Intraoperative image guidance for cervical spine surgery.

Intraoperative image-guidance in spinal surgery has been influenced by various technological developments in imaging science since the early 1990s. The technology has evolved from simple fluoroscopic-based guidance to state-of-art intraoperative computed tomography (iCT)-based navigation systems. Although the intraoperative navigation is more commonly used in thoracolumbar spine surgery, this newer imaging platform has rapidly gained popularity in cervical approaches. The purpose of this manuscript is to address the applications of advanced image-guidance in cervical spine surgery and to describe the use of intraoperative neuro-navigation in surgical planning and execution. In this review, we aim to cover the following surgical techniques: anterior cervical approaches, atlanto-axial fixation, subaxial instrumentation, percutaneous interfacet cage implantation as well as minimally invasive posterior cervical foraminotomy (PCF) and unilateral laminotomy for bilateral decompression. The currently available data suggested that the use of 3D navigation significantly reduces the screw malposition, operative time, mean blood loss, radiation exposure, and complication rates in comparison to the conventional fluoroscopic-guidance. With the advancements in technology and surgical techniques, 3D navigation has potential to replace conventional fluoroscopy completely.

Multidisciplinary approach to degenerative cervical myelopathy.

INTRODUCTION: Degenerative cervical myelopathy (DCM) is a prevalent condition causing significant impairment spanning several domains of health. A multidisciplinary approach to the care of DCM would be ideal in utilizing complex treatments from different disciplines to address broad patient needs. AREAS COVERED: In this article the authors will discuss the importance of multidisciplinary care and establish a general framework for its use. The authors will then highlight the potential role of a multidisciplinary team in each aspect of DCM care including assessment, diagnosis, decision-making, surgical intervention, non-operative therapy, monitoring, and postoperative care. EXPERT OPINION: In order to provide comprehensive personalized care to DCM patients, it is necessary to have a multidisciplinary team composed by a combination of the patient, surgeon, primary care practitioner, neurologist, anesthesiologist, radiologist, physiatrist, nurses, physiotherapist, occupational therapist, pain specialist, and social workers all functioning independently and communicating to achieve a common goal.

Recommendations for Diagnosis and Treatment of Odontoid Fractures in Geriatric Patients. / Empfehlungen zu Diagnostik und Behandlung von Frakturen des Dens axis bei geriatrischen Patienten.

BACKGROUND: Odontoid fractures in geriatric patients represent an entity of increasing incidence with a high rate of morbidity and mortality. The optimal diagnostic and therapeutic management is being controversially discussed in the literature. METHODS: In a consensus process and based on the current literature, the members of the working groups "Osteoporotic Fractures" and "Upper Cervical Spine" of the German Society for Orthopaedics and Trauma Surgery (DGOU) defined recommendations for the diagnostics and treatment of odontoid fractures in geriatric patients. RESULTS: For the diagnosis of odontoid fractures in symptomatic patients, computed tomography represents the gold standard, along with conventional radiographs. Magnetic resonance and dynamic imaging can be used as ancillary imaging modalities. With regard to fracture classification, the systems described by Anderson/D'Alonzo and by Eysel/Roosen have proved to be of value. A treatment algorithm was developed based on these classifications. Anderson/D'Alonzo type 1, type 3, and non-displaced type 2 fractures usually can be treated non-operatively. However, a close clinical and radiological follow-up is essential. In Anderson/D'Alonzo type 2 fractures, operative treatment is associated with better fracture healing. Displaced type 2 and type 3 fractures should be stabilized operatively. Type 2 fractures with suitable fracture patterns (Eysel/Roosen 2A/B) can be stabilized anteriorly. Posterior C I/II-stabilization procedures are well established and suitable for all fracture patterns.

Recommendations for the Diagnostic Testing and Therapy of Atlas Fractures. / Empfehlungen zur Diagnostik und Therapie oberer Halswirbelsäulenverletzungen: Atlasfrakturen.

