Bone Graft and its substitutes

Introduction
Need for bone grafting:
To replace skeletal defects To augment bony recontruction Bridge joints in arthrodesis To provide bone blocks to limit joint motion [arthroereisis] Establish union in pseudoarthrosis To promote union : in fresh #s, delayed unions, non unions and osteotomies.

Bone Graft Terminology

Based on anatomic placement:
Orthotopic: Transplantation to similar anatomic site Heterotopic: Grafting to anatomically dissimilar site

Based on tissue architecture: Cortical, cancellous,

corticocancellous, Osteochondral

Based on source:
Autograft: same individual,different site a] non vascularised b] vascularised Allograft: same species but genetically different individual Xenograft: different species Isograft: monozygotic twin

Bone Graft Function

Osteogenesis

Mechanical support

Biology of Bone Grafts

Bone regeneration: Osteoinduction Osteoconduction Osteoprogenetor cells Osteoinduction: stimulation of host bed to synthesise new bone.

Graft derived Low molecular wgt protiens stimulate mesenchymal stem cells to differentiate into bone forming cells. This induction of stem cells does not require viable graft cells because it is a property of bone matrix. infiltration and ingrowth of new host bone, this process is reffered as osteoconduction. A three dimentional configuration for ingrowth into graft of host capillaries, perivascular tissues, and osteoproginator cells from the recepient. [creeping sunstitution]

Osteoconduction:The Matrix/ scaffolding that permits cell

Incorporation of the graft

Haematoma formation Inflamatory response release of cytokines and growth factors. Osteoinduction drives chemotaxis, mitosis, and differentiation of osteoproginetor cells Day5 chondrocyts form Day 10- osteoblasts Host blood vessels infiltrate through harvesian and volkmanns canals and bring with them osteoclasts for resorption. Remodelling occurs along the lines of biomechanical forces. Hence succesful incorporation needs: good blood supply, osteogenesis, grafts response to load applied.

Auto grafts
Cancellous Cortical

Vascularised Non Vascularised

Cancellous autografts
Larger surface area Faster incorporation [ 4 weeks- healing
6 months complete remodelling]

Good osteoinductive, osteoconductive and osteogenetic properties. No ability to confer structural strength

Cortical Autografts
Due to density- revascularisation and remodelling are slower Unlike cancellous grafts these are incorporated by appositional bone growth over a necrotic area. Good structural support Minimal osteogenetic, moderate osteoinductive and conductive properties Types: Vascularised , non vascularised.

Advantages of autograft
Gold standard Histocompatible Disease transmission is not at all a concern Fresh / viable

Disadvantages of autografts
A separate donor site is required Increased surgical time Another potential site for infection created Additional amount of blood loss Weaknening of normal structure Local complications Limited availability relative paucity of osteogenic cells in the graft in older individuals

Vascularised auto graft

Incorporates independent of host bed and functions even in biologically defecient host environment Advantages:
Compromised vascularity in the host bed causing poor osteogenic cells, poor surrounding tissues If infection at surgical site poor soft tissue coverage Systemic chemotherapy

Disadvantages:
Time consuming Technically very demanding Limited donor sites [ proximal fibula, ribs]

Allografts
Graft taken from two genetically different individuals of the same species. Mode of availability: Frozen Freeze dried [morcellised] Cancellous allografts: mainly to fill the cavitory defects Cortical allografts: for structural support

How are they Preserved

Freezing Freeze drying [ helps in better incorporation as it reduces immunogenecity] Decalcification and demineralisation [ these grafts have not much mechanical strength]

Sterilisation techniques
Irradiation : destroys osteoinductive property Chemosterilisation Autolysed Antigen extraction [ last three has good osteoinduction but poor mechanical strength]

Advantages
Abundantly available in amount, shapes and sizes No donor site morbidity Good mechanical strength Good Osteoconductive property

Disadvantages
Immunogenic Higher failure rate notes Graft incorporation very much delayed [ more than 2 yrs] Risk of disease transmission Low osteoinductive property If these grafts fracture unlikely to heal

Bone Banking
Tissues recovered under sterile conditions from young donors with strong bone after careful screening for neoplasm and infection If cartilage present graft is first treated by dimethylsulfoxide and later freezed to preserve the viability of chondrocytes The muscular, teninous, and ligamentous attachments are preserved After biplanar radiographs taken, specimens are cultured, rapidly frozen, and maintained at -80*c until they are used

Factors for success of a bone grafting

Clean, well vascularised host bed is critical Wide excision of scar tissue Treatment of infection Protection of blood supply Satisfactory soft tissue coverage Appropriate selection of graft material as per the desired clinical function Firmly/ tight apposition of graft bone and host bone Stable fixation of the graft

Bone Substitutes

Types
Naturally Derived Substitutes:
Demineralised Bone Matrix [DBM] Bone Marrow and Bone Marrow Products

Synthetically derived substitutes

Calcium sulphates Tricalcium Phosphates Calcium phosphate cements Corralline based hydroxyapatites Bone Morphogenetic Proteins

Synthetically derived substitutes

Less chances of viral transmission compared to natural derived substitutes Less variability They are tested rigorously for safety and efficacy It mainly provides a scaffold for osteoproginetor cells to proliferate and differentiate.

Calcium sulphates [POP]

First used in in 1892 complete healing of nine cavitory lesions Has no weight bearing ability Resorbs very quickly [6 weeks] [i.e: dissappears from implantation site whether bone formation has taken place or not] A promising carrier for antibiotics, DBMs,BMPs,or any other molecules being delivered to defect site.

Tricalcium Phosphates
TCPs Less crystalline Two types: Alpha and beta Alpha soluble and resorbs fast Beta less soluble and resorbs by osteoclastic activity only : hence it will disappear only after new bone formation Has only osteoconductive property

Calcium Phosphate Cements

No weight bearing capability Powder and solvent is mixed and the resultant ceremic paste injected/ moulded into non weight bearing defect. Setting time 10 to 30 minutes depending on formulations After curing they form a apatitic compound similar to bone mineral These cements do not degrade during a patients lifetime.

Coral based hydroxyapatite

Calcium carbonate exoskeleton of reef building marine corals processed to form calcium phosphates. Corals of scleractinian genus used Goniopora species- first used- its pores are similar to cancellous bone pores- 500 to 600microm Porites species similar to cortical bone pore diameter- 200microm. Useful to fill defects after tumour excision with wide defects.

Collagen Based technology

Type 1 collagen extracted from animal source, mostly from bovine source Good osteoconductive property Disadv: Hypersensitivity to bovine collagen Uses: Mainly as a carrier along with other materials.

Naturally Derived
Available clinically from 1990s. Disadv: High tissue variability Viral transmission