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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 

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