Bone grafts and bone grafts substitutes

Bone Grafting and Bone Graft Substitutes

Dr. Gurvinder Singh Dr. Siddharth Gupta

Residents UCMS & GTB, HOSPITAL ,DELHI

Bone Graft Uses

• To fill cavities or defects resulting from cysts, tumors, or other cause

• To bridge joints and provide arthrodesis• To bridge major defects or establish the continuity

of a long bone• To provide bone blocks to limit joint motion

(arthroereisis) • To establish union in a pseudarthrosis• To promote union or fill defects in delayed union,

malunion, fresh fractures, or osteotomies

Mesenchymal Stem cells

• Progenitor cells that provide a source of cells to differentiate into chondroblasts and osteoblasts during endochondral and intramembranous bone formation

• In the elderly the pool of these cells diminishes

• Bone marrow is the source of adult MSCs

Types of Bone Grafts:on the basis of source

• Autogenous: source is the patient , usually from tibia , fibula or ilium. Also rib

• Allogenic : source is an individual other than the patient

• Xenograft: derived from different species

Properties of auto and allografts

Autogenous Bone Graft

• “Gold standard”

• May provide osteoconduction, osteoinduction and osteogenesis

• Drawbacks– Limited supply– Donor site pain, haematoma, neuromas , fracture

and heterotopic bone formation

Autogenous Bone Grafts

• Cancellous• Cortical• Free vascular transfers• Muscle pedicle bone graft• Bone marrow aspirate

Autogenous Cancellous Bone Grafts

• Three dimensional scaffold (osteoconductive)

• Osteocytes and stem cells (osteogenic)• A small quantity of growth factors

(osteoinductive)ss• CREEPING SUBSTITUION: process by which

graft is replaced by new bone (I year)• Used in boneloss: depressed tibial plateau

fractures, revision hip and knee arthroplasty

Creeping Substituition

• Creeping substitution, the process of bone remodeling by osteoclastic resorption and creation of new vascular channels with osteoblastic bone formation resulting in new haversian systems, is the method by which strong cortical bone is formed from grafted material.

Autogenous Cortical Bone GraftsSources:• Ribs

• Fibula • Crest of the ilium (also called as tricortical graft)

• It can be of two types:• Conventinal nov vascular • Vascularised bone graft

Non vascular versus vascular bone graft

Non vascular • Mainly osteoconductive

with littile osteoinductive and no osteogenic properties.

• Revascularisation is slow till cortex is resorbed.

• Remodelling -2years• Used in defects <6cm

Vascular• It has immediately

restored blood supply

• More viable, more survival of osteocytes

• Can be used in defects upto 12 cm or even in inadequate host.

Bone Marrow Aspirate

• RIA(REAMER IRRIGATOR AND ASPIRATOR)• It is a technique to harvest sizable amount of

bone marrow,which is particularly rich in mesenchymal stem cells .

• Growth factors supplied:

Fibroblasts growth factor(FGF)-2

Insulin like growth factor(IGF)-2

Transforming growth factor(TGF) beta

Absence of bone morphogenetic protein-2

Advantages of RIA

• Provides enriched osteogenesis

• Decrease intramedullary canal pressure

• Minimal risk of fat embolism

• Potential source of autologous bone,

mesenchymal cells and bone growth factors.

Complications of RIA

• Perforation of the meduallary canal which

may require prophylactic intramedullary

fixation.

• Significant blood loss

Steps to minimize risks

• Preoperatively donor radigraph should be used to measure isthmus

• Blood should be arranged for replacement.• Switch off the aspirator when there is no

reaming• Postp of ambulation should be protective• Check haematocrit• Avoid in metabolic bone diseases

Wolfe kawamatto technique

Complications of iliac crest graft• Full thickness iliac crest graft lead to

herniation.• The lateral femoral cutaneous and ilioinguinal

nerves are at risk during harvest of bone from the anterior ilium

• Alter the contour of the anterior crest, producing significant cosmetic deformity

• Arteriovenous fistula, pseudoaneurysm, ureteral injury, anterior superior iliac spine avulsion, and pelvic instability

Iliac crest graft

Grafts from tibia

• The subcutaneous anteromedial aspect of

tibia is the source of structural autografts.

