Biologics in spine arthrodesis.

Spine fusion is a tool used in the treatment of spine trauma, tumors, and degenerative disorders. Poor outcomes related to failure of fusion, however, have directed the interests of practitioners and scientists to spinal biologics that may impact fusion at the cellular level. These biologics are used to achieve successful arthrodesis in the treatment of symptomatic deformity or instability. Historically, autologous bone grafting, including iliac crest bong graft harvesting, had represented the gold standard in spinal arthrodesis. However, due to concerns over potential harvest site complications, supply limitations, and associated morbidity, surgeons have turned to other bone graft options known for their osteogenic, osteoinductive, and/or osteoconductive properties. Current bone graft selection includes autograft, allograft, demineralized bone matrix, ceramics, mesenchymal stem cells, and recombinant human bone morphogenetic protein. Each pose their respective advantages and disadvantages and are the focus of ongoing research investigating the safety and efficacy of their use in the setting of spinal fusion. Rh-BMP2 has been plagued by issues of widespread off-label use, controversial indications, and a wide range of adverse effects. The risks associated with high concentrations of exogenous growth factors have led to investigational efforts into nanotechnology and its application in spinal arthrodesis through the binding of endogenous growth factors. Bone graft selection remains critical to successful fusion and favorable patient outcomes, and orthopaedic surgeons must be educated on the utility and limitations of various biologics in the setting of spine arthrodesis.

A supramolecular polymer-collagen microparticle slurry for bone regeneration with minimal growth factor.

Recombinant bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive growth factor that can promote bone regeneration for challenging skeletal repair and even for ectopic bone formation in spinal fusion procedures. However, serious clinical side effects related to supraphysiological dosing highlight the need for advances in novel biomaterials that can significantly reduce the amount of this biologic. Novel biomaterials could not only reduce clinical side effects but also expand the indications for use of BMP-2, while at the same time lowering the cost of such procedures. To achieve this objective, we have developed a slurry containing a known supramolecular polymer that potentiates BMP-2 signaling and porous collagen microparticles. This slurry exhibits a paste-like consistency that stiffens into an elastic gel upon implantation making it ideal for minimally invasive procedures. We carried out in vivo evaluation of the novel biomaterial in the rabbit posterolateral spine fusion model, and discovered efficacy at unprecedented ultra-low BMP-2 doses (5 µg/implant). This dose reduces the growth factor requirement by more than 100-fold relative to current clinical products. This observation is significant given that spinal fusion involves ectopic bone formation and the rabbit model is known to be predictive of human efficacy. We expect the novel biomaterial can expand BMP-2 indications for difficult cases requiring large volumes of bone formation or involving patients with underlying conditions that compromise bone regeneration.

Arthroscopic Single-Portal Suprapectoral Biceps Tenodesis With All-Suture Anchor.

Tenodesis of the long head of the biceps tendon can be performed through arthroscopic and open techniques with various fixation methods and at different locations on the humerus. Many techniques have been described, with controversy surrounding the advantages and disadvantages of each. In this Technical Note, we describe an all-arthroscopic, intra-articular, single-portal, suprapectoral biceps tenodesis with an all-suture anchor. This technique also allows for suture passage through the biceps tendon before tenotomy to ensure proper maintenance of the length-tension relationship of the biceps musculotendinous unit.

Capsule Closure of Periportal Capsulotomy for Hip Arthroscopy.

Multiple approaches for management of the hip capsule during hip arthroscopy for femoroacetabular impingement syndrome have been reported. Capsular closure is advocated in the setting of larger capsulotomies, including interportal and T-capsulotomies, to reduce the risk of iatrogenic instability or microinstability of the hip. The periportal capsulotomy technique has been described for conservative management of the capsule that would not necessitate closure. However, hip arthroscopy for patients with ligamentous laxity or joint hypermobility may warrant capsule closure or plication even with use of conservative capsulotomy techniques. We introduce a technique for closure of periportal capsulotomy as a means to repair or plicate the hip capsule in the at-risk hypermobile patient.

Postless Tape Augmentation for Anterior Cruciate Ligament (ACL) Reconstruction.

