Bone grafts and substitutes

S.K IMRAN ALI

PG IN MS ORTHOPAEDICS

GANDHI MEDICAL COLLEGE

Bone grafts are bone that is transplanted from one area of the skeleton to another to aid in healing, strengthening or improving function.

Bone or bone-like materials used in bone grafts may come from same person, from a donor or from a man-made source.

Bone grafting is used to repair bone fractures that are extremely complex,pose a significant risk to the patient,fail to heal properly.

Bone grafting is also used to help fusion between vertebrae, correct deformities, provide structural support for fractures of the spine.

In addition to fracture repair ,bone grafting is used to repair defects in bone caused by

congenital disorders traumatic injury or surgery for bone cancer

http://www.surgeryencyclopedia.com/Fi-La/Fracture-Repair.html

Types 0f Bone graftBased on source:

Autograft ,Isograft ,Allograft, Xenograft

Based on contents: Cortical, Cortico-cancellousCancellous

Based on Vascularity: vascular, Non-Vascular

Based on method of preservation: fresh, frozen, freeze dried, demineralized

Synthetic grafts or Substitutes

Orthopic transfer: host site is of same tissue as that from which graft was donated

Heterotopic transfer: here bone is transferred to a new environment (e.g bone placed in a bed of soft tissue)

Types of Bone Graft Substitutes

Allograft bone used alone or in combination with other materials

Eg; Allogro , Dynagraft Grafton

Mesenchymal stem cells (marrow)

TGF-β, BMP-7-(OP)-1 , FGF

BMP-2—Infuse

PDGF + TGF-β + autograft

Osteograf , Norian STS, ProOsteon , Osteostet

Cortoss, OPLA, Immix,

Allograft-based

Cell-based

Factor-based

Ceramic-based

Polymer-based

Four types of bone cells are located within and around bone matrix.

Osteoblasts, which produce the bone matrix Osteocytes, mature osteoblasts that maintain the bone Osteoclasts, which break down and remove bone tissue.

Bone lining cells, which cover bone surfaces.

Together, these four types of cells are responsible for building the bone matrix, maintaining it, and remodeling the bone as needed.

There are three ways that a bone graft can help repair a defect.

Osteogenesis, the formation of new bone by the cells contained within the graft.

Osteoinduction, a chemical process in which molecules contained within the graft (bone morphogenetic proteins,) convert the patient's cells into cells capable of forming bone.

Osteoconduction, a physical effect whereby the graft matrix configures a scaffold on which cells in the recipient form new bone.

Types of Bone Grafts Autograft

Allograft

Bone graft substitutes

Most have osteoconductive properties

Osteoinductive agents

rhBMP-2 (Infuse) and rhBMP-7 (OP-1)

Autografts“Gold standard”

Standard by which other materials are judged

May provide osteoconduction, osteoinduction and osteogenesis

Drawbacks

Limited supply

Donor site morbidity

Autografts types Cancellous

Cortical

Free vascular transfers

Bone marrow aspirate

Cancellous Bone Grafts

Three dimensional scaffold (osteoconductive)

Osteocytes and stem cells (osteogenic)

A small quantity of growth factors (osteoinductive)

Little initial structural support

Can gain support quickly as bone is formed

Cortical Bone Grafts

Less biologically active than cancellous bone

Less porous, less surface area, less cellular matrix

Prolonged time to revascularizarion

Provides more structural support

Can be used to span defects

Vascularized cortical grafts

Better structural support due to earlier incorporation

Also osteogenic, osteoinductive.

Bone Marrow Aspirate Osteogenic

Mesenchymal stem cells (osteoprogenitor cells) exist in a 1:50,000 ratio to nucleated cells in marrow aspirate

Numbers decrease with advancing age

Can be used in combination with an osteoconductive matrix

Cancellous bone

Iliac crest (most common) Anterior- taken from

gluteus medius pillar

Posterior- taken from posterior ilium near SI joint

Metaphyseal bone

May offer local source for graft harvest

Greater trochanter,

distal femur,

proximal or distal tibia,

calcaneus,

olecranon,

distal radius, proximal humerus

Autograft HarvestCancellous harvest technique

Cortical window made with osteotomes

Cancellous bone harvested with gouge or currette

Can be done with trephine instrument

Circular drills for dowel harvest

Commercially available trephines or “harvesters”

Can be a percutaneus procedure

Autograft Harvest Cortical

Fibula common donor

Avoid distal fibula to protect ankle function

Preserve head to keep LCL, hamstrings intact

Iliac crest

Cortical or tricortical pieces can be harvested in shape to fill defect

Bone Allografts Cancellous or cortical

Plentiful supply

Limited infection risk (varies based on processing method)

Provide osteoconductive scaffold

May provide structural support

Available in various forms

Processing methods may vary between companies / agencies

Bone Allografts Fresh

Highly antigenic

Limited time to test for immunogenicity or diseases

Use limited to joint replacement using shape matched osteochondral allografts

Highest risk of disease transmission and immunogenicity ,BMP preserved and therefore osteoinductive

Bone Allografts Fresh frozen

Less antigenic

Time to test for diseases

Strictly regulated by FDA

Preserves biomechanical properties

Good for structural grafts

Less immunogenicity than fresh

BMP preserved and therefore osteoinductive

Bone AllograftsFreeze-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

Least structural integrity

BMP depleted (purely osteoconductive)

