Bone grafts and bone morphogenic proteins is an implanted material that promotes bone healing alone or in combination with other materials, through the mechanism of osteogenesis, osteoinduction, and osteoconduction.
Classification of bone graft
Based on the source/origin
- Autograft– graft obtained from the same individual on whom bone grafting has to be performed.
- Allograft– graft obtained from the cortical bone of dead donor of same species within 12 hours of death.
- Isograft– graft obtained from the identical twin.
- Xenograft– bone products obtained from different species
Based on the potential
- Osteogenic graft– that has the potential to form/develop new bone from the cells contained in the graft itself.
Eg; Autografts
- Osteoinductive graft– which undergoes a chemical process by which the molecules contained in the graft convert the neighboring cells into the osteoblasts which in turn form the bone.
Eg; allografts like Demineralized freeze-dried bone allograft (DFDBA)
- Osteoconductive graft– which undergoes a physical process by which the matrix of the graft forms a scaffold that favors surrounding cells to penetrate that graft and form new bone.
Eg; allografts like Freeze-dried bone allograft (FDBA)
- Osteopromotive graft– that enhances the osteoinduction without the possession of osteoinductive properties.
Eg; enamel matrix derivative (EMD)
- Osteoneutral graft– that only fills the bone defect without producing any effect and which often gets encapsulated.
Eg; Hydroxyapatite (HA)
Bone grafts
Autograft
Considered ‘gold standard’ due to possession of all three properties i.e. osteogenic, osteoinductive, and osteoconductive.
Sources; Iliac crest, Tibia, etc.
Methods of the collection- using rotary burs, hand chisels, or piezo-surgical devices.
Different forms;
Osseous coagulum- a mixture of bone dust (small particles from cortical bone) and blood.
Bone blend – bone removed from a predetermined site is triturated in the capsule to a workable plastic-like mass to be packed into a bony defect.
| Advantage | Disadvantage |
|---|---|
| Has osteogenic properties | Increased patient morbidity |
| No risk of disease transmission | Operative complication -associated with harvesting of the bone from the donor site |
| No risk of antigenic reaction | Limited availability of the graft material |
| Easy patient acceptance | Resorbs faster than the alloplastic material therefore less favorable to be used for space maintenance purposes in guided bone regeneration (GBR) |
| Higher predictability of successful outcome | Higher operative cost |
Allografts
Method of the processing
Cortical bone obtained from the dead donor within 12 hours – deflated, cut into pieces, washed in absolute alcohol, and deep-frozen – then maybe further demineralized and subsequently ground and sieved to the particle size of 250-750 micron and freeze-dried – and finally vacuum-sealed in glass vials. It is also treated with chemical agents or strong acids to inactivate viruses if present.
Types:
Freeze-dried bone allograft (FDBA),
Demineralized freeze-dried bone allograft (DFDBA).
| Advantage | Disadvantage |
|---|---|
| No need for a second incision site, reduced operative time | Higher resorption rate than autograft |
| Osteoconductive (FDBA) or even osteoinductive (DFDBA) property | High material cost |
| Availability of more material volume | Chance of disease transmission from the cadaver |
Chance of disease transmission
The risk of HIV transmission is 1 in 1-8million
Commercially available as; Puros, Grafton DBS
Xenograft
Commercially available as; Bio-Oss, Bo plant, Kiel’s bone, an organic bone
| Advantage | Disadvantage |
|---|---|
| No need for a second surgical site, reduced operative time | Unpredictable results |
| Osteoconductive | Risk of disease transmission |
| Availability of more material volume | High material cost Ethical issues and unacceptance by patient |
Methods to suppress the antigenic potential of allograft and xenograft
1. Radiation:
(Disadv- may destroy even the bone induction potential)
2. Freezing
3. Chemical treatment:
(Disadvantages- If remnants such as ethylene oxide present on the graft can have a negative effect on the fibroblast)
Size of bone graft and inter-particulate space
Bone graft
| If too large | If too small (<125 microns) |
| will be resorbed at a very slow rate thus, will act merely as a space-filler (primarily) | may induce inflammation which induces macrophage response- and thus be readily phagocytosed—leading to early resorption |
| offers reduced surface area. | offers a higher surface area. But results in reduced inter particulate space-inconducive to cellular migration and growth |
Inter-particulate space
It should be >100 microns to allow osteoid cells to migrate and occupy to form bone.
If< 100-micron space:- it possesses less mineralization potential.
