F C Oner

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (145)364.88 Total impact

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    ABSTRACT: To develop a bio-assay for measuring long-term bioactivity of released anti-inflammatory compounds and to test the bioactivity of celecoxib (CXB) and triamcinolone acetonide (TA) released from a new PLGA-based microsphere platform.
    Pharmaceutical research. 08/2014;
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    ABSTRACT: Bone defect healing is highly dependent on the simultaneous stimulation of osteogenesis and vascularization. In bone regenerative strategies, combined seeding of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) proves their mutual stimulatory effects. Here, we investigated whether stromal cell-derived factor-1α (SDF-1α) stimulates vascularization by EPCs and whether SDF-1α could replace seeded cells in ectopic bone formation. Late EPCs of goat origin were characterized for their endothelial phenotype and showed to be responsive to SDF-1α in in vitro migration assays. Subsequently, subcutaneous implantation of Matrigel plugs that contained both EPCs and SDF-1α showed more tubule formation than constructs containing either EPCs or SDF-1α. Addition of either EPCs or SDF-1α to MSC-based constructs showed even more elaborate vascular networks after 1 week in vivo, with SDF-1α/MSC laden groups showing more prominent interconnected networks than EPC/MSC laden groups. The presence of abundant mouse specific CD31/PECAM-1 expression in these constructs confirmed ingrowth of murine vessels and discriminated between angiogenesis and vessel networks formed by seeded goat cells. Importantly, implantation of EPC/MSC or SDF-1α/MSC constructs resulted in indistinguishable ectopic bone formation. In both groups, bone onset was apparent at week 3 of implantation. Taken together, we demonstrated that SDF-1α stimulated the migration of EPCs in vitro and vascularization in vivo. Furthermore, SDF-1α addition was as effective as EPCs in inducing the formation of vascularized ectopic bone based on MSC seeded constructs, suggesting a cell replacement role for SDF-1α. These results hold promise for the design of larger cm-scale cell free vascular bone grafts.
    Stem cells and development. 07/2014;
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    ABSTRACT: Human fully upright ambulation, with fully extended hips and knees, and the body's center of gravity directly above the hips, is unique in nature, and distinguishes humans from all other mammalians. This bipedalism is made possible by the development of a lordosis between the ischium and ilium; it allows to ambulate in this unique bipedal manner, without sacrificing forceful extension of the legs. This configuration in space introduces unique biomechanical forces with relevance for a number of spinal conditions. The aim of this study was to quantify the development of this lordosis between ischium and ilium in the normal growing and adult spine and to evaluate its correlation with the well-known clinical parameter, pelvic incidence.
    05/2014;
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    ABSTRACT: Timely vascularization is essential for optimal performance of bone regenerative constructs. Vascularization is efficiently stimulated by vascular endothelial growth factor (VEGF), a substance with a short half-life time. This study investigates the controlled release of VEGF from gelatin microparticles (GMPs) as a means to prolong VEGF activity at the preferred location within 3D bioprinted scaffolds, and the effects on subsequent vascularization. Release of VEGF from GMPs was continuous for 3weeks during in vitro studies, and bioactivity was confirmed using human endothelial progenitor cells (EPCs) in migration assays. Traditional and real-time migration assays showed immediate and efficient EPC migration in the presence of GMP-released VEGF, indistinguishable from VEGF-solution that was added to the medium. Matrigel scaffolds containing EPCs and VEGF, which was released either in a fast or sustained fashion by application of GMPs, were investigated for their in vivo vasculogenic capacity. Implantation in subcutaneous pockets in nude mice for one week demonstrated that vessel formation was significantly higher in the VEGF sustained-release group compared to the fast release group. In addition, regional differences with respect to VEGF release were introduced in 3D bioprinted EPC-laden scaffolds and their influence on vasculogenesis was investigated in vivo. The different regions were retained and vessel formation occurred analogous with the results seen in the Matrigel plugs. We conclude that GMPs are suitable to generate sustained release profiles of bioactive VEGF, and that they can be used to create defined differentiation regions in 3D bioprinted heterogeneous constructs, allowing a new generation of smart scaffold design. The prolonged presence of VEGF led to a significant increase in scaffold vascularization when applied in vivo.
