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We are developing ovine models of spinal cord injury to test novel neuromodulation-based methods on spasticity. The hemisection has been reported in a number of large animal studies. Our aim is to duplicate a hemisection injury in the sheep. Our effort is explored here. Methods and Results: Three sheep underwent hemi-sectioning of the spinal cord. Quantitative gait analysis was completed both pre- and post-injury. While measurable differences in most of the 20 gait metrics were observed, relatively few were above the predicted thresholds based on error levels expected from the data. Variations in severity of injury across the three sheep were observed. Conclusions: The hemisection ovine model of spinal cord injury shows promise as a large-animal platform for developing new therapies for treating spinal cord injuries. While variability in injury severity was observed across animals, as has been observed with weight drop-based SCI models, the hemi-section approach has the advantages of procedural ease and reduced technical complexity. [ABSTRACT FROM AUTHOR]

Introduction: Translating basic science research into a safe and effective therapy for spinal cord injury (SCI) requires suitable large animal models for testing both implantable devices and biologic approaches to better approximate human anatomy and function. Hemisection lesions, routinely used for investigational purposes in small animals, are less frequently described in large animals that might be appropriate for translational studies. Size constraints of small animals (mice and rats) limits the predictability of the findings when scaled up. Our goal is to review the status of hemisection SCI in large animals across species and time to prepare for the testing of a novel intradural spinal cord stimulation device for control of spasticity in an ovine model. Methods and Results: We surveyed the literature on hemisection in quadrupeds and nonhuman primates, and catalogued the species, protocols and outcomes of the experimental work in this field. Feline, lapine, canine, simian, porcine, ovine and bovine models were the primary focal points. There is a consistent body of literature reporting use of the hemisection approach in large animals, but with differences in surgical technique depending on the goals and nature of the individual studies. While the injuries are not always consistent, the experimental variability is generally lower than that of the contusion-based approach. In general, as the body size of the animal increases, animal care requirements and the associated costs follow. In most cases, this is inversely correlated with the number of animals used in hemisection models. Conclusions: The hemisection approach to modeling SCI is straightforward compared with other methods such as the contusive impact and enables the transection of isolated ascending and descending tracts and segment specific cell bodies. This has certain advantages in models investigating post-injury axonal regrowth. However, this approach is not generally in line with the patho-physiologies encountered in SCI patients. Even so, the ability to achieve more control over the level of injury makes it a useful adjunct to contusive and ischemic approaches, and suggests a useful role in future translational studies. [ABSTRACT FROM AUTHOR]

Background: Calcium phosphate materials have been employed clinically as bone void fillers for several decades. These materials are most often provided in the form of small, porous granules that can be packed to fill the wide variety of size and shape of bony defects encountered. ReBOSSIS-85 (RB-85) is a synthetic bioresorbable bone void filler for the repair of bone defects with handling characteristics of glass wool-like (or cotton ball-like). The objective of this study is to evaluate the in vivo performance of RB-85 (test material), compared to a commercially available bone void filler, Mastergraft Putty (predicate material), when combined with bone marrow aspirate and iliac crest autograft, in an established posterolateral spine fusion rabbit model., Methods: One hundred fifty skeletally mature rabbits had a single level posterolateral fusion performed. Rabbits were implanted with iliac crest bone graft (ICBG), Mastergraft Putty™ plus ICBG, or one of 4 masses of ReBOSSIS-85 (0.2, 0.3, 0.45, or 0.6 g) plus ICBG. Plain films were taken weekly until euthanasia. Following euthanasia at 4, 8, and 12 weeks, the lumbar spine were tested by manual palpation. Spinal columns in the 12 week group were also subjected to non-destructive flexibility testing. MicroCT and histology were performed on a subset of each implant group at each euthanasia period., Results: Radiographic scoring of the fusion sites indicated a normal healing response in all test groups. Bilateral radiographic fusion rates for all test groups were 0% at 4 weeks; ICBG 43%, Mastergraft Putty 50%, RB-85-0.2g 0%, RB-85-0.3g 13%, RB-85-0.45g 38%, and RB-85-0.6g 63% at 8 weeks; and ICBG 50%, Mastergraft Putty 50%, RB-85-0.2g 0%, RB-85-0.3g 25%, RB-85-0.45g 36%, and RB-85-0.6g 50% at 12 weeks.Spine fusion was assessed by manual palpation of the treated motion segments. At 12 weeks, ICBG, MGP, and RB-85-0.6g were fused mechanically in at least 50% of the rabbits. All groups demonstrated significantly less range of motion in both flexion/extension, lateral bending, and axial rotation compared to normal unfused controls.Histopathology analysis of the fusion masses, in all test groups, indicated an expected normal response of mild inflammation with macrophage and multinucleated giant cell response to the graft material at 4 weeks and resolving by 12 weeks. Regardless of test article, new bone formation and graft resorption increased from 4 to 12 weeks post-op., Conclusions: This animal study has demonstrated the biocompatibility and normal healing features associated with the ReBOSSIS-85 bone graft (test material) when combined with autograft as an extender. ReBOSSIS-85 was more effective when a larger mass of test article was used in this study., Clinical Relevance: ReBOSSIS-85 can be used as an extender negating the need for large amounts of local or iliac crest bone in posterolateral fusions., Competing Interests: Disclosures: The authors report no potential conflicts of interest related to this study., (Copyright © The Iowa Orthopaedic Journal 2019.)

