Bone Grafts and Substitutes

Overview
Max. healing; function from tissue/device; complications; cost, preferred materials at hospitals

most current materials combine different products to mimic autogenous bone

Indications:

o Reconstructive procedures (calc. osteotomies); delayed/non-/mal-unions; fusions; pseudoarthrosis

o Bone cyst removal use as substitute
Osteoconduction

o provides scaffold for direct bone deposition

o used for backfill
Osteogenesis

o provides cells which grow bone (red marrow, periosteum, matrix)

o autogenous bone
Osteoinduction

o provides signal molecules to mesenchymal cell activity

o ancillary use for revisional sx + poor wound base
Autograft
Gold standard for grafting

o Scaffold surface of bone chips allow for direct bone deposition (osteoconduction)
o Cells provides cells which grow bone (ie: red marrow, periosteum, matrix) (osteogenesis)
o Signal provides signaling molecules to induce bone formation (osteoinduction)
Advantages:

o Histocompatible no immunologic reaction

o No disease transmission
o Ideal graft properties (scaffold, cells, signal)
Autogenous bone factors

o Cortical/cancellous ratio
o Graft size
o Ease of procurement
o Callus distraction (to produce new bone)
Iliac crest

o Cortical, cancellous, corticocancellous (with 1, 2 or 3 cortices possible)

o Excellent material characteristics: holds fixation, rich cancellous material
o Largest quantity of autogenous bone, osteoprogenitor cells
o Complications: bone graft donor site (31% had site pain @ 24 months)
Tibia

o Metaphyseal area (proximal or distal); more dense cortical bone

o Adjacent to surgical site, immunocompatible, osteoprogenitor cells
o Complications: Stress fx, hematoma, excessive blood loss, pain, infection, ankle/knee instability
Fibula

o Cortical cancellous bone, adjacent surgical site (not common; more common for vascularized grafts)
o From middle 1/3 (free vascularized donor site)
Prox 1/3 CPN worry about possible entrapment
Distal 1/3 dont want to disrupt syndesmosis
o Can harvest long cortical struts
o Complications: hematoma, pain, infection, damage to peroneal nerve (prox graft), ankle instability (distal graft)
Calcaneus

o Cortical cancellous bone, cancellous chips

o Posterior superior calcaneous (lateral approach leaves medial wall intact; doesnt fracture through tarsal tunnel)
o Trephine graft from calcaneus used to core bone; cylindrical blade that cuts out in hole
o Adjacent to surgical site, osteogenic
o Complications: infection, fracture, sural nerve injury, lesser saphenous vein injury, hematoma, bleeding
Allogenic Bone
Properties: Conduction, Induction (- gensesis)

Forms: Frozen, freeze-dried (MC), demineralized, sections, chips, paste

o Demineralized have no structural stability

Sources: tissue banks (self-regulated industry), hospital tissue banks (rare)

Advantages: inexpensive, clinical performance may be adequate (not as good as autograft)

Disadvantages: potential for infectious agent transfer, sourcing unreliable, inconsistent quality

NOT regulated by FDA

Bone Graft Substitute

Properties: Osteoconduction, osteoinduction

o De-mineralized bone matrix (DBM) found in all preps

o Collagen
o Biologic-synthetic domposites
o Synthetics (ceramics)
Rapidly resorbing ceramics
Slowly resorbing ceramics
Injectable ceramic cements
Ultraporous beta-TCP
Commercially Available

o Grafton DBM + glycerol or starch

o Dynagraft DBM + pluronic-F127 copolymer or collagen
o Osteofil DBM (24%) + porcine gelatin (17%) +H2O
o Ooteforrn DBM + corticocancellous chips
o DBX DBM + hyaluronic acid
o Allomatrix DBM + Calcium sulfate (CaSO4) + methyl cellulose
o Inetergro = DBM + lecithin (lipid carrier)
Ideal Graft Properties:

o Osteogenesis
Bone Marrow
MSCs
o Osteoconduction
HA, Calcium sulfate
Tricalcium PO4
Ceramics
o Osteoinduction
BMPs
Growth factors
Osteoconductive Products
Corraline hydroxyapatite (material that comes from coral)