    Journal of Controlled Release 04/2014; · 7.63 Impact Factor
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    ABSTRACT: Although radiotherapy is effective in achieving pain relief in most patients, it is not completely understood why some patients respond well to radiotherapy and others do not. Our hypothesis was that metastatic bone pain, if predominantly caused by mechanical instability of the spine, responds less well to radiotherapy than metastatic bone pain caused by local tumor activity. Recently, the Spinal Instability Neoplastic Score (SINS) was proposed as a standardized referral tool for non-spine specialists in order to facilitate early diagnosis of spinal instability. To investigate the association between spinal instability as defined by the SINS and response to radiotherapy in patients with spinal metastases. A retrospective matched case-control study in an academic tertiary referral center, conducted according to the STROBE guidelines. Thirty-eight patients with spinal metastases who were retreated after initial palliative radiotherapy from January 2009 to December 2010 were matched to 76 control patients who were not retreated. Radiotherapy failure as defined by retreatment (radiotherapy, surgery, conservative) after palliative radiotherapy for spinal metastases. Radiotherapy planning CT scans were scored by a blinded spine surgeon according to the SINS criteria. The association between SINS and radiotherapy failure was estimated by univariate and multivariate conditional logistic regression analysis. No funding was received and no conflicts of interest exist. Median SINS was 10 (range 4-16) for cases and 7 (range 1-16) for controls. The SINS was significantly and independently associated with radiotherapy failure (adjusted odds ratio, 1.3; 95% confidence interval, 1.1-1.5; p = 0.01). This study shows that a higher spinal instability score increases the risk of radiotherapy failure in patients with spinal metastases, independent of performance status, primary tumor and symptoms. These results may support the hypothesis that metastatic spinal bone pain, predominantly caused by mechanical instability, responds less well to radiotherapy than pain mainly resulting from local tumor activity.
    The spine journal: official journal of the North American Spine Society 04/2014; · 2.90 Impact Factor
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    ABSTRACT: Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All patients underwent intralesional excision, 21 with local adjuvants, 5 radiotherapy, 3 IFN-α, 1 bisphosphonates. Functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) score. Statistics were performed with Kaplan-Meier, Cox regression, log rank and Mann-Whitney U. Recurrence rate was 14/26 after median 13 (3-139) months and was highest after isolated curettage (4/5). Soft tissue masses >10 cm increased recurrence risk (HR = 3.3, 95 % CI = 0.81-13, p = 0.09). Complications were reported in 12/26 patients. MSTS was superior in patients without complications (27 vs. 21; p = 0.024). Recurrence rate for sacral GCT was highest after isolated curettage, indicating that (local) adjuvant treatment is desired to obtain immediate local control. Complications were common and impaired function.
    European Spine Journal 03/2014; · 2.47 Impact Factor
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    ABSTRACT: Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion.Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis 100 patients (18-75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled trial in which the silicon nitride cage is compared with the PEEK cage in patients with symptomatic degenerative lumbar disc disorders.Trial registration: NCT01557829.
    BMC Musculoskeletal Disorders 02/2014; 15(1):57. · 1.88 Impact Factor
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    ABSTRACT: Polyetheretherketone (PEEK) cages have been widely used during the past decade in patients with degenerative disorders of the cervical spine. Their radiolucency and low elastic modulus make them attractive attributes for spinal fusion compared with titanium and bone graft. Still, limitations are seen such as pseudoarthrosis, subsidence, and migration of the cages. Limited evidence on the clinical outcome of PEEK cages is found in the literature other than noncomparative cohort studies with only a few randomized controlled trials. To assess the clinical and radiographic outcome of PEEK cages in the treatment of degenerative disc disorders and/or spondylolisthesis in the cervical spine. Systematic review of all randomized controlled trials and prospective and retrospective nonrandomized comparative studies with a minimum follow-up of 6 months and all noncomparative cohort studies with a long-term follow-up of more than 5 years. The primary outcome variable was clinical performance. Secondary outcome variables consisted of radiographic scores. The MEDLINE, EMBASE, and Cochrane Library databases were searched according to the Preferred Reporting Items of Systematic reviews and Meta-Analyses statement and Meta-analysis Of Observational Studies in Epidemiology guidelines. No conflict of interest reported. No funding received. A total of 223 studies were identified, of which 10 studies were included. These comprised two randomized controlled trials, five prospective comparative trials, and three retrospective comparative trials. Minimal evidence for better clinical and radiographic outcome is found for PEEK cages compared with bone grafts in the cervical spine. No differences were found between PEEK, titanium, and carbon fiber cages. Future studies are needed to improve methodology to minimize bias. Publication of lumbar interbody fusion studies needs to be promoted because differences in clinical and/or radiographic scores are more likely to be demonstrated in this part of the spine.
