Surgical repair of annulus defect with biomimetic multilamellar nano/microfibrous scaffold in a porcine model.

Annulus defect is associated with reherniation and disc degeneration after discectomy; currently there is no effective treatment that addresses this problem. The annulus is a hierarchical lamellar structure, where each lamella consists of aligned collagen fibres, which are parallel and tilted at 30° to the spinal axis. In this study, a biomimetic biodegradable scaffold consisting of multilamellar nano/microfibres, sharing nanotopography and microporosity similar to the native lamellar structure, was assessed in a porcine model, aided by sealing with fascia and medical glue and subsequent suture fixation. After 6- and 12-week observation, we found that this treatment restored nucleus volume and slowed down disc degeneration, as indicated by magnetic resonance imaging of T1/T2-weighted, T2-mapping, T1-ρ imaging. Histological analysis showed aligned collagen fibres organized in the scaffold and integrated with surrounding native annulus tissue. The autologous bone marrow concentrate-seeded scaffolds showed slightly earlier collagen fibre formation at 6 weeks. This novel treatment could efficiently close the annulus defect with newly formed, organized and integrated collagen fibres in a porcine model. Copyright © 2016 John Wiley & Sons, Ltd.

[Nephrotic syndrome and microhematuria in a patient with nutcracker syndrome: Report of a case and review of the literature]. / Nephrotisches Syndrom und Mikrohämaturie bei einer Patientin mit Nussknacker-Syndrom: Ein Fallbericht mit Literaturübersicht.

We report about a 43-year-old woman with polyvalent drug addiction (i.e. alcohol, nicotine, methadone maintenance program with parallel consumption of heroin) who presented to the emergency department with peripheral edema, generalized weakness, and arthralgia. Laboratory findings revealed, among others, proteinuria, hyperlipoproteinemia and hypoproteinemia defining nephrotic syndrome. Computed tomography of the abdomen and iliocavography further revealed compression of left renal vein between aorta and superior mesenteric artery with distention of left ovarian vein as a possible cause of nephrotic syndrome (i. e. nutcracker syndrome). After excluding other possible causes of nephrotic syndrome, we decided against an interventional procedure due to poor compliance of the patient and potential risk of secondary stent dislocation. Instead, we opted for a surgical approach (i. e. veno-venous bypass, meaning transposition of left vena ovarica on vena cava inferior). The operative and postoperative course was uneventful. Postoperatively, proteinuria, microhematuria, arthralgia and edema receded.

First Evidence for cos2ß>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity.

We present first evidence that the cosine of the CP-violating weak phase 2ß is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2ß=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2ß=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle ß of the CKM Unitarity Triangle is ß=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2ß>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-ß=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.

Surgery for metastatic spine tumors in the elderly. Advanced age is not a contraindication to surgery!

BACKGROUND: With recent advances in oncologic treatments, there has been an increase in patient survival rates and concurrently an increase in the number of incidence of symptomatic spinal metastases. Because elderly patients are a substantial part of the oncology population, their types of treatment as well as the possible impact their treatment will have on healthcare resources need to be further examined. PURPOSE: We studied whether age has a significant influence on quality of life and survival in surgical interventions for spinal metastases. STUDY DESIGN: We used data from a multicenter prospective study by the Global Spine Tumor Study Group (GSTSG). This GSTSG study involved 1,266 patients who were admitted for surgical treatments of symptomatic spinal metastases at 22 spinal centers from different countries and followed up for 2 years after surgery. PATIENT SAMPLE: There were 1,266 patients recruited between March 2001 and October 2014. OUTCOME MEASURES: Patient demographics were collected along with outcome measures, including European Quality of Life-5 Dimensions (EQ-5D), neurologic functions, complications, and survival rates. METHODS: We realized a multicenter prospective study of 1,266 patients admitted for surgical treatment of symptomatic spinal metastases. They were divided and studied into three different age groups: <70, 70-80, and >80 years. RESULTS: Despite a lack of statistical difference in American Society of Anesthesiologists (ASA) score, Frankel neurologic score, or Karnofsky functional score at presentation, patients >80 years were more likely to undergo emergency surgery and palliative procedures compared with younger patients. Postoperative complications were more common in the oldest age group (33.3% in the >80, 23.9% in the 70-80, and 17.9% for patients <70 years, p=.004). EQ-5D improved in all groups, but survival expectancy was significantly longer in patients <70 years old (p=.02). Furthermore, neurologic recovery after surgery was lower in patients >80 years old. CONCLUSIONS: Surgeons should not be biased against operating elderly patients. Although survival rates and neurologic improvements in the elderly patients are lower than for younger patients, operating the elderly is compounded by the fact that they undergo more emergency and palliative procedures, despite good ASA scores and functional status. Age in itself should not be a determinant of whether to operate or not, and operations should not be avoided in the elderly when indicated.

