Intervertebral disc and stem cells cocultured in biomimetic extracellular matrix stimulated by cyclic compression in perfusion bioreactor.

BACKGROUND CONTEXT: Intervertebral disc (IVD) degeneration often causes back pain. Current treatments for disc degeneration, including both surgical and nonsurgical approaches, tend to compromise the disc movement and cannot fully restore functions of the IVD. Instead, cell-based IVD tissue engineering seems promising as an ultimate therapy for IVD degeneration. PURPOSE: To tissue-engineer an IVD ex vivo as a biological substitute to replace degenerative IVD. STUDY DESIGN: An extracellular matrix (ECM) structure-mimetic scaffold, cocultured human IVD cells and human mesenchymal stem cells (hMSCs), and mechanical stimulation were used to biofabricate a tissue-engineered IVD. METHODS: An optimal ratio of human annulus fibrosus (hAF) cells to hMSCs for AF generation within aligned nanofibers, and that of human nucleus pulposus (hNP) cells to hMSCs for NP generation within hydrogels were first determined after comparing different coculture ratios of hAF or hNP cells to hMSCs. Nanofibrous strips seeded with cocultured hAF cells/hMSCs were constructed into multilayer concentric rings, enclosing an inner core of hydrogel seeded with hNP cells/hMSCs. A piece of nonwoven nanofibrous mat seeded with hMSC-derived osteoblasts was assembled on the top of the cellular nanofiber/hydrogel assembly, as an interface layer between the cartilagenous end plate and vertebral body. The final assembled construct was then maintained in an osteochondral cocktail medium and stimulated with compressive loading to further enhance the hAF and hNP cells differentiation and increase the IVD ECM production. RESULTS: Among all cocultured groups, hAF cells and hMSCs in the ratio of 2:1 cultured in nanofibers showed the closest mRNA expression levels of AF-related markers to positive control hAF cells, whereas hNP cells and hMSCs in the ratio of 1:2 cultured in hydrogels showed the closest expression levels of NP-related markers to positive control hNP cells. The effects of compressive loading on chondrogenesis of hAF or hNP cell and hMSC coculture were dependent on the scaffold structure; the expression of cartilage-related markers in AF nanofibers was downregulated, whereas that in NP hydrogel was upregulated. Interestingly, we found that hMSC-derived osteogenic cells in the interface layer were turned into chondrogenic lineage cells, with decreased expression of osteogenic markers and increased expression of chondrogenic markers. CONCLUSIONS: We demonstrate a unique approach using a biomimetic scaffold, IVD and stem cell coculture, and mechanical stimulation to tissue-engineer a biological IVD substitute. The results show that our approach provides both favorable physical and chemical cues through cell-matrix and cell-cell interactions and mechanobiological induction to enhance IVD generation ex vivo. Our findings may lead to viable tissue engineering applications of generating a functional biological IVD for the treatment of disc degeneration.

Epidural anesthesia as a novel anesthetic technique for anterior lumbar interbody fusion.

STUDY OBJECTIVE: To determine if epidural anesthesia is a reasonable technique for anterior lumbar interbody fusion. DESIGN: Retrospective chart review. SETTING: Academic university hospital. MEASUREMENTS: The charts of patients who underwent an anterior lumbar interbody fusion between January 1, 2001 and November 1, 2008 were reviewed. A total of 102 consecutive patients, of whom 19 received an epidural and 83 underwent general anesthesia, met inclusion criteria. Postoperative pain, nausea, opioid administration, operating room time, anesthesia time, Postanesthesia Care Unit (PACU) time, and total hospital time were compared. MAIN RESULTS: In the PACU, patients receiving epidural anesthesia showed reductions in median immediate [numerical rating scale (NRS) 0 vs 7; P < 0.001] and peak (NRS 4 vs 8; P = 0.001) postoperative pain scores, and postoperative mean arterial pressure (69.7 vs 90.3; P < 0.001). Epidural anesthesia patients also needed significantly less intravenous morphine-equivalent medication both intraoperatively (5 vs 29; P < 0.001) and postoperatively (3.34 vs 10; P = 0.021). CONCLUSIONS: Epidural anesthesia for anterior lumbar interbody fusion is potentially beneficial compared with general anesthesia, showing improved perioperative pain control.

