| Spinal fusion is a well-accepted procedure for the treatment ofdisorders such as trauma, deformity, tumor inflammation or infection, andcommon degenerative pathology. The aim of a spinal fusion is toeliminate the instability of the spine caused by these pathologies. Bydefinition, spinal fusion means the achievement of a bony union betweenthe involved vertebrae. However numerous systemic risk factors, such asadvanced age of the patient, concomitant use of tobacco or other drugs,and metabolic comorbidities (eg, diabetes or osteoporosis) that are allknown to inhibit bone formation, successful fusion of the spine may alsobe limited by structural instability, improper preparation of host bone,poor vascularity and other local considerations. The presence of any ofthese detrimental conditions may diminish the osteogenic potential of thefusion site and contribute to the development of a pseudarthrosis. Inorder to optimize the biological environment of the spinal segment to befused, in the vast majority of cases some type of bone graft material isemployed to enhance bone healing and reduce the risk of nonunion. As aresult, successful spinal fusion is clearly influenced by the cellular,biochemical and mechanical properties of the bone graft substance thatis implanted.Bone grafting, the procedure of replacing missing bone with materialfrom either the patient's own body (autografting) or that of a donor(allografting) was first established in the 1800s. Theprocess ofbone regeneration requires three critical elements: osteogenic cells thathave the capacity to synthesize new bone, osteoinductive factors.(ie,growth factors and cytokines) that promote the osteoblasticdifferentiation of pluripotential stem cells and an osteoconductivescaffold that facilitates neovascularization and supports the ingrowth of bone. In modern medicine, autografting possesses all three of theseproperties essential for bone formation and is regarded as the "goldstandard"; however the amount of bone that can be safely harvested islimited, while the additional surgical procedure may be complicated bydonor-site pain and morbidity. Modern allografting using material storedwithin regulated bone banks overcomes these difficulties. However, thedemand for outstrips the supply, there is no assurance of freedom fromdisease and healing can be inconsistent. Consequently, there is anincreasing demand for synthetic bone-graft products that would avoidthese complications, in addition to overcoming the problem of aninadequate supply of material.In an attempt to augment the limited quantity of autogenous bone that isaccessible to the surgeon and minimize the morbidity of graftingprocedures while maintaining an acceptable rate of fusion, several bonegraft substitutes have been developed, A better understanding of themechanisms underlying arthrodesis of the spine has stimulated interestin a growing number of biologically active materials that have beenadvocated as alternatives to autograft. Like autogenous bone, an idealbone graft substitute would not only be osteogenic, osteoinductive andosteoconductive, but also provide adequate mechanical support; however,none of the existing strategies exhibit all of these characteristics whenimplemented alone. The introduction to this thesis explores developmentsin the bone biology, the etiology of the spinal instability, bone graftsubstitute for spinal fusion over the. previous decades, and providesinsight into interesting new thought which offer much potential to thebone graft substitutes.Posterolateral lumbar transverse process fusion using recombinanthuman OP-1 (also name bone morphogenetic protein-7 (rhBMP-7)) carried byInsoluble Bone Gelatin (ISBG) was compared with fusion achieved using autogenous bone graft, ISBG alone, and OP-1 alone. This study examinedthe efficacy of ISBG as a carrier of OP-1 for lumbar intertransverseprocess arthrodesis. Thirty-two adult rabbits underwent bilateral lumbarintertransverse process arthrodeses at L5-L6. The animals were dividedinto four groups based on the type of procedure performed: (1) Autologousbone group - grafted autologous corticocancellous bone harvested from theiliac crest; (2) ISBG group; (3) OP-1 group, and; (4) ISBG+OP-I group.Spinal fusion was evaluated by radiographic analysis, manual palpation,biomechanical testing, and histologic examination 6 weeks after surgery.One rabbit died due to anaesthesia-related complications. Another twowere sacrificed when they encountered deep wound infection. TheISBG+OP-1 group demonstrated higher fusion rates based on manualpalpation with significantly higher tensilestrength and stiffer fusion.Radiographs at 3 and 6 weeks post-operativley demonstrated a homogeneousfusion mass at the inter-transverse gap which was confirmed by similarhistological findings. The combination of insoluble bone gelatin (ISBG)and OP-1 resulted in significantly higher fusion rates in posterolaterallumbar transverse fusion. |
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