In a consensus process with four sessions in 2017, the working group on "the upper cervical spine" of the German Society for Orthopaedic and Trauma Surgery (DGOU) formulated "Therapeutic Recommendations for the Diagnosis and Treatment of Fractures to the Upper Cervical Spine", incorporating their own experience and current literature. The following article describes the recommendations for the atlas vertebra. About 10% of all cervical spine injuries include the axis vertebra. The diagnostic process primarily aims to detect the injury and to determine joint incongruency and integrity of the atlas ring. For classification purposes, the Gehweiler classification and the Dickman classification are suitable. The Canadian c-spine rule is recommended for clinical screening for c-spine injuries. CT is the preferred imaging modality; MRI is needed to determine the integrity of the Lig. transversum atlantis in complete atlas ring fractures. Conservative treatment is appropriate in very many atlas fractures. Surgical treatment is recommended in existing or potential joint incongruity or instability, which are frequently seen in Gehweiler IIIB or Gehweiler IV fractures. Posterior atlanto-axial stabilisation and fusion using transarticular screws or an internal fixator are regarded as a gold standard in the majority of surgical cases. Especially in young patients, the possibility of isolated atlas osteosynthesis should be checked. A possible option for Gehweiler IV fractures is halo-fixation with mild distraction for ligamentotaxis. Secondary dislocation should be checked for frequently. Involvement of the occipito-atlantal joint complex requires stabilisation of the occiput as well.

Recommendations for Diagnosis and Treatment of Fractures of the Ring of Axis. / Empfehlungen zur Diagnostik und Therapie oberer Halswirbelsäulenverletzungen: Axisringfrakturen.

In a consensus process with four sessions in 2017, the working group "upper cervical spine" of the German Society for Orthopaedics and Trauma Surgery (DGOU) formulated "Therapeutic Recommendations for the Diagnosis and Treatment of Upper Cervical Fractures", taking their own experience and the current literature into consideration. The following article describes the recommendations for axis ring fractures (traumatic spondylolysis C2). About 19 to 49% of all cervical spine injuries include the axis vertebra. Traumatic spondylolysis of C2 may include potential discoligamentous instability C2/3. The primary aim of the diagnostic process is to detect the injury and to determine potential disco-ligamentous instability C2/3. For classification purposes, the Josten classification or the modified Effendi classification may be used. The Canadian C-spine rule is recommended for clinical screening for C-spine injuries. CT is the preferred imaging modality and an MRI is needed to determine the integrity of the discoligamentous complex C2/3. Conservative treatment is appropriate in case of stable fractures with intact C2/3 motion segment (Josten type 2 and 2). Patients should be closely monitored, in order to detect secondary dislocation as early as possible. Surgical treatment is recommended in cases of primary severe fracture dislocation or discoligamentous instability C2/3 (Josten 3 and 4) and/or secondary fracture dislocation. Anterior cervical decompression and fusion (ACDF) C2/3 is the treatment of choice. However, in case of facet joint luxation C2/3 with looked facet (Josten 4), a primary posterior approach may be necessary.

Expression of a metalloproteinase family of ADAMTS in human vulnerable carotid lesions.

