Bone Graft
Introduction
⦁ A material with either osteoconductive, osteoinductive, and/or osteogenic properties
⦁ autografts
⦁ allografts
⦁ demineralized bone matrix (DBM)
⦁ synthetics
⦁ bone morphogenetic protein (BMP)
⦁ stem cells
⦁ Epidemiology
⦁ incidence
⦁ almost 1 million bone grafting procedures performed in US each year, with a growth of almost 13% per year
⦁ Indications
⦁ assist in healing of fractures, delayed unions, or nonunions
⦁ assist in arthrodeses and spinal fusions
⦁ replace bone defects from trauma or tumor
⦁ Resorption rates
⦁ relative resorption rates of bone graft substitutes
⦁ fastest to slowest
⦁ calcium sulfate > tricalcium phosphate > hydroxyapatite
⦁ Outcomes
⦁ allograft retrieval
⦁ retrieval studies are helpful in understanding the body's response to allografts
⦁ 5 years after implantation, allograft articular cartilage is completely acellular - no donor or recipient chondrocytes will be present

Properties
⦁ Bone graft has aspects of one or more of these three properties
⦁ osteoconductive
⦁ material acts as a structural framework for bone growth
⦁ demineralized bone matrices (DBMs)
⦁ the various three-dimensional makeups of the material dictate the conductive properties
⦁ osteoinductive
⦁ material contains factors that stimulate bone growth and induction of stem cells down a bone-forming lineage
⦁ bone morphogenetic protein (BMP) is most common from the transforming growth factor beta (TGF-B) superfamily
⦁ osteogenic
⦁ material directly provides cells that will produce bone including primitive mesenchymal stem cells, osteoblasts, and osteocytes
⦁ mesenchymal stem cells can potentially differentiate down any cell line
⦁ osteoprogenitor cells differentiate to osteoblasts and then osteocytes
⦁ cancellous bone has a greater ability than cortical bone to form new bone due to its larger surface area
⦁ autologous bone graft (fresh autograft and bone marrow aspirate) is the only bone graft material that contains live mensenchymal precursor cells

Antigenicity
⦁ Allograft is a composite material and therefore has many potential antigens (cell surface glycoproteins)
⦁ Class I and Class II antigens on graft are recognized by host T lymphocytes and elicit an immune response
⦁ immunogenic cells are marrow-based, endothelium, and retinacular-activating cells
⦁ bone marrow cells elicit the greatest immune response
⦁ extracellular matrix also acts as an antigen
⦁ type I collagen stimulates both humoral and cell-mediated responses
⦁ noncollagenous matrix (proteoglycans, osteocalcin)
⦁ hydroxyapatite has not been shown to elicit an immune response
⦁ primary rejection is cell-mediated related to the major histocompatibility complex (MHC) incompatibility

