Abstract
Arthrodesis of the spine is the preferred surgical treatment for a number of pathological disorders. This process is dependent on three primary components: osteogenic cells with osteoblastic potential, osteoinductive growth factors and an osteoconductive scaffold that facilitates bone formation and vascular ingrowth. Several systemic and local factors are known to affect the rate of spinal fusion. Autogenous bone graft remains the gold standard graft material for spinal fusion. It is the only graft material that supplies the three primary components necessary for a solid fusion. Unfortunately autogenous bone is only available in limited quantities and the procurement of autograft is associated with significant donor site morbidity. A number of different bone graft materials have been developed as alternatives to autograft. These materials may be classified into two major groups, bone graft extenders used to augment autograft, or bone graft substitutes. Several different bone graft materials have been developed including allograft, osteoconductive matrices, demineralised bone matrices, bone marrow aspiration, autologous platelet concentration, growth factors and gene therapy.
Allograft is currently the most widely used substitute for autogenous bone. Because any osteogenic cells are eradicated during the tissue processes, allograft is primary osteoinductive with minimal osteoinductive potential. Processing may affects the structural and biological characteristics of a graft. The incorporation of allograft occurs by a process similar to that observed with autograft but more slowly and is less complete.
Osteoconductive scaffolds do not contain any osteogenic cells or osteoinductive factors and are used as a composite graft as a carrier for either osteogenic cells or osteoinductive growth factors. They are biocompatible and do not illicit a response. There is also no inherent risk of infection and availability is unlimited. These materials are brittle with poor mechanical properties and need to be protected from excessive biomechanical forces until fully incorporated. A number of osteoconductive scaffolds have been developed including ceramics, calcium sulfate, mineralized collagen, bioactive glasses, and porous metals.
Dematerialized bone matrices (DMPs) are osteoinductive with variable osteoconductive properties. DMPs consist of Type I collagen and non-collagenous proteins including multiple signaling proteins. The osteoinductive activity of DMPs is due to a small fraction of bone morphogenic proteins. There is significant variability in the osteoinductive potentials and clinical efficacy of DBMs. DBMs are most effective when combined with autograft or bone marrow aspirate.
Bone marrow aspiration provides osteogenetic cells and osteoinductive growth factors but must be combined with an osteoconductive carrier to form a composite graft. It is associated with minimal morbidity compared to the use of autograft and is easily obtained. Unfractionated bone marrow contains only moderate osteogenic potential. Selective retention technology can increase the number of osteogenic cells then combined with an osteoconductive carrier such as a collagen sponge or DBM.
Activated platelets release multiple factors that may enhance bone formation by promoting chemotaxis, cellular proliferation and differentiation of stem cells. Platelets do not release BMPs so this autologous platelet concentrate is not inductive. Concentrated platelet rich plasma gel is combined with an osteoconductive scaffold or osteogenic cells to form a composite graft for implantation. The capacity for fusion by this technique may be inferior to autologous graft.
Bone morphogenetic proteins are low molecular weight proteins related to the transforming growth factor beta superfamily. They bind receptors on the surface of osteoprogenitor stem cells and activate intracellular signal transduction cascades resulting in the osteoblastic differentiation of pluripotential stem cells. Recombinant BMPs are typically combined with an osteoconductive carrier to form a composite graft. Recombinant BMPs have been used successfully in spinal fusions and may be superior to autograft.
Gene therapy involves the transfer of specific DNA sequence into target cells that express the protein of interest. Gene therapy may provide a more potent osteoinductive signal than recombinant growth factors because the sustained local release of osteogentic proteins may be more physiologic than the administration of a single large dose of recombinant factors. There are potential safety concerns and economic issues.
Autogenous bone remains the gold standard of graft material; however composite grafts consisting of multiple materials may prove to be efficacious for stimulating a spinal fusion.
The abstracts were prepared by Assoc Prof Bruce McPhee. Correspondence should be addressed to him at the Division of Orthopaedics, The University of Queensland, Clinical Sciences Building, Royal Brisbane Hospital, Herston, Brisbane, 4029, Australia.