Biodegradable polymeric stents for vascular application in a porcine carotid artery model: English version.

Over the past years the development of biodegradable polymeric stents has made great progress; nevertheless, essential problems must still be solved. Modifications in design and chemical composition should optimize the quality of biodegradable stents and remove the weaknesses. New biodegradable poly-L-lactide/poly-4-hydroxybutyrate (PLLA/P4HB) stents and permanent 316L stents were implantedendovascularly into both common carotid arteries of 10 domestic pigs. At 4 weeks following implantation, computed tomography (CT) angiography was carried out to identify the distal degree of stenosis. The PLLA/P4HB group showed a considerably lower distal degree of stenosis by additional oral application of atorvastatin (mean 39.81 ± 8.57 %) compared to the untreated PLLA/P4HB group without atorvastatin (mean 52.05 ± 5.80 %). The 316L stents showed no differences in the degree of distal stenosis between the group treated with atorvastatin (mean 44.21 ± 2.34 %) and the untreated group (mean 35.65 ± 3.72 %). Biodegradable PLLA/P4HB stents generally represent a promising approach to resolving the existing problems in the use of permanent stents. Restitutio ad integrum is only achievable if a stent is completely degraded.

Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into account. The aim of this study was to ascertain whether receptors are associated with survival, when the disease has progressed up to SBM. All patients who were treated for SBM from breast cancer between 2005 and 2012 were included in this international multi-center retrospective study (n = 111). Reports were reviewed for ER, PR and HER2 status and subsequently subdivided into one of four categories; luminal A, luminal B, HER2 and triple negative. Survival time was calculated as the difference between start of treatment for SBM and date of death. Analysis was performed using the Kaplan-Meier method and log-rank tests. Median follow-up was 3.7 years. Survival times in the luminal B and HER2 categories were not significantly different to the luminal A category and were joined into a single receptor positive category. Eighty-five patients (77 %) had a receptor positive phenotype and 25 (23 %) had a triple negative phenotype. Median survival time was 22.5 months (95 %CI 18.0-26.9) for the receptor positive category and 6.7 months (95 %CI 2.4-10.9) for the triple negative category (p < 0.001). Patients with SBM from breast cancer with a triple negative phenotype have a shorter survival time than patients with a receptor positive phenotype. Models estimating survival should be adjusted accordingly.

Influence of local hemostatic and antiplatelet agents on the incidence of bleeding complications in carotid endarterectomies.

BACKGROUND: For the reduction of cardio- and cerebrovascular events in carotid endarterectomies continuation of antiplatelet medication is recommended perioperatively. As a result, this patient population is at increased risk for postoperative bleeding complications. Intraoperative application of local hemostatic agents might reduce the incidence of bleeding complications. MATERIAL AND METHODS: All 565 patients undergoing carotid endarterectomy between January 2005 and January 2011 were analysed retrospectively. Most patients in the earlier cohort years of the study had no perioperative antiplatelet medication. In contrast antiplatelet medication was usually continued perioperatively in the later cohort years. To reduce the risk of perioperative bleeding local hemostatic agents were applied increasingly. RESULTS: Revision surgery, due to postoperative bleeding or massive hematoma, was necessary in 20 cases (3.5 %). Overall, 383 carotid endarterectomies (67.8 %) were performed with perioperative antiplatelet medication. Local hemostatic agents were applied in 259 cases (45.8 %) intraoperatively. Initially, operations performed in patients taking antiplatelet medication resulted in an increased need for surgical revision. Following an accelerated practice of using local hemostatic agents, the need for revision surgeries fell. Nevertheless, when patients from all years were analysed together there was no significant benefit from the application of local hemostatic agents. CONCLUSION: Application of local hemostatic agents might have contributed to a reduction of bleeding complications in carotid endarterectomies. However, this could not be shown of statistical significance. Other confounding factors such as different operative techniques or forms of anesthesia might also have influenced this decline.

Transforaminal lumbar interbody fusion vs. posterolateral instrumented fusion: cost-utility evaluation along side an RCT with a 2-year follow-up.