    The spine journal: official journal of the North American Spine Society 12/2013; · 2.90 Impact Factor
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    ABSTRACT: When used to fixate traumatic thoracolumbar burst fractures, pedicle screw constructs may fail in the presence of severe vertebral body comminution as the intervertebral disc can creep through the fractured endplates leading to insufficient anterior column support. Balloon-assisted endplate reduction (BAER) and subsequent calcium phosphate cement augmentation may prevent this event by restoring the disc space boundaries. The results of the first studies using BAER after pedicle screw fixation are encouraging showing good fracture reduction, few complications and minimal loss of correction at two years of follow up. To present the clinical and radiological outcome of twenty patients treated for traumatic thoracolumbar burst fractures with pedicle screws and BAER after a minimum of six years follow up. Prospective trial. Twenty consecutive neurologically intact adult patients with traumatic thoracolumbar burst fractures were included. Radiological parameters (wedge/Cobb angle on plain radiographs and midsagittal anterior/central vertebral body height on MRI scans) and patient reported parameters (EQ-5D and Oswestry Disability Index) were used. All patients had previously undergone pedicle screw fixation and BAER with calcium phosphate cement augmentation. The posterior instrumentation was removed approximately 1,5 years after index surgery. Radiographs were obtained preoperatively, postoperatively, after removal of the pedicle screws and at final follow up (minimum six years posttrauma). MRI scans were obtained preoperatively, one month after index surgery and one month after pedicle screw removal. Health questionnaires were filled out during the last outpatient visit. The pedicle screw instrumentation was removed uneventfully in all patients and posterolateral fusion was observed in every case. The mean wedge and Cobb angle converged to almost identical values (5,3 and 5,8 degrees respectively) and the midsagittal anterior and central endplates were reduced to approximately 90% and 80% of the estimated preinjury vertebral body height respectively; this reduction was sustained at follow up. Patient reported outcomes showed favorable results in 79% of the patients. One patient required (posterior) reoperation due to adjacent osteoporotic vertebral body collapse after pedicle screw removal. Balloon-assisted endplate reduction is a safe and low-demanding adjunct to pedicle screw fixation for the treatment of traumatic thoracolumbar burst fractures. It may help achieve minimal residual deformity and reduce the number of secondary (anterior) procedures. Despite these positive findings, one in five patients experienced daily discomfort and disability.
    The spine journal: official journal of the North American Spine Society 12/2013; · 2.90 Impact Factor
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    ABSTRACT: Regenerative Medicine (RM) interventions, such as (stem) cell transplantation, scaffolds, gene transfer, and tissue engineering, are likely to change the field of orthopedics considerably. These strategies will significantly differ from treatments in current orthopedic practice, as they treat the underlying cause of disease and intervene at a biological level, preferably in an earlier stage. Whereas most of the RM interventions for orthopedics are still in the preclinical phase of research, the amount of clinical studies is expected to increase rapidly in the future. The debate about the challenging scientific and ethical issues of translating these innovative interventions into (early) clinical studies is developing. However, no empirical studies that have systematically described the attitudes, opinions, and experiences of experts in the field of orthopedic RM concerning these challenges exist. The aim of this study is to identify ethical issues which experts in the area of RM for musculoskeletal disorders consider to be relevant to address in order to properly translate RM interventions into (early) clinical studies. Study design/setting: In-depth qualitative interviews were conducted with 36 experts in the field, mainly spine surgeons and musculoskeletal scientists from the Netherlands and the United Kingdom(UK). A topic list of open questions, based on existing literature and pilot interviews, was used to guide the interviews. Data analysis was based on the constant comparative method, which means going back and forth from the data to develop codes, concepts and themes. Four ethical themes emerged from the interview data. First, the risks to study participants. Second, the appropriate selection of study participants. Third, setting relevant goal(s) for measuring outcome, varying from regenerating tissue to improving well-being of patients. Finally, the need for evidencebased medicine and scientific integrity, which is considered challenging in orthopedics. The overall attitude towards the development of RM was positive, especially since current surgical treatments for spine disorders lack satisfactory effectiveness. However, efforts should be taken to adequately address the ethical and scientific issues in the translation of RM interventions into clinical research. This is required to prevent unnecessary risks to study participants, to prevent exposure of future patients to useless clinical applications, as well as to prevent this young field from developing a negative reputation. Not only will the orthopedic RM field benefit from ethically and scientifically sound clinical studies, but the rise of RM also provides an opportunity to stimulate evidence-based practice in orthopedics and address hype- and profit driven practices in orthopedics.
