Advances in Bone Graft Substitutes in Spinal Fusion

17 Advances in Bone Graft Substitutes in Spinal Fusion Michael N. Tzermiadianos, Alexander G. Hadjipavlou, and John N. Gaitanis University of Kriti Medical School Iraklio Kriti, Greece Bone grafting is essential for reconstruction of spinal defects and a prerequisite to obtaining solid arthrodesis imperative to spinal stability after reconstructive surgery [1]. Spinal fusion is commonly achieved by the adjunctive use of interbody or onlay cortical bone grafts (autograft or allograft). Success depends on factors such as the patient’s age, sufficiency of local blood supply, degrees of postoperative movement, and, importantly, the physical and biological charac- teristics of the graft matrix. Early attempts at bone grafting date back more than 500 years to the Arab, indigenous Peruvian, and Aztec cultures. In modern times, the first documented case of autogenous bone grafting was reported by Merem in 1810, and the first successful allografting case has been attributed to Macewn in 1881 [2]. Our present knowledge and scientific base for understanding the biology, banking, and widespread clinical applications of bone grafting is largely due to the work of Albee [3], Barth [4], Lexter [5], Phemister [6], and Seen [7] during the late nineteenth and early twentieth centu- ries. These substantive scientific contributions have made bone grafting techniques common and relatively effective clinical procedures. There are three biological processes that impact the success or failure of bone graft: osteogenesis, osteoconduction, and osteoinduction [8]. Osteogenesis refers to the process whereby bone forms directly from living cells, such as the stem cells within autogenous bone. Osteoconduction describes the process in which bone grows into and along the surface of a biocompatible structure when placed in direct apposition to host bone through the process of intramembranous bone formation. The ability to osteoconduct is a passive characteristic of bone that allows it to act as a platform on which vascular invasion, resorption, and new bone formation can occur [1]. Osteoinduction is endochondral bone growth stimulated by specific growth factors (morphogens and/or mitogens) on pluripotential cells, such as mesenchymal stromal or stem cells. In particular, bone morphogenic proteins (BMPs), identified through the seminal work of Urist and colleagues [9], has demonstrated the capacity for inducing the differentiation of host perivascular mesenchymal cells into cartilage and bone [10]. In varying degrees, bone grafting source materials and techniques use these mechanisms of bioincorporation. Thus, the ideal bone graft should be capable of these processes and also © 2004 by Marcel Dekker, Inc. be free of immunological antigens and microbial pathogens. There are a variety of bone grafts to choose from, each presenting a unique set of advantages and disadvantages. Autografts, because they are harvested from host bone stock from one body site for transfer to another location in the same individual, offer the maximum biological potential and histocom- patibility. Immunological considerations and disease transmission are obviated through the use of autogenous bone. The possibilities of meeting the needs of size, shape, and quantity of bone for any given procedure, however, are limited in autografting. The potential for morbidity by harvesting autologous iliac bone graft is ever- present [11] and can be caused by nerve injuries [12,15], vascular injuries [16,17], hernia through the iliac bone donor site [18,19], bowel obstructions [20], and other noteworthy drawbacks. Furthermore, harvesting fibular graft is related to a sense of instabil- ity or weakness in the lower extremity [21]. Operating room time is extended, as is the period during which the patient must remain under anesthesia. Any complications arising from these events, especially if compounded by the sequelae of donor site morbidity, may also increase the duration of hospitalization. Moreover, such a procedure often renders the bone donor site unacceptable for a subsequent operation. Despite these disadvantages, what makes the autograft the gold standard for bone grafting is that it fulfills the three requirements necessary for bioincorporation: it is osteogenic, osteoconductive, and osteoinductive. Available autologous bone grafts include cancellous, vascularized or nonvascularized cortical, and autologous bone marrow grafts. Bone formation from autologous grafts is believed to occur in two phases. The first phase lasts approximately 4 weeks, during which bone formation is mainly contributed from the cells of the graft. Cells from the host begin to contribute to the process during the second phase [22,23]. Autologous cancellous bone is easily revascularized and rapidly incorporated, leading to a