Suture or tape augmentation for anterior cruciate ligament (ACL) reconstruction has been described as a technique to increase biomechanical strength and potentially improve clinical outcomes. However, the suture or tape used for augmentation usually requires independent tibial fixation from the ACL graft in the form of an anchor or post. This may introduce the potential for graft and augment tension mismatch, while increasing surgical cost. We present our technique for ACL reconstruction with postless tape augmentation. The ACL graft and tape are fixed at the same tension with interference fixation using a single tibial sheath and screw construct, which allows for ACL augmentation without the need for an additional post or implant.

Lateral T-Capsulotomy with Hip Arthroscopy for Access and Excision of Posterior Intra-Articular Mass.

There is a lack of literature regarding arthroscopic access to the posterior peripheral compartment of the hip. Compared with open surgery, arthroscopy offers less-invasive treatment for intra-articular mass excision. Arthroscopic hip mass excision has focused on selective resection of lesions in the central compartment and anterior peripheral compartment due to difficult and previously undescribed posterior access. We introduce a technique for arthroscopic excision of a posterior intra-articular hip mass consistent with pigmented villonodular synovitis, also known as tenosynovial giant cell tumor, using a modified T-capsulotomy based on the lateral aspect of the hip capsule. This modified capsulotomy allows for more posterior and lateral access to the central and peripheral compartments while minimizing violation of the iliofemoral ligament.

Correlating Biomechanical Gait Analysis With Patient-Reported Outcomes After Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

Background: Postoperative biomechanics after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) are an outcome of interest, but correlation with patient-reported outcomes (PROs) remains unclear. Purpose/Hypothesis: The purpose of this study was to assess the correlation between changes in hip biomechanics in FAIS patients after hip arthroscopy and changes in PRO scores. We hypothesized that gait analysis would demonstrate significant correlations between pre- and postoperative changes in biomechanics and changes in PRO scores. Study Design: Descriptive laboratory study. Methods: FAIS patients without dysplasia or arthritis who underwent primary hip arthroscopy for labral repair and femoroplasty underwent preoperative and 1-year postoperative 3-dimensional motion tracking and biomechanical testing during normal gait. Joint kinematics calculated included flexion/extension (sagittal plane), abduction/adduction (frontal plane), and internal/external rotation (transverse plane). Peak hip angles and moments were compared between baseline and 1-year postoperative measures. At baseline, 1-year, and 2-year postoperatively, patients completed the following PRO surveys: 12-Item Short Form Health Survey (SF-12), modified Harris Hip Score (mHHS), and Hip disability and Osteoarthritis Outcome Score (HOOS). Joint kinematics that significantly improved 1 year after surgery were assessed for correlations with PRO scores. Results: A total of 10 patients (12 hips) were enrolled prospectively. PROs significantly improved at 1 and 2 years postoperatively compared with baseline values for HOOS, mHHS, and SF-12 Physical Component Score, with all patients achieving the minimal clinically important difference (MCID) on the HOOS Sport/Recreation and Quality of Life subscales. From preoperatively to 1-year postoperatively, significant improvements were seen in peak hip abduction angle (from -2.3° ± 1.8° to -4.6° ± 1.8°; P = .0058) and peak hip extension moment (from -1.03 ± 0.19 to -0.85 ± 0.20 N·m/kg; P = .014); however, there were no significant correlations between these changes and the pre- to postoperative changes on any PRO scores. Conclusion: Gait analysis of FAIS patients after hip arthroscopy demonstrated small, albeit significant, changes in postoperative hip kinetics and kinematics; however, these changes did not correlate with the large, clinically significant improvements in PROs at 1 year after surgery. Clinical Relevance: The results of this study suggest that the degree of improvement in short-term PROs after hip arthroscopy for FAIS may not be related to small changes in biomechanics postoperatively.

The effect of local steroid application on bony fusion in a rat posterolateral spinal arthrodesis model.

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 micro-CT. These findings suggest that local triamcinolone may not increase pseudarthrosis in spine fusion procedures. Further large animal and clinical studies to verify its safety and efficacy are warranted.