Introduction: Spinal fusion surgery is an effective but costly treatment for select spinal pathology. Historically iliac crest bone graft (ICBG) has remained the gold standard for achieving successful arthrodesis. Given well-established morbidity autograft harvest, multiple bone graft replacements, void fillers, and extenders have been developed. The objective of this study was to evaluate the in vivo efficacy and safety of two mineralized collagen bone void filler materials similar in composition. Both bone void fillers were composed of hydroxyapatite (HA), tricalcium phosphate (TCP) and bovine collagen. The first test article (Bi-Ostetic bioactive glass foam or "45S5") also contained 45S5 bioactive glass particles while the second test article (Formagraft or "FG") did not. 45S5 and FG were combined with bone marrow aspirate and iliac crest autograft and compared to ICBG in an established posterolateral spine fusion rabbit model., Materials and Methods: Sixty-nine mature New Zealand White rabbits were divided into 3 test cohorts: ICBG, 45S5, and FG. A Posterolateral fusion model previous validated was utilized to assess fusion efficacy. The test groups were evaluated for spine fusion rate, new bone formation, graft resorption and inflammatory response using radiographic, μCT, biomechanical and histological endpoints at 4, 8 and 12 weeks following implantation., Results: There were 4 clinical complications unrelated to the graft materials and were evenly split between groups (ICBG graft harvest complications; hind limb mobility, chronic pain) and were euthanized. These omissions did not affect the overall outcome of the study. Radiographic scoring of the fusion sites indicated a normal healing response in all test groups, with no adverse reactions and similar progressions of new bone formation observed over time. All groups demonstrated significantly less range of motion in both flexion/extension and lateral bending compared to normal not-fused controls, which supports fusion results observed in the other endpoints. Fusion occurred earlier in the 45S5 group: ICBG 0%, FG 0%, and 45S5 20% at 4 weeks; ICBG 43%, FG 38%, and 45S5 50% at 8 weeks; and ICBG 50%, FG 56%, and 45S5 56% at 12 weeks. Histopathology analysis of the fusion masses, from each test article and time point, indicated an expected normal response for resorbable calcium phosphate (HA/TCP) and collagen graft material. Mild inflammation with macrophage and multinucleated giant cell response to the graft material was evident in all test groups., Discussion: This study has confirmed the biocompatibility, safety, efficacy and bone healing characteristics of the HA-TCP collagen (with or without 45S5 bioactive glass) composites. The results show that the 3 test groups had equivalent long-term fusion performance and outcome at 12 weeks. However, the presence of 45S5 bioactive glass seemed to accelerate the fusion process as evidenced by the higher fusion rates at 4 and 8 weeks for the HA-TCP-collagen composite containing bioactive glass particles. The results also demonstrate that the HA-TCP-45S5 bioactive glass-collagen composite used as an extender closely mirrors the healing characteristics (i.e. amount and quality of bone) of the 100% autograft group., Competing Interests: The authors declare no relevant conflicts of interest.