In vivo Assessment of AMP2, a Novel Ceramic-Binding BMP-2, in Ovine Lumbar Interbody Fusion.

STUDY DESIGN: Assessment of bone formation in an ovine interbody fusion study. OBJECTIVE: To compare OsteoAdapt SP which consists of AMP-2, a modified variant of recombinant human bone morphogenetic protein (rhBMP-2) bound to a tricalcium phosphate-containing carrier, to autologous iliac crest bone graft (ICBG) in a lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Treatment of lumbar disc degeneration often involves spinal fusion to reduce pain and motion at the affected spinal segment by insertion of a cage containing bone graft material. Three graft materials were compared in this study - ICBG and OsteoAdapt SP (low or high dose). METHODS: Sheep underwent lateral lumbar fusion surgery with PEEK or Titanium interbody cages packed with OsteoAdapt SP (low or high dose) or ICBG. Outcomes were evaluated at 8-, 16- and 26- weeks. Newly formed bone quality, bone mineralization, and fusion were assessed by manual palpation, qualitative and semi-quantitative histopathology, histomorphometry, computed tomography (CT) and microCT (mCT) analysis. RESULTS: OsteoAdapt SP was implanted into 43 animals and ICBG into 21 animals (L3-L4). No group showed evidence of systemic toxicity by multiple assessments. All levels were fused by manual palpation at 26-weeks. Serial CT scans showed increasing fusion scores over time. Both doses of OsteoAdapt SP resulted in robust new bone formation and progression of fusion in the interbody cage. Range of motion tests for treatment groups were lower compared to ICBG at 8- and 16-weeks. Similarly, histology at 8-weeks demonstrated more robust new bone formation for both OsteoAdapt SP groups compared to autograft. CONCLUSION: We have demonstrated the preclinical safety and efficacy of OsteoAdapt SP in a clinically relevant large animal model; supporting faster and more robust new bone formation within the interbody cage, comparable to or better than the gold standard, ICBG, in all measures.

Characterization of an advanced bone graft material with a nanocrystalline hydroxycarbanoapatite surface and dual phase composition.

The bone formation response of ceramic bone graft materials can be improved by modifying the material's surface and composition. A unique dual-phase ceramic bone graft material with a nanocrystalline, hydroxycarbanoapatite (HCA) surface and a calcium carbonate core (TrelCor®-Biogennix, Irvine, CA) was characterized through a variety of analytical methods. Scanning electron microscopy (SEM) of the TrelCor surface (magnification 100-100,000X) clearly demonstrated a nanosized crystalline structure covering the entire surface. The surface morphology showed a hierarchical structure that included micron-sized spherulites fully covered by plate-like nanocrystals (<60 nm in thickness). Chemical and physical characterization of the material using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy Energy Dispersive X-ray Spectroscopy (SEM-EDX) showed a surface composed of HCA. Analysis of fractured samples confirmed the dual-phase composition with the presence of a calcium carbonate core and HCA surface. An in vitro bioactivity study was conducted to evaluate whether TrelCor would form a bioactive layer when immersed in simulated body fluid. This response was compared to a known bioactive material (45S5 bioactive glass - Bioglass). Following 14-days of immersion, surface and cross-sectional analysis via SEM-EDX showed that the TrelCor material elicited a bioactive response with the formation of a bioactive layer that was qualitatively thicker than the layer that formed on Bioglass. An in vivo sheep muscle pouch model was also conducted to evaluate the ability of the material to stimulate an ectopic, cellular bone formation response. Results were compared against Bioglass and a first-generation calcium phosphate ceramic that lacked a nanocrystalline surface. Histology and histomorphometric analysis (HMA) confirmed that the TrelCor nanocrystalline HCA surface stimulated a bone formation response in muscle (avg. 11% bone area) that was significantly greater than Bioglass (3%) and the smooth surface calcium phosphate ceramic (0%).

Implant Strength Contributes to the Osseointegration Strength of Porous Metallic Materials.

Creating the optimal environment for effective and long term osseointegration is a heavily researched and sought-after design criteria for orthopedic implants. A validated multimaterial finite element (FE) model was developed to replicate and understand the results of an experimental in vivo push-out osseointegration model. The FE model results closely predicted global force (at 0.5 mm) and stiffness for the 50-90% porous implants with an r2 of 0.97 and 0.98, respectively. In addition, the FE global force at 0.5 mm showed a correlation to the maximum experimental forces with an r2 of 0.90. The highest porosity implants (80-90%) showed lower stiffnesses and more equitable load sharing but also failed at lower a global force level than the low porosity implants (50-70%). The lower strength of the high porosity implants caused premature plastic deformation of the implant itself during loading as well as significant deformations in the ingrown and surrounding bone, resulting in lower overall osseointegration strength, consistent with experimental measurements. The lower porosity implants showed a balance of sufficient bony ingrowth to support osseointegration strength coupled with implant mechanical properties to circumvent significant implant plasticity and collapse under the loading conditions. Together, the experimental and finite element modeling results support an optimal porosity in the range of 60-70% for maximizing osseointegration with current structure and loading.