Burden of Sciatica on US Medicare Recipients.

OBJECTIVE: This study evaluates the disease burden of sciatica on the US Medicare cohort. BACKGROUND DATA: Sciatica is a common disability that has important physical, mental, and economic effects. The Medicare Health Outcomes Survey (HOS) is a demographic and outcomes survey used to monitor the performance of Medicare Advantage health plans in the United States. The HOS includes data on demographics, chronic medical conditions, and patient-reported outcomes. METHODS: Medicare HOS data for cohorts from 2007 to 2013 were obtained. Patients were placed into two categories based on the survey results: with or without a history of sciatica. Baseline demographics, chronic medical conditions, and physical health symptoms were aggregated. In addition, average VR-12 physical component summary and mental component summary scores were calculated for each group at baseline and at 2-year follow-up. A Fisher exact test was used to assess significance for categorical variables, and a t-test was used for continuous variables. VR-12 changes as small as 1 to 2 units have been found to be clinically and socially relevant. RESULTS: The baseline cohort data of 1,000,952 patients yielded 250,869 patients (25%) who reported the diagnosis of sciatica, compared with 750,083 patients (75%) without sciatica. Patients with a history of sciatica tended to be younger, less educated, and notably with more medical comorbidities. Physical component summary outcomes were approximately 8 units lower in the sciatica group at baseline and 7 units lower at 2-year follow-up. Mental component summary outcomes were 6 units lower in the sciatica group at baseline and 5 units lower at 2-year follow-up. CONCLUSION: A large percentage of the US Medicare cohort suffers from symptomatic sciatica. Our study identified a 25% prevalence in the Medicare cohort. In addition, sciatica is associated with an increased incidence of comorbid medical conditions and poor health-related quality of life. LEVEL OF EVIDENCE: Level III STUDY DESIGN:: Observational-Cohort Study.

Risk Factors for Prolonged Postoperative Opioid Use After Spine Surgery: A Review of Dispensation Trends From a State-run Prescription Monitoring Program.

INTRODUCTION: Opioid abuse and dependence have a detrimental effect on elective orthopaedic surgeries, yet pain control is an important predictor of postoperative satisfaction. We aimed at better defining risk factors for prolonged postoperative opioid requirements and risk factors for patients requiring higher doses of opioids after spine surgery. METHODS: The Illinois Prescription Monitoring Program was queried to analyze opioid dispensation patterns at 3 and 6 months postoperatively for adult patients who had spine surgery at a tertiary care hospital by a single surgeon over a 5-year period. Patients were divided into three groups: group 1 patients had opioid dispensed to them 3 and 6 months preoperatively, group 2 patients had opioid dispensed to them only at 3 months preoperatively, and group 3 patients did not have preoperative opioid prescriptions. Demographic characteristics, psychiatric history, smoking status, alcohol use, body mass index, surgical region, and presence of multiple prescribers were abstracted. Statistical analysis included multivariate modified Poisson regression, linear regression, and chi-squared testing when appropriate. RESULTS: Patients in group 1 were at significantly increased risk of continued opioid usage than those in group 2 (relative risk, 3.934; 95% confidence interval, 1.691 to 9.150; P = 0.0015) and those in group 3 (relative risk, 4.004; 95% confidence interval, 1.712 to 9.365; P = 0.0014) at 6 months postoperatively. Group 1 patients also had larger quantities of opioid dispensed to them relative to patients in group 2 or group 3 (P < 0.0001) at 6 months postoperatively. DISCUSSION: Use of opioid medications at 6 months preoperatively is a risk factor for continued usage and at higher doses 6 months postoperatively. LEVEL OF EVIDENCE: Level III: retrospective cohort study.

Intra-Articular Vancomycin Powder Eliminates Methicillin-Resistant S. aureus in a Rat Model of a Contaminated Intra-Articular Implant.

