Mario Cabraja

Regeneration of intervertebral disc tissue by resorbable cell-free polyglycolic acid-based implants in a rabbit model of disc degeneration.

Study Design. Different biologic strategies exist to treat degenerative disc disease. Tissue engineering approaches favor autologous chondrocyte transplantation. In our one-step-approach, a resorbable cell-free polyglycolic acid (PGA)-based implant is immersed in serum from whole blood and implanted into the disc defect directly after discectomy. Objectives. The aim of our study was to investigate the capacity of a cell-free implant composed of a PGA felt, hyaluronic acid, and serum to recruit disc cells and stimulate repair tissue formation in vivo after microdiscectomy in a rabbit model. Summary of the Background Data. Disc tissue has a limited ability to regenerate after the degeneration process was once initiated. Therefore, we developed a cell-free resorbable implant that is able to attract local cells into the defect and induce proper repair tissue formation. Methods. The cell-free implant consisting of PGA and hyaluronic acid was immersed in allogenic serum and implanted into the disc defect after discectomy in New Zealand white rabbits. One week and 6 months after the operation, the disc height index and the T2-weighted signal intensity index were determined using plane radiographs and magnetic resonance imaging. Finally, discs were explanted and investigated histologically. Animals with discectomy only served as controls. Results. In our animal studies, we could demonstrate that the T2-weighted signal intensity of the operated discs decreased in both groups 1 week after surgery. However, after 6 months, the T2-weighted signal intensity index increased by 45% in the implanted group whereas the index decreased further by 11% in the sham group. This corresponded to changes in the disc height index. Furthermore, the histologic examinations indicated cell migration into the defect and showed tissue regeneration. Conclusion. The implantation of a cell-free PGA-hyaluronic acid implant immersed in serum after discectomy induces regeneration, resulting in improvement of the disc water content and preservation of the disc height 6 months after surgery.

Anterior cervical discectomy and fusion: Comparison of titanium and polyetheretherketone cages

BackgroundTitanium (TTN) cages have a higher modulus of elasticity when compared with polyetheretherketone (PEEK) cages. This suggests that TTN-cages could show more frequent cage subsidence after anterior cervical discectomy and fusion (ACDF) and therefore might lead to a higher loss of correction. We compared the long term results of stand-alone PEEK- and TTN-cages in a comparable patient collective that was operated under identical operative settings.MethodsFrom 2002 to 2007 154 patients underwent single-level ACDF for degenerative disc disease (DDD). Clinical and radiological outcome were assessed in 86 eligible patients after a mean of 28.4 months. 44 patients received a TTN- and 42 patients a PEEK-cage.ResultsSolid arthrodesis was found in 93.2% of the TTN-group and 88.1% of the PEEK-group. Cage subsidence was observed in 20.5% of the TTN- and 14.3% of the PEEK-group. A significant segmental lordotic correction was achieved by both cage-types. Even though a loss of correction was found at the last follow-up in both groups, it did not reach the level of statistical significance. Statistical analysis of these results revealed no differences between the TTN- and PEEK-group.When assessed with the neck disability index (NDI), the visual analogue scale (VAS) of neck and arm pain and Odom’s criteria the clinical data showed no significant differences between the groups.ConclusionsClinical and radiological outcomes of ACDF with TTN- or PEEK-cages do not appear to be influenced by the chosen synthetic graft. The modulus of elasticity represents only one of many physical properties of a cage. Design, shape, size, surface architecture of a cage as well as bone density, endplate preparation and applied distraction during surgery need to be considered as further important factors.