Porous Cage Macro-Topography Improves Early Fusion Rates in Anterior Cervical Discectomy and Fusion.

Objectives: Anterior cervical discectomy and fusion (ACDF) aims to improve pain, relieve neural compression, achieve rapid solid bony arthrodesis, and restore cervical alignment. Bony fusion occurs as early as 3 months and up to 24 months after ACDF. The correlations between bony fusion and clinical outcomes after ACDF remain unclear. Macro-topographic and porous features have been introduced to interbody cage technology, aiming to improve the strength of the bone-implant interface to promote early fusion. In this study, we aimed to compare clinical outcomes and CT-evaluated fusion rates in patients undergoing ACDF using one of two different interbody cages: traditional NanoMetalene™ (NM) cages and NM cages with machined porous features (NMRT). Methods: This was a prospective, observational, nonrandomised, cohort study of consecutive patients undergoing ACDF. The NM cage cohort was enrolled first, then the NMRT cohort second. The visual analogue scale, neck disability index, and 12-item Short Form Survey scores were evaluated preoperatively and at 6 weeks, 3 months, and 6 months. The minimum clinical follow-up period was 12 months. Plain radiographs were obtained on postoperative day 2 to assess instrumentation positioning, and computed tomography (CT) was performed at 3 and 6 months postoperatively to assess interbody fusion (Bridwell grade). Results: Eighty-nine (52% male) patients with a mean age of 62 ± 10.5 years were included in this study. Forty-one patients received NM cages, and 48 received NMRT cages. All clinical outcomes improved significantly from baseline to 6 months. By 3 months, the NMRT group had significantly higher CT fusion rates than the NM group (79% vs 56%, p=0.02). By 6 months, there were no significant differences in fusion rates between the NMRT and NM groups (83% vs 78%, p=0.69). The mean Bridwell grade at 6 months was 1.4 ± 0.7 in the NMRT group and 1.8 ± 1.0 in the NM group (p=0.08). Conclusions: With both NM and NMRT cages, serial improvements in postoperative clinical outcomes were associated with fusion progression on CT. NMRT cages demonstrated significantly better fusion at 3 months and a trend toward higher quality of fusion at 6 months compared with NM cages, suggesting earlier cage integration with NMRT. An early 3-month postoperative CT is adequate for fusion assessment in almost 80% of patients undergoing ACDF with an NMRT cage, permitting an earlier return to activity.

The influence of polyimide MP-1™ wear particles on a rodent closed fracture healing model.

Joint replacements provide pain free movement for the injured or our aging population. Current prothesis mainly consist of hard metal on metal, or ceramic femoral head on ultra-high-molecular weight polyethylene (UHMWPE). In this study, a rodent fracture model was used to test the influence of wear debris from a high-performance polymer (polyimide MP-1™). Saline, MP-1™ Low Dose in Saline (1%), or MP-1 High Dose (2%) in Saline was injected directly into a standard closed unilateral femoral fracture in 12-week old Sprague Dawley rats (n = 25) for 1, 3 and 6 weeks. Endpoints included radiography, micro-computed tomography, mechanical testing and paraffin histology. No adverse effects from the wear particles were observed from the current study based on radiology, mechanical or histological data. Although the particles were present, histological analysis revealed a progression in healing between the Polyimide treated groups and the non-treated saline control groups over the duration of 1, 3, and 6 weeks, with no inhibition from the particles. The MP-1™ wear debris generated are larger than 1 µm thus are not able to be engulfed by macrophages and cause osteolysis. This family of polymers (polyimides) may be an ideal material to consider for articulating joints and other implants in the human body.

Pedicle screw pull-out testing in polyurethane foam blocks: Effect of block orientation and density.

Synthetic bone models such as polyurethane (PU) foam are a well-established substitute to cadaveric bone for screw pull-out testing; however, little attention has been given to the effect of PU foam anisotropy on orthopaedic implant testing. Compressive and screw pull-out performance in three PU foam densities; 0.16 g/cm3 (PCF 10), 0.32 g/cm3 (PCF 20) and 0.64 g/cm3 (PCF 40) were performed in each of the X, Y or Z orientations. The maximum compressive force, stiffness in the linear region, maximum stress and modulus were determined for all compression tests. Pedicle screws were inserted and pulled out axially to determine maximum pull-out force, energy to failure and stiffness. One-way ANOVA and post hoc tests were used to compare outcome variables between PU foam densities and orientations, respectively. Compression tests demonstrated the maximum force was significantly different between all orientations for PCF 20 (X, Y and Z) while stiffness and maximum stress were different between X versus Y and X versus Z. Maximum pull-out force was significantly different between all orientations for PCF 10 foam. No significant differences were noted for other foam densities. There is potential for screw pull-out testing results to be significantly affected by orientation in lower density PU foams. It is recommended that a single, known orientation of the PU foam block be used for experimental testing.