PURPOSE: Long-lasting low back pain is an increasing problem, and for some patients surgery is the final option for improvement. Several techniques for spinal fusion are available and the optimal technique remains uncertain. The objective of this study was to assess the cost-effectiveness and cost-utility of transforaminal lumbar interbody fusion (TLIF) compared to posterolateral instrumented fusion (PLF) from the societal perspective. METHODS: 100 Patients were randomized to TLIF or PLF (51/49) and followed for 2 years. Cost data were acquired from national registers, and outcomes were measured using the Oswestry Disability Index and SF-6D questionnaires. Conventional cost-effectiveness methodology was employed to estimate net benefit and to illustrate cost-effectiveness acceptability curves. The statistical analysis was based on means and bootstrapped confidence intervals. RESULTS: Results showed no statistically significant difference in either cost or effects although a tendency for the TLIF regimen being more costly on bed days (2,554) and production loss (1,915) was observed. The probability that TLIF would be cost-effective did not exceed 30 % for any threshold of willingness to pay per quality-adjusted life year. Sensitivity analysis was conducted and supported the statistical model for handling of missing data. CONCLUSION: TLIF does not seem to be a relevant alternative to PLF from a socioeconomic, societal point of view.

Control of proliferation and osteogenic differentiation of human dental-pulp-derived stem cells by distinct surface structures.

The ability to control the behavior of stem cells provides crucial benefits, for example, in tissue engineering and toxicity/drug screening, which utilize the stem cell's capacity to engineer new tissues for regenerative purposes and the testing of new drugs in vitro. Recently, surface topography has been shown to influence stem cell differentiation; however, general trends are often difficult to establish due to differences in length scales, surface chemistries and detailed surface topographies. Here we apply a highly versatile screening approach to analyze the interplay of surface topographical parameters on cell attachment, morphology, proliferation and osteogenic differentiation of human mesenchymal dental-pulp-derived stem cells (DPSCs) cultured with and without osteogenic differentiation factors in the medium (ODM). Increasing the inter-pillar gap size from 1 to 6 µm for surfaces with small pillar sizes of 1 and 2 µm resulted in decreased proliferation and in more elongated cells with long pseudopodial protrusions. The same alterations of pillar topography, up to an inter-pillar gap size of 4 µm, also resulted in enhanced mineralization of DPSCs cultured without ODM, while no significant trend was observed for DPSCs cultured with ODM. Generally, cells cultured without ODM had a larger deposition of osteogenic markers on structured surfaces relative to the unstructured surfaces than what was found when culturing with ODM. We conclude that the topographical design of biomaterials can be optimized for the regulation of DPSC differentiation and speculate that the inclusion of ODM alters the ability of the cells to sense surface topographical cues. These results are essential in order to transfer the use of this highly proliferative, easily accessible stem cell into the clinic for use in cell therapy and regenerative medicine.

Osteopontin functionalization of hydroxyapatite nanoparticles in a PDLLA matrix promotes bone formation.

We studied the osteoconductive tissue response of hydroxyapatite (HA) nanoparticles functionalized with osteopontin (OPN) in a matrix of poly-D,L-lactic-acid (PDLLA). In a canine endosseus 0.75-mm gap implant model, we tested the osteointegrative impact of the OPN functionalized composite as an implant coating, and a non-functionalized composite was used as reference control. During the four weeks of observation, the OPN functionalized composite coating significantly increased the formation of new bone in the porosities of the implant, but no differences were observed in the gap. The study provides evidence of its potential use either alone or in combination with other osteoconductive compounds.

Cell shape and spreading of stromal (mesenchymal) stem cells cultured on fibronectin coated gold and hydroxyapatite surfaces.

In order to identify the cellular mechanisms leading to the biocompatibility of hydroxyapatite implants, we studied the interaction of human bone marrow derived stromal (mesenchymal) stem cells (hMSCs) with fibronectin-coated gold (Au) and hydroxyapatite (HA) surfaces. The adsorption of fibronectin was monitored by Quartz Crystal Microbalance with Dissipation (QCM-D) at two different concentrations, 20 µg/ml and 200 µg/ml, and the fibronectin adsorption experiments were complemented with antibody measurements. The QCM-D results show that the surface mass uptake is largest on the Au surfaces, while the number of polyclonal and monoclonal antibodies directed against the cell-binding domain (CB-domain) on the fibronectin (Fn) is significantly larger on the (HA) surfaces. Moreover, a higher number of antibodies bound to the fibronectin coatings formed from the highest bulk fibronection concentration. In subsequent cell studies with hMSC's we studied the cell spreading, cytoskeletal organization and cell morphology on the respective surfaces. When the cells were adsorbed on the uncoated substrates, a diffuse cell actin cytoskeleton was revealed, and the cells had a highly elongated shape. On the fibronectin coated surfaces the cells adapted to a more polygonal shape with a well-defined actin cytoskeleton, while a larger cell area and roundness values were observed for cells cultured on the coated surfaces. Among the coated surfaces a slightly larger cell area and roundness values was observed on HA as compared to Au. Moreover, the results revealed that the morphology of cells cultured on fibronectin coated HA surfaces were less irregular. In summary we find that fibronectin adsorbs in a more activated state on the HA surfaces, resulting in a slightly different cellular response as compared to the fibronectin coated Au surfaces.