BACKGROUND: Periprosthetic joint infection following hip and knee arthroplasty leads to poor outcomes and exorbitant costs. Topical vancomycin powder has been shown to decrease infection in many procedures such as spine surgery. The role of vancomycin powder in the setting of total joint arthroplasty remains undefined. Our aim was to evaluate the efficacy of intra-articular vancomycin powder in preventing infection in a rat model of a contaminated intra-articular implant. METHODS: Thirty-two female Sprague-Dawley rats underwent knee arthrotomy and implantation of a femoral intramedullary wire with 1 mm of intra-articular communication. The knee joint was also inoculated with 1.5 × 10 colony forming units (CFU)/mL of methicillin-resistant Staphylococcus aureus (MRSA). Four treatment groups were studied: (1) no antibiotics (control), (2) preoperative systemic vancomycin, (3) intra-articular vancomycin powder, and (4) both systemic vancomycin and intra-articular vancomycin powder. The animals were killed on postoperative day 6, and distal femoral bone, joint capsule, and the implanted wire were harvested for bacteriologic analysis. Statistical analyses were performed using Wilcoxon rank sum and Fisher exact tests. RESULTS: There were no postoperative deaths, wound complications, signs of vancomycin-related toxicity, or signs of systemic illness in any of the treatment groups. There were significantly fewer positive cultures in the group that received vancomycin powder in combination with systemic vancomycin compared with the group that received systemic vancomycin alone (bone: 0% versus 75% of 8, p = 0.007; Kirschner wire: 0% versus 63% of 8, p = 0.026; whole animal: 0% versus 88% of 8, p = 0.01). Only animals that received both vancomycin powder and systemic vancomycin showed evidence of complete elimination of bacterial contamination. CONCLUSIONS: In a rat model of a contaminated intra-articular implant, use of intra-articular vancomycin powder in combination with systemic vancomycin completely eliminated MRSA bacterial contamination. Animals treated with systemic vancomycin alone had persistent MRSA contamination. CLINICAL RELEVANCE: This animal study presents data suggesting that the use of intra-articular vancomycin powder for reducing the risk of periprosthetic joint infections should be investigated further in clinical studies.

Mechanistic insight into the effects of Aryl Hydrocarbon Receptor activation on osteogenic differentiation.

While inhibition of bone healing and increased rates of pseudarthrosis are known adverse outcomes associated with cigarette smoking, the underlying mechanisms by which this occurs are not well understood. Recent work has implicated the Aryl Hydrocarbon Receptor (Ahr) as one mediator of the anti-osteogenic effects of cigarette smoke (CS), which contains numerous toxic ligands for the Ahr. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a high-affinity Ahr ligand frequently used to evaluate Ahr pathway activation. The purpose of this study was to elucidate the downstream mechanisms of dioxin action on bone regeneration and investigate Ahr antagonism as a potential therapeutic approach to mitigate the effects of dioxin on bone. Markers of osteogenic activity and differentiation were assessed in primary rat bone marrow stromal cells (BMSC) after exposure to dioxin, Ahr antagonists, or antagonist + dioxin. Four Ahr antagonists were evaluated: α-Naphthoflavone (ANF), resveratrol (Res), 3,3'-Diindolylmethane (DIM), and luteolin (Lut). Our results demonstrate that dioxin inhibited ALP activity, migratory capacity, and matrix mineralization, whereas co-treatment with each of the antagonists mitigated these effects. Dioxin also inhibited BMSC chemotaxis, while co-treatment with several antagonists partially rescued this effect. RNA and protein expression studies found that dioxin down-regulated numerous pro-osteogenic targets, whereas co-treatment with Ahr antagonists prevented these dioxin-induced expression changes to varying degrees. Our results suggest that dioxin adversely affects bone regeneration in a myriad of ways, many of which appear to be mediated by the Ahr. Our work suggests that the Ahr should be investigated as a therapeutic target to combat the adverse effects of CS on bone healing.

Epidemiology and Outcomes of Vertebral Artery Injury in 16 582 Cervical Spine Surgery Patients: An AOSpine North America Multicenter Study.