Comparison of perioperative oral multimodal analgesia versus IV PCA for spine surgery.

STUDY DESIGN: A preintervention and postintervention design was used to examine a total of 200 patients. OBJECTIVE: After successful implementation at our institution of a perioperative oral multimodal analgesia protocol in major joint arthroplasty, a modified regimen was provided to patients undergoing spine procedures. SUMMARY OF BACKGROUND DATA: A proactive, multimodal approach is currently recommended for the management of acute postoperative pain. Inadequate postoperative analgesia can negatively influence surgical outcome and duration of rehabilitation. Routine use of intravenous patient controlled analgesia (IV PCA) after surgery can result in substantial functional interference, side effects, and lead to untoward events as a result of programming errors. METHODS: A preintervention and postintervention design was used to compare a historical control group of spine surgery patients who received conventional IV PCA (N=100) with a prospective group who received some form of perioperative oral multimodal analgesia (N=100). The new regimen included preoperative and postoperative scheduled extended-release oxycodone, gabapentin, and acetaminophen, intraoperative dolasetron and as-needed postoperative short-acting oral oxycodone. Patient surveys and chart audits were used to measure pain intensity, functional interference from pain, opioid consumption, analgesic-related side effects, and patient satisfaction over the first 24 hours postoperatively. RESULTS: Patients who received the new perioperative multimodal oral regimen had significantly less opioid consumption (P<0.001), lower ratings of Least Pain (P<0.01), and experienced less nausea (P<.001), drowsiness (P<0.05), interference with walking (P=0.05), and coughing and deep breathing (P<0.05) compared with the IV PCA group. CONCLUSIONS: This quality improvement study shows some safety and significant advantages of a multimodal perioperative oral analgesic regimen compared with standard IV PCA after spine surgery.

Use of patella allograft for anterior cervical diskectomy and fusion.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study is to determine the fusion rates of a consecutive series of anterior cervical decompressions and fusions with allograft patella using both static and dynamic plates. SUMMARY OF BACKGROUND DATA: Anterior cervical diskectomy and fusion (ACDF) has been shown to improve symptoms of radiculopathy and myelopathy. The gold standard for obtaining fusion is using autogenous iliac crest bone graft (ICBG). The complication rate of using ICBG can be as high as 20%. To minimize this morbidity, various forms of allograft are presently used. We have used patellar allograft that we hypothesize exhibits a good combination of strength and sufficient porosity to facilitate fusion. METHODS: A consecutive series of 179 levels in 136 patients who underwent single and multilevel ACDF with allograft patella were retrospectively investigated. Final follow-up lateral cervical spine radiographs were evaluated for evidence of bony fusion. Fusions were graded independently by 2 of the investigators according to an interbody fusion classification proposed by Bridwell and colleagues, Spine, 1995. Fusion rates were compared with historical controls for single-level ACDF with autogenous ICBG and plating. Multivariate analysis was used to evaluate plate type, smoking, revision rate, and Odom's criteria compared with fusion. RESULTS: Ninety-one consecutive single and 81 multilevel anterior cervical decompression and fusions with allograft patella were reviewed. Demographics were similar (average age 47.75 y). Average follow-up was 19.3 months. Fusion rates were 86% (159/179). Our revision rate was 8%. Eighty-one percent (85/98) union rate was noted in the single-level group, and 85% (69/81 levels) or 74% (28/38 patients) in the multilevel group. CONCLUSIONS: Fusion rates were 86%. Plate design (static vs. dynamic) did not seem to affect fusion rates or clinical outcomes. There was a higher nonunion rate at the most inferior level of the multilevel fusions. Nonunions in the dynamic group were more commonly revised and had more kyphosis at final follow-up.

