Early-term and mid-term histologic events during single-level posterolateral intertransverse process fusion with rhBMP-2/collagen carrier and a ceramic bulking agent in a nonhuman primate model: implications for bone graft preparation.

STUDY DESIGN: We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. OBJECTIVE: To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic bulking agents in 3 different configurations. SUMMARY OF BACKGROUND DATA: rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. METHODS: Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/ß-tricalcium phosphate ceramic bulking agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic bulking agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. RESULTS: Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. CONCLUSIONS: At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic bulking agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic bulking agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.

Impact of implant metal type and vancomycin prophylaxis on postoperative spine infection: an in-vivo study.

PURPOSE: To evaluate the effectiveness of vancomycin prophylaxis on spinal implant metal types. METHODS: 42 rabbits underwent posterior, single-level instrumentation at L5-L6 with stainless steel (n = 18), cobalt chrome (n = 12), or titanium (n = 12) wire. All implants were inoculated with 1 × 106 colony forming units (CFU) of methicillin-resistant S. Aureus (MRSA). In the intrawound vancomycin subgroup (n = 18, 6 from each metal type), 40 mg of vancomycin powder was placed in the wound. In the IV vancomycin subgroup (n = 6, all stainless steel), 15 mg/kg of IV vancomycin was given preoperatively. Local soft tissue and implants were harvested 1-week postoperatively and separately cultured. RESULTS: Intrawound vancomycin significantly reduced the rate of soft tissue infection (44.4% vs 100%) and implant infection (27.8% vs 100%) (p < 0.001). Within the intrawound vancomycin subgroup, cobalt chrome implants were associated with higher median soft tissue MRSA growth (130 CFU) than stainless steel (0 CFU) or titanium (0 CFU) (p = 0.02). Cobalt chrome implants were also more likely to develop soft tissue MRSA infection (83.3%) as compared to stainless steel (16.7%) or titanium (33.3%) (p = 0.04). Median soft tissue MRSA growth among stainless steel implants without prophylaxis, with IV vancomycin, and with vancomycin powder was 1.18 × 107, 195, and 0 CFU, respectively. The rate of soft tissue MRSA infection without prophylaxis, with IV vancomycin, and with vancomycin powder was 100, 66.7, and 16.7%, respectively (p = 0.015). CONCLUSION: Intrawound vancomycin is more effective than IV vancomycin and effectively reduces the risk of infection, but is less effective in cobalt chrome implants due to residual soft tissue infection.

Positive security screening episodes of patients with spinal implants are influenced by detector type and not implant material.

BACKGROUND CONTEXT: Previous research on rates of spinal detection showed a low frequency of patients (5%) experienced delays and additional screening going through airport security. With continuous technology advances in screenings and the rise in cobalt chrome implantation, updated data on patient experiences was needed. PURPOSE: 1) Assess the rates of detection and additional screening by traditional metal detectors and full body scanners in patients with metal spinal implants, 2) Compare the rates of detection of various metal types (Titanium and cobalt-chrome, titanium only, and stainless steel) STUDY DESIGN: Retrospective PATIENT SAMPLE: All spine surgical follow-ups over survey period. OUTCOME MEASURES: Self-reported open questionnaire; frequency of airport screening, patients' feelings and attitudes towards screening. METHODS: Patients were surveyed in the outpatient setting on exposure to metal detectors (Traditional and full-body scanners) after spinal surgery with metallic implants at a single institution. A total of 182 patients were identified and consented. The medical records were reviewed for details on implant material and location. RESULTS: Mean age at surgery was 53 years (range=12-88) with a mean 5.9 levels fused (range 2-20). Mean time from surgery to survey was 34 months (range=2-351) and number of airport screenings was 5.8 (range=0-54). The most common implants were titanium/cobalt-chrome (Ti/CoCr) (n=96, 53%) and titanium only (n=72, 40%). Overall, 40% of patients reported a detector alert at an airport requiring processing delay and additional screening: 86% from full body scanners, 54% from traditional metal detectors, and 41% of patients reporting both. Full body scanners were more likely to detect implants compared to traditional metal detectors (OR 5.1, p<.0001). No significant difference in number of screenings between patients who set off detectors and patients who did not (p=.185). Twenty percent of patients reported trouble at non-airport locations with detectors due to their spinal implants, with 70% of these patients reporting additional manual screenings. There was no correlation between levels spanned by the construct and number of times detected by traditional metal detectors or full body scanners, and no significant difference between levels spanned by constructs, or construct locations, in patients who set off detectors and those who did not. There was no significant difference between Ti/CoCr vs. titanium or other constructs in positive screenings. Subanalysis of fusions <5 levels demonstrated Ti/CoCr implants did not have an impact on positive screenings vs. other metal types (OR 0.88, p=.756). Interestingly, there was a significant difference in age and the positive screenings (p=.0025). Patients 60+ years of age had statistically significant greater positive screening than patients 0 to 40 years and 41 to 60 years. This data raises the possibility the presence of total joint arthroplasties (Mean age of patients with arthroplasty 65.5 years, range 50-88) likely play a significant role in the frequency of positive screenings. CONCLUSIONS: 40% of patients had their spinal implants detected at airports and 20% reported detections at other non-airport locations. Full body scanners detect spinal implants more frequently compared to traditional metal detectors (86% vs. 54% of detections, respectively). There was no difference in rate of airport and non-airport detection in patients with cobalt chrome implants compared to other materials. The presence of total joint arthroplasties likely has a significant contribution to the detector alerts.