AIMS: ADAMTS family of metalloproteases (a disintegrin and metalloprotease with thrombospondin motifs) possesses high proteolytic activity especially regarding proteoglycans. Their expression pattern in carotid plaques is as-yet unknown. The aim of the study was therefore the analysis of expression of ADAMTS1, 4, 5, and 13 and their inhibitors TIMP-1 and TIMP-3 in stable and unstable carotid plaques. METHODS: Atherosclerotic plaques were collected from 40 patients (29 men, 11 women, mean age 70 years) undergoing carotid endarterectomy. The specimens were categorized into two groups (stable/unstable) according to Redgrave und Rothwell (The Oxford Plaque Study, 2008). SYBR Green-based real-time PCR, histology, and immunohistochemistry were performed. RESULTS: All ADAMTS tested in our study were expressed in both stable and unstable plaques, especially in smooth muscle cells (SMCs) and macrophages. Analysis of the expression pattern on mRNA level showed significant higher expression of ADAMTS1 in unstable plaques compared with stable plaques (1.7-fold, P = 0.049). The expression of ADAMTS4 and 5 was also increased in unstable lesions; however, these changes were not statistically significant (1.2-fold, P = 0.667 and 1.6-fold, P = 0.077). Expression of TIMP-1 was significantly reduced in unstable plaques compared with stable ones (1.9-fold, P = 0.014). CONCLUSION: SMCs seem to be an important source of ADAMTS analyzed in our study. Furthermore, expression of ADAMTS1 was found to be increased in unstable carotid lesions and might potentially contribute to plaque vulnerability.

Adult Degenerative Scoliosis with Spinal Stenosis Treated with Stand-Alone Cage via an Extreme Lateral Transpsoas Approach; a Case Report and Literature Review.

We report the case of a 73-year-old female with severe degenerative scoliosis and back and leg pain that was successfully treated with stand- alone cages via an extreme lateral transpsoas approach. This patient had declined open surgery and instrumentation due to her advanced age concerns about potential side effects.

Comparison of navigated versus non-navigated pedicle screw placement in 260 patients and 1434 screws: screw accuracy, screw size, and the complexity of surgery.

OBJECTIVE: Computer 3D navigation (3D NAV) techniques in spinal instrumentation can theoretically improve screw placement accuracy and reduce injury to critical neurovascular structures, especially in complex cases. In this series, we analyze the results of 3D NAV in pedicle screw placement accuracy, screw outer diameter, and case complexity in comparison with screws placed with conventional lateral fluoroscopy. METHODS: Pedicle screws placed in the cervical, thoracic, or lumbar spine using either standard lateral fluoroscopy or 3D NAV using isocentric fluoroscopy were retrospectively analyzed. The accuracy of each individual screw was graded on a 4-tiered classification system. Screw and pedicle diameter measurements were also made in both cohorts, and case complexity was compared between the 2 cohorts. Complex cases were defined as deformity surgery, re-do cases, and minimally invasive surgery. RESULTS: A total of 708 screws were placed under 3D NAV guidance and 726 screws were placed without stereotaxy. Eighty-eight percent of 3D NAV-guided pedicle screws were graded nonbreach versus 82% of cases with lateral fluoroscopy (P<0.001). The ratio of screw/pedicle diameter was significantly larger in the 3D NAV cohort (0.71 vs. 0.63, P<0.05). Seventy-six percent of 3D NAV cases had a predefined aspect of complexity, whereas 44% of non-3D NAV cases met criteria to be labeled complex (P<0.001). Reoperation occurred less frequently in 3D NAV cases than fluoroscopy alone. CONCLUSIONS: The use of 3D NAV was associated with improved screw placement accuracy, improved screw-to-pedicle diameter measurements, and was used in cases with a higher degree of surgical complexity. We conclude that 3D NAV is a valuable tool in current spinal instrumentation, especially for more complex surgeries.

Tissue-engineered intervertebral discs: MRI results and histology in the rodent spine.

