen-based matrices, calcium phosphate, calcium
sulfate, coralline hydroxyapatite, and bioactive glass. These products are osteoconductive only and
have no osteoinductive properties unless an osteoinductive product is added.
Calcium phosphate, an injectable calcium paste, has 4 to 10 times the compressive strength of
cancellous bone. Calcium phosphate cement has the highest mechanical compression strength of any of
the oseteoconductive bone-graft substitutes and is useful where additional mechanical strength is
desired. Studies have demonstrated that 95 percent of calcium phosphate is resorbed in 26 to 86 weeks.
Coralline hydroxyapatite, is produced from marine coral exoskeleton that have pore structures
resembling cancellous bone. Coralline hydroxyapatite has been proven effective for managing
metaphyseal defects. Blocks of implanted coralline hydroxyapatite may remain visible on radiographs
for up to 10 years.
Calcium sulfate was first introduced as plaster of paris in 1892. Calcium sulphate or plaster of paris
was first used as a bone filler in the early 1900s Calcium sulfate resorbs in 4 to 12 weeks, making it the
quickest of any of the osteoconductive products currently available.Wound drainage occasionally is
noted and is hypothesized to be the result of the osmotic effect of the calcium sulfate. Due to its rapid
rate of resorption, calcium sulfate is better used as a bone-graft extender rather than for structural
support.
Tricalcium phosphate (TCP) is a fast resorbing ceramic that undergoes partial conversion to HA once
implanted into the body. The HA is resorbed more slowly and will remain in place for years.

Bioactive glass (bioglass) is a biologically active silicate-based glass. Its high modulus and brittle
nature make its applications limited, but it has been used in combination with polymethylmethacrylate
to form bioactive bone cement and with metal implants as a coating to form a calcium-deficient
carbonated calcium phosphate layer. This layer facilitates the chemical bonding of the implant to
surrounding bone.

Collagen-based matrices, are xenografts consisting of spongelike strips of bovine collagen combined
with hydroxyapatite. The collagen-based matrices act primarily as osteoconductive bone-graft
substitutes. Because their compressive strength is less than that of cancellous bone, they are better used
as a surface-only graft rather than for metaphyseal defect
POLYMER BASED BONE GRAFT SUBSTITUTES: The polymers used today can be loosely
divided into natural polymers and synthetic polymers. These, in turn, can be divided further into
degradable and nondegradable types.
Degradable synthetic polymers, like natural polymers, are resorbed by the body. The benefit of having
the implant resorbed by the body is that the body is able to completely heal itself without remaining
foreign bodies, such as polylactic acid and poly(lactic-co-glycolic acid) .
FUTURE DIRECTIONS:
Tissue engineering
Advances in tissue engineering and the integration of the biological, physical, and engineering
sciences, will create new carrier constructs that regenerate and restore functional state. These constructs
are likely to encompass additional families of growth factors, evolving biological scaffolds, and
incorporation of mesenchymal stem cells. Ultimately, the development of ex vivo bioreactors capable of
bone manufacture with the appropriate biomechanical cues will provide tissue-engineered constructs
for direct use in the skeletal system
Genetic engineering
Studies have successfully demonstrated several safe, effective strategies to form new bone via gene
therapy in animals. The vehicle for gene delivery can be either viral (adenovirus, retrovirus) or nonviral (liposomes, DNA-ligand complexes). The gene can be selectively transferred to a targeted cell
(osteoblast, fibroblasts) at the bone induction site.
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6. Bone Grafts and Bone Graft Substitutes in Orthopaedic Trauma Surgery,A Critical Analysis-William
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9.Clinical and Radiographic Analysis of an Optimized rhBMP-2 Formulation as an Autograft
Replacement in Posterolateral Lumbar Spine Arthrodesis
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