Six-year outcomes of anterior lumbar interbody arthrodesis with use of interbody fusion cages and recombinant human bone morphogenetic protein-2.

BACKGROUND: Twenty-four-month outcomes have been reported for patients with degenerative lumbar disc disease who were treated with stand-alone anterior lumbar interbody arthrodesis with use of dual tapered interbody fusion cages and recombinant human bone morphogenetic protein-2. This report represents an update of the clinical and radiographic results of this treatment at six years. METHODS: Two hundred and seventy-seven patients with single-level degenerative disc disease with up to grade-I spondylolisthesis were enrolled in two prospective, multicenter, U.S. Food and Drug Administration-approved investigational device exemption studies and were treated with an open or a laparoscopic surgical procedure. The patients received recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge with lumbar fusion cage implants. One hundred and forty-six patients completed the six-year clinical follow-up evaluations, and 130 patients had complete radiographic follow-up at six years. Outcomes were determined with use of well-established clinical outcome measurements (Oswestry Disability Index, Short Form-36, and back and leg pain scores) and radiographic assessments. RESULTS: At six years, 128 (98%) of the 130 patients treated with recombinant human bone morphogenetic protein-2 and stand-alone fusion cages had a fusion. The second surgery rate was 6.7% (eighteen patients) prior to two years and 3.7% (seven patients) from two to six years. A worst-case scenario analysis, which includes all second surgical procedures due to pseudarthrosis, resulted in a fusion rate at seventy-two months of 91% (128 of 141). Significant improvements in the Oswestry Disability Index scores, Short Form-36 health survey physical component summary scores, and back and leg pain scores were achieved by six weeks in both the open and laparoscopic groups and were sustained at six years (p < 0.001). The percentage of patients who were working at six months (63%) was higher than the percentage who had been working preoperatively (52%), and this improvement was sustained at six years (68%). CONCLUSIONS: The use of dual tapered threaded fusion cages and recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge obtained and maintained intervertebral spinal fusion, improved clinical outcomes, and reduced pain after anterior lumbar interbody arthrodesis in patients with degenerative lumbar disc disease.

Emergency evaluation, imaging, and classification of thoracolumbar injuries.

Thoracolumbar injuries usually are the result of high-energy trauma and frequently are associated with multisystem concomitant injuries. Whenever a thoracolumbar injury is suspected, a prompt and thorough evaluation should be performed in the emergency department, using the guidelines of the American College of Surgeons and including full primary and secondary surveys as well as resuscitation. Protection of the spine and spinal cord is of paramount importance during the initial evaluation. A careful and complete neurologic examination is warranted as part of the secondary survey. Plain radiography, CT, and MRI studies are useful in diagnosing and classifying thoracolumbar injuries. At many trauma centers, CT has become the standard imaging technology for the initial evaluation of the spine. MRI is particularly accurate in detecting injury to the posterior ligamentous complex of the thoracolumbar spine. Classification and treatment of thoracolumbar injuries are controversial. The comprehensive, reproducible classification system of the Spine Trauma Study Group has prognostic significance and can guide treatment decisions. The Thoracolumbar Injury Classification and Severity scale classifies thoracolumbar injures based on three pivotal characteristics: the morphology of the injury, the integrity of the posterior ligamentous complex, and the patient's neurologic status. A total severity score is used in conjunction with the classification system to determine the treatment.

Nonsurgical treatment of thoracolumbar spinal fractures.

The transitional anatomy of the thoracolumbar spine makes it vulnerable to injury from high-energy vehicular crashes and falls. The definitive management of patients with thoracolumbar spinal fractures is dependent on the presence and extent of neurologic injury, the presence and magnitude of acute deformity, and an estimate concerning spinal stability. It is well established that neurologic deficits generally improve without surgery. Nonsurgical treatment leads to decreased pain and improved function. Although there is a dearth of high-quality studies comparing surgical with nonsurgical treatment, the natural course of thoracolumbar fractures usually is benign, and nonsurgical methods should be the standard treatment with few exceptions.