Tricalcium phosphate (absorbed rapidly)

Type I collagen + CaPO4 composites

Live Autogenous Bone

Freeze-dried Allogenic Bone

Calcium Phosphate Ceramics (Osteoconductive)

o Porous blocks of hydroxyapatite (Pro Osteon and Endobon)

o Porous tricalcium PO4 (Vitoss)
o Synthetic CaSO4 (Osteoset,MIIG and Calcigen S)
o Carbonated apatite + collagen (Healos)
o Endothermically setting calcium phosphate (-BSM)
o -Tricalcium PO4 (Conduit)
Combination Materials: Ignite, ProDense, Osteocel Plus

Healos: Depuy, Carbonated apatite with collagen, sponge-like consistency when saturated (gets into fusion sites)

Osteoinductors
Bone morphogenic proteins (BMP)

Platelet-Derived Growth Factors (PDGF)

Insulin-like Growth Factors (IGF 1&2)

Fibroblast Growth Factors (FGF)

Epidermal Growth Factors (EGF)

Tumor Growth Factors (TGF 1&2)

Growth Factor Technology

o New systems developed to concentrate and activate platelets

o Blood drawn from patient and spun down in centrifuge to isolate Platelet Rich Plasma
o Platelet concentrates then combined with various bone grafting materials or sprayed in wound
Platelet Concentrate Products

o Magellin = Medtronics
o AGF = Interpore-cross
o Secquire = PPAI Medical
o GPS System = Biomet/Cell Factor Tech.
o SYMPHONY = Depuy Ace
o MTF = Cascade
rh-BMP2/ACS (INFUSE)

o Recombinant human BMP-2 + absorbable collagen sponge

o Discovered by Genetics Institute
o Approved by FDA for lumbar fusions
o InFuse Product Overview

30 years, 600 million in development

Osteoinductive signal: recruits cells to the surgical site, stimulates undifferentiated cells to osteoblasts
Excellent osteoinductive agents, collagen is non-ideal delivery matrix (preclinical and clinical experience)
May be a good choice for pts that cost and safety profile can be justified in on-label applications
Sizes:
Small 2.8cc (4.2mg BMP2) - $3600

Medium 5.6cc (8.4mg BMP2) - $4692

Large 8.0cc (12mg BMP2) - $5202

o Indications
Treatment of acute open tibial shaft fractures in adults
Used after stabilization with IM nail
Need appropriate wound care management
Improves fracture healing and decreases rate of infection
Must be applied within 14 days after initial fracture
o Contraindications
Allergy/Hypersensitivity to RHBMP-2, bovine type I collagen, or other components
Not used in vicinity of a resected/extant tumors
Skeletally immature (<18 y/o)
Pregnancy
Active infection
Allergy to titanium or titanium alloy
o Side effects
constipation, N/V, allergica reaction at surgical site, local and surgical inflammation, altered mental status, altered
sensation, respiratory difficulties, abnormal healing at fracture site
Abnormal labs:
Pancreatic enzyme levels

Liver function

Anemia

Decrease conc. Ca and K

Stryker OP 1
o 3.5mg recombinant BMP-7 + 1g bovine collagen
o No history of malignancy
o No pediatrics
o Pregnancy negative
o Effects of maternal antibodies to OP1 are unknown
o Indications
Long bone non-unions
Recalcitrant to other treatments
Where autogenous bone is unavailable
Offlabel use: revisional or reconstructive surgeries
o Contraindications
no hx malignancy, pregnancy; no children
Summary
o Autogenous bone Gold Standard
o Osteoconductors backfill
o Osteoinductors: Ancillary for revisional cases, poor wound base
o Combination materials current trend, can combine materials to mimic autogenous bone