• The plateau of tibia supplies cancellous bone.

Tibial graft harvest

Disadvantages of tibial graft

Normal limb is jeopardized

Increased duration of surgery

Protected weight bearing for atleast 6 to 12

months .

Bone graft from fibula• Entire proximal two third of the fibula can be

used for bone graft• The proximal rounded configuration of the

fibula is covered with hyaline cartilage.• May replace distal radius or even distal third

of fibula• The middle third of fibula can serve as the

peroneal artery based vascular graft

Points to remember for fibular bone graft

• The peroneal nerve must not be damaged;

• The distal fourth of the bone must be left to

maintain a stable ankle

• The peroneal muscles should not be cut.

Phemister bone graft

• It is subcortical cancellous bone grafting

• A bone graft of cortical bone with cancellous

bone chips to enhance callus formation.

• Bone-grafting without disturbing the pre-

existing callus

• Bone graft is taken by elevating the

osteoperiosteal flaps.

Requisites for phemister graft

• Petalling should carried out at the fracture site

• The mobility at the fracture site should be

minimal

• The fracture should have an acceptable

alignment

• The knee joint should have a good range of

motion

Urist AAA bone graft

• Composed of bone morphogenic protein and autolysed , antigen-extracted and autogenic bone.

• h-BMP/AAA composite implants represent adjunctive treatment of difficult nonunions

• Composite implants may be implanted in either partial or complete segmental defects of long bones

Allograft

The morbidity and limited amount of autogenic

bone graft calls for a need of allogenic bone

Graft.

They are indicated in

1.Children 2. Elderly 3.Poor surgical risk

4.Enough graft cannot be harvested

Allograft types

Cortical • Frozen• Freeze dried

Cancellous• Frozen • Freeze dried

Bone Allografts

• Cancellous or cortical– Plentiful supply– Limited infection risk (varies based on processing

method)– Provide osteoconductive scaffold– May provide structural support

Bone Allografts

• Freeze-dried– Even less antigenic– Time to test for diseases– Strictly regulated by FDA– Can be stored at room temperature up to 5 years– Mechanical properties degrade

Bone Bank

• It is a facilitiy to provide safe and efficient allograft material.

• Hosts should be screened for : infections,malignancies(except for basal cell carcinoma of the skin), collagen vascular diseases, metabolic bone diseases and presence of toxins.

Technique

• Bone is collected in clean and unsterile environment.

• It is nibbled to remove the articular cartilage.• It can be sterilized by irradiation, ethylene

oxide or strong acid( 0.55 % HCl)• It is subject to deep freeze upto -70 to -80

degrees celcius(frozen)• Freeze drying involves removal of water and

vacuum packaging of the tissue

Freeze dried bone graft

• Decreases expression of MHC 1 complex in osteoblasts

• Decreased osteoinductive properties• Reduced mechanical integrity • Decreased number of viable cells • Slow revascularisation and delaye remodelling• Histologically mono nuclear cells surround the

newly developed blood vessels

Demineralized Bone Matrix

• Prepared from cadaveric human bone• Acid extraction of bone leaving– Collagen(type 1)– Noncollagenous proteins– Bone growth factors• BMP quantity extremely low and variable

• Sterilized which may decrease the availability of BMP

Demineralized Bone Matrix• Available from multiple vendors in multiple

preparations– Gel– Putty– Strip– Combination products with cancellous bone and

other bone graft substitute products

Demineralized Bone Matrix

• Growth factor activity varies between tissue banks and between batches

• While they may offer some osteoinductive potential because of available growth factors, they mainly act as an osteoconductive agents

Han B et al. J Orthop Res. 21(4):648-54, 2003.Blum B, et al. Orthopedics. 27 (1 Suppl): S161 – S165, 2004.