Comparison between anterior and posterior decompression with instrumentation for cervical spondylotic myelopathy: sagittal alignment and clinical outcome

OBJECT A variety of anterior, posterior, and combined approaches exist to decompress the spinal cord, restore sagittal alignment, and avoid kyphosis, but the optimal surgical strategy remains controversial. The authors compared the anterior and posterior approach used to treat multilevel cervical spondylotic myelopathy (CSM), focusing on sagittal alignment and clinical outcome. METHODS The authors studied 48 patients with CSM who underwent multilevel decompressive surgery using an anterior or posterior approach with instrumentation (24 patients in each group), depending on preoperative sagittal alignment and direction of spinal cord compression. In the anterior group, a 1-2-level corpectomy was followed by placement of an expandable titanium cage. In the posterior group, a multilevel laminectomy and posterior instrumentation using lateral mass screws was performed. Postoperative radiography and clinical examinations were performed after 1 week, 12 months, and at last follow-up (range 15-112 months, mean 33 months). The radiological outcome was evaluated using measurement of the cervical and segmental lordosis. RESULTS Both the posterior multilevel laminectomy (with instrumentation) and the anterior cervical corpectomy (with instrumentation) improved clinical outcome. The anterior group had a significantly lower preoperative cervical and segmental lordosis than the posterior group. The cervical and segmental lordosis improved in the anterior group by 8.8 and 6.2 degrees, respectively, and declined in the posterior group by 6.5 and 3.8 degrees, respectively. The loss of correction was higher in the anterior than in the posterior group (-2.0 vs -0.7 degrees, respectively) at last follow-up. CONCLUSIONS These results demonstrate that both anterior and posterior decompression (with instrumentation) are effective procedures to improve the neurological outcome of patients with CSM. However, sagittal alignment may be better restored using the anterior approach, but harbors a higher rate of loss of correction. In cases involving a preexisting cervical kyphosis, an anterior or combined approach might be necessary to restore the lordotic cervical alignment.

Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration model

Degeneration of the intervertebral disc is the most common cause of lower back pain. Interestingly, all available treatments are limited to treat the symptoms and not the underlying biologic alterations of the disc. Freeze-dried resorbable non-woven polyglycolic acid (PGA) - hyaluronan implants were used in a degenerated disc disease (DDD) model in New Zealand white rabbits. The constructs were immersed in allogenic serum and implanted into the disc defect. Animals with discectomy only served as controls. The T2-weighted/fat suppression sequence signal intensity of the operated discs as assessed by magnet resonance imaging decreased in both groups one week after the operation compared to a healthy disc. After 12 months the implanted group showed an increase of 51% in the signal intensity compared to the 1-week results whereas the signal intensity in the sham group remained on the same level from one week to 12 months. Histological and quantitative immunohistochemical examination after 12 months indicated cell migration into the defect and showed formation of disc repair tissue. In controls, repair tissue containing type II collagen was not evident. In conclusion, the implantation of polymer-based constructs after discectomy induces tissue regeneration resulting in improvement of the disc water content.

Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration

OBJECT The object of this study was to characterize the regenerative potential of cells isolated from herniated disc tissue obtained during microdiscectomy. The acquired data could help to evaluate the feasibility of these cells for autologous disc cell transplantation. METHODS From each of 5 patients (mean age 45 years), tissue from the nucleus pulposus compartment as well as from herniated disc was obtained separately during microdiscectomy of symptomatic herniated lumbar discs. Cells were isolated, and in vitro cell expansion for cells from herniated disc tissue was accomplished using human serum and fibroblast growth factor-2. For 3D culture, expanded cells were loaded in a fibrin-hyaluronan solution on polyglycolic acid scaffolds for 2 weeks. The formation of disc tissue was documented by histological staining of the extracellular matrix as well as by gene expression analysis of typical disc marker genes. RESULTS Cells isolated from herniated disc tissue showed significant signs of dedifferentiation and degeneration in comparison with cells from tissue of the nucleus compartment. With in vitro cell expansion, further dedifferentiation with distinct suppression of major matrix molecules, such as aggrecan and Type II collagen, was observed. Unlike in previous reports of cells from the nucleus compartment, the cells from herniated disc tissue showed only a weak redifferentiation process in 3D culture. However, propidium iodide/fluorescein diacetate staining documented that 3D assembly of these cells in polyglycolic acid scaffolds allows prolonged culture and high viability. CONCLUSIONS Study results suggested a very limited regenerative potential for cells harvested from herniated disc tissue. Further research on 2 major aspects in patient selection is suggested before conducting reasonable clinical trials in this matter: 1) diagnostic strategies to predict the regenerative potential of harvested cells at a radiological or cell biology level, and 2) clinical assessment strategies to elucidate the metabolic state of the targeted disc.