high success rate. It does not provide substantial structural support but is a good space filler. Because only the osteoblasts and endosteal lining cells on the surface of the graft survive the transplant, a cancellous graft acts mainly as an osteoconductive substrate [24–27]. Osteoinductive factors released from the graft may also contribute to bone formation, but this is only a theory based on circumstantial evidence and has not yet been substantiated by scientific documentation [22,28,29]. Cancellous graft achieves strength equivalent to that of a cortical graft after 6–12 months [30]. Autologous cortical grafts include the fibula, ribs, and iliac crest. These grafts can be vascularized or nonvascularized. Autologous cortical grafts are mostly osteoconductive and have little or no osteoinductive properties, but the surviving osteoblasts provide some osteogenic properties [31,32]. Cortical grafts also provide excellent structural support, but nonvascularized cortical grafts become weaker than vascularized ones during the initial 6 weeks after transplantation as a result of resorption and revascularization [31,33]. Vascularized cortical grafts incorporate rapidly, and their remodeling is similar to that of normal bone. They do not undergo resorption and revascularization, thus providing superior strength during the first 6 weeks [31]. However, little difference in strength between vascularized and nonvascularized cortical grafts is evident by 6–12 months [31]. Allografts, usually obtained from cadaveric sources or incidental to operative procedures, offer satisfactory biological potential and eliminate the chance of donor site morbidity. Allografts provide an abundant supply of bone tissue, but their use for spinal fusion has been disappointing, especially for onlay intertransverse bone grafts [34–36]. Their use in scoliosis surgery has been flawed, with poor results in the 1960s [37]. In a recent study in humans, allografts in the form of fresh-frozen human femoral head were found to be at least as effective as autologous bone © 2004 by Marcel Dekker, Inc. ininstrumentedposterolateralspinalfusionsurgerywhentheresultswereassessedintermsof clinicaloutcome[38]. Allografts,includingfibularallografts,tricorticaliliumallografts,andfemoralshaftcorti- cal‘‘rings,’’havebeensuccessfullyutilizedforanteriorinterbodyfusions[39–41].Structural femoralringallograftshaveprovedeffectiveinsalvagingfailedlumbarfusionswithareported fusionrateof79–98%[39,42].Femoralringallograftswiththemedullarycanalpackedwith cancellousautografthavebeenfoundalmostaseffectiveastricorticaliliacautografts(6%vs. 0%pseudarthrosisrate)inanteriorfusionsinrevisionsurgeriesforpseudarthrosisorflatback deformity.Althoughlong-termcorticalallograftresorptionhasbeenobservedinfemoralrings packedwithcancellousallograftchipsthathadbeenusedforanteriorlumbarintervertebral fusion,thecenterofthegraftusuallyachievessolidarthrodesis[37]. Theuseofallograftsposesbiohazardsarisingfromtheirpotentialtoactasconduitsfor diseasetransmissionfromdonortorecipientandthetriggeringofimmunologicalreactions. Thus,strictadherencetobonebankingmethodologyandsterilizationproceduresareessential toproperhandlingofallografts[43]. Xenograft,orcross-speciesbonetissue,althoughinabundantsupply,hasbeenfoundto bealessreliablegraftmaterialthanautogenousandallogeneicbone.Theemergenceofsuch concernsasmajorhistocompatibilitydifferenceleadingtoimmuneresponseprovocation,the incompatibilityofotherspecies’anatomieswithhumananatomicalparts,lessenedbiological activity,andtheneedforrigorous,meticulousprocessingandsterilizationofbonederivedfrom nonhumanspecieshavelargelyreducedtheopportunitiesforeffectiveorthopedicreconstructive useofxenograftbone. Bonecageshavedemonstratedgreatpromiseforspinalfusion,buttheystillrequirea substantialamountofbonegraftmaterial,especiallyformultiple-levelfusion.Itistherefore likelythattheuseofbonecagesdoesnotdiminishthepotentialforseriouscomplications associatedwithharvestingautologousiliacbonegraft.Forthesereasons,researchershavedi- rectedtheirattentiontothesearchforsuitablesubstitutesforautograftandallograftbone.The endeavortotranscendthenumerousdrawbacksassociatedwithnaturalsourcesofbonetissue hasgivenrisetothedevelopmentandmanufactureofbonesubstitutesinvariousosteoinductive andosteoconductiveforms(Table1)[1,44]. Osteoconductiveagentsarecollagen,tricalciumphosphateceramics(TCP),hydroxyapa- tites(Ht),coral-derivedbiomaterials,mineralizedcollagenmatrix(Healos),someosteoactive polymers,andcalciumsulfate(plasterofParis;POP).Materialswithosteoinductiveproperties containoneormorefactorssuchasbonemorphogeneticproteins(BMPs).Whereasnumerous growthfactorsmaybeinvolvedinnewboneformation,includingplatelet-derivedgrowthfactor (PDGF),transforminggrowthfactor-␤(TGF-␤),andvascularendothelialgrowthfactor(VEGF),

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