Surgical treatment of thoracolumbar fractures.

Surgical management of a thoracolumbar fracture varies according to many factors. Fracture morphology, neurologic status, and surgeon preference play major roles in deciding on an anterior, a posterior, or a combined approach. The goal is to optimize neural decompression while providing stable internal fixation over the least number of spinal segments. Short-segment constructs through a single-stage approach (anterior or posterior) have become viable options with advances in instrumentation and techniques. Unstable burst fractures can be treated with anterior-only fixation using a strut graft and a modern thoracolumbar plating system or with a posterior-only construct using pedicle screws and possibly hooks. A circumferential construct is considered for extremely unstable injuries.

Sacral fractures.

Sacral fractures are a treatment challenge for the orthopaedic surgeon. The relative rarity of sacral fractures limits physician exposure to these injuries and has resulted in questions regarding their optimal treatment. Proper diagnosis and classification also are subjects of considerable debate. Studies of sacral fractures have been mainly retrospective in nature and have involved heterogeneous and small patient populations. The current literature is, therefore, limited.

Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial.

OBJECT: The authors report the results of a prospective randomized multicenter study in which the results of cervical disc arthroplasty were compared with anterior cervical discectomy and fusion (ACDF) in patients treated for symptomatic single-level cervical degenerative disc disease (DDD). METHODS: Five hundred forty-one patients with single-level cervical DDD and radiculopathy were enrolled at 32 sites and randomly assigned to one of two treatment groups: 276 patients in the investigational group underwent anterior cervical discectomy and decompression and arthroplasty with the PRESTIGE ST Cervical Disc System (Medtronic Sofamor Danek); 265 patients in the control group underwent decompressive ACDF. Eighty percent of the arthroplasty-treated patients (223 of 276) and 75% of the control patients (198 of 265) completed clinical and radiographic follow-up examinations at routine intervals for 2 years after surgery. Analysis of all currently available postoperative 12- and 24-month data indicated a two-point greater improvement in the neck disability index score in the investigational group than the control group. The arthroplasty group also had a statistically significant higher rate of neurological success (p = 0.005) as well as a lower rate of secondary revision surgeries (p = 0.0277) and supplemental fixation (p = 0.0031). The mean improvement in the 36-Item Short Form Health Survey Physical Component Summary scores was greater in the investigational group at 12 and 24 months, as was relief of neck pain. The patients in the investigational group returned to work 16 days sooner than those in the control group, and the rate of adjacent-segment reoperation was significantly lower in the investigational group as well (p = 0.0492, log-rank test). The cervical disc implant maintained segmental sagittal angular motion averaging more than 7 degrees. In the investigational group, there were no cases of implant failure or migration. CONCLUSIONS: The PRESTIGE ST Cervical Disc System maintained physiological segmental motion at 24 months after implantation and was associated with improved neurological success, improved clinical outcomes, and a reduced rate of secondary surgeries compared with ACDF.

A quantitative analysis of strain at adjacent segments after segmental immobilization of the cervical spine.