Anterior cruciate ligament zoobiquity: Can man's best friend tell us we are being too cautious with the implementation of osteotomy to correct posterior tibial slope.

Anterior cruciate ligament (ACL) reconstruction (ACLR) is used to treat clinical instability post ACL rupture, however, there is a high rate of incomplete return to sport and rerupture. There is increasing interest in posterior tibial slope as an intrinsic risk factor for ACLR failure and persistent instability. Zoobiquity describes the collaboration between the human and veterinary professions in order to advance the scientific understanding of both fields. Given the cranial cruciate ligament (CCL) in dogs is synonymous with the anterior cruciate ligament in humans, functioning to control internal rotation and anterior translation, but osteotomies, rather than ligament reconstruction, are the mainstay of treatment for CCL rupture, this editorial sort to gain insights into this form of treatment from the veterinary world. Level of Evidence: Level V, evidence.

Lateral fenestration of lumbar intervertebral discs in rabbits: development and characterisation of an in vivo preclinical model with multi-modal endpoint analysis.

PURPOSE: To evaluate the biological and biomechanical effects of fenestration/microdiscectomy in an in vivo rabbit model, and in doing so, create a preclinical animal model of IVDD. METHODS: Lateral lumbar IVD fenestration was performed in vivo as single- (L3/4; n = 12) and multi-level (L2/3, L3/4, L4/5; n = 12) fenestration in skeletally mature 6-month-old New Zealand White rabbits. Radiographic, micro-CT, micro-MRI, non-destructive robotic range of motion, and histological evaluations were performed 6- and 12-weeks postoperatively. Independent t tests, one-way and two-way ANOVA and Kruskal-Wallis tests were used for parametric and nonparametric data, respectively. Statistical significance was set at P < 0.05. RESULTS: All rabbits recovered uneventfully from surgery and ambulated normally. Radiographs and micro-CT demonstrated marked reactive proliferative osseous changes and endplate sclerosis at fenestrated IVDs. Range of motion at the fenestrated disc space was significantly reduced compared to intact controls at 6- and 12-weeks postoperatively (P < 0.05). Mean disc height index percentage for fenestrated IVDs was significantly lower than adjacent, non-operated IVDs for both single and multi-level groups, at 6 and 12 weeks (P < 0.001). Pfirrmann MRI IVDD and histological grading scores were significantly higher for fenestrated IVDs compared to non-operated adjacent and age-matched control IVDs for single and multi-level groups at 6 and 12 weeks (P < 0.001). CONCLUSIONS: Fenestration, akin to microdiscectomy, demonstrated significant biological, and biomechanical effects in this in vivo rabbit model and warrants consideration by veterinary and human spine surgeons. This described model may be suitable for preclinical in vivo evaluation of therapeutic strategies for IVDD in veterinary and human patients.

Effect of gamma irradiation and supercritical carbon dioxide sterilization with Novakill™ or ethanol on the fracture toughness of cortical bone.

Sterilization of structural bone allografts is a critical process prior to their clinical use in large cortical bone defects. Gamma irradiation protocols are known to affect tissue integrity in a dose dependent manner. Alternative sterilization treatments, such as supercritical carbon dioxide (SCCO2 ), are gaining popularity due to advantages such as minimal exposure to denaturants, the lack of toxic residues, superior tissue penetration, and minor impacts on mechanical properties including strength and stiffness. The impact of SCCO2 on the fracture toughness of bone tissue, however, remains unknown. Here, we evaluate crack initiation and growth toughness after 2, 6, and 24 h SCCO2 -treatment using Novakill™ and ethanol as additives on ~11 samples per group obtained from a pair of femur diaphyses of a canine. All mechanical testing was performed at ambient air after 24 h soaking in Hanks' balanced salt solution (HBSS). Results show no statistically significant difference in the failure characteristics of the Novakill™-treated groups whereas crack growth toughness after 6 and 24 h of treatment with ethanol significantly increases by 37% (p = .010) and 34% (p = .038), respectively, compared to an untreated control group. In contrast, standard 25 kGy gamma irradiation causes significantly reduced crack growth resistance by 40% (p = .007) compared to untreated bone. FTIR vibrational spectroscopy, conducted after testing, reveals a consistent trend of statistically significant differences (p < .001) with fracture toughness. These trends align with variations in the ratios of enzymatic mature to immature crosslinks in the collagen structure, suggesting a potential association with fracture toughness. Additional Raman spectroscopy after testing shows a similar trend with statistically significant differences (p < .005), which further supports that collagen structural changes occur in the SCF-treated groups with ethanol after 6 and 24 h. Our work reveals the benefits of SCCO2 sterilization compared to gamma irradiation.