May 30, 2024

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

  1. Autograft– graft obtained from the same individual on whom bone grafting has to be performed.
  2. Allograft– graft obtained from the cortical bone of dead donor of same species within 12 hours of death.
  3. Isograft– graft obtained from the identical twin.
  4. 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.

AdvantageDisadvantage
Has osteogenic propertiesIncreased patient morbidity
No risk of disease transmissionOperative complication -associated with harvesting of the bone from the donor site
No risk of antigenic reactionLimited availability of the graft material
Easy patient acceptanceResorbs faster than the alloplastic material therefore less favorable to be used for space maintenance purposes in guided bone regeneration (GBR)
Higher predictability of successful outcomeHigher 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).

AdvantageDisadvantage
No need for a second incision site, reduced operative timeHigher resorption rate than autograft
Osteoconductive (FDBA) or even osteoinductive (DFDBA) propertyHigh material cost
Availability of more material volumeChance 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

AdvantageDisadvantage
No need for a second surgical site, reduced operative timeUnpredictable results
OsteoconductiveRisk of disease transmission
Availability of more material volumeHigh 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 largeIf 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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