Atlanto-axial rotary instability (Fielding type 1): characteristic clinical and radiological findings, and treatment outcomes following alignment, fusion, and stabilization.

Atlanto-axial instability (AAI) is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) syndromes, where it typically presents as a rotary subluxation due to incompetence of the alar ligament. This retrospective, IRB-approved study examines 20 subjects with Fielding type 1 rotary subluxation, characterized by anterior subluxation of the facet on one side, with a normal atlanto-dental interval. Subjects diagnosed with a heritable connective tissue disorder, and AAI had failed non-operative treatment and presented with severe headache, neck pain, and characteristic neurological findings. Subjects underwent a modified Goel-Harms posterior C1-C2 screw fixation and fusion without complication. At 15 months, two subjects underwent reoperation following a fall (one) and occipito-atlantal instability (one). Patients reported improvement in the frequency or severity of neck pain (P < 0.001), numbness in the hands and lower extremities (P = 0.001), headaches, pre-syncope, and lightheadedness (all P < 0.01), vertigo and arm weakness (both P = 0.01), and syncope, nausea, joint pain, and exercise tolerance (all P < 0.05). The diagnosis of Fielding type 1 AAI requires directed investigation with dynamic imaging. Alignment and stabilization is associated with improvement of pain, syncopal and near-syncopal episodes, sensorimotor function, and exercise tolerance.

Research progress on the biological modifications of implant materials in 3D printed intervertebral fusion cages.

Anterior spine decompression and reconstruction with bone grafts and fusion is a routine spinal surgery. The intervertebral fusion cage can maintain intervertebral height and provide a bone graft window. Titanium fusion cages are the most widely used metal material in spinal clinical applications. However, there is a certain incidence of complications in clinical follow-ups, such as pseudoarticulation formation and implant displacement due to nonfusion of bone grafts in the cage. With the deepening research on metal materials, the properties of these materials have been developed from being biologically inert to having biological activity and biological functionalization, promoting adhesion, cell differentiation, and bone fusion. In addition, 3D printing, thin-film, active biological material, and 4D bioprinting technology are also being used in the biofunctionalization and intelligent advanced manufacturing processes of implant devices in the spine. This review focuses on the biofunctionalization of implant materials in 3D printed intervertebral fusion cages. The surface modifications of implant materials in metal endoscopy, material biocompatibility, and bioactive functionalizationare summarized. Furthermore, the prospects and challenges of the biofunctionalization of implant materials in spinal surgery are discussed. Fig.a.b.c.d.e.f.g As a pre-selected image for the cover, I really look forward to being selected. Special thanks to you for your comments.

Understanding the Future Prospects of Synergizing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery with Ceramics and Regenerative Cellular Therapies.

Transforaminal lumber interbody fusion (TLIF) is the last resort to address the lumber degenerative disorders such as spondylolisthesis, causing lower back pain. The current surgical intervention for these abnormalities includes open TLIF. However, in recent years, minimally invasive TLIF (MIS-TLIF) has gained a high momentum, as it could minimize the risk of infection, blood loss, and post-operative complications pertaining to fusion surgery. Further advancement in visualizing and guiding techniques along with grafting cage and materials are continuously improving the safety and efficacy of MIS-TLIF. These assistive techniques are also playing a crucial role to increase and improve the learning curve of surgeons. However, achieving an appropriate output through TLIF still remains a challenge, which might be synergized through 3D-printing and tissue engineering-based regenerative therapy. Owing to their differentiation potential, biomaterials such as stem/progenitor cells may contribute to restructuring lost or damaged tissues during MIS-TLIF, and this therapeutic efficacy could be further supplemented by platelet-derived biomaterials, leading to improved clinical outcomes. Thus, based on the above-mentioned strategies, we have comprehensively summarized recent developments in MIS-TLIF and its possible combinatorial regenerative therapies for rapid and long-term relief.

A comparison of contiguous two-level anterior cervical discectomy and fusion using a structural allograft versus a Polyetheretherketone (PEEK) cage: the results of a three-year follow-up.