OBJECT: Tissue-engineered intervertebral discs (TE-IVDs) represent a new experimental approach for the treatment of degenerative disc disease. Compared with mechanical implants, TE-IVDs may better mimic the properties of native discs. The authors conducted a study to evaluate the outcome of TE-IVDs implanted into the rat-tail spine using radiological parameters and histology. METHODS: Tissue-engineered intervertebral discs consist of a distinct nucleus pulposus (NP) and anulus fibrosus (AF) that are engineered in vitro from sheep IVD chondrocytes. In 10 athymic rats a discectomy in the caudal spine was performed. The discs were replaced with TE-IVDs. Animals were kept alive for 8 months and were killed for histological evaluation. At 1, 5, and 8 months, MR images were obtained; T1-weighted sequences were used for disc height measurements, and T2-weighted sequences were used for morphological analysis. Quantitative T2 relaxation time analysis was used to assess the water content and T1ρ-relaxation time to assess the proteoglycan content of TE-IVDs. RESULTS: Disc height of the transplanted segments remained constant between 68% and 74% of healthy discs. Examination of TE-IVDs on MR images revealed morphology similar to that of native discs. T2-relaxation time did not differ between implanted and healthy discs, indicating similar water content of the NP tissue. The size of the NP decreased in TE-IVDs. Proteoglycan content in the NP was lower than it was in control discs. Ossification of the implanted segment was not observed. Histological examination revealed an AF consisting of an organized parallel-aligned fiber structure. The NP matrix appeared amorphous and contained cells that resembled chondrocytes. CONCLUSIONS: The TE-IVDs remained viable over 8 months in vivo and maintained a structure similar to that of native discs. Tissue-engineered intervertebral discs should be explored further as an option for the potential treatment of degenerative disc disease.

Short-term exercise-induced changes in hydration state of healthy Achilles tendons can be visualized by effects of off-resonant radiofrequency saturation in a three-dimensional ultrashort echo time MRI sequence applied at 3 Tesla.

PURPOSE: Off-resonant RF saturation influences signal intensity dependent on free and bound water fractions as well as the macromolecular content. The extent of interaction between these compartments can be evaluated by using the off-resonance saturation ratio (OSR). Combined with UTE sequences quantification of OSR even in tendinous tissues with extremely fast signal decay is possible. The aim of this prospective study was to investigate short-term exercise-induced effects of hydration state of the Achilles tendon by means of OSR and tendon volume. MATERIALS AND METHODS: Measurements of OSR and tendon volume before and after ankle-straining activity were performed in seven healthy male volunteers (median age 29 years) using a 3D UTE sequence with implemented off-resonance saturation pulse at 3T (off-resonance frequency 2/3 kHz) and by an automated contour detection in isotropic T2-weighted MR images with sub-millimeter resolution, respectively. Different tendon regions were evaluated. Reproducibility of OSR was measured in subsequent imaging sets. Root-mean-square-deviation (RMSD) and coefficient of variations (CV) were determined. RESULTS: RMSD of OSR in resting position were between 0.006 and 0.01 for different tendon regions and off-resonance frequencies (CV 2 to 3%). A significant increase (P < 0.05) of OSR after exercise was seen in all tendon regions except at the insertion (off-resonance frequency 3 kHz). Tendon volume was decreased significantly after ankle-straining activity (P = 0.003). CONCLUSION: The observed decreased tendon volume and increased OSR directly after exercise indicates a short-term change in tendinous proton compartments, most likely a loss of free water molecules within the tendon.

The use of an ultraportable universal serial bus endoscope for education and training in neuroendoscopy.

BACKGROUND: Video endoscopy systems are typically very expensive and not particularly portable. We evaluated an inexpensive and ultraportable system for laboratory training in skull base endoscopic dissections. METHODS: In June 2010, we assembled commercially available components consisting of a universal serial bus-powered video camera, a battery-charged light-emitting diode (LED) light source, and a 13-inch laptop to perform skull base endoscopic dissection at our anatomy laboratory. We evaluated its cost, portability, and image quality as a valid tool for neurosurgical and rhinology training. RESULTS: The system performed smoothly with no clinical perception of image delay during video recording. The LED light source and the overall image quality were considered adequate, providing appropriate detail for endoscopic surgical simulation in the laboratory. The cost is around 1/10 to 1/100 of a standard or high-definition endoscopy system, and the entire system weighs only 5 pounds. CONCLUSIONS: The combination of a portable computer's video processing allied to a highly energy-efficient video camera and LED light source is useful for training in neuroendoscopy. Its clinical role in settings with limited resources requires further research.

Image-based tissue engineering of a total intervertebral disc implant for restoration of function to the rat lumbar spine.

