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

⦁ 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)