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Bone grafts and bone graft substitutes

Introduction

Bone is the second most commonly transplanted tissue after blood transfusions. In the US, there are more than 500,000 bone grafting procedures each year.

Osteogenesis, osteoinduction and osteoconduction are three properties in which a bone graft may possess. Osteogenesis is the process of new bone formation by cells from the host or the graft. Both autologous cancellous and cortical grafts can provide cells capable of producing bone, but cancellous autografts with their trabecular structure lined with osteoblasts and large surface area provide for much more potent osteogenesis. Osteoinduction is the process by which mesenchymal stem cells from the graft or the host tissue are induced to differentiate into chondroblasts or osteoblasts. Growth factors such as BMP's, interleukins and PDGF can influence the recruitment and differentiation of mesenchymal stem cells. Osteoconduction is the process by which the graft provides a three dimensional structure that facilitates the ingrowth of capillaries and mesenchymal stem cells to support new bone formation on the graft.

Autografts

Autograft bone graft is the transplantation of bone from one site to another site within the same person. Autograft may be of cancellous, cortical or a combination of cortical and cancellous. Autografts, unlike allografts, may osteogenic potential in addition to ostoinductive and osteoconductive potential. Additionally, there are no immunogenic complications. The down sides to autograft are the finite quanity available and donor site morbidity.

Autogenous Bone Marrow

Bone marrow may be aspirated and injected into a desired recipient site. Bone marrow will provide mesenchymal stem cells that in the presence of cytokines and growth factors can become osteogenic. Bone marrow may be mixed with demineralized bone matrix to decrease the tendency of the bone marrow to diffuse from the desired location. Additinally, efforts have been made to centrifuge bone marrow aspirate to increase the concentration of mesenchymal stem cells which can range from 1 per 50,000 nucleated cells in the bone marrow of a young adult to 1 per 1 million nucleated cells in the elderly.

Cancellous Autograft

Cancellous autograft, usually harvested from the iliac crest remains the gold standard for bone grafting. Cancellous autograft provides trabecular bone lined with osteoblasts providing for osteogenesis under the influence of local cytokines and growth factors. These grafts are vascularized and incorporated quickly and the low oxygen content of the graft as it is incorporated attracts host stem cells to the graft site. Cancellous autograft lacks significant structural qualities.

Cortical Autograft

Cortical autograft is rarely used due to donor site morbidity. When used, they provide structural support and supply osteoblast, although significantly fewer than cancellous autograft. In contrast to cancellous autograft, incorporation is initiated by osteoclasts that must resorb the dense cortical structure prior to allowing for accelerated revascularization. This can result in up to a 75% reduction in the strength of the graft. Vascualrized grafts, such as fibular shafts may be used to treat osteonecrosis of the femoral head or fill diaphyseal long bone defects.

Allografts

Over 200,000 of these procedures involve allografts. The increase in bone allografting has been linked to the increase in sterilization and reliable tissue banks. Allografts currently undergo stringent testing and sterilization to ensure the safety of the grafts. Screening of cadaveric donors consists of detailed past medical, social and sexual histories as well as testing for hepatitis C antibody, hepatitis B surface antigen, hepatitis B core antigen, HIV-1, HIV-2, syphilis, human T-lymphocyte virus I antibody and HIV p24 antigen. Only two confirmed cases of HIV transmission bone allografting have been reported in the literature.

Allograft processing may proceed by a number of methods including low dose irradiation, antibiotic washing and physical debridement. These methods attempt to reduce the antigenicity of the bone graft while providing sterilization. More extensive sterilization may be provided through gamma irradiation, electron beam irradiation or ethylene oxide treatment. These measures, however, cause a dose dependent decrease in the mechanical properties of the graft. Sterilization methods should include a method that can kill bacterial spores which have been linked to deaths from allografts.

To store grafts they typically undergo a cooling process. Fresh grafts can be cooled and transplanted within 24 hours, however this is rarely used as the background testing necessary to ensure safety precludes transplantation this rapidly. Thus, grafts are typically frozen or freeze dried. Freezing has minimal effect on the structural properties, but does not reduce the immunogenicity of the graft to the extent that freeze drying.

Cancellous Allograft

The results of cancellous allograft for bone healing are inferior to those of cancellous autograft due to the inflammatory response incited by the foreign cells as well as the lack of osteogenic potential. However, cancellous allograft provides a medium for osteoconduction.

Cortical Allograft

The incorporation of cortical allograft is slow and the graft loses significant strength as it undergos resorption and revascularization. Freeze drying may decrease the mechanical properties of the graft and rehydrating is required to minimize the effects of freeze-drying.

Massive Osteochondral Allografts

Massive osteochondral allografts contain diaphyseal cortical bone, metaphyseal cancellous bone and articular cartilage and are used mainly in limb salvage. The periosteum and soft tissues except for the joint capsule and ligament and tendon insertions are removed during the processing of the graft. The grafts are size matched and are frozen to decrease antigenicity.

Demineralized Bone Marix

Demineralized bone matrix consists of most of the non-mineralized components of bone. It is obtained from allograft through the process of acid extraction, which removes the mineral compents of bone. This leaves many of the components that give allograft bone its osteoinductive potential such as collagen and BMP's. It also retains the trabecular structure of its collagen which also gives it osteoconductive properties. It comes in many forms including gels, paste and putty. DMB results in rapid revasularization and causes release of local cytokines and growth factors that recruit mesenchymal stem cell that promote bone formation. DMB does not have the same osteoinductive potential as autograft, but is an alternative for patients for whom autograft is not an option or would result in significant morbidity.

Bone Graft Substitutes

Bone graft substitutes are synthetic materials that possess osteoconductive and structural properties. They do not provide osteoinductive or osteogenic properties.

Calcium Phosphates

These are ceramic scaffolds that induce a biologic response similar to bone. Hydroxyapatite is a form of calcium phosphate that is stable, osteoconductive and resorbed very slowly. It is brittle and often combined with autograft to improve its resoptive properties.

Tricalcium phosphate resembles amorphous bone precursors in its structure and thus is resobed more quickly than the more ordered structure of hydroxyapatite. These products come in cements that provide support and a scaffold for osteoconduction. The compressive strength of these products is greater than that of cancellous bone.

Brushite is another calcium phosphate mineral that has the strength of hydroxapatite, but a higher solubility that allows for more rapid replacement by bone on the order of 2-4 years.
Coralline hydroxyapatite compounds are derived from processed sea coral. Specific species posses a calcium carbonate exoskeleton that is similar cancellous bone. This material is converted to calcium phosphate and comes in blocks, wedges or small pellets and may be used for structural support. However, coralline hydroxyapatite is brittle, has low tensile strength and resorbs slowly.

Calcium Sulfate

More commonly known as plaster of paris, this substance can be used as a bone void filler. It is rapidly resorbed and replaced by bone. It resorbs so quickly, on the order of a couple of weeks, that wound drainage may become an issue. The structure is mechanically unreliable, which prevents it use is unstable situations. It is mainly used for antibiotic delivery.

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