BACKGROUND: Allografts and polyetheretherketone (PEEK) cages are the two most commonly used materials in anterior cervical discectomy and fusion (ACDF). However, their effectiveness in two-level ACDF remains controversial. The primary aim of this retrospective study was to compare the clinical and radiological outcomes of two-level ACDF with plate fixation using either a structural allograft or a PEEK cage. METHODS: From 2010 to 2015, 88 consecutive patients underwent two-level ACDF, of whom 53 received an allograft and 35 patients received a PEEK cage. All PEEK cages were filled with local autografts. All clinical outcomes were prospectively collected before and six months and two years after surgery. Clinical efficacy was evaluated using a visual analogue scale for neck pain and limb pain, the Neck Pain and Disability Score, the Neck Disability Index, the Neurogenic Symptom Score, and the Japanese Orthopedic Association score. Radiological outcomes were assessed preoperatively, immediately after surgery, and at the final follow-up. RESULTS: A preoperative comparison revealed no difference between the two patient groups in terms of age, sex, body mass index, smoking status, preoperative symptoms, operation level, or follow-up (mean = 42.8 months). No differences in the improvements in clinical outcomes were observed between the two groups. Both groups showed significant improvement in mean disc height, segmental height, and segmental lordosis postoperatively. The fusion rate for the PEEK cage was 100% at both levels, while the fusion rate for the allograft group was 98.1% at the cephalad level and 94.2% at the caudad level (p > 0.05). Subsidence at the cephalad level occurred in 22.9% (8/35) of segments in the PEEK group and 7.7% (4/52) of segments in the allograft group (p = 0.057). At the caudal level, a higher incidence of cage subsidence was noted in the PEEK group than in the allograft group [37.1% (13/35) versus 15.4% (8/52)] (p = 0.02). Overall, subsidence was noted in 30% (21/70) of the PEEK group and in 11% (12/104) of the allograft group (p <  0.05). CONCLUSION: The use of PEEK cages resulted in a higher rate of subsidence in two-level ACDF than the use of allografts. Two-level ACDF using either allografts or PEEK cages resulted in similar clinical outcomes, radiological improvements in alignment and fusion rates.

Minimally invasive spinal fixation in an aging population with osteoporosis: clinical and radiological outcomes and safety of expandable screws versus fenestrated screws augmented with polymethylmethacrylate.

OBJECTIVE: The goal of this study was to compare the clinical and radiological outcomes between fenestrated pedicle screws augmented with cement and expandable pedicle screws in percutaneous vertebral fixation surgical procedures for the treatment of degenerative and traumatic spinal diseases in aging patients with osteoporosis. METHODS: This was a prospective, single-center study. Twenty patients each in the expandable and cement-augmented screw groups were recruited. Clinical outcomes included visual analog scale (VAS), Oswestry Disability Index (ODI), and satisfaction rates. Radiographic outcomes comprised radiological measurements on the vertebral motion segment of the treated levels. Intraoperative data including complications were collected. All patients completed the clinical and radiological outcomes. Outcomes were compared preoperatively and postoperatively. RESULTS: An average shorter operative time was found in procedures in which expandable screws were used versus those in which cement-augmented screws were used (p < 0.001). No differences resulted in perioperative blood loss between the 2 groups. VAS and ODI scores were significantly improved in both groups after surgery. There was no significant difference between the 2 groups with respect to baseline VAS or ODI scores. The satisfaction rate of both groups was more than 85%. Radiographic outcomes also showed no significant difference in segment stability between the 2 groups. No major complications after surgery were seen. There were 4 cases (20%) of approach-related complications, all in fenestrated screw procedures in which asymptomatic cement extravasations were observed. In 1 case the authors detected a radiologically evident osteolysis around a cement-augmented screw 36 months after surgery. In another case they identified a minor loosening of an expandable screw causing local back discomfort at the 3-year follow-up. CONCLUSIONS: Expandable pedicle screws and polymethylmethacrylate augmentation of fenestrated screws are both safe and effective techniques to increase the pullout strength of screws placed in osteoporotic spine. In this series, clinical and radiological outcomes were equivalent between the 2 groups. To the authors' knowledge, this is the first report comparing the cement augmentation technique versus expandable screws in the treatment of aging patients with osteoporosis.