STUDY DESIGN: A multicenter retrospective case series was compiled involving 21 medical institutions. Inclusion criteria included patients who underwent cervical spine surgery between 2005 and 2011 and who sustained a vertebral artery injury (VAI). OBJECTIVE: To report the frequency, risk factors, outcomes, and management goals of VAI in patients who have undergone cervical spine surgery. METHODS: Patients were evaluated on the basis of condition-specific functional status using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) score, the Nurick scale, and the 36-Item Short-Form Health Survey (SF-36). RESULTS: VAIs were identified in a total of 14 of 16 582 patients screened (8.4 per 10 000). The mean age of patients with VAI was 59 years (±10) with a female predominance (78.6%). Patient diagnoses included myelopathy, radiculopathy, cervical instability, and metastatic disease. VAI was associated with substantial blood loss (770 mL), although only 3 cases required transfusion. Of the 14 cases, 7 occurred with an anterior-only approach, 3 cases with posterior-only approach, and 4 during circumferential approach. Fifty percent of cases of VAI with available preoperative imaging revealed anomalous vessel anatomy during postoperative review. Average length of hospital stay was 10 days (±8). Notably, 13 of the 14 (92.86%) cases resolved without residual deficits. Compared to preoperative baseline NDI, Nurick, mJOA, and SF-36 scores for these patients, there were no observed changes after surgery (P = .20-.94). CONCLUSIONS: Vertebral artery injuries are potentially catastrophic complications that can be sustained from anterior or posterior cervical spine approaches. The data from this study suggest that with proper steps to ensure hemostasis, patients recover function at a high rate and do not exhibit residual deficits.

The effect of vancomycin powder on bone healing in a rat spinal rhBMP-2 model.

OBJECTIVE This study aims to quantify the impact of vancomycin powder application on new bone formation and spine fusion rates in a rat posterolateral arthrodesis model. METHODS Thirty-six female Sprague-Dawley rats underwent a posterolateral lumbar spinal fusion (PLF) at the L-4 and L-5 vertebrae. Fusion was elicited via implantation of an absorbable collagen sponge containing 3 µg rhBMP-2. Rats were divided into 3 groups: no vancomycin (control), standard-dose vancomycin, and high-dose vancomycin, based on what was applied to the fusion bed. Clinical studies typically describe the application of 1 g vancomycin into the surgical wound. Presuming an average individual patient weight of 70 kg, a weight-based equivalent dose of vancomycin powder was applied subfascially in the PLF model constituting a "standard-dose" treatment group (14.3 mg/kg, n = 12). To determine whether there is a critical threshold beyond which vancomycin increases the risk of pseudarthrosis, a 10-fold higher dose was administered to a "high-dose" treatment group (143 mg/kg, n = 12). No vancomycin powder was applied to the surgical site in the control group (n = 12). Fusion was evaluated with plain radiographs at 4 and 8 weeks after surgery. The spines were harvested after the 8-week radiographs were obtained and evaluated using manual palpation, microCT analysis, and histological analysis. RESULTS Radiographs demonstrated equivalent bridging bone formation in all groups. No significant differences in fusion scores were seen in the standard-dose (mean 2.25) or high-dose (2.13) treatment groups relative to untreated control animals (1.78). Similarly, fusion rates did not differ significantly different between vancomycin-treated animals (100% for both groups) and control animals (92%). Quantification of new bone formation via microCT imaging revealed no significant between-groups differences in the volume of newly regenerated bone (control vs standard-dose vancomycin, p = 0.57; control vs high-dose vancomycin, p = 0.53). CONCLUSIONS This is the first in vivo study to specifically address the development of pseudarthrosis after intrawound application of vancomycin during fusion surgery. Our results demonstrate that vancomycin powder does not inhibit fusion rates at a dose that is the weight-percentage equivalent of what is routinely used by surgeons. Moreover, bone formation and fusion rates were not reduced even after administration of a vancomycin dose that is 10-fold higher than that which is typically administered clinically. Our findings suggest that if there is a critical threshold above which vancomycin inhibits bone healing, such a dose is out of the range which might be considered reasonable for clinical use.

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

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.

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

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 × 10(3) p/s/cm(2) /sr (Group A) and 1.11 × 10(4) p/s/cm(2) /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. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016.

Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial.

Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic-co-glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm(3)/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.

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.