Nonbiological total disc replacement is currently being used for the treatment of intervertebral disc (IVD) disease and injury, but these implants are prone to mechanical wear, tear and possible dislodgement. Recently, tissue-engineered total disc replacement (TE-TDR) has been investigated as a possible alternative to more fully replicate the native IVD properties. However, the performance of TE-TDRs has not been studied in the native disc space. In this study, MRI and microcomputed tomography imaging of the rat spine were used to design a collagen (annulus fibrosus)/alginate (nucleus pulposus) TE-TDR to a high degree of geometric accuracy, with less than 10% difference between TE-TDR and the native disc dimensions. Image-based TE-TDR implants were then inserted into the L4/L5 disc space of athymic rats (n = 5) and maintained for 16 weeks. The disc space was fully or partially maintained in three of five animals and proteoglycan and collagen histology staining was similar in composition to the native disc. In addition, good integration was observed between TE-TDR and the vertebral bodies, as well as remnant native IVD tissue. Overall, this study provides evidence that TE-TDR strategies may yield a clinically viable treatment for diseased or injured IVD.

Tissue-engineered intervertebral discs produce new matrix, maintain disc height, and restore biomechanical function to the rodent spine.

Lower back and neck pain are leading physical conditions for which patients see their doctors in the United States. The organ commonly implicated in this condition is the intervertebral disc (IVD), which frequently herniates, ruptures, or tears, often causing pain and limiting spinal mobility. To date, approaches for replacement of diseased IVD have been confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Here we present the evaluation of a living, tissue-engineered IVD composed of a gelatinous nucleus pulposus surrounded by an aligned collagenous annulus fibrosus in the caudal spine of athymic rats for up to 6 mo. When implanted into the rat caudal spine, tissue-engineered IVD maintained disc space height, produced de novo extracellular matrix, and integrated into the spine, yielding an intact motion segment with dynamic mechanical properties similar to that of native IVD. These studies demonstrate the feasibility of engineering a functional spinal motion segment and represent a critical step in developing biological therapies for degenerative disc disease.

Biological intervertebral disc replacement: an in vivo model and comparison of two surgical techniques to approach the rat caudal disc.

STUDY DESIGN: Prospective randomized animal study. OBJECTIVE: To determine a surgical technique for reproducible and functional intervertebral disc replacement in an orthotopic animal model. METHODS: The caudal 3/4 intervertebral disc (IVD) of the rat tail was approached by two surgical techniques: blunt dissection, stripping and retracting (Technique 1) or incising and repairing (Technique 2) the dorsal longitudinal tendons. The intervertebral disc was dissected and removed, and then either discarded or reinserted. Outcome measures were perioperative complications, spontaneous tail movement, 7T MRI (T1- and T2-sequences for measurement of disc space height (DSH) and disc hydration). Microcomputed tomographic imaging (micro CT) was additionally performed postmortem. RESULTS: No vascular injuries occurred and no systemic or local infections were observed over the course of 1 month. Tail movements were maintained. With tendon retraction (Technique 1) gross loss of DSH occurred with both discectomy and reinsertion. Tendon division (Technique 2) maintained DSH with IVD reinsertion but not without. The DSH was demonstrated on MRI measurement. A new scoring system to assess IVD appearances was described. CONCLUSIONS: The rat tail model, with a tendon dividing surgical technique, can function as an orthotopic animal model for IVD research. Mechanical stimulation is maintained by preserved tail movements. 7T MRI is a feasible modality for longitudinal monitoring for the rat caudal disc.

Tissue-engineered total disc replacement: final outcomes of a murine caudal disc in vivo study.

Consistent with EBSJ's commitment to fostering quality research, we are pleased to feature some of the most highly rated abstracts from the 9th Annual AOSpine North America Fellows Forum in Banff, Canada. Enhancing the quality of evidence in spine care means acknowledging and supporting the efforts of young researchers within our AOSpine North America network. We look forward to seeing more from these promising researchers in the future.