Neurophysiological intraoperative monitoring in neurosurgery: aid or handicap? An international survey.

OBJECT Neurophysiological intraoperative monitoring (IOM) is regarded as a useful tool to provide information about physiological changes during surgery in eloquent areas of the nervous system, to increase safety and reduce morbidity. Nevertheless, numerous older studies report that very few patients benefit from IOM, and that there are high rates of false-positive and false-negative changes of neurophysiological parameters during surgery. There is an ongoing discussion about the effectiveness of neurophysiological IOM. This questionnaire study was performed to evaluate the attitude of neurosurgeons toward neurophysiological IOM and the availability of this tool. METHODS One hundred fifty neurosurgeons from 60 institutions in 16 countries were asked to answer anonymously a questionnaire with 11 questions. The questionnaire covered aspects of personal experience, the neurosurgical institution, and availability of neurophysiological IOM as well as asking the surgeons opinion of the procedure. RESULTS One hundred nine questionnaires were returned (73%). Seven questionnaires were excluded because of failure to complete the form correctly or completely, leaving 102 respondents from 44 institutions in 16 countries in the study; 79.5% of the included institutions provided neurophysiological IOM. Young neurosurgeons did not put more trust in IOM than experienced neurosurgeons. With growing IOM experience, surgeons seem to allow less influence of the findings on the course of their operation. At large institutions in which > 1500 operations per year are done, IOM is performed by the neurosurgeons themselves in most cases. In institutions with fewer operations, the IOM team consists mostly of nonneurosurgeons. Regardless of the availability of neurophysiological IOM, all surgeons stated that IOM is gaining increasing importance. CONCLUSIONS Neurophysiological IOM represents an established tool in neurosurgery. Although the importance of IOM is emphasized by the majority of neurosurgeons, the relevance of this tool to the course of the operation changes with increasing neurophysiological IOM experience.

Atypical cervical spondylotic myelopathy mimicking intramedullary tumor.

Study Design. Case report and a review of the literature. Objective. We report the case of a young man with a short course of progressive cervical myelopathy (CM). Cervical magnetic resonance imaging (MRI) revealed a stenosis of the cervical spinal canal at C4–C6 and an atypically enlarged intramedullary high intensity extending from C1–T1 (T2-weighted) with contrast enhancement at C4–C5 (T1-weighted). Neurologic and radiologic diagnosis therefore favored a tumor of the spinal cord. Summary of Background Data. CM is a clinical diagnosis of mostly degenerative origin in older patients that features circumscribed high-intensity signals near the point of compression in T2-weighted MRI. Contrast enhancement in those high-intense areas is rarely described in the literature, and the differentiation from neoplastic and infective lesions might be very difficult in these cases. Methods. Retrospective case study with follow-up examination and MRI-control 3 months after surgery. Results. The patient was decompressed and stabilized from dorsally, and a biopsy was taken. The exact diagnosis of a myelopathy and an exclusion of a neoplastic origin succeeded through histopathological examination. Three months after first surgery, the patient had improved significantly and underwent an additional anterior stabilization, while the MRI remained almost unchanged. Conclusion. In case of a fast progressive CM with atypical radiographic appearance initial decompression with inspection of the spinal cord and a short-term clinical follow-up with an MRI control might be the procedure of choice, if a clear diagnosis for a causative treatment cannot be made. In still suspicious cases, a biopsy could be considered to exclude a neoplastic or inflammatory process.