STUDY DESIGN: A biomechanical study on human cadaveric cervical spines with segmental fixation. OBJECTIVES: To quantify the strains across all segments of the spine after simulated fusion. SUMMARY OF BACKGROUND DATA: Clinical evidence suggests that degenerative changes occur at adjacent levels after cervical fusion. This may, in part be due to increased stress and motion at the adjacent segments. MATERIALS AND METHODS: Seven fresh frozen human cervical cadaveric spines were used. The spines were mounted onto frames at C2 and C7. Biomechanical testing was performed on a modified MTS tester. The specimens were tested in rotation control. To simulate fusion, a block was used to replace the disc. Fixation was enhanced using an anterior plate and stainless steel wire through the spinous processes. Testing was then performed with the same displacement magnitudes used for the intact spine. Displacement across 5 disc spaces was recorded using extensometers. The same preparation and testing was done for 1, 2, and 3-level simulated fusions. All data were normalized to the individual intact specimen. RESULTS: After 1-level simulated fusion at C5-6, flexion-extension rotation increased by 60% at the superior adjacent level (C4-5) and by 15% at the adjacent inferior level (C6-7). Lateral bending increased by 51% at C4-5 and by 16% at C6-7. Axial rotation increased by 25% at C4-5 and by 200% at C6-7. Flexion-extension, lateral bending and axial rotation increased at all other segments, not only at adjacent segments, after 1, 2 and 3-level fixation. CONCLUSIONS: Cervical fusion results in increased strains at adjacent levels, and to all other levels, inferiorly and superiorly. This study represents the first to quantify the increased strain at all adjacent levels.

The correlation between preoperative disc space height and clinical outcomes after anterior lumbar interbody fusion.

OBJECTIVE: To determine whether preoperative disc space height (DSH) influences the clinical outcomes of patients diagnosed with single-level symptomatic discogenic disease and treated with a stand-alone anterior lumbar interbody fusion with two tapered threaded fusion cages, we performed a retrospective analysis of 392 patients. METHODS: Preoperative radiographs were used to establish four study groups based on the patients' DSH: the tall disc group: DSH >15 mm; the intermediate tall group: DSH ranging from 10 to 15 mm; the intermediate collapsed group: DSH ranging from 5 to 10 mm; and the collapsed disc group: DSH <5 mm. RESULTS: All of the patient groups exhibited improvement in their clinical outcomes. However, patients in the collapsed disc group (DSH of <5 mm) tended to have earlier and greater improvement in Oswestry Disability Index scores, Physical Component Summary scores of the Short Form-36, and Visual Analog Scale scores for low back pain. CONCLUSION: Symptomatic disc degeneration can be readily identified with plain radiographic findings, and patients' symptoms can often be relieved predictably with a stand-alone interbody fusion procedure.

The management of acute thoracolumbar burst fractures with anterior corpectomy and Z-plate fixation.

STUDY DESIGN: A retrospective review of a consecutive series of patients with acute thoracolumbar burst fractures who were surgically treated with an anterior corpectomy and fusion with anterolateral Z-plate fixation. OBJECTIVES: To evaluate the clinical and radiographic success of the management of acute thoracolumbar burst fractures by corpectomy, structural grafting, and anterolateral internal fixation. SUMMARY OF BACKGROUND DATA: Burst fractures are frequently associated with instability or neurologic deficit. Modern surgical procedures for these fractures have been performed via both anterior and posterior approaches. Anterior surgical treatment allows direct decompression of the neural elements and correction of deformity. Newer anterior instrumentation devices, combined with a structural graft, allow a stable construct that may obviate a posterior procedure. An anterior procedure generally requires fusion of only two levels compared to posterior fusion, which generally requires more. METHODS: A retrospective review of a consecutive series of patients with thoracolumbar burst fractures treated with anterior surgery, strut graft, and fixation with a Z-plate was carried out. Fractures were considered acute if surgically treated within 30 days. Clinical and radiographic evaluation was performed on all 35 patients with acute thoracolumbar burst fractures. Surgical indications were incomplete neurologic deficit, segmental kyphotic deformity, or significant comminution. All patients with acute thoracolumbar burst fractures with spinal cord injury were treated with an intravenous steroid protocol and were operated on within 24 hours of admission unless medically precluded. Forty-six percent (16 of 35) of patients with acute thoracolumbar burst fractures presented with a neurologic deficit. RESULTS: All 16 patients with neurologic deficit demonstrated at least one Frankel grade improvement on final observation, with 11 (69%) patients demonstrating complete neurologic recovery. Thirty-three patients were treated with anterolateral instrumentation only. Twenty-nine of thirty patients demonstrated radiographic healing. Five were lost to follow-up observation. One patient required subsequent posterior fusion for increasing kyphotic deformity. There were no instances of hardware failure. Sagittal alignment was improved from a mean preoperative kyphosis of 18 degrees to 6 degrees at final follow-up observation. CONCLUSIONS: Anterior corpectomy, strut graft, and Z-plate fixation is an effective treatment for thoracolumbar burst fractures. It allows direct decompression of the spinal cord in the acute setting and was associated with a high rate of neurologic improvement, no instances of neurologic worsening in any case, and a low complication rate.

