Sohaib Z. Hashmi

Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis.

Peptide amphiphile (PA) nanofibers formed by self-assembly can be customized for specific applications in regenerative medicine through the use of molecules that display bioactive signals on their surfaces. Here, the use of PA nanofibers with binding affinity for the bone promoting growth factor BMP-2 to create a gel scaffold for osteogenesis is reported. With the objective of reducing the amount of BMP-2 used clinically for successful arthrodesis in the spine, amounts of growth factor incorporated in the scaffolds that are 10 to 100 times lower than that those used clinically in collagen scaffolds are used. The efficacy of the bioactive PA system to promote BMP-2-induced osteogenesis in vivo is investigated in a rat posterolateral lumbar intertransverse spinal fusion model. PA nanofiber gels displaying BMP-2-binding segments exhibit superior spinal fusion rates relative to controls, effectively decreasing the required therapeutic dose of BMP-2 by 10-fold. Interestingly, a 42% fusion rate is observed for gels containing the bioactive nanofibers without the use of exogenous BMP-2, suggesting the ability of the nanofiber to recruit endogenous growth factor. Results obtained here demonstrate that bioactive biomaterials with capacity to bind specific growth factors by design are great targets for regenerative medicine.

Sulfated glycopeptide nanostructures for multipotent protein activation

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with very different polysaccharide binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signaling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than expected. These super-bioactive nanostructures may enable many therapies in the horizon involving proteins.

Differences in bone mineral density of fixation points between lumbar cortical and traditional pedicle screws

BACKGROUND CONTEXT The use of a novel lumbar pedicle cortical bone trajectory (CBT) screw has recently gained popularity, allowing for a minimally invasive approach and potentially improved screw purchase. However, to date, no studies have identified the ideal patient population to utilize this technology. PURPOSE This study reports the bone mineral density (BMD) using Hounsfield units (HUs) along a CBT screw pathway. Patients with a greater difference in density of bone in the lumbar vertebrae between the fixation points of the CBT and traditional pedicle screw may be optimal candidates to realize the advantages of this technique. STUDY DESIGN/SETTING A cross-sectional observational anatomic study was carried out. PATIENT SAMPLE The sample comprised 180 randomly selected patients with lumbar computed tomography imaging from L1 to L5 spinal levels. OUTCOME MEASURES This study used computed tomography image-derived HUs as a metric for BMD. METHODS A total of 180 patients without previous lumbar surgery with computed tomography imaging of the lumbar spine met the inclusion criteria. Patients were chosen randomly from an institutional database based on age (evenly distributed by decade of life) and gender. Hounsfield units were measured at the expected end fixation point for both a cortical (superior/posterior portion of the vertebral body) and traditional pedicle trajectory (mid-vertebral body). RESULTS Hounsfield unit values measured at the end fixation point for the CBT screw were significantly greater than that of the traditional pedicle screw in all age groups. The relative difference in HU values significantly increased with each decade of age (p<.001) and caudal lumbar level (p<.001). In the osteoporotic group, as determined by well-established HU values, there was a significantly greater difference in the BMD of the CBT fixation point compared with the traditional trajectory (p=.048-<.001). CONCLUSIONS Bone mineral density as measured by HU values for the fixation point of the CBT screw is significantly greater than that of the traditional pedicle screw. This difference is even more pronounced when comparing osteoporotic and elderly patients to the general population. The data in this study suggest that the potential advantages from the CBT screw such as screw purchase may increase linearly with age and in osteoporotic patients.