Overview
⦁ Allograft is a composite material and therefore has many potential antigens (cell surface glycoproteins)
⦁ Class I and Class II antigens on graft are recognized by host T lymphocytes and elicit an immune response
⦁ immunogenic cells are marrow-based, endothelium, and retinacular-activating cells
⦁ bone marrow cells elicit the greatest immune response
⦁ extracellular matrix also acts as an antigen
⦁ type I collagen stimulates both humoral and cell-mediated responses
⦁ noncollagenous matrix (proteoglycans, osteocalcin)
⦁ hydroxyapatite has not been shown to elicit an immune response
⦁ primary rejection is cell-mediated related to the major histocompatibility complex (MHC) incompatibility
Autograft |
Cancellous |
Less structural support
Greater osteoconduction
Rapid incorporation via creeping substitution
|
Cortical |
- Slower incorporation due to need to remodel existing Haversion canals
- Interstitial lamellae preserved
- Provides more structural support
- 25% of massive grafts sustain insufficiency fractures
|
Vascularized bone graft |
- Technically challenging with quicker union and cell preservation
- Examples include: free fibula strut graft (peroneal artery), free iliac crest (deep circumflex iliac arteries), distal radius used for scaphoid fx (1-2 intercompartmental superretinacular artery branch of radial artery)
|
Allograft |
Fresh |
- Highest risk of disease transmission and immunogenicity
- BMP preserved and therefore osteoinductive
|
Fresh frozen |
- Least immunogenic
- Least structural integrity
- BMP depleted (purely osteoconductive)
- Lowest likelihood of viral transmission
|
Freeze dried (croutons) |
- Least immunogenic
- Least structural integrity
- BMP depleted (purely osteoconductive)
- Lowest likelihood of viral transmission
|
Demineralized Bone Matrix |
Grafton DBM |
- Osteoinductive and osteoconductive
- Contains: collagen, bone morphogenetic proteins, transforming growth factor-beta, residual calcium
- Does NOT contain mesenchymal precursor cells
|
Synthetics |
Aluminum oxide |
Alumina ceramic bonds bind to bone in response to stress and strain
|
Calcium phosphate grafts |
- Osteoconduction and osteointegration
- Biodegrade very slowly
- Highest compressive strength
- Many prepared as ceramics (heated to fuse into crystals)
- Examples include: tricalcium phosphate, Norian (Synthes), hydroxyapatitie (tradename Collagraft by Zimmer)
|
Calcium sulfate |
- Osteoconductive
- Quick resorption
- Examples include: OsteoSet (Wright medical)
|
Coralline hydroxyapatine |
- Calcium carbonate skeleton is converted to calcium phosphate via a thermoexchange process (Interpore)
|
Calcium carbonate |
- Chemically unaltered marine coral
- Osteoconductive
- Examples include: Biocora (Inoteb, france)
|
Bone Growth Factors
|
BMP / TGF-B / IGF-II / PDGF |
see Rank-L and Bone Growth Factors
|
Autograft
⦁ Bone graft transferred from one body site to another in the same patient
⦁ Indications
⦁ gold standard
⦁ Properties
⦁ osteogenic, osteoinductive, and osteoconductive
⦁ least immunogenic
⦁ cortical, cancellous, or corticocancellous
⦁ vascular or nonvascular
⦁ Donor sites
⦁ bone marrow aspirate
⦁ source of osteogenic mesenchymal precursor cells
⦁ iliac crest and vertebral body most common sites
⦁ variable number of cells depending on patient age
⦁ iliac crest is the most common site for autograft
⦁ provides both cancellous and cortical graft
⦁ higher complication rate with anterior versus posterior harvesting
⦁ 2% to 36% complication rate
⦁ blood loss and hematoma
⦁ injury to lateral femoral cutaneous or cluneal nerves
⦁ hernia formation
⦁ infection
⦁ fracture
⦁ cosmetic defect
⦁ chronic pain
⦁ fibula and ribs are most common sources of vascularized autografts
⦁ tibial metaphysis
Allograft
⦁ Bone graft obtained from a cadaver and inserted after processing
⦁ Most commonly used bone substitute
⦁ Properties
⦁ osteoconductive only due to lack of viable cells
⦁ the degree of osteoconduction available depends on the processing method (fresh, frozen, or freeze-dried) and type of graft (cortical or cancellous)
⦁ cortical, cancellous, corticocancellous, and osteoarticular (tumor surgery)
⦁ Osteoarticular allograft
⦁ immunogenic
⦁ preserved with glycerol or dimethyl sulfoxide (DMSO)
⦁ cryogenically preserved (few viable chondrocytes remain)
⦁ tissue-matched (syngeneic) grafts decrease immunogenicity
⦁ Processing methods
⦁ debridement of soft tissue, wash with ethanol (remove live cells), gamma irradiation (sterilization)
⦁ dose-dependent higher doses of irradiation kills bacteria and viruses but may impair biomechanical properties
⦁ fresh allograft
⦁ cleansing and processing removes cells and decreases the immune response improving incorporation
⦁ indications
⦁ rarely used due to disease transmission and immune response of recipient
⦁ frozen or freeze-dried
⦁ reduces immunogenicity while maintaining osteoconductive properties
⦁ reduces osteoinductive capabilities
⦁ shelf life
⦁ one year for fresh frozen stored at -20 degrees C
⦁ five years for fresh frozen stored at -70 degrees C
⦁ indefinite for freeze-dried
Demineralized bone matrix (DBM)
⦁ Acidic extraction of bone matrix from allograft
⦁ removes the minerals and leaves the collagenous and noncollagenous structure and proteins
⦁ Properties
⦁ osteoconductive without structural support
⦁ minimally osteoinductive despite preservation of osteoinductive molecules
⦁ interproduct and interlot variability is common
Synthetics
⦁ Alternative to autografts and allografts
⦁ Various compositions available (see summary above)
⦁ Made in powder, pellet, or putty form
⦁ Properties
⦁ osteoconductive only
⦁ Outcomes
⦁ Level I evidence shows that calcium-phosphate bone substitutes allow for bone defect filling, early rehabilitation, and prevention of articular subsidence in distal radius and tibial plateau fractures
Bone morphogenetic proteins (BMP)
⦁ Osteoinductive properties
⦁ stimulates undifferentiated perivascular mesenchymal cells to differentiate into osteoblasts throughserine-threonine kinase receptors
⦁ rhBMP-2 and rhBMP-7 are FDA-approved for application in long bones and spine
⦁ Complications
⦁ under or overproduction of bone
⦁ inflammatory responses
⦁ early bone resorption
Reamer Aspirator Irrigator
⦁ Provides large volume of bone graft from intramedullary source
⦁ femur (most common)
⦁ tibia
⦁ Possible iatrogenic complications
⦁ femoral shaft fracture due to eccentric reaming
⦁ insertion site pain (hip abductors)
Risks & Complications
⦁ Disease Transmission
⦁ hepatitis B
⦁ risk of hepatitis B disease transmission in musculoskeletal fresh-frozen allograft transplantation is 1 in 63,000
⦁ hepatitis C
⦁ risk of hepatitis C disease transmission in musculoskeletal fresh-frozen allograft transplantation is 1 in 100,000
⦁ HIV
⦁ risk of transmission of HIV in fresh-frozen allograft bone is 1 in 1,000,000
⦁ allografts are tested for HIV, HBV, HCV, HTLV-1, and syphilis
⦁ Serous wound drainage
⦁ calcium sulfate bone graft substitute associated with increased serous wound drainage