The effectiveness of rhBMP-2 in replacing autograft: an integrated analysis of three human spine studies.

In anterior lumbar spinal fusion, patients treated with rhBMP-2 on a collagen sponge carrier had statistically superior outcomes compared to patients treated with autogenous bone graft. A collagen sponge carrier should replace autogenous bone graft for this patient population.

Anterior lumbar interbody fusion for the management of chronic lower back pain: current strategies and concepts.

In a retrospective analysis of two large multicenter clinical studies, 321 patients with degenerative lumbar disc disease were divided into two groups who underwent anterior lumbar interbody fusion using two threaded titanium fusion cages. To determine whether differences in surgical procedures and cage design affect anterior and posterior annular distraction and clinical outcomes, the authors evaluated the clinical and radiographic outcomes of patients treated with a stand-alone ALIF procedure. End-plate preservation techniques were associated with improved anterior and posterior disc space distraction compared with standard end-plate preparation techniques. Similarly, the use of the LT-CAGE device led to greater improvements in restoration of segmental lordosis than did the use of standard cylindric cages. Furthermore, these surgical benefits resulted in improved clinical outcomes as early as 3 months and were maintained over a 2-year follow-up period in patients with improved postoperative disc space distraction and lordosis. Placing cylindric cages in a lordotic or trapezoidal disc space can be accomplished only through asymmetric reaming of the vertebral end plates. In a lordotic disc space, the posterior portion of the disc must be reamed more than the anterior portion. This over-reaming inhibits distraction of the posterior disc space and limits restoration of neuroforaminal height. Reduced reaming and symmetric reaming of the vertebral end plates enable the surgeon to restore anatomic segmental lordosis across the disc space. The tapered cage configuration aids in maintaining segmental lordosis. Anatomic restoration of disc space contours has an impact on a patient's outcome after stand-alone anterior interbody fusion surgery.

Interbody cage devices.

STUDY DESIGN: A literature review was conducted of basic science research and clinical experiences describing the use of interbody cage devices for the management of degenerative spinal abnormalities. OBJECTIVES: To summarize current knowledge regarding the use of interbody fusion cages. SUMMARY OF BACKGROUND DATA: Degenerative conditions of the lumbar and cervical spine are a major societal expense and a leading cause of disability. Fusion surgery may be used to treat patients with some of these conditions. During the past decade, interbody cages have been popularized as a useful fusion technique with high rates of clinical and radiographic success reported. Cages may be implanted using a variety of surgical approaches to the disc space and can be used alone or with supplemental posterior fixation. METHODS: A literature review of biomechanical, biologic, and clinical studies of threaded interbody cages was performed. RESULTS: Interbody cages have been shown to successfully promote fusion in a variety of animal models. In biomechanical studies, anteriorly placed threaded cages significantly stabilize the motion segment in all directions except extension. Posteriorly placed cages provide less stability as a result of the facetectomy required for placement of an appropriately sized device. Successful clinical and radiographic results have been reported with the use of interbody cages. Most reported cage failures are the result of technical difficulties with implantation or poor patient selection. Accurate radiographic assessment of fusion in the presence of a metal interbody cage remains challenging, and studies evaluating alternate biomaterial cages are underway. CONCLUSION: Interbody cages are a useful technique for achieving spinal fusion and have been shown to have an acceptable clinical success rate in appropriately selected patients.