Application of titanium and polyetheretherketone cages in the treatment of pyogenic spondylodiscitis

OBJECTIVE Surgical treatment of a pyogenic spondylodiscitis (PSD) involves a fixation and debridement of the affected segment combined with a specific antibiotic therapy. To achieve a proper stability and to avoid pseudarthrosis and kyphotic malposition many surgeons favour the interposition of an anterior graft. Besides autologous bone grafts titanium (TTN) cages have gained acceptance in the treatment of PSD. Polyetheretherketone (PEEK) cages have a more favourable modulus of elasticity than TTN. We compared both cage types. Primary endpoints were the rate of reinfection and radiological results. METHODS From 2004 to 2013 51 patients underwent surgery for PSD with fixation and TTN or PEEK cage-implantation. While lumbar patients underwent a partial discectomy by the posterior approach, discs of the cervical and thoracic patients had been totally removed from anterior. Clinical and radiological parameters were assessed in 37 eligible patients after a mean of 20.4 months. 21 patients received a PEEK- and 16 patients a TTN-cage. RESULTS A reinfection after surgery and 3 months of antibiotic therapy was not observed. Solid arthrodesis was found in 90.5% of the PEEK-group and 100% of the TTN-group. A segmental correction could be achieved in both groups. Nonetheless, a cage subsidence was observed in 70.3% of all cases. Comparison of radiological results revealed no differences between both groups. CONCLUSIONS A debridement and fixation with anterior column support in combination with an antibiotic therapy appear to be the key points for successful treatment of PSD. The application of TTN- or PEEK-cages does not appear to influence the radiological outcome or risk of reinfection, neither does the extent of disc removal in this clinical subset.

Towards biological anulus repair: TGF-β3, FGF-2 and human serum support matrix formation by human anulus fibrosus cells

Closure and biological repair of anulus fibrosus (AF) defects in intervertebral disc diseases is a therapeutic challenge. The aim of our study was to evaluate the anabolic properties of bioactive factors on cartilaginous matrix formation by AF cells. Human AF cells were harvested from degenerated lumbar AF tissue and expanded in monolayer culture. AF cell differentiation and matrix formation was initiated by forming pellet cultures and stimulation with hyaluronic acid (HA), human serum (HS), fibroblast growth factor-2 (FGF-2), transforming growth factor-β3 (TGF-β3) and TGF-β3/FGF-2 for up to 4 weeks. Matrix formation was assessed histologically by staining of proteoglycan, type I and type II collagens and by gene expression analysis of typical extracellular matrix molecules and of catabolic matrix metalloproteinases MMP-2 and MMP-13. AF cells, stimulated with HS, FGF-2 and most pronounced with TGF-β3 or TGF-β3/FGF-2 formed a cartilaginous matrix with significantly enhanced expression of matrix molecules and of MMP-13. Stimulation of AF cells with TGF-β3 was accompanied by induction of type X collagen, known to occur in hypertrophic cartilage cells having mineralizing potential. HA did not show any chondro-inductive characteristics. These findings suggest human serum, FGF-2 and TGF-β3 as possible candidates to support biological treatment strategies of AF defects.

A 3D environment for anulus fibrosus regeneration

OBJECT Biological repair strategies for the treatment of degenerated intervertebral discs are of growing interest. In addition to the development of nucleus pulposus implants to restore disc height and relieve pain, there is growing demand for an appropriate method for reconstructing the anulus fibrosus (AF). The aim of this pilot study was to evaluate the applicability of a resorbable 3D polymer of pure polyglycolic acid (PGA) combined with hyaluronan for the use in cell-free and cell-based regeneration and repair of the AF. METHODS Adult human AF cells were expanded in vitro using human serum and rearranged three dimensionally in hyaluronan-PGA scaffolds that were stabilized with fibrin for in vitro analyses. The capacity of dedifferentiated AF cells to redifferentiate was evaluated after 2 weeks of culture, using propidium iodide/fluorescein diacetate staining, gene expression analysis of typical marker genes, and histological staining of proteoglycans. RESULTS The propidium iodide/fluorescein diacetate staining demonstrated that vital human AF cells were evenly distributed within the construct. The induction of typical AF marker genes such as collagen Types I-III indicated the initiation of AF redifferentiation by 3D assembly in hyaluronan-PGA. Histological analysis of the constructs showed initial formation of an AF-like matrix comprising proteoglycans. CONCLUSIONS The results suggest that the 3D arrangement of human AF cells in resorbable hyaluronan-PGA scaffolds cultured in the presence of human serum is an excellent system for AF cell redifferentiation.