    The spine journal: official journal of the North American Spine Society 10/2013; · 2.90 Impact Factor
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    ABSTRACT: Histology is an important outcome variable in basic science and pre-clinical studies regarding intervertebral disc degeneration (IVD). Nevertheless, an adequately validated histological classification for IVD degeneration is still lacking and the existing classifications are difficult to use for inexperienced observers. Therefore the aim of this study was to develop and to validate a new histological classification for IVD degeneration. Moreover, the new classification was compared to the frequently used non-validated classification. The new classification was applied to human IVD sections. The sections were scored twice by 2 independent inexperienced observers, twice by 2 experienced IVD researchers and once by an pathologist. For comparison, the sections were also scored according to the classification described by Boos et al. by two experienced IVD researchers. Macroscopic grading according Thompson et al, glycosaminoglycan (GAG) content and age were used for validation. The new classification had an excellent intra- and a good inter-observer reliability. Intraclass Correlation Coefficients (ICC) were 0.83 and 0.74, respectively. Intra and inter-observer reliability were comparable for experienced and inexperienced observers. Statistically significant correlations were found between the new classification, macroscopic score, GAG content in the nucleus pulposus and age; Correlation coefficient (CC) 0.79, -0.62 and 0.68, respectively. The CCs of the Boos classification were all lower compared to the new classification. the new histological classification for IVD degeneration is a valid instrument for evaluating IVD degeneration in human IVD sections and is suitable for inexperienced and experienced researchers.
    Osteoarthritis and Cartilage 10/2013; · 4.26 Impact Factor
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    ABSTRACT: The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.
    Biotechnology & genetic engineering reviews 10/2013; 29(2):206-20. · 1.31 Impact Factor
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    European Spine Journal 09/2013; · 2.47 Impact Factor
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    ABSTRACT: The goal of this systematic review was to evaluate if the influence of methodological features on treatment effect differs between types of intervention. MEDLINE, Embase, Web of Science, Cochrane methodology register, and reference lists were searched for meta-epidemiologic studies on the influence of methodological features on treatment effect. Studies analyzing influence of methodological features related to internal validity were included. We made a distinction among surgical, pharmaceutical, and therapeutical as separate types of intervention. Heterogeneity was calculated to identify differences among these types. Fourteen meta-epidemiologic studies were found with 51 estimates of influence of methodological features on treatment effect. Heterogeneity was observed among the intervention types for randomization. Surgical intervention studies showed a larger treatment effect when randomized; this was in contrast to pharmaceutical studies that found the opposite. For allocation concealment and double blinding, the influence of methodological features on the treatment effect was comparable across different types of intervention. For the remaining methodological features, there were insufficient observations. The influence of allocation concealment and double blinding on the treatment effect is consistent across studies of different interventional types. The influence of randomization although, may be different between surgical and nonsurgical studies.