Odontoid Fusion.

Anterior odontoid screw fixation allows for the internal fixation of unstable odontoid fractures with low morbidity, good fusion rates, and preservation of the atlanto-axial range of motion when applied in appropriate clinical cases. Advances in surgical techniques have allowed for safer, more minimally invasive approaches that reduce the risk of injury to vital prevertebral structures and minimize soft tissue retraction. Moreover, improvements in surgical image guidance technology for spinal surgery that have been applied to odontoid screw placement have helped improve surgeon confidence about exact screw trajectories. In this chapter, we review traditional screw placement techniques and highlight the trends in technical improvements that improve the safety and efficacy of these procedures.

Bone morphogenetic protein in spine surgery: current and future uses.

The clinical use of bone morphogenetic protein (BMP) in spinal fusion surgery has recently become controversial. After its approval by the US FDA in July 2002, BMP was adopted by many spine surgeons as a replacement for the more traditional iliac crest bone graft to avoid the complications associated with bone graft harvest. However, as broad clinical use escalated, reports increased of potentially serious complications associated with BMP. Controversy continues, particularly regarding the safety of BMP and whether it should routinely replace iliac crest bone graft for spinal fusion surgery.

Outcome of Surgery for Congenital Craniovertebral Junction Anomalies with Atlantoaxial Dislocation/Basilar Invagination: A Retrospective Study of 94 Patients.

OBJECTIVE: To evaluate the results of surgery for congenital craniovertebral junction (CVJ) anomalies with atlantoaxial dislocation (AAD)/basilar invagination (BI) and compare the results of transoral odontoidectomy and posterior fusion (TOO+PF) with only posterior fusion (PF) in patients with irreducible AAD/BI. METHODS AND RESULTS: All 94 patients with congenital CVJ anomalies with AAD/BI operated on during the 3-year study period (June 2013-May 2016) were included. Of these patients, 55 had irreducible AAD/BI and the remaining 39 had reducible AAD/BI. TOO+PF was restricted to patients (34/94; 36.2%) with irreducible AAD/BI when reduction and realignment by intraoperative C1-C2 facet joint manipulation were considered technically difficult and risky. The remaining patients with irreducible AAD/BI and all the patients with reducible AAD/BI (60/94; 63.8%) were managed with only posterior fusion. Poor preoperative Nurick grade, preoperative dyspnea/lower cranial nerve deficits, and syringomyelia were associated with significantly higher incidence of postoperative pulmonary complications. Follow-up ≥3 months (final follow-up) was available for 87 patients. Good outcome (Nurick grade 0-3) at final follow-up was noted in 90% (45/50) of the patients with irreducible AAD/BI and 91.9% (34/37) of the patients with reducible AAD/BI. Preoperative poor Nurick grade (4-5) was the only factor associated with poor outcome. No significant difference in perioperative complications, outcome, and fusion was noted between patients who underwent TOO+PF or only PF for irreducible AAD/BI. CONCLUSIONS: Many of the patients with congenital AAD/BI showed remarkable recovery after surgery. Preoperative poor Nurick grade (4-5) is associated with poor outcome. TOO+PF is a safe alternative treatment option for irreducible AAD/BI when only PF techniques are technically difficult/risky.

Surface Technologies in Spinal Fusion.

Patients with symptomatic instability of the spine may be treated surgically with interbody fusion. Cost and complexity in this procedure arises owing to the implanted materials involved with facilitating fusion such as titanium or polyetheretherketone. Surface modifications have been developed to augment these base materials such as plasma-spraying polyetheretherketone with titanium or coating implants with hydroxyapatite. Although some evidence has been gathered on these novel materials, additional study is needed to establish the true efficacy of surface modifications for interbody fusion devices in improving long-term patient outcomes.