Lowest likelihood of viral transmission

Graft Incorporation Hematoma formation

Release of cytokines and growth factors



Inflammation

Development of fibrovascular tissue



Inflammation


Vascular ingrowth

Often extending Haversian canals



Inflammation


Vascular ingrowth


Focal osteoclastic resorption of graft



Inflammation


Vascular ingrowth


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

Partial incorporation of hydroxyapatite bone graft substitute\

Biopsy of material obtained 1 year post-op

Bone Graft Substitute Incorporation

WHY ARE WE INTERESTED IN BONE GRAFT ALTERNATIVES

BONE GRAFT MORBIDITY- 9%1. PROLONGED WOUND DRAINAGE2. HEMATOMAS 3. INFECTIONS4. NERVE INJURY5. PROLONGED PAINLARGER THE AMOUNT OF GRAFT MORE ARE THE LIKELIHOOD OF COMPLICATIONSAUTOLOGUS BONE GRAFT IS NOT SUFFICIENT IN SOME CASES LIKEBONE CYSTS, BONE DEFECTS, TUMORS ETC….

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

Ideal bone graft substitute Should be

biocompatible,

bioresorbable,

osteoconductive,

osteoinductive,

structurally similar to bone,

easy to use

cost-effective.

Currently marketed products are variable in their composition, their mechanism of action and the claims made about them.

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


Calcium phosphate

Calcium sulfate

Collagen based matrices

Demineralized bone matrix

Hydroxyapatite

Tricalcium phosphate

Osteoinductive proteins


Resorption rates vary widely

Dependant on composition

Calcium sulfate - very rapid

Hydroxyapatite (HA) – very, very slow

Some products may be combined to optimize resorptionrate

Also dependant on porosity, geometry

Bone Graft Substitutes 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

Calcium PhosphateInjectable pastes of calcium and phospate

Norian SRS (Synthes/Stratec)

Alpha BSM (Etex/Depuy)

Callos Bone Void Filler (Skeletal Kinetics)

Calcium Phosphate

• 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 resorbs

May be used as a autogenous graft extender

- Available from numerous companies

- Osteoset, Calceon 6, Bone Blast, etc.

Calcium Sulfate

Pellets

Pellet injectors

Bead kits

Allows addition of antibiotics

Injectable

May be used to augment screw purchase

Calcium Sulfate

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

Demineralized Bone Matrix Prepared from cadaveric human bone

Acid extraction of bone leaving

Collagen

Noncollagenous proteins

Bone growth factors

BMP quantity extremely low and variable

Sterilized which may decrease the availability of BMP

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

Demineralized Bone Matrix

Hydroxyapatite

Produced from marine coral exoskeletons that are hydrothermically converted to hydroxyapatite, the natural mineral composition of bone

Interconnected porous structure closely resembles the porosity of human cancellous bone

Coralline hydroxyapatite

Cancellous Bone

Hydroxyapatite Available in various size blocks & granules

ProOsteon 500

Very slow resorption

ProOsteon 500 R

Only a thin layer of HA

Faster resorption

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)

Bone Morphogenetic Proteins

Produced by recombinant technology

Two most extensively studied and commercially available

BMP-2 (Infuse) Medtronics

BMP-7 (OP-1) Stryker Biotech

Demineralized Bone Matrix 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 Silicate based grafts Aluminum oxideAlumina 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

Bone morphogenetic proteins (BMP) Osteoinductive properties

stimulates undifferentiated perivascular mesenchymalcells to differentiate into osteoblasts through serine-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 Irrigator Aspirator System Indications – To clear the medullary canal of bone

marrow and reaming debris – To clear the medullary canal of

infected bone tissue – To effectively size the medullary canal

for the acceptance of an intramedullaryimplant or prosthesis

To harvest finely morselizedautogenous bone and bonemarrow for any surgical procedures that require bone graft in order to facilitate fusion and/or fill bone defects.

These procedures include spinal fusion, joint arthrodesis, total joint replacement, fracture repair, nonunion, maxillofacial reconstruction, and tumor removal

BONE BANK Deals with procurement, storage & supply of Bone Goals : to preserve integrity of graft

to reduce immunogenicityto ensure sterility

Procedure:Legal status- permission from donor or from next of kinDonor selection: no infection by Hx or physical exam

no deep tissue woundsafebrile hospital coursemax 72 hrs 0f Resp assistanceno prolonged steroid therapy or on long actingisotopesno hx of IV drug abuse

Time interval between death and harvest should be <12hrs for unrefrigerated body & <24hrs for a refregirated one

Procurement Procedure:

Performed in regular OT within12-24 hrs of death.

Ileum , femur, tibia, humerus ,ribs.

Capsules , tendons & ligaments retained.

Pelvis procured at the end to prevent contamination frombowel.

Grafts are placed in cold tissue culture medium(RL) to which100mg/L of Sterptomycin sulfate & 80mg/L of Gentamycinsulfate are added.

After removal of grafts, bodyframe is reconstructed withsticks cut to the length of extremity &fixed by plaster.

Storage :Bones are wrapped in sterile cloth with 2-3 layers of sterile drapes.Cartilagenous ends are soaked in 8%DMSO in RL which acts as

cryoprotectant for the cartilage .Sterilisation : When cadaver grafts have been obtained under aseptic conditions there is

no need to employ sterilisation procedures. They were used in the past and are rarely used now due to deleterious effect on bone.

Diadvantages :Bone becomes discoloured and brittle.Solubility of collagen & GAG is increased.Fibrillar network of bone matrix is destroyed.Reduces bone inductive capacity.Retrieval of bone: bones are thawed just prior to use in RL /NS to which

antibiotics are added.Bones preserved at freezing temparatures require atleast 1hr at room

temparatue before use.

Bone grafts and substitutes

Health & Medicine

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