Autograft Extender Research Articles

Efficacy of a synthetic calcium phosphate with submicron surface topography as autograft extender in lapine posterolateral spinal fusion.

Posterolateral spinal fusion (PLF) is a common procedure in orthopedic surgery that is performed to fuse adjacent vertebrae to reduce symptoms related to spinal conditions. In the current study, a novel synthetic calcium phosphate with submicron surface topography was evaluated as an autograft extender in a validated rabbit model of PLF. Fifty‐nine skeletally mature New Zealand white rabbits were divided into three groups and underwent single‐level intertransverse process PLF at L4‐5 using (1) autologous bone graft (ABG) alone or in a 1:1 combination with (2) calcium phosphate granules (ABG/BCPgranules), or (3) granules embedded in a fast‐resorbing polymeric carrier (ABG/BCPputty). After 6, 9, and 12 weeks, animals were sacrificed and spinal fusion was assessed by manual palpation, Radiographs, micro‐CT, mechanical testing (12 weeks only), histology, and histomorphometry. Based on all endpoints, all groups showed a gradual progression in bone formation and maturation during time, leading to solid fusion masses between the transverse processes after 12 weeks. Fusion assessments by manual palpation, radiography and histology were consistent and demonstrated equivalent fusion rates between groups, with high bilateral fusion rates after 12 weeks. Mechanical tests after 12 weeks indicated substantially lower range of motion for all groups, compared to non‐operated controls. By histology and histomorphometry, the gradual formation and maturation of bone in the fusion mass was confirmed for each graft type. With these results, we describe the equivalent performance between autograft and a novel calcium phosphate material as an autograft extender in a rabbit model of PLF using an extensive range of evaluation techniques. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2080–2090, 2019.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters

BACKGROUND CONTEXT Posterolateral lumbar arthrodesis by autologous bone graft is a commonly performed procedure for the treatment of degenerative spine conditions. However, because autograft is associated with considerable disadvantages (eg, donor-site morbidity), alternative technologies are under investigation. Calcium phosphates (CaP) with submicron-scale surface topography have attracted attention due to their excellent performance in regeneration of bone defects. PURPOSE Evaluating the efficacy of a biphasic calcium phosphate (BCP) ceramic with a novel surface topography of submicron-scale epitaxial polygon crystals as autograft extender in the “Boden” rabbit posterolateral spine fusion model. STUDY DESIGN/SETTING BCP granules with the submicron-scale surface topography, either alone or combined with a fast-resorbing polymer binder, were mixed with autologous bone at a volume ratio of 50%:50%. Subsequently, grafts were implanted in the rabbit posterolateral spine environment with autologous bone graft as reference treatment, after which outcomes were assessed after 6, 9 and 12 weeks. PATIENT SAMPLE N/A. OUTCOME MEASURES Spinal fusion was determined by manual palpation (MP), X-ray and micro CT scan (based on the Lenke scale), mechanical testing (range of motion testing at 12 weeks only) and histology (decalcified and undecalcified). METHODS Sixty skeletally mature New Zealand white rabbits were divided into three groups and underwent single-level bilateral posterolateral intertransverse process spine arthrodesis at L4-5. Animals were euthanized 0, 6, 9 and 12 weeks for analysis of outcomes. RESULTS Based on all endpoints, the three groups showed an equivalent and gradual progression in bone formation and implant resorption during time leading to mature fusion masses at 12 weeks. No adverse reactions were observed in any of the groups. Bilateral fusion rates by MP were consistent with the literature (0%–20% at 6 weeks, 60% at 9 weeks, 75% at 12 weeks) and similar trends were seen by radiographic assessment (both X-ray and uCT). Flexion–extension and lateral bending results at 12 weeks demonstrated fusion of the treated level consistent with the MP results. By histology, from 6 weeks onwards, bone formation was observed on and between the BCP granules and within the residual autograft particles. At 9 and 12 weeks, progressive bone formation with developing marrow spaces was observed in all groups. Gradual resorption of BCP granules was evident with resorbing multinucleated or osteoclastic cells on the material surface and a decrease in material proportion over time. Histological fusion, ie, continuous bone formation between the transverse processes, for the three groups ranged 0%–20% at 6 weeks to 20%–40% at 9 weeks and 75%–87.5% at 12 weeks. CONCLUSIONS These results show that BCP with submicron-scale surface topography could achieve equivalent fusion rates to ABG when used as graft extender in a single level rabbit intertransverse process posterolateral lumbar arthrodesis model. During time, a progression in bone healing, graft resorption and remodeling was seen with all experimental endpoints, with consistency between the groups.

Efficacy of silicate-substituted calcium phosphate with enhanced strut porosity as a standalone bone graft substitute and autograft extender in an ovine distal femoral critical defect model.

A synthetic bone graft substitute consisting of silicate-substituted calcium phosphate with increased strut porosity (SiCaP EP) was evaluated in an ovine distal femoral critical sized metaphyseal defect as a standalone bone graft, as an autologous iliac crest bone graft (ICBG) extender (SiCaP EP/ICBG), and when mixed with bone marrow aspirate (SiCaP EP/BMA). Defects were evaluated after 4, 8, and 12 weeks with radiography, decalcified paraffin-embedded histopathology, non-decalcified resin-embedded histomorphometry, and mechanical indentation testing. All test groups exhibited excellent biocompatibility and osseous healing as evidenced by an initial mild inflammatory response followed by neovascularization, bone growth, and marrow infiltration throughout all SiCaP EP-treated defects. SiCaP EP/ICBG produced more bone at early time points, while all groups produced similar amounts of bone at later time points. SiCaP EP/ICBG likewise showed more favorable mechanical properties at early time points, but was equivalent to SiCaP EP and SiCaP EP/BMA at later time points. This study demonstrates that SiCaP EP is efficacious as a standalone bone graft substitute, mixed with BMA, and as an autograft extender.

Hybrid Biosynthetic Autograft Extender for Use in Posterior Lumbar Interbody Fusion: Safety and Clinical Effectiveness

Autologous iliac crest bone graft is the preferred option for spinal fusion, but the morbidity associated with bone harvest and the need for graft augmentation in more demanding cases necessitates combining local bone with bone substitutes. The purpose of this study was to document the clinical effectiveness and safety of a novel hybrid biosynthetic scaffold material consisting of poly(D,L-lactide-co-glycolide) (PLGA, 75:25) combined by lyophilization with unmodified high molecular weight hyaluronic acid (10-12% wt:wt) as an extender for a broad range of spinal fusion procedures. We retrospectively evaluated all patients undergoing single- and multi-level posterior lumbar interbody fusion at an academic medical center over a 3-year period. A total of 108 patients underwent 109 procedures (245 individual vertebral levels). Patient-related outcomes included pain measured on a Visual Analog Scale. Radiographic outcomes were assessed at 6 weeks, 3-6 months, and 1 year postoperatively. Radiographic fusion or progression of fusion was documented in 221 of 236 index levels (93.6%) at a mean (±SD) time to fusion of 10.2+4.1 months. Single and multi-level fusions were not associated with significantly different success rates. Mean pain scores (+SD) for all patients improved from 6.8+2.5 at baseline to 3.6+2.9 at approximately 12 months. Improvements in VAS were greatest in patients undergoing one- or two-level fusion, with patients undergoing multi-level fusion demonstrating lesser but still statistically significant improvements. Overall, stable fusion was observed in 64.8% of vertebral levels; partial fusion was demonstrated in 28.8% of vertebral levels. Only 15 of 236 levels (6.4%) were non-fused at final follow-up

Hybrid Biosynthetic Autograft Extender for Use in Posterior Lumbar Interbody Fusion: Safety and Clinical Effectiveness

Hybrid Biosynthetic Autograft Extender for Use in Posterior Lumbar Interbody Fusion: Safety and Clinical Effectiveness

Assessment of MASTERGRAFT PUTTY as a Graft Extender in a Rabbit Posterolateral Fusion Model

Randomized, controlled study in a laboratory setting. Blinded observations/assessment of study outcomes. The purpose of this study was to determine the performance characteristics of MASTERGRAFT PUTTY as a bone graft extender in a rabbit posterolateral spine fusion model. The rabbit posterolateral fusion model is an established environment for testing of fusion concepts. It offers the opportunity to obtain radiographical, histological, and biomechanical data on novel fusion materials. Thirty-six rabbits were entered into the study with 30 used for analysis. Bilateral posterolateral lumbar intertransverse fusions were performed at L5-L6. The lateral two-thirds of the transverse processes were decorticated and covered with graft material: autograft only (2.5-3.0 cc per side), 25% MASTERGRAFT PUTTY/75% autograft (3.0 cc total per side), or 50% MASTERGRAFT PUTTY and 50% autograft (3.0 cc total per side). Animals were humanely killed at 8 weeks postsurgery. The autograft group had a 63% radiographical fusion rate (5 of 8) and correlated with manual palpation results (63%). The 25% MASTERGRAFT PUTTY group had a 73% radiographical fusion rate (8 of 11) and a manual palpation fusion rate of 64%. The 50% MASTERGRAFT PUTTY group demonstrated a 91% (10 of 11) radiographical fusion rate and 73% manual palpation fusion rate. Histologically, no inflammatory reactions were evident regardless of implant. The 2 MASTERGRAFT PUTTY groups had new bone in direct apposition to the MASTERGRAFT ceramic granules. In this commonly used rabbit posterolateral fusion model, MASTERGRAFT PUTTY in an autograft extender mode produces clinically and radiographically similar results to autograft fusion alone.

Application of Resorbable Poly(Lactide-co-Glycolide) with Entangled Hyaluronic Acid as an Autograft Extender for Posterolateral Intertransverse Lumbar Fusion in Rabbits

Facilitating fusion between bony segments in a reliable and reproducible manner using a synthetic bone graft material has a number of benefits for the surgeon as well as the patient. Although autograft remains the gold standard, associated comorbidities continue to drive the development of new biomaterials for use in spinal fusion. The ability of autograft alone and autograft combined with a radiolucent biomaterial composed of resorbable osteoconductive poly(lactide-co-glycolide) with entangled hyaluronic acid to facilitate fusion was examined in a single-level noninstrumented posterolateral intertransverse lumbar fusion model in New Zealand White rabbits. Progressive bone formation was demonstrated radiographically for the extender group (synthetic biomaterial plus autograft) between 3 and 6 months. Computed tomography revealed a new cortical shell in the fusion mass at 3 and 6 months for both study groups. Tensile testing at 6 months demonstrated that the quality of bone formed between the intertransverse space was equivalent for both study groups. Histologic evaluation of the fusion mass revealed new bone on and adjacent to the transverse processes with the synthetic biomaterial group that extended laterally, supporting the osteoconductive nature of the material. Histological evidence of endochondral bone growth in the intertransverse space was observed for the autograft plus synthetic biomaterial group. Bone remodeling, new marrow spaces, and peripheral cortices were observed for each study group at 3 months that matured by 6 months. These findings support the use of a radiolucent biosynthetic material comprising poly(lactide-co-glycolide) with integrated hyaluronic acid as an autograft extender for lumbar intertransverse fusion.

Effect of bioabsorbable calcified triglyceride on spinal fusion in a rodent model

Autogenous bone grafting has traditionally been considered the “gold standard” for spinal fusion. However, the associated morbidity and limitations of autogenous bone grafts have prompted the search for bone graft alternatives, such as a bioabsorbable-calcified triglyceride (BCT). We aimed to assess the capability of BCT in a rat spinal fusion model. Thirty-six Sprague-Dawley rats underwent lumbar fusion surgery: Group 1 rats were implanted with an autograft from the iliac crest; Group 2 rats were implanted with BCT; and Group 3 rats were implanted with BCT and autograft. In Group 2, 66.7% of rats and in Group 3, 83.3% of rats, were judged to have undergone complete fusion. Only 25% of rats in Group 1 showed bridging bone from the transverse processes with some gaps. Our study demonstrated that osteoconductive BCT is a promising autograft extender when applied as an adjunct to spinal fusion.

A poly(propylene glycol-co-fumaric acid) based bone graft extender for lumbar spinal fusion: in vivo assessment in a rabbit model

An animal model of posterolateral intertransverse process lumbar spinal fusion compared fusion rates amongst autologous bone (group 1), a porous, bioabsorbable, scaffold based on the biopolymer, poly(propylene glycol-co-fumaric acid) (PPF) (group 2), and a combination of autograft and the bioabsorbable scaffold (group 3). To evaluate the feasibility of augmenting spinal fusion with an osteoconductive and bioabsorbable scaffold as an alternative or as an adjunct, i.e., an extender, to autograft. There is little preclinical data on applications of bioabsorable bone graft extenders in spinal fusion. New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were treated with one of three materials: autologous bone (group 1), a bioabsorable material based on PPF (group 2), and the PPF biopolymer scaffold with autologous bone graft (group 3). Animals were evaluated at 6 weeks, and fusion was evaluated by manual palpation, and radiographic, histologic, and histomorphometric analyses. Radiographic and manual palpation showed evidence of fusion in all three groups. Histomorphometric measurement of bone ingrowth showed the highest quantity of new bone in group 3 (91%), followed by group 1 (72%) and group 2 (53%). Results of this study suggested that osteoconductive bioabsorbable scaffolds prepared from PPF might be used as an autograft extender when applied as an adjunct to spinal fusion.

Tissue Engineering Designs for the Future: New Logics, Old Molecules

Tissue Engineering Designs for the Future: New Logics, Old Molecules

Experimental posterolateral lumbar spinal fusion with a demineralized bone matrix gel.

A controlled rabbit model of lumbar posterolateral intertransverse process arthrodesis was used to evaluate a bone graft substitute. To determine the efficacy of demineralized bone matrix gel as an autograft extender, using different ratios of demineralized bone matrix to autograft and to determine the efficacy of demineralized bone matrix as an autogenous bone graft enhancer by adding it to the usual quantity of autograft. Autogenous bone is considered the most effective bone graft material for posterolateral lumbar arthrodesis, yet nonunions occur in up to 30% of patients. In addition, donor site complications may occur in 25-30% of patients. This has prompted the search for and investigation of bone graft extenders, enhancers, and substitutes. Commercially available demineralized bone matrix gel is one possible graft extender and enhancer, which, unlike mineralized allografts, has osteoinductive properties. Although the gel is in common use, the efficacy of demineralized bone matrix when used for posterolateral spine arthrodesis has not been examined in prospective clinical studies. Furthermore, no known animal studies have tested demineralized bone matrix gel in a posterolateral arthrodesis model. Forty-seven New Zealand white rabbits underwent bilateral posterolateral spine arthrodesis at L5-L6 using autogenous iliac crest bone graft alone or in combination with demineralized bone matrix. Four groups were formed on the basis of the ratio of autograft to demineralized bone matrix: autograft alone (3 mL), 100:0 group; autograft (3 mL) and demineralized bone matrix (1.5 mL), 100:50 group; autograft (1.5 mL) and demineralized bone matrix (1.5 mL), 50:50 group; and autograft (0.75 mL) and demineralized bone matrix (2.25 mL), 25:75 group. Rabbits were killed 6 weeks after surgery. Inspection, manual palpation, radiographic film, and histologic evaluation were used to assess fusion. All groups had similar fusion rates (66-73%) based on manual palpation. Rabbits implanted with demineralized bone matrix had more mature fusion masses, evidenced by the greater trabecular bone formation seen on radiographic film and histologic study. Demineralized bone matrix was effective as a graft extender when used in up to a 3:1 ratio with autograft in a rabbit posterolateral spine fusion model. When less than the standard volume of autograft was used, the addition of demineralized bone matrix gel lead to fusion success rates comparable to those of the standard amount of autograft alone. However, demineralized bone matrix did not increase the frequency of successful fusion when added to the standard amount of autograft.

Demineralized bone matrix. Enhancement of spinal fusion.

A study was conducted to determine the ability of demineralized bone matrix gel to act as an osteoconductive/osteoinductive material to enhance canine spinal fusion. Seven dogs underwent posterior spinal fusion. Four-level fusions were performed with one of four procedures at each level: decortication alone, with gel added, with autograft, or with both gel and autograft. Dogs were killed at 6 weeks and early histologic response was studied. At untreated control sites, little bone formation was evident. Gel-filled sites showed abundant osteoid, with 60% of demineralized particles fused to or surrounded by new bone. Sites filled with autograft had more new bone, but there was more osteoid at gel-treated sites. Autograft augmented with gel showed the most vigorous response, with extensive bridging between demineralized particles, host bone, autograft, and new bone. Significantly less autograft was needed to induce a similar amount of new bone formation when gel was added. Use of the gel as an autograft extender may improve the chance for successful spinal fusion.