Artrodese na coluna cervical utilizando SICAP como substituto de enxerto ósseo / Artrodesis en la columna cervical utilizando SICAP como sustituto de injerto óseo / Cervical spine fusion utilizing silicated calcium phosphate bone graft substitute SICAP

OBJETIVO: Substitutos de enxerto ósseo autólogo foram desenvolvidos para evitar as complicações da retirada de enxerto ósseo autólogo. SiCaP (Actifuse, ApaTech EUA, Reino Unido) é um enxerto ósseo composto de cálcio-fosfato com um substituição de silicato na estrutura química, com uma estrutura tridimensional que parece osso natural. MÉTODOS: 19 pacientes foram submetidos à fusão óssea cervical e analisados retrospectivamente. A avaliação radiográfica e avaliação clínica foram realizadas utilizando o questionário Neck Disability Index e a escala análoga da dor (VAS) pré- e pós-operação. RESULTADOS: O período médio de acompanhamento pós-operatório foi de 14 meses ± 5 meses (7-30 meses). 11 pacientes foram submetidos à fusão via anterior; 5 pacientes via posterior e 3 pacientes via anterior e posterior. A revisão radiográfica mostrou 19/19 (100 por cento) de fusão óssea, nenhum caso apresentou subsidência, quebra ou soltura de material de implante ou movimento nos níveis fusionados. Nenhum exemplo de ossificação heterotópica ou de crescimento ósseo intracanal foi observado. Clinicamente, os escores médios do Neck Disability decresceram 13,3 pontos (media pré-op. de 34,5, pós-op. de 21,2, melhora de 39 por cento), a média da VAS para dor cervical decresceu 2 pontos (2,7 pré-op para 0,7 pós-op.; melhora de 74,1 por cento). Não foram observadas complicações como infecção, osteólise ou edema excessivo das partes moles. CONCLUSÃO: Os resultados preliminares obtidos nesta série foram encorajadores com o uso do SICaP como enxerto ósseo, com sólida fusão óssea obtida em todos os casos e sem formação de ossificação heterotópica ou crescimento de osso intracanal. SIcaP demonstra ser um substituto confiável para o enxerto ósseo autólogo na coluna cervical.

OBJECTIVE: Bone graft substitutes have been developed to obviate the need for autograft from the iliac crest and its resultant complications. SiCaP (Actifuse, ApaTech US, UK) is a calcium phosphate bone graft substitute with selective controlled silicate substitution in a patented 3-dimensional structure resembling natural bone. METHODS: 19 patients who underwent cervical spine fusion were retrospectively reviewed. Radiographic evaluation and clinical evaluation were performed using Neck Disability Index questionnaire and Visual Analog Scale (VAS) pre- and post-operatively. RESULTS: The mean post-operative follow-up was 14 ± 5 months, range 7-30 months. Eleven patients had an anterior approach, five patients had a posterior approach, and 3 had combined anterior-posterior approaches. Radiographic review showed 19/19 (100 percent) patients were considered fused, with no subsidence, hardware breakage, or hardware loosening. No instances of heterotopic bone formation or intracanal boney ingrowths were observed. Clinically, average Neck Disability scores decreased 13.3 points (pre-op 34.5, post-op 21.2, a 39 percent improvement); average VAS neck pain scores decreased 2.2 points (4.9 pre-op to 1.9 post-op; a 44.9 percent improvement; average VAS arm pain decreased 2.0 points (2.7 pre-op to 0.7 post-op, a 74.1 percent improvement). There were no complications such as infection, osteolysis, or abnormal swelling of soft tissues. CONCLUSIONS: Preliminary results from this series with the use of SiCaP bone graft substitute were encouraging, with solid fusion occurring in all subjects, and no heterotopic bone formation or intracanal bone ingrowths. SiCaP seems to be a reliable alternative to autograft on cervical spine fusion achieving solid fusion with no complications.