Review of metastatic spine tumour classification and indications for surgery: the consensus statement of the Global Spine Tumour Study Group.

Choosing the right operation for metastatic spinal tumours is often difficult, and depends on many factors, including life expectancy and the balance of the risk of surgery against the likelihood of improving quality of life. Several prognostic scores have been devised to help the clinician decide the most appropriate course of action, but there still remains controversy over how to choose the best option; more often the decision is influenced by habit, belief and subjective experience. The purpose of this article is to review the present systems available for classifying spinal metastases, how these classifications can be used to help surgical planning, discuss surgical outcomes, and make suggestions for future research. It is important for spinal surgeons to reach a consensus regarding the classification of spinal metastases and surgical strategies. The authors of this article constitute the Global Spine Tumour Study Group: an international group of spinal surgeons who are dedicated to studying the techniques and outcomes of surgery for spinal tumours, to build on the existing evidence base for the surgical treatment of spinal tumours.

Up-regulation of ICAM-1 during cold ischemia triggers early neutrophil infiltration in human pancreas allograft reperfusion.

BACKGROUND: Graft pancreatitis is induced by ischemia/reperfusion injury in which neutrophil infiltration is believed to be a crucial early event. This observation suggests the presence of adhesion molecules already at the time of reperfusion. Therefore, this study was performed to evaluate the pattern of ICAM-1 and P-Selectin expression on human pancreas allografts following cold ischemia and reperfusion. PATIENTS AND METHODS: We performed an analysis of pancreas biopsy specimens taken from 13 patients undergoing pancreas transplantation compared with pancreas specimens from 10 patients following resection. Cryostat sections were stained with monoclonal antibodies against CD11b, a neutrophil marker, and the adhesion molecules ICAM-1 and P-Selectin. RESULTS: Extensive infiltration of CD11b-positive cells was detected in venules and capillaries of pancreas allografts after reperfusion (18.38 +/- 0.87) compared with controls (T1 4.22 +/- 0.55) or with tissue specimens at about 10 hours of cold ischemia (2.60 +/- 0.35; P < .001). Similarly, the pattern of P-Selectin showed a moderate expression before organ harvest (1.54 +/- 0.21) and in samples during cold ischemia (1.46 +/- 0.24) followed by a significantly greater number of P-Selectin-positive cells after reperfusion (2.54 +/- 0.18; P = .005). ICAM-1 was only weakly expressed on the surface of the venular endothelium in all controls (0.77 +/- 0.12). In contrast to P-Selectin, ICAM-1 showed prominent up-regulation during cold ischemia (2.23 +/- 0.23; P < .001) with no further increase after reperfusion (2.23 +/- 0.17). CONCLUSION: The data suggested that ICAM-1 was already up-regulated during cold ischemia, possibly representing the mechanism of early neutrophil infiltration observed in human pancreatic ischemia/reperfusion injury.

Investigation of particle-functionalized tissue engineering scaffolds using X-ray tomographic microscopy.

A low-density, porous chitosan/poly-(dl-lactide-co-glycolide) (PLGA) microparticle composite scaffold was produced by thermally induced phase separation followed by lyophilization, to provide a bicontinuous microstructure potentially suitable for tissue engineering and locally controlled drug release. PLGA particles were mixed into the chitosan solution and subsequent phase separation during chitosan solidification forced PLGA particles into chitosan phase (Plateau borders). The distributions of volume, surface area, and elongation of 15,422 inclusions of agglomerated PLGA particles were calculated and approximated with log-normal distribution functions from nanotomography reconstructions. Cluster analysis revealed a homogenous inclusion distribution throughout the scaffold. The spatial location and orientation of individual inclusions within the Plateau borders of the scaffold were determined and from these the nearest-neighbor inter-inclusion distance distribution calculated, showing a mean of 2.5 microm. The depth of the inclusions in Plateau borders peaks at 700 or 125 nm, respectively, indicating a step-wise drug release from inclusions successively exposed during scaffold decomposition. Particle diameter ranged from 400 nm to 3 microm and inclusion Feret lengths ranged from 800 nm to 12 microm. These findings on composite morphology and distribution of inclusions are fundamental for predicting scaffold deterioration and particle-mediated drug release during ex vivo and in vivo cell cultivation.