Odontoid Fractures: A Critical Review of Current Management and Future Directions.

Odontoid fractures represent one of the most common and controversial injury types affecting the cervical spine, being associated with a high incidence of nonunion, morbidity, and mortality. These complications are especially common and important in elderly patients, for which ideal treatment options are still under debate. Stable fractures in young patients maybe treated conservatively, with immobilization. Although halo-vest has been widely used for their conservative management, studies have shown high rates of complications in the elderly, and therefore current evidence suggests that the conservative management of these fractures should be carried out with a hard cervical collar or cervicothoracic orthosis. Elderly patients with stable fractures have been reported to have better clinical results with surgical treatment. For these and for all patients with unstable fractures, several surgical techniques have been proposed. Anterior odontoid fixation can be used in reducible fractures with ideal fracture patterns, with older patients requiring fixation with 2 screws. In other cases, C1-C2 posterior fixation maybe needed with the best surgical option depending on the reducibility of the fracture and vertebral artery anatomy. In this paper, current evidence on the management of odontoid fractures is discussed, and an algorithm for treatment is proposed.

Difficulties in Treating Postirradiation Kyphosis in Adults: A Series of Five Cases.

STUDY DESIGN: Clinical case series. OBJECTIVE: To assess objective outcomes of surgical correction of post-external beam radiation therapy (ERBT) kyphosis in a series of five adults. SUMMARY OF BACKGROUND DATA: EBRT is a well-established treatment for many cancers in children and adults. One complication associated with EBRT is postirradiation spine deformity. Scoliosis is the most common deformity, but kyphosis also occurs frequently. Differences in deformity patterns are likely related to the location and intensity of radiation. To our knowledge, no studies have addressed treatment of these deformities in adults, and the most recent case series (of children) was published in 2005. METHODS: We present a series of five adults who underwent surgery for postirradiation kyphosis, with a mean follow-up of 3.8 years (range, 2.5-6.2 years). RESULTS: Surgery improved the kyphotic deformity in all patients. Overall mean kyphotic deformity correction was 56° and was larger for cervical/cervicothoracic deformities (mean, 76°) than for lumbar deformities (mean, 42°) at midterm follow-up. Patients reported significant improvements in pain and self-image. Consistent with prior case series of children, we observed a high rate of complications (mean, 1.4 complications per patient) in adults. Three patients each underwent an unplanned surgical procedure because of a complication. CONCLUSION: The surgical treatment of postirradiation kyphotic spinal deformity is challenging, with common postoperative complications such as infection, instrumentation failure, and pseudarthrosis. However, with modern surgical techniques and spinal instrumentation, excellent deformity correction can be achieved and maintained. We recommend performing a two-stage procedure for cervicothoracic deformity, with anterior release followed by posterior fusion and instrumentation. In thoracolumbar deformities, correction can be achieved through single-stage posterior fusion. Rigid spinopelvic fixation with sacral-alar-iliac screws and second-stage anterior lumbar interbody fusion at L5-S1 is recommended to reduce nonunion risk. Cement augmentation of proximal and distal anchors can help prevent junctional failure. LEVEL OF EVIDENCE: Level IV.

Pedicle Screw with Cement Augmentation in Unilateral Transforaminal Lumbar Interbody Fusion: A 2-Year Follow-Up Study.

OBJECTIVE: To evaluate safety and efficacy of pedicle screw with polymethyl methacrylate (PMMA) augmentation in unilateral transforaminal lumbar interbody fusion (uTLIF) in osteoporotic patients. METHODS: We randomly divided 50 osteoporotic patients with degenerative lumbar diseases diagnosed between February 2014 and November 2015 into 2 groups. One group underwent standard uTLIF, and the other group underwent uTLIF with PMMA augmentation. All patients were scheduled to attend a series of regular follow-up evaluations. Oswestry Disability Index, Japanese Orthopaedic Association score, visual analog scale score, lumbar lordotic angle, segmental lordotic angle, and disc space height (DSH) at each follow-up were collected and analyzed. RESULTS: The 2-year follow-up was completed by 24 patients in the uTLIF group and 23 patients in the PMMA group. Oswestry Disability Index, Japanese Orthopaedic Association score, and visual analog scale score showed significant improvements after surgery in both groups, with no significant difference between groups. DSH in the uTLIF group was 8.7 ± 2.3 mm and in the PMMA group was 10.7 ± 1.6 mm. Fusion rate in the uTLIF group was 19/24 and in the PMMA group was 21/23. DSH and fusion rate in the PMMA group were higher than those in the uTLIF group. No severe complications were observed after PMMA injection. CONCLUSIONS: Pedicle screw with PMMA augmentation can increase fixation stability and reduce DSH loss in uTLIF. Moreover, PMMA in the vertebral body did not impede the interbody fusion ability in uTLIF.

Mortality Rates After Posterior C1-2 Fusion for Displaced Type II Odontoid Fractures in Octogenarians.

STUDY DESIGN: Retrospective cohort study OBJECTIVE.: To assess 30-day and 1-year mortality rates as well as the most common complications associated with posterior C1-2 fusion in an octogenarian cohort. SUMMARY OF BACKGROUND DATA: Treatment of unstable type II odontoid fractures in elderly patients can present challenges. Recent evidence indicates in patients older than 80 years, posterior C1-2 fusion results in improved survival as compared to other modes of treatment. METHODS: Retrospective analysis of 43 consecutive patients (25 female and 18 male; mean age 84.3 yr, range 80-89 yr; mean Charlson Comorbidity Index 1.4, (range 1-6); mean body mass index 24.8 ±â€Š4.2 kg/m, who underwent posterior C1-C2 fusion for management of unstable type II odontoid fracture by four fellowship trained spine surgeons at a single institution between January 2006 to June 2016. RESULTS: Mean fracture displacement was 5.1 ±â€Š3.6 mm and mean absolute value of angulation was 19.93°â€Š±â€Š12.93°. The most common complications were altered mental status (41.9%, n = 18), dysphagia (27.9%, n = 12) with 50% of those patients (6/12) requiring a feeding tube, and emergency reintubation (9.3%, n = 4). To the date of review completion, 25 of 43 patients expired (58.1%), median survival of 1.76 years from the date of surgery. Thirty-day and 1-year mortality rates were 2.3% and 18.6%, respectively. Patients who developed dysphagia were 14.5 times more likely to have expired at 1 year; dysphagia was also found to be significantly associated with degree of displacement. Fracture displacement was found to be associated with increased odds for 1-year mortality when accounting for age and requirement of a feeding tube. CONCLUSION: Posterior C1-2 fusion results in acceptably low mortality rates in octogenarians with unstable type II odontoid fractures when compared to nonoperative management mortality rates in current literature. Initial fracture displacement is associated with higher mortality rate in this patient population. LEVEL OF EVIDENCE: 4.

Quality of Life After Combined Endonasal Endoscopic Odontoidectomy and Posterior Suboccipital Decompression and Fusion.

BACKGROUND: Basilar invagination can result from systemic diseases that can weaken structural integrity of the craniocervical junction. Definitive treatment often requires ventral decompression and posterior decompression and fusion. Endonasal odontoidectomy is a relatively new minimal access procedure; quality of life (QOL) after this procedure has not been reported. METHODS: We reviewed a consecutive database of endonasal odontoidectomy cases and identified patients having posterior decompression and fusion. Two QOL questionnaires were administered postoperatively: Sino-Nasal Outcome Test and 36-Item Short Form Survey. Comparisons with other endonasal or Chiari procedures were performed. RESULTS: The study comprised 14 patients; 79% had Chiari malformation in addition to basilar invagination. Mean follow-up was 17.2 months. Symptomatic improvement occurred in 78.6% after surgery. Average postoperative Sino-Nasal Outcome Test scores were 39.2 ± 17.93, with worst scores in areas related to fatigue and sleep patterns but not nasal function. 36-Item Short Form Survey scores were lower in areas of physical function and general health but better for emotional health and pain. Compared with patients undergoing Chiari malformation surgery without endonasal odontoid resection or fusion, patients undergoing odontoidectomy had higher QOL in areas of role emotional, emotional well-being, and pain but worse QOL in general health and role physical. CONCLUSIONS: Patients undergoing posterior decompression and fusion with endonasal odontoidectomy do well after surgery with respect to nasal function and emotional health. Patients who also have severe basilar invagination associated with systemic diseases demonstrate reduced QOL after surgery in areas of physical function and sleep leading to fatigue, irritability, and concentration difficulty, likely related to their systemic disease.

Percutaneous vertebroplasty and kyphoplasty for the stand-alone augmentation of osteoporosis-induced vertebral compression fractures: present status and future directions.

Enormous research efforts are being expended on two minimally invasive procedures: percutaneous vertebroplasty (VP) and kyphoplasty (KP). The present report, which is a detailed critical review of VP and KP that emphasizes their biomechanics aspects, is divided into six parts. In the first two parts, succinct descriptions are given of osteoporosis-induced vertebral body (VB) compression fractures as the underlying pathology to be treated with VP and KP, the theory of VP and KP, and the techniques used in performing these procedures. Concerns about VP and KP, such as the high radiation exposure burden that may be imposed on both patient and medical personnel and extravasation of the injectable bone cement, are discussed in the third part. Detailed discussions of fourteen issues/questions, such as the extent to which VP or KP affects various biomechanical measures of the augmented VB and those adjacent to it and the appropriate volume of the cement to use, are presented in the fourth part. Ideas for future research, such as development of a new generation of injectable bone cements and identification of an appropriate animal model, are covered in the fifth part. The final section contains a summary of the most salient points/observations made in the report.

Comparison of allograft and polyetheretherketone (PEEK) cage subsidence rates in anterior cervical discectomy and fusion (ACDF).

Structural allografts and PEEK cages are commonly used interbody fusion devices in ACDF. The subsidence rates of these two spacers have not yet been directly compared. The primary aim of this study was to compare the subsidence rate of allograft and PEEK cage in ACDF. The secondary aim was to determine if the presence of subsidence affects the clinical outcome. We reviewed 67 cases (117 levels) of ACDF with either structural allograft or PEEK cages. There were 85 levels (48 cases) with PEEK and 32 levels (19 cases) with allograft spacers. Anterior and posterior disc heights at each operative level were measured at immediate and 6months post-op. Subsidence was defined as a decrease in anterior or posterior disc heights >2mm. NDI of the subsidence (SG) and non-subsidence group (NSG) were recorded. Chi-square test was used to analyze subsidence rates. T-test was used to analyze clinical outcomes (α=0.05). There was no statistically significant difference between subsidence rates of the PEEK (29%; 25/85) and allograft group (28%; 9/32) (p=0.69). Overall mean subsidence was 2.3±1.7mm anteriorly and 2.6±1.2mm posteriorly. Mean NDI improvement was 11.7 (from 47.1 to 35.4; average follow-up: 12mos) for the SG and 14.0 (from 45.8 to 31.8; average follow-up: 13mos) for the NSG (p=0.74). Subsidence rate does not seem to be affected by the use of either PEEK or allograft as spacers in ACDF. Furthermore, subsidence alone does not seem to be predictive of clinical outcomes of ACDF.

Comparison of Clinical Outcomes of Posterior C1-C2 Temporary Fixation Without Fusion and C1-C2 Fusion for Fresh Odontoid Fractures.