Bioactive in situ crosslinkable polymer-peptide hydrogel for cell delivery to the intervertebral disc in a rat model.

Degeneration of the intervertebral disc (IVD) is associated with significant biochemical and morphological changes that include a loss of disc height, decreased water content and decreased cellularity. Cell delivery has been widely explored as a strategy to supplement the nucleus pulposus (NP) region of the degenerated IVD in both pre-clinical and clinical trials, using progenitor or primary cell sources. We previously demonstrated an ability for a polymer-peptide hydrogel, serving as a culture substrate, to promote adult NP cells to undergo a shift from a degenerative fibroblast-like state to a juvenile-like NP phenotype. In the current study, we evaluate the ability for this peptide-functionalized hydrogel to serve as a bioactive system for cell delivery, retention and preservation of a biosynthetic phenotype for primary IVD cells delivered to the rat caudal disc in an anular puncture degeneration model. Our data suggest that encapsulation of adult degenerative human NP cells in a stiff formulation of the hydrogel functionalized with laminin-mimetic peptides IKVAV and AG73 can promote cell viability and increased biosynthetic activity for this population in 3D culture in vitro. Delivery of the peptide-functionalized biomaterial with primary rat cells to the degenerated IVD supported NP cell retention and NP-specific protein expression in vivo, and promoted improved disc height index (DHI) values and endplate organization compared to untreated degenerated controls. The results of this study suggest the physical cues of this peptide-functionalized hydrogel can serve as a supportive carrier for cell delivery to the IVD. STATEMENT OF SIGNIFICANCE: Cell delivery into the degenerative intervertebral disc has been widely explored as a strategy to supplement the nucleus pulposus. The current work seeks to employ a biomaterial functionalized with laminin-mimetic peptides as a cell delivery scaffold in order to improve cell retention rates within the intradiscal space, while providing the delivered cells with biomimetic cues in order to promote phenotypic expression and increase biosynthetic activity. The use of the in situ crosslinkable material integrated with the native IVD, presenting a system with adequate physical properties to support a degenerative disc.

Prospective multicenter assessment of risk factors for rod fracture following surgery for adult spinal deformity.