Anastomotic stenting in a porcine aortoiliac graft model.

The purpose of the study was to evaluate the feasibility of anastomotic stent application in a porcine aortoiliac graft model. In a total of 10 pigs, a polytetrafluoroethylene aortobi-iliac graft was implanted through a midline abdominal incision. The lower edge of the iliac vessel was graft-inverted about 1 mm to produce irregularities at the downstream anastomosis. After transverse graft incision, six stainless-steel stents, six poly-L-lactic acid (PLLA) stents and four PLLA stents with 10% polycaprolactone (PCL) were implanted at the iliac anastomotic site using a 6 mm balloon dilatation catheter. Four anastomotic sites were left untreated. After two weeks, the patency of graft limbs was evaluated by contrast-enhanced computed tomography (CT). Both metal and polymeric stent designs provided adequate flexibility to manoeuvre across the anastomotic site for expansion in the chosen position. After deployment, the stent-arterial wall contact was complete on a macroscopic view. On CT scan, all metal and PLLA-stented graft limbs were free of stenosis, whereas all PLLA/PCL stents were occluded. The non-stented graft limbs showed a stenosis of 50-70%. In summary, this model is feasible to assess preclinically the deployment and patency rate of an anastomotic stent and to test future stent developments.

Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs.

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own. ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor.

Bone nanostructure near titanium and porous tantalum implants studied by scanning small angle x-ray scattering.

Bone sections including either titanium or porous tantalum implant devices used for interbody spinal fusion were investigated with position-resolved small angle X-ray scattering (sSAXS). The samples were obtained from six-month-old pigs that had undergone surgery three months prior to sacrifice. The aim of the study was to explore the possibility of using sSAXS to obtain information about thickness, orientation and shape/arrangement of the mineral crystals in bone near the implant surfaces. Detailed sSAXS scans were carried out in two different regions of bone adjacent to the implant in each of the implant samples. In the implant vicinity the mineral crystals tended to be aligned with the surface of the implants. The mean crystal thickness was between 2.1 and 3.0 nm. The mineral crystal thickness increased linearly with distance from the implant in both regions of the porous tantalum implant and in one of the regions in the titanium sample. In the second region of the titanium sample the thickest mineral crystals were found close to the implant surface. The observed differences in mineral thickness with distance from the implant surfaces might be explained by differences in mechanical load induced by the implant material and the geometrical design of the implant. The study shows that sSAXS is a powerful tool to characterize the nanostructure of bone near implant surfaces.

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.

Stabilisation surgery for chronic low back pain: indications, surgical procedures, and outcome.

Spinal fusion was introduced as a treatment option for chronic low back pain >70 years ago. However, few areas of spinal surgery have caused as much controversy. The debate about whether to use an anterior-, posterior- or anterior + posterior approach has persisted since the 1930s. Within the last 10 years, the effects of different spinal fusion procedures have been tested in 10 randomized controlled trails (RCT). A highly significant improvement over preoperative status was found in all 10 studies. Two recent RCTs have dealt with the question of conservative versus operative treatment of patients with low back pain, and both studies have shown a significant better functional outcome for spinal fusion in situ, compared with a more or less organized exercise programme at 2-year follow-up. The choice of postoperative rehabilitation strategy has also been shown to be of importance for overall functional outcome. One study has demonstrated the importance of the inclusion of coping schemes, and questioned the role of intensive exercises in a rehabilitation programme for spinal fusion patients.

Biocompatibility and surface structure of chemically modified immunoisolating alginate-PLL capsules.

Grafting of encapsulated living cells has the potential to cure a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules. A major factor in the biocompatibility of capsules is inadequate covering of the inflammatory poly-L-lysine (PLL) on the capsules' surface. In the present study, we investigate whether tissue responses against alginate-PLL capsules can be reduced by crosslinking the surface of the capsules with heparin or polyacrylic acid. Our transplant study in rats shows a tissue response composed of fibroblasts and macrophages on alginate-PLL-alginate and alginate-PLL-heparin capsules that was completely absent on alginate-PLL-polyacrylic acid capsules. Atomic force microscopy analyses of the capsules demonstrates that the improved biocompatibility of alginate-PLL-capsules by polyacrylic acid coating should not only be explained by a more adequate binding of PLL but also by the induction of a smoother surface. This study shows for the first time that biologic responses against capsules can be successfully deleted by chemically crosslinking biocompatible molecules on the surface of alginate-PLL capsules.