Grafts and Bone Graft Substitutes 133

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From: Bone Regeneration and Repair: Biology and Clinical Applications
Edited by: J. R. Lieberman and G. E. Friedlaender Humana Press Inc., Totowa, NJ

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Grafts and Bone Graft Substitutes
Doug Sutherland, MD and Mathias Bostrom, MD
INTRODUCTION
The value of bone transplantation is demonstrated by the frequency of its use today. Surgeons transplant
bone at least 10 times more often than they do any other transplantable organ. The procedure
has a rich history, dating back over 300 years to when Job van Meekeren performed the first bone
graft using a canine xenograft to repair a cranial defect (138). Bone grafting became critical during
World War II, prompting the US Navy to establish bone banks to better treat fractures sustained in
battle (9). During that period a successful graft was thought to be one that could withstand the forces
applied to it by the individual. Today we consider the bone graft to be a dynamic tool that should not
only support normal forces, but also incorporate itself into the bed, revascularize as new bone forms,
and assume the specific shape required for the healing defect. Furthermore, accelerating the normal
healing process whenever possible is an obvious goal. Recombinant DNA technology might achieve
this goal by allowing surgeons to apply growth factors to defects in therapeutic quantities in an effort
to speed regeneration.
The ideal bone graft or bone graft substitute should provide three essential elements: (1) an osteoconductive
matrix; (2) osteoinductive properties or factors; and (3) osteogenic cells. Osteoconductivity
can be defined as the process of infiltration of capillaries, perivascular tissue, and osteoprogenitor cells
from the host bed into the transplant (18). The matrix need not be viable. However, as we will see, if
the graft does not simulate the porosity and microstructure of human cancellous bone, incorporation
into the bed will be delayed. Osteoinduction is the stimulation of a tissue to produce osteogenic elements
(18). This process is controlled primarily by growth factors such as bone morphogenetic proteins
(BMPs) that are capable of inducing differentiation of mesenchymal cells into cartilage and boneproducing
cells. Osteogenetic cells are mesenchymal-type cells, and they can be summoned from host
or graft bone marrow (18). The inclusion of osteogenic cells into grafts today remains procedurally
difficult. Because few cells survive transplant, most osteogenic cells found in the graft are recruited
there from the host bed by osteoinduction. This poses an obvious problem when the viability of the
bed is compromised, such as a densely fibrotic defect. Thus, the creation of a bone graft or bone graft
substitute that can function independently of the host bed condition is desirable.
Today, the autogenous cancellous bone graft still satisfies all three categories most completely.
Hydroxyapatite and collagen serve as the osteoconductive framework, stromal cells lining the microcavities
possess the necessary osteogenic potential, and the endogenous family of growth factors within
the bone and adjacent hematoma fully induce both the regenerative and augmentation processes. For
these reasons, the autogenous cancellous bone graft is considered the gold standard of bone transplantation.
There are several potential complications involved with autogenous grafting, however,
such as donor-site morbidity, limited availability for harvest, and increased operative blood loss. It has
therefore become necessary to find suitable alternatives, particularly when a large graft is required.