Abstract
BACKGROUND CONTEXTSynthetic bone graft substitutes are commonly used in spinal fusion surgery. Preclinical data in a model of spinal fusion to support their efficacy is an important component in clinical adoption to understand how these materials provide a biological and mechanical role in spinal fusion. PURPOSETo evaluate the in vivo response of a nanosynthetic silicated calcium phosphate putty (OstP) combined with autograft compared to autograft alone or a collagen-biphasic calcium phosphate putty (MasP) combined with autograft in a rabbit spinal fusion model. STUDY DESIGNEfficacy of a nanosynthetic silicated calcium phosphate putty as an extender to autograft was studied in an experimental animal model of posterolateral spinal fusion at 6, 9, 12 and 26 weeks, compared to a predicate device. METHODSSkeletally mature female New Zealand White rabbits (70) underwent single level bilateral posterolateral intertransverse process lumbar fusion, using either autograft alone (AG), a nanosynthetic silicated calcium phosphate putty (OstP) combined with autograft (1:1), or a collagen-biphasic calcium phosphate putty (MasP) combined with autograft (1:1). Iliac crest autograft was harvested for each group, and a total of 2 cc of graft material was implanted in the posterolateral gutters per side. Fusion success was assessed at all time points by manual palpation, radiographic assessment, micro-CT and at 12 weeks only using non-destructive range of motion testing. Tissue response, bone formation and graft resorption were assessed by decalcified paraffin histology and by histomorphometry of PMMA embedded sections. RESULTSAssessment of fusion by manual palpation at the 12 week endpoint showed 7 out of 8 (87.5%) bilateral fusions in the OstP extender group, 4 out of 8 (50%) fusions in the MasP extender group, and 6 out of 8 (75%) fusions in the autograft alone group. Similar trends were observed with fusion scores of radiographic and micro-CT data. Histology showed a normal healing response in all groups, and increased bone formation in the OstP extender group at all timepoints compared to the MasP extender group. New bone formed directly on the OstP granule surface within the fusion mass while this was not a feature of the Collagen-Biphasic CaP material. After 26 weeks the OstP extender group exhibited 100% fusions (5 out of 5) by all measures, whereas the MasP extender group resulted in bilateral fusions in 3 out of 5 (60%), assessed by manual palpation, and fusion of only 20 and 0% by radiograph and micro-CT scoring, respectively. Histology at 26 weeks showed consistent bridging of bone between the transverse processes in the Ost P extender group, but this was not observed in the MasP extender group. CONCLUSIONSThe nanosynthetic bone graft substituted studied here, used as an extender to autograft, showed a progression to fusion between 6 and 12 weeks that was similar to that observed with autograft alone, and showed excellent fusion outcomes, bone formation and graft resorption at 26 weeks. CLINICAL SIGNIFICANCEThis preclinical study showed that the novel nanosynthetic silicated CaP putty, when combined with autograft, achieved equivalent fusion outcomes to autograft. The development of synthetic bone grafts that demonstrate efficacy in such models can eliminate the need for excessive autograft harvest and results from this preclinical study supports their effective use in spinal fusion surgery.
Highlights
The past two decades has seen a significant number of new synthetic bone grafts products translated from concept to the clinic
Autograft bone harvested from the iliac crest has long been considered the gold standard bone graft, the complications from this additional procedure, most notably donor site pain [22,23], have motivated the search for alternatives
Considerable research has been carried out in the development of improved synthetic calcium phosphatebased bone grafts, which have progressed from the macroporous sintered ceramics of hydroxyapatite (HA), b-tricalcium phosphate (b-TCP) or biphasic calcium phosphate (BCP) that were the basis of many of the clinically used bone graft substitutes of the last 20 years. Examples of these advances include developing synthetic materials that have microstructures that are closer in size-scale to the mineral component of bone [24,25], have a sub-micron topography [3,5] or introduce larger quantities of microporosity [11], with these having the effect of increasing the surface area of the material
Summary
The past two decades has seen a significant number of new synthetic bone grafts products translated from concept to the clinic. These include the development of chemically modified calcium phosphates [11], incorporation of a submicron surface topography to the granules [1,3] and using nanoscale materials in manufacturing the bone graft [12] The efficacy of such materials is typically evaluated by comparison to autograft in a pre-clinical model of posterolateral spinal fusion [5,6,13,14,15], using the validated Boden model in rabbits that shows fusion rates with autograft that are similar to this in humans [16]. A recently published randomised clinical study compared a microporous synthetic bone graft substitute putty, comprising a biphasic composition of HA+TCP, in instrumented posterolateral fusion, compared to autograft [17] This level 1 study showed non-inferiority of the synthetic material to autograft, based on fusion rates after 12 months from 87 patients.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