OBJETIVO: Sustitutos de injerto óseo autólogo fueron desarrollados para evitar las complicaciones de la recogida de injerto óseo autólogo. SiCaP (Actifuse, ApaTech EE.UU, Reino Unido) es un injerto óseo compuesto de calcio-fosfato con una sustitución de silicato en la estructura química, con una estructura tridimensional que parece hueso natural. MÉTODOS: 19 pacientes fueron sometidos a fusión ósea cervical y analizados retrospectivamente. La evaluación radiográfica y la evaluación clínica fueron realizadas utilizandose el cuestionario Neck Disability Index y la escala análoga del dolor (VAS) pre y postoperación. RESULTADOS: El período promedio de seguimiento postoperatorio fue de 14 meses ± 5 meses (7-30 meses). Once pacientes fueron sometidos a fusión vía anterior; 5 pacientes vía posterior y 3 pacientes vía anterior y posterior. La revisión radiográfica mostró 19/19 (100 por ciento) de fusión ósea, ningún caso presentó subsidencia, rotura o soltura de material de implante o movimiento en los niveles fusionados. Ningún ejemplo de osificación heterotópica o de crecimiento óseo intracanal fue observado. Clínicamente, el promedio de las puntuaciones del Neck Disability disminuyeron 13,3 puntos (promedio preop. de 34,5, postop. de 21,2, mejora de 39 por ciento), el promedio de VAS para dolor cervical disminuyó 2 puntos (2,7 preop. para 0,7 postop.; mejora de 74,1 por ciento). No fueron observadas complicaciones como infección, osteólisis o edema excesivo de las partes blandas. CONCLUSIÓN: Los resultados preliminares obtenidos en esta serie feuron estimulantes con el uso de SICaP como injerto óseo, con sólida fusión ósea obtenida en todos los casos y sin formación de osificación heterotópica o crecimiento de hueso intracanal. SIcaP demuestra ser un sustituto confiable para el injerto óseo autólogo en la columna cervical.

Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results.

STUDY TYPE: Basic science Introduction: Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3 Figure 1 Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)-Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time Objective: The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics. METHODS: Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5). Figure 2 Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: BoneFigure 3 Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc spaceFigure 4 Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a-c H&E (overall tissue staining for light micrsocopy) d-f Alcian blue (proteoglycans) g-i Picrosirius red (collagen I and II)Figure 5 Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body boneFigure 6 MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NPFigure 7 7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP) Results: The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months. CONCLUSIONS: This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d-f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants.

Bioabsorbable instrumentation for single-level cervical degenerative disc disease: a radiological and clinical outcome study.

OBJECT: The authors present the radiological and clinical outcome data obtained in patients who underwent single-level anterior cervical discectomy and fusion (ACDF) for cervical spondylosis and/or disc herniation; bioabsorbable plates were used for instrumentation. The use of metallic plates in ACDF has gained acceptance as a stabilizing part of the procedure to increase fusion rates, but when complications occur with these devices, the overall effectiveness of the procedure is compromised. As a possible solution, bioabsorbable implants for ACDF have been developed. This study investigates the feasibility and radiological and clinical outcomes of the bioabsorbable plates for ACDF. METHODS: The radiological and clinical outcomes of 30 patients were investigated retrospectively. All patients presented with cervical radiculopathy or myelopathy and underwent single-level ACDF in which a bioabsorbable anterior cervical plate and an allograft bone spacer were placed at a level between C-3 and C-7. Radiological outcome was assessed based on the fusion rate, subsidence, and Cobb angle of the surgical level. Clinical outcome was determined by using a visual analog scale, the Neck Disability Index, and the Odom criteria. RESULTS: There were no intraoperative complications, and no hardware failure was observed. No signs or symptoms of adverse tissue reaction caused by the implant were seen. Two reoperations were necessary due to postoperative blood collections. The overall complication rate was 16.7%. After 6 months, radiographic fusion was seen in 92.3% of patients. Subsidence at 11.3 +/- 7.2 months was 3.1 +/- 5.8 mm (an 8.2% change over the immediately postoperative results), and the change in the sagittal curvature was -2.7 +/- 2.7 degrees . The visual analog scale score for neck and arm pain and Neck Disability Index improved significantly after surgery (p < 0.001). Overall at 19.5 months postoperatively, 83% of the patients had favorable outcomes based on the Odom criteria. CONCLUSIONS: Absorbable instrumentation provides better stability than the absence of a plate but graft subsidence and deformity rates may be higher than those associated with metal implants. There were no device-related complications, but adverse late effects cannot be excluded. The fusion rate and outcome are comparable to the results achieved with metallic plates. The authors were satisfied with the use of bioabsorbable plates as a reasonable alternative to metal, avoiding the need for lifelong metallic implants.