    Journal of clinical epidemiology 09/2013; · 5.33 Impact Factor
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    ABSTRACT: The use of growth factors in osteogenic constructs to promote recruitment of bone forming endogenous cells is not clear, while the advantage of circumventing cell seeding techniques prior to implantation is highly recognized. Therefore, the additive effect of the chemokine stromal cell-derived factor-1α (SDF-1α) on endogenous cell recruitment and vascularization was investigated in a hybrid construct, consisting of a ceramic biomaterial, hydrogel and SDF-1α, in an ectopic mouse model. We demonstrated in vivo that local presence of low concentrations of SDF-1α resulted in a significant increase in recruited endogenous cells, which remained present for several weeks. SDF-1α stimulated vascularization in these hybrid constructs, as shown by the enhanced formation of erythrocyte-filled vessels. The presence of CD31-positive capillaries/small vessels after 6 weeks in vivo substantiated this finding. The SDF-1α treatment showed increased numbers of cells that could differentiate to the osteogenic lineage after 6 weeks of implantation, demonstrated by expression of collagen I and osteocalcin. Altogether, we show here the beneficial effects of the local application of a single growth factor in a hybrid construct on angiogenesis and osteogenic differentiation, which might contribute to the development of cell-free bone substitutes.
    Tissue Engineering Part A 09/2013; · 4.64 Impact Factor
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    ABSTRACT: The clinical outcome of patients with ankylosing spinal disorders (ASDs) sustaining a spinal fracture has been described to be worse compared with the general trauma population. To investigate clinical outcome (neurologic deficits, complications, and mortality) after spinal injury in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) compared with control patients. Retrospective cohort study. All patients older than 50 years and admitted with a traumatic spinal fracture to the Emergency Department of the University Medical Center Utrecht, the Netherlands, a regional level-1 trauma center and tertiary referral spine center. Data on comorbidity (Charlson comorbidity score), mechanism of trauma, fracture characteristics, neurologic deficit, complications, and in-hospital mortality were collected from medical records. With logistic regression analysis, the association between the presence of an ASD and mortality was investigated in relation to other known risk factors for mortality. A total of 165 patients met the inclusion criteria; 14 patients were diagnosed with AS (8.5%), 40 patients had DISH (24.2%), and 111 patients were control patients (67.3%). Ankylosing spinal disorder patients were approximately five years older than control patients and predominantly of male gender. The Charlson comorbidity score did not significantly differ among the groups, but Type 2 diabetes mellitus and obesity were more prevalent among DISH patients. In many AS and DISH cases, fractures resulted from low-energy trauma and showed a hyperextension configuration. Patients with AS and DISH were frequently admitted with a neurologic deficit (57.1% and 30.0%, respectively) compared with controls (12.6%; p=.002), which did not improve in the majority of cases. In AS and DISH patients, complication and mortality rates were significantly higher than in controls. Logistic regression analysis showed the parameters age and presence of DISH to be independently, statistically significantly related to mortality. Many patients with AS and DISH showed unstable (hyperextension) fracture configurations and neurologic deficits. Complication and mortality rates were higher in patients with ASD compared with control patients. Increasing age and presence of DISH are predictors of mortality after a spinal fracture.
    The spine journal: official journal of the North American Spine Society 08/2013; · 2.90 Impact Factor
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    ABSTRACT: Bone regeneration is one of the focus points in the field of regenerative medicine. A well-known stimulus of bone formation is bone morphogenetic protein-2 (BMP-2), which has already been extensively used in clinical applications. However due to a short half-life, supraphysiological doses are applied resulting in severe side effects such as ectopic bone formation or even loss of bone. We compared the effectivity of transient BMP-2 gene delivery with BMP-2 protein at clinical (high) and physiological (low) doses by subcutaneous implantation of alginate-based constructs in mice. After 6 weeks of implantation, both the protein-laden constructs and BMP-2 plasmid DNA-based constructs showed similar early bone onset and elevated bone formation compared to controls without any BMP-2 added. We found no differences in efficiency by using BMP-2 plasmid DNA or any of the BMP-2 protein dosages. Therefore we conclude that BMP-2 plasmid DNA based gene therapy in alginate is a promising new strategy for BMP-2 administration for bone (re)generation.
    Tissue Engineering Part A 07/2013; · 4.64 Impact Factor
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    ABSTRACT: The most common application of bone grafts is spinal fusion surgery, in which the use of iliac crest autograft is the gold standard. Harvesting of autograft however, requires an extra surgical procedure, which is associated with additional morbidity. Allograft is the well-known alternative, but is generally considered less effective in posterior fusions. Therefore the need for an effective alternative remains. Recently, it was shown that ceramics can be endowed with biