In order to stimulate new bone growth between two vertebral bodies, the surgeon must select an implant with adequate osteoconductive, osteoinductive, and/or osteogenic properties. Orthobiologic implants, such as bone grafts, stem cells, and proteins, possess some or all of these properties, and are used to create an environment favorable for new bone formation and successful fusion. Autologous bone Autologous grafts used in spine surgery are commonly derived from cancellous and non-vascularized cortical bone.
Study Design. Prospective, randomized, controlled preclinical study.Objective. The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model. Summary of Background Data. Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed. Methods. Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following implants: 1) type I absorbable collagen sponge (ACS) alone; 2) 10 mg rhBMP-2/ACS; or 3) the 3DP HA-DBM composite scaffold (n ¼ 20). The host inflammatory response was assessed using magnetic resonance imaging, while the local and circulating cytokine expression levels were evaluated by enzyme-linked immunosorbent assays at subsequent postoperative time points (N ¼ 5/time point). Results. At both 2 and 5 days postoperatively, treatment with the HA-DBM scaffold produced significantly less soft tissue edema at the fusion bed site relative to rhBMP-2-treated animals as quantified on magnetic resonance imaging. At every postoperative time point evaluated, the level of soft tissue edema in HA-DBM-treated animals was comparable to that of the ACS control group. At 2 days postoperatively, serum concentrations of tumor necrosis factor-a and macrophage chemoattractant protein-1 were significantly elevated in the rhBMP-2 treatment group relative to ACS controls, whereas these cytokines were not elevated in the HA-DBM-treated animals. Conclusion. The 3D-printed HA-DBM composite induces a significantly reduced host inflammatory response in a preclinical spinal fusion model relative to rhBMP-2.
Study Design. This was a preclinical study. Objective. Evaluate sex-dependent differences in the bone healing response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat posterolateral spinal fusion model. Summary of Background Data. Minimal and conflicting data exist concerning potential sex-dependent differences in rhBMP-2-mediated bone regeneration in the context of spinal fusion. Materials and Methods. Forty-eight female and male Sprague-Dawley rats (N=24/group), underwent L4–L5 posterolateral fusion with bilateral placement of an absorbable collagen sponge, each loaded with 5 µg of bone morphogenetic protein-2 (10 µg/animal). At eight weeks postoperative, 10 specimens of each sex were tested in flexion-extension with quantification of range of motion and stiffness. The remaining specimens were evaluated for new bone growth and successful fusion via radiography, blinded manual palpation and microcomputed tomography (microCT). Laboratory microCT quantified bone microarchitecture, and synchrotron microCT examined bone microstructure at the 1 µm level. Results. Manual palpation scores differed significantly between sexes, with mean fusion scores of 2.4±0.4 in females versus 3.1±0.6 in males (P<0.001). Biomechanical stiffness did not differ between sexes, but range of motion was significantly greater and more variable for females versus males (3.7±5.6° vs. 0.27±0.15°, P<0.005, respectively). Laboratory microCT showed significantly smaller volumes of fusion masses in females versus males (262±87 vs. 732±238 mm3, respectively, P<0.001) but significantly higher bone volume fraction (0.27±0.08 vs. 0.12±0.05, respectively, P<0.001). Mean trabecular thickness was not different, but trabecular number was significantly greater in females (3.1±0.5 vs. 1.5±0.4 mm−1, respectively, P<0.001). Synchrotron microCT showed fine bone structures developing in both sexes at the eight-week time point. Conclusions. This study demonstrates sex-dependent differences in bone regeneration induced by rhBMP-2. Further investigation is needed to uncover the extent of and mechanisms underlying these sex differences, particularly at different doses of rhBMP-2.
Introduction: Local steroid administration during anterior cervical spine surgery has been shown to improve postoperative dysphagia. However, concerns over potential complications remain. This study aims to evaluate the effect of local steroid administration on bone regeneration and spine fusion in a preclinical model, as well as the impact on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in a 3D culture system.Materials and methods: Forty-five rats underwent bilateral L4-L5 posterolateral lumbar fusion (PLF) utilizing local delivery of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2; 0.5 μg/implant). Rats were divided into three groups: no steroid (control), low dose (0.5 mg/kg), and high dose (2.5 mg/kg) of triamcinolone. Bone growth and fusion were assessed using radiography, blinded manual palpation, and micro-CT analysis and were visualized by histology. The impact of triamcinolone exposure on osteogenic differentiation of hBM-MSCs was evaluated by gene expression analysis, alkaline phosphatase activity assay, and alizarin red staining.Results: No significant differences in fusion scores or rates were seen in the low-or high-dose steroid treatment groups relative to untreated controls. Quantification of new bone formation via micro-CT imaging revealed no significant between-group differences in the volume of newly regenerated bone. Triamcinolone also had no negative impact on pro-osteogenic gene transcript levels, and ALP activity was enhanced in the presence of triamcinolone. Mineral deposition appeared comparable in cultures grown with and without triamcinolone.Conclusions: Local steroid application does not seem to inhibit rhBMP-2-mediated spine fusion in rats, though our study may not be adequately powered to detect differences in fusion as measured by manual palpation or bone volume as measured by Abhishek Kannan and Silvia Minardi contributed equally to this study.
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