The macrophage alphaMbeta2 integrin alphaM lectin domain mediates the phagocytosis of chilled platelets.

alpha(M)beta(2) integrin receptors on myeloid cells mediate the adhesion or uptake of diverse ligands. Ligand binding occurs in the alpha(M) chain, which is composed of an I domain and a lectin domain. The alpha(M) I domain binds iC3b, fibrinogen, intercellular adhesion molecule-1, and other ligands and mediates the adhesion of neutrophils to platelet glycoprotein Ibalpha (GPIbalpha). alpha(M)beta(2) also recognizes beta-GlcNAc residues on GPIbalpha that are clustered on platelets after cooling. The phagocytosis of chilled platelets could be reconstituted when Chinese hamster ovary cells were transfected with alpha(M)beta(2). Replacement of the I domain or the lectin domain of the alpha(M) chain with the corresponding domain from the alpha(X) chain (p150) revealed that the activity of the alpha(M)beta(2) integrin toward chilled platelets resides within the lectin domain and does not require the I domain. Additional evidences for this conclusion are: 1) Sf9 cells expressing solely the alpha(M) lectin domain bound chilled platelets, and 2) soluble recombinant alpha(M) lectin domain inhibited the phagocytosis of chilled platelets by alpha(M)beta(2)-expressing THP-1 cells, whereas I domain substrates showed no inhibitory effect. Therefore chilled platelets are removed from blood by an interaction between beta-GlcNAc residues on clustered GPIbalpha and the lectin domain of alpha(M) chain of the alpha(M)beta(2) integrin, distinguishing this interaction from those mediated by the alpha(M) I domain.

Influence of orthopedic particulate biomaterials on inflammation and synovial microcirculation in the murine knee joint.

The purpose of the present study was to examine changes in the synovial microcirculation as well as synovial tissue responses to exposure to titanium, polymethylmethacrylate (PMMA), ceramic (Al(2)O(3)), cobalt-chromium alloy (Co-Cr), and polyethylene (PE) particles in an in vivo model. The particulate biomaterials were injected into the left knee joint of female Balb/c mice and assessment of the synovial microcirculation using intravital fluorescence microscopy as well as histological evaluation of the synovial tissue response were performed on day 7 after particle administration. Intravital microscopic measurements revealed that all tested biomaterials caused significantly (p < 0.05) enhanced leukocyte-endothelial cell interactions and an increase of functional capillary density compared to controls. In the histological examination PMMA, Al(2)O(3), PE, and Co-Cr particles provoked significantly (p < 0.05) enhanced inflammatory tissue responses in comparison to tissue from control animals. Titanium particles showed significantly (p < 0.05) less leukocyte-endothelial cell interactions than the other particulate biomaterials and caused significantly (p < 0.05) minor membrane thickening compared to PE and PMMA particles. In conclusion, all tested particulate biomaterials were capable of inducing inflammatory responses in the present study. Our data suggest that titanium particles may cause less leukocyte activation and inflammatory tissue responses than other particulate biomaterials used in total joint arthroplasty.