BONE GRAFTS, BONE MORPHOGENETIC PROTEINS, AND BONE SUBSTITUTES
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Bone Healing
Primary bone healing
Occurs with constructs that provide absolute stability
1. Fixation of bony surfaces enables primary healing by creating a low-strain environment.
2. Bone heals directly by cortical remodeling.
3. Areas not in direct apposition may be filled by woven bone that is subsequently remodeled to the lamellar bone.
Secondary bone healing
Involves responses in the periosteum and surrounding soft tissues
Two types of secondary healing occur:
1. Endochondral
2. Intramembranous
Factors that impair bone healing
a. Excessive instability at the fracture site or non-opposition of bone
b. Lack of blood supply because of the local vascular anatomy or periosteal stripping from injury/dissection
c. Anti-inflammatory medications (NSAIDs, steroids)
d. Smoking
e. Systemic disease: metabolic bone conditions
Role of Bone Grafts
1. Fracture healing, treatment of delayed unions or nonunions
2. Arthrodesis
3. Replacement of osseous defects occurring as a result of trauma, tumor, or wear
Osteogenesis:
Directly provides cells that are capable of in vivo bone formation.
Osteoprogenitor cells can proliferate and differentiate to osteoblasts and eventually to osteocytes.
Mesenchymal stem cells are multipotent
Induced to differentiate into bone-forming cells by the local environment.
Examples: Autologous bone graft, bone marrow aspirate
Osteoinduction:
Osteoinductive graft material has factors that induce progenitor cells down a bone-forming lineage via cytokines
Acts as chemoattractants and differentiation factors.
Example: BMPs
Osteoconduction:
Osteoconductive materials serve as a mechanical scaffold into which new bone can form.
Three-dimensional configuration and building-block material dictate osteoconductive properties.
Cancellous bone has greater bone-forming potential than cortical bone but less structural support
Examples: Acellular cancellous chips
Bone Graft Materials
AUTOGRAFTS:
The gold standard of bone graft material
Osteogenic, osteoinductive, and osteoconductive
Cortical, cancellous, or cortico-cancellous
Nonvascularized or vascularized.
Iliac crest bone graft (ICBG) is the most frequently used
Potential to provide abundant cancellous and/or cortical graft
Others ribs, fibula, and tibial metaphysis.
Fibula and rib are the most common potentially vascularized options considered.
Allograft
harvested from a cadaver
cortical, cancellous, or cortico-cancellous.
qNon Osteogenic
low Osteoinductive factors
primarily osteoconductive
Types of allograft
Fresh allograft
potential for an immune response and disease transmission
Frozen allograft
Reduces immunogenicity
Osteoconductive properties
shelf life when maintained at −20°C is 1 year;
5 years if kept at −70°C.
Freeze-dried allograft
Prepared by freeze-drying
Stored at room temperature
The shelf life of freeze-dried bone is indefinite but the sterilization of packaging may expire.
Demineralized bone matrix (DBM)
Processed with a mild acid extraction
leave behind the collagenous structure (mostly type I, with some types IV and X) and noncollagenous proteins.
Autologous bone marrow aspirate
The potential source of mesenchymal stem cells and osteoprogenitors
Aspirated percutaneously from the iliac crest, vertebral body, or other sources
Can be Mixed with other bone graft extenders and ceramics to create a composite graft material
The potency of marrow aspirates could be increased
Selective precursor selection
Centrifugation
Clonal expansion.
Collagen
Contributes:
Mineral deposition
Vascular ingrowth
Growth factor binding,
Providing a favorable environment for bone regeneration.
Does not provide structural support but may carry immunogenic potential
Inorganic compounds and synthetic bioceramics
Ionically or covalently bonded calcium phosphate compounds composed of metallic and nonmetallic elements
Relatively inert.
Easily bond with living tissues.
Good scaffolds for the addition of potentially osteogenic cells
Osteoconductive effect
Alumina, zirconia, bioactive glass, hydroxyapatite (HA), and tricalcium phosphate (TCP).
Bone Morphogenetic Proteins
Transforming growth factor-β (TGF-β) superfamily.
Osteoinductive primarily
BMPs (BMP-2, -4, -6, and -7) are potent osteoinductive factors
Highly water soluble
Currently available: recombinant human BMP-2 (rhBMP-2) and rhBMP-7
Other Modalities to Enhance Bone Healing
Electromagnetic stimulation
Bone tissue has bioelectric potential
Types:
Pulsed electromagnetic field
Capacitively coupled electrical stimulation.
Direct current electrical stimulation
Low-intensity ultrasound may affect bone healing
SUMMARY
Bone healing progresses through three stages: early (inflammation), middle (reparative), and late (remodeling).
Bone grafts may be osteogenic, osteoinductive, and/or osteoconductive.
Autograft is the gold standard of bone graft materials.
Bone marrow aspirates provide potential access to osteogenic mesenchymal precursor cells.
Bioceramics are inorganic compounds consisting of metallic and nonmetallic elements held together by ionic or covalent bonds.
BMPs (BMP-2, -4, -6, and -7) are potent osteoinductive factors of the TGF-β superfamily.
Hyaline cartilage serves as the precursor for bone formation via endochondral ossification.
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