Graft Incorporation

• Hematoma formation– Release of cytokines and growth factors

Graft Incorporation


• Inflammation– Development of fibrovascular tissue (18 hours)

Graft Incorporation


• Inflammation– Development of fibrovascular tissue

• Vascular ingrowth– Often extending Haversian canals

Graft Incorporation


• Inflammation– Development of fibrovascular tissue(18 hours)

• Vascular ingrowth– Often extending Haversian canals (10 -12 days)

• Focal osteoclastic resorption of graft

Graft Incorporation


• Inflammation– Development of fibrovascular tissue

• Vascular ingrowth– Often extending Haversian canals

• Focal osteoclastic resorption of graft• Intramembranous and/or endochondral bone

formation on graft surfaces…….

Graft Incorporation

• Cortical allograft strut graft placed next to cortex of host

• After 4 years of incorporation

Bone Graft Substitutes

• Need for bone graft alternatives has lead to development of numerous bone graft substitutes

• Avoid morbidity of autogenous bone graft harvest• Mechanical properties vary• Most offer osteoconductive properties• Some provide osteoinductive properties

Bone Graft SubstitutesPotential Roles

• Extender for autogenous bone graft– Large defects– Multiple level spinal fusion

• Enhancer– To improve success of autogenous bone graft

• Substitute– To replace autogenous bone graft

Properties of bone graft substitutes

Classification

Laurencin et al, classification

• Allograft based• Factor based• Cell based• Ceramic based• Polymer based• Composite

Ideal bone graft substitute

• Scaffolding for osteoconduction• Growth factors for osteoinduction• Progenitor cells for osteogenesis• Biocompatible and biodegradable and

mechanical properties similar to the surrounding bone

• Each substitute available nowadays fulfill only some of the criteria


• Resorption rates vary widely– Dependant on composition• Calcium sulfate - very rapid• Hydroxyapatite (HA) – very, very slow• Some products may be combined to optimize

resorption rate

– Also dependant on porosity, geometry


• Mechanical properties vary widely– Dependant on composition• Calcium phosphate cement has highest compressive

strength• Cancellous bone compressive strength is relatively low• Many substitutes have compressive strengths similar to

cancellous bone• All designed to be used with internal fixation

Allograft based

• Includes allograft bone used alone or in combination with other materials

• Available as demineralised bone matrix

Factor based

• Involves natural or recombinant factors• Factors responsible for differentiation of

progenitor cells and regulation of activities• Mechanism of action: based mostly on

activation of protein kinase• Combined and simultaneous activity of

various factors controlled resorption and formation of new bone

• Factor + receptors on the cell surface

• Activation of protein kinase

• Transcription of mRNA

• Protein synthesis

• Regulation of cell activities

• Includes TGF-beta, IGF-I&II,PDGF,FGF and BMPs

• Mostly in research phase• Recombinant BMP-2 as INFUSE bone graft

Bone Morphogenic Proteins

BMP 2 and 7BMP 2• Acts as a disulfide

linked homodimer and helps in bone and cartilage formation

• It is a candidate as retinoid mediator and helps osteoblastic differentiation

BMP 7

• It plays a key role in osteoblastic differentiation

• It induces the prodution of SMAD 1

• It plays a key role in renal development and repair

Bone Morphogenetic Proteins• Produced by recombinant technology• Two most extensively studied and

commercially available– BMP-2 (Infuse) Medtronics– BMP-7 (OP-1)Stryker ss– BMP-2 and BMP-7 are water soluble and

require a carrier to remain in the operative area to be effective

BMP-2 for Open Tibial Fractures

• Prospective, randomized study

• 450 patients

BESTT Study Group, et al. J Bone Joint Surg 84A: 2123, 2002.

• All received IM nail (vast majority with UNREAMED technique) and appropriate soft tissue management

• Randomized to 3 treatments at time of definitive wound closure • Placebo• 0.75 mg/ml BMP-2/ACS• 1.50 mg/ml BMP-2/ACS

Results• 44% reduction in risk of

nonunion/delayed union with high dose BMP-2

• Significantly faster fracture healing

• Significantly fewer – invasive interventions– hardware failures– infections

BESTT Study Group, et al. J Bone Joint Surg 84A: 2123, 2002.