BACKGROUND: Posterior C1-C2 temporary-fixation technique can spare the range of motion (ROM) of the atlantoaxial joint after odontoid fracture healing. However, few studies analyze the difference in clinical outcome between this technique and posterior C1-C2 fusion technique for new odontoid fracture. OBJECTIVE: To verify whether the clinical outcome of the posterior C1-C2 temporary-fixation technique is superior to that of the posterior C1-C2 fusion technique in the treatment of a new odontoid fracture. METHODS: Twenty-one of 22 patients who underwent posterior C1-C2 temporary fixation of an odontoid fracture achieved fracture healing and regained motion of the atlantoaxial joint. The functional outcomes of these 21 patients were compared with that of a control group, which consisted of 21 randomly enrolled cases with posterior C1-C2 fixation and fusion. The differences between the 2 groups in the visual analog scale score for neck pain, neck stiffness, Neck Disability Index, 36-Item Short Form Health Survey, and time to fracture healing were analyzed. RESULTS: Significantly better outcomes were observed in the temporary-fixation group for visual analog scale score for neck pain, Neck Disability Index, and neck stiffness. The outcomes in the temporary-fixation group was superior to those in the fusion group in all dimensions of the 36-Item Short Form Health Survey. There were no significant differences in fracture healing rate and time to fracture healing between the 2 techniques. CONCLUSION: Functional outcomes were significantly better after posterior C1-C2 temporary fixation than after fusion. Temporary fixation can be used as a salvage treatment for an odontoid fracture with an intact transverse ligament in cases of failure of, or contraindication to, anterior screw fixation.

Bone tissue engineering and spinal fusion: the potential of hybrid constructs by combining osteoprogenitor cells and scaffolds.

In this paper, we discuss the current knowledge and achievements on bone tissue engineering with regard to spinal fusion and highlight the technique that employs hybrid constructs of porous scaffolds with bone marrow stromal cells. These hybrid constructs potentially function in a way comparable to the present golden standard, the autologous bone graft, which comprises besides many other factors, a construct of an optimal biological scaffold with osteoprogenitor cells. However, little is known about the role of the cells in autologous grafts, and especially survival of these cells is questionable. Therefore, more research will be needed to establish a level of functioning of hybrid constructs to equal the autologous bone graft. Spinal fusion models are relevant because of the increasing demand for graft material related to this procedure. Furthermore, they offer a very challenging environment to further investigate the technique. Anterior and posterolateral animal models of spinal fusion are discussed together with recommendations on design and assessment of outcome parameters.

Spinal fusion surgery: animal models for tissue-engineered bone constructs.

Animal models have been used extensively to investigate the biology of fracture healing and spinal fusion. The goal of each spinal fusion model is to try and reproduce the correct sequence of events during osseous healing in humans. Animal models allow us the capability of dialing in fusion rates and fusion parameters depending upon the study conditions. These models have become invaluable in assessing the clinical potential of emerging technologies such as recombinant growth factors and gene therapy.

Biology of lumbar spine fusion and use of bone graft substitutes: present, future, and next generation.

Posterolateral lumbar spine arthrodesis is a commonly performed procedure, yet the biology of healing is poorly understood. Nonunion, or failure to achieve a solid bony fusion, occurs in up to 40% of patients. We first developed and validated a rabbit model to characterize the healing process by measuring macroscopic parameters, microscopic parameters, and gene expression. We found that presently available osteoconductive and weakly osteoinductive materials were insufficient to replace autografts, but could in some cases serve as bone graft extenders. In contrast, two osteoinductive growth factors currently in development could replace autograft in non-human primates and in humans, but may be limited by the high dose required, carrier variability, and high cost. We identified, cloned, and sequenced a novel complementary DNA (cDNA) encoding for an intracellular protein LMP-1, which is expressed during the first few hours of osteoblast differentiation. LMP-1 expression is able to induce many BMPs, their receptors, and other bone growth factors. Local implantation of bone marrow cells transfected with LMP-1 cDNA induced spine fusion in 100% of sites tested; no bone formed at the control sites without LMP-1. This strategy of local gene therapy may provide a basis for the next generation of bone graft substitutes.