Dioxin Exposure Impairs BMP-2-Mediated Spinal Fusion in a Rat Arthrodesis Model

BACKGROUND Cigarette smoking inhibits bone-healing and leads to increased rates of pseudarthrosis. However, the mechanisms behind these effects are controversial. Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin)--a cigarette smoke constituent and potent activator of the aryl hydrocarbon receptor (Ahr)--negatively impacts bone quality and osteoblast differentiation. We hypothesized that activation of the Ahr by dioxin would inhibit bone morphogenetic protein (BMP)-2-mediated spinal fusion in a rat arthrodesis model. METHODS Female Long-Evans rats were pretreated with dioxin or vehicle in six weekly doses, followed by bilateral posterior lumbar spinal fusion across the L4-L5 transverse processes using recombinant human BMP (rhBMP)-2. Treatments continued until sacrifice at four weeks postoperatively. A third group was treated with dioxin for six weeks, followed by a recovery period of four elimination half-lives to assess the reversible effects of dioxin exposure on spinal fusion capacity. Bone formation and fusion capacity were evaluated using fusion scoring, radiography, micro-computed tomography, and histologic analysis. RESULTS Fusion scores for dioxin-treated and dioxin-recovery rats were significantly lower than those for controls. Although fusion rates were also significantly reduced in dioxin-treated animals relative to controls (50% versus 100%, respectively), rates were not significantly reduced in dioxin-recovery animals (80%). CONCLUSIONS Dioxin treatment significantly inhibited spinal fusion in a rat arthrodesis model, and a prolonged cessation of dioxin exposure facilitated only a partial recovery of bone-healing capacity. This finding indicates that, although the effects of dioxin are persistent, an extended recovery from exposure could potentially restore bone regeneration in vivo. CLINICAL RELEVANCE Development of a pharmacologic agent that reduces the adverse effects of cigarette smoke on bone-healing could prove useful to orthopaedic surgeons. Since dioxin and other similar cigarette smoke toxins exert their effects through Ahr pathway activation, the receptor represents a potential therapeutic target to improve spinal fusion rates in patients who smoke.

Surgical Site Infections in Spinal Surgery.

Surgical site infections (SSIs) are a potentially devastating complication of spine surgery. SSIs are defined by the Centers for Disease Control and Prevention as occurring within 30 days of surgery or within 12 months of placement of foreign bodies, such as spinal instrumentation. SSIs are commonly categorized by the depth of surgical tissue involvement (ie, superficial, deep incisional, or organ and surrounding space). Postoperative infections result in increased costs and postoperative morbidity. Because continued research has improved the evaluation and management of spinal infections, spine surgeons must be aware of these modalities. The controversies in evaluation and management of SSIs in spine surgery will be reviewed.

Factors Associated with Financial Relationships between Spine Surgeons and Industry

Study Design. A retrospective review of Centers for Medicare and Medicaid Services Database. Objective. Utilizing Open Payments data, we aimed to determine the prevalence of industry payments to orthopedic and neurospine surgeons, report the magnitude of those relationships, and help outline the surgeon demographic factors associated with industry relationships. Summary of Background Data. Previous Open Payments data revealed that orthopedic surgeons receive the highest value of industry payments. No study has investigated the financial relationship between spine surgeons and industry using the most recent release of Open Payments data. Methods. A database of 5898 spine surgeons in the United States was derived from the Open Payments website. Demographic data were collected, including the type of residency training, years of experience, practice setting, type of medical degree, place of training, gender, and region of practice. Multivariate generalized linear mixed models were utilized to determine the relationship between demographics and industry payments. Results. A total of 5898 spine surgeons met inclusion criteria. About 91.6% of surgeons reported at least one financial relationship with industry. The median total value of payments was

Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2–Dependent Rat Posterolateral Arthrodesis Model

994.07. Surgeons receiving over

Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

1,000,000 from industry during the reporting period represented 6.6% of the database and accounted for 83.5% of the total value exchanged. Orthopedic training (P < 0.001), academic practice setting (P < 0.0001), male gender (P < 0.0001), and West or South region of practice (P < 0.0001) were associated with industry payments. Linear regression analysis revealed a strong inverse relationship between years of experience and number of payments from industry (r = -0.967, P < 0.0001). Conclusion. Financial relationships between spine surgeons and industry are highly prevalent. Surgeon demographics have a significant association with industry-surgeon financial relationships. Our reported value of payments did not include ownership or research payments and thus likely underestimates the magnitude of these financial relationships. Level of Evidence: 3

Patients With Thumb Carpometacarpal Arthritis Have Quantifiable Characteristic Expectations That Can Be Measured With a Survey.

Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 μg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro–computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats.

Primary Dural Repair in Minimally Invasive Spine Surgery

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30–90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP‐2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty‐six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre‐treated with vehicle control (Group A) or rhBMP‐2 (Group B) prior to implantation. At 4 weeks post‐implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post‐implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 103 p/s/cm2/sr (Group A) and 1.11 × 104 p/s/cm2/sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age‐matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP‐2 does not promote the growth of A549 lung cancer spine lesions.