OBJECT: Improved understanding of rod fracture (RF) following adult spinal deformity (ASD) surgery could prove valuable for surgical planning, patient counseling, and implant design. The objective of this study was to prospectively assess the rates of and risk factors for RF following surgery for ASD. METHODS: This was a prospective, multicenter, consecutive series. Inclusion criteria were ASD, age > 18 years, ≥5 levels posterior instrumented fusion, baseline full-length standing spine radiographs, and either development of RF or full-length standing spine radiographs obtained at least 1 year after surgery that demonstrated lack of RF. ASD was defined as presence of at least one of the following: coronal Cobb angle ≥20°, sagittal vertical axis (SVA) ≥5 cm, pelvic tilt (PT) ≥25°, and thoracic kyphosis ≥60°. RESULTS: Of 287 patients who otherwise met inclusion criteria, 200 (70%) either demonstrated RF or had radiographic imaging obtained at a minimum of 1 year after surgery showing lack of RF. The patients' mean age was 54.8 ± 15.8 years; 81% were women; 10% were smokers; the mean body mass index (BMI) was 27.1 ± 6.5; the mean number of levels fused was 12.0 ± 3.8; and 50 patients (25%) had a pedicle subtraction osteotomy (PSO). The rod material was cobalt chromium (CC) in 53%, stainless steel (SS), in 26%, or titanium alloy (TA) in 21% of cases; the rod diameters were 5.5 mm (in 68% of cases), 6.0 mm (in 13%), or 6.35 mm (in 19%). RF occurred in 18 cases (9.0%) at a mean of 14.7 months (range 3-27 months); patients without RF had a mean follow-up of 19 months (range 12-24 months). Patients with RF were older (62.3 vs 54.1 years, p = 0.036), had greater BMI (30.6 vs 26.7, p = 0.019), had greater baseline sagittal malalignment (SVA 11.8 vs 5.0 cm, p = 0.001; PT 29.1° vs 21.9°, p = 0.016; and pelvic incidence [PI]-lumbar lordosis [LL] mismatch 29.6° vs 12.0°, p = 0.002), and had greater sagittal alignment correction following surgery (SVA reduction by 9.6 vs 2.8 cm, p < 0.001; and PI-LL mismatch reduction by 26.3° vs 10.9°, p = 0.003). RF occurred in 22.0% of patients with PSO (10 of the 11 fractures occurred adjacent to the PSO level), with rates ranging from 10.0% to 31.6% across centers. CC rods were used in 68% of PSO cases, including all with RF. Smoking, levels fused, and rod diameter did not differ significantly between patients with and without RF (p > 0.05). In cases including a PSO, the rate of RF was significantly higher with CC rods than with TA or SS rods (33% vs 0%, p = 0.010). On multivariate analysis, only PSO was associated with RF (p = 0.001, OR 5.76, 95% CI 2.01-15.8). CONCLUSIONS: Rod fracture occurred in 9.0% of ASD patients and in 22.0% of PSO patients with a minimum of 1-year follow-up. With further follow-up these rates would likely be even higher. There was a substantial range in the rate of RF with PSO across centers, suggesting potential variations in technique that warrant future investigation. Due to higher rates of RF with PSO, alternative instrumentation strategies should be considered for these cases.

Importance of the peridural membrane in percutaneous vertebroplasty.

OBJECTIVE: The peridural membrane is a fibrous membrane that lies anterior to the posterior longitudinal ligament and attaches to its deep layer. It spans the width of the vertebral body and encircles the bony canal around the outside of the dura. The purpose of this study was to determine if the peridural membrane helps contain posterior cement leakage during percutaneous vertebroplasty. METHODS: Compression fractures were experimentally created in cadaveric spines. The bodies were stabilized using bipedicular injection of cement, and injection was continued until cement was evident beyond the posterior border of the vertebral body. The vertebral segments were then dissected and the extravasated cement localized anatomically. CONCLUSIONS: All extravasated cement was constrained by the peridural membrane, and no direct contact of the cement with the dura was seen.

The effects of BMP-7 in a rat posterolateral intertransverse process fusion model.

The use of autologous bone grafting is an essential component in spine fusion because it is the key factor in achieving long-term stable arthrodesis between spinal motion segments. However, harvesting autologous iliac crest bone graft can be associated with significant morbidity and its supply is limited. Although no current substitute for autologous graft is available, multiple studies have already established the success of bone morphogenetic proteins (BMPs) in augmenting spinal fusion in models using larger animals. The purpose of our study was to evaluate the ability of BMP to augment a posterolateral intertransverse process single-level fusion in a rat. To our knowledge, this model has not been used to evaluate the effects of recombinant BMPs. A posterolateral intertransverse process fusion was attempted in white male Sprague-Dawley rats. The following are the four study groups: insoluble collagen bone matrix (ICBM) alone, 3 microg BMP-7 + 25 mg ICBM, 10 microg BMP-7 + 25 mg ICBM, and a sham group with no implanted material. The animals were killed on postoperative day 21 and were evaluated for signs of clinical and/or radiographic fusion. All of the rats in the 10 microg BMP-7 + 25 mg ICBM group demonstrated clinical fusion and had solid bilateral fusion masses on radiographs. None of the rats in the sham group, ICBM group, or 3 microg BMP-7 + 25 mg ICBM group fused clinically; however, the rats in the 3 microg BMP-7 + 25 mg ICBM group did show evidence of new bone formation. Our study demonstrates that a rat posterolateral intertransverse process fusion model is inexpensive and efficient and produces consistent results. It also shows that BMP can augment fusion in a rat and that dosing plays a role in successful fusion. This is consistent with results that have been studied in larger animal models.