Cell Based

• Based on in vitro differentiation of mesenchymal stem cells to osteoblastic lineage

• They have been used along with ceramics• Proposed to be used in bone repair prosthetic

setting

Ceramic based

• About 60% BGS involves ceramics- alone or in combination

• Eg : calcium sulfate, calcium phosphate, bioactive glass

• Primary inorganic componet is calcium hyroxyapatite

• Property of osteointegration, newly formed mineralised tissue forms intimate bond with implant materials

Calcium Phosphate Ceramics

• Enable osteoconduction but use is limited due to poor tensile strength and brittleness• Injectable pastes of calcium and phospate – Norian SRS (Synthes/Stratec)– Alpha BSM (Etex/Depuy)– Callos Bone Void Filler (Skeletal Kinetics)

Calcium Phosphat Ceramics

• It is produced by the process of Sintering(heating over 1000degrees C)

• Injectable• Very high compressive strength once

hardens• Some studies of its use have allowed

earlier weightbearing and range of motion

• Osteoconductive void filler

• Low compressive strength – no structural support

• Rapidly and complete resorption

• May be used as a autogenous graft extender

- Available from numerous companies

- Osteoset, Calceon 6, Bone Blast, etc.

Calcium Sulfate(plaster of

paris)

Calcium Sulfate

• Pellets– Pellet injectors

• Bead kits– Allows addition of

antibiotics• Injectable–May be used to augment

screw purchase• Combination of DMB and

calcium sulfate

Hydroxyapatite(HA)

• It is a slowly resorbing compound of calcium phosphate

• Source :synthetic and animal• Hydrothermal process converts it from its

native coral form to more stable HA form with pore diameters between 200 to 400 micron

Hydroxyapatite

• Interconnected porous structure closely resembles the porosity of human cancellous bone

Coralline hydroxyapatite

Cancellous Bone

Hydroxyapatite

• Interpore(Interpore International, Irvine,CA):first calcium phosphate based BGS approved by FDA

• Marketed as ProOsteon by Interpore Cross• Available in various size blocks & granules• ProOsteon 500– Very slow resorption

• ProOsteon 500 R– Only a thin layer of HA– Faster resorption

Hydroxyapatite:indications

• Valgus instability following lateral tibial plateau fracture

• Varus instability following medial condyle fracture of tibia

• Articular incongruence of 10 mm or more• Translation of major condylar fragment of

more than 5mm

Tricalcium Phosphate(TCP)

• TCP composition is similar to calcium and phosphate phase of human bone and has porous nature

• TCP undergoes partial resorption and some of it may be converted to HA once implanted in the human body

• Complete resorption at 6 months

Tricalcium Phosphate

• Wet compressive strength slightly less than cancellous bone

• Available as blocks, wedges, and granules• Numerous tradenames– Vitoss (Orthovita)– ChronOS (Synthes)– Conduit (DePuy)– Cellplex TCP (Wright Medical)– Various Theri__ names (Therics)

Calcium Phosphate Cements(CPC)

• CPC is used as void filler in defects• It consists of inorganic calcium and phosphate

combined to form an injectable paste

Polymer based

• Can be divided: natural/synthetic• Further divided into: biodegradable/non

biodegradable• eg: Healoss(depuy)-natural• Eg :Cortoss- injectable resin based product• Eg : Rhakoss(Orthovita)

Collagen Based Matrices

• Highly purified Type 1 bovine dermal fibrillar collagen

• Bone marrow is added to provide bone forming cells

• Collagraft (Zimmer)– Collagen / HA / Tricalcium

phosphate• Healos (Depuy)

– Collagen / HA

Composite graft

• In this two or more type of bone graft

substitutes combined together

• So that osteoconductive and osteoinductive properties of different BGS, is combined

Calcium Phosphate-Collagen Composite

• Collagen provides binding sites for matrix proteins

• Type I and III is added to HA,TCP and autologous bone marrow to form a graft material

• Although no structural support but augments frature healing

Bone Graft Substitute Incorporation

• Partial incorporation of hydroxyapatite bone graft substitute\

• Biopsy of material obtained 1 year post-op

Bone grafts and bone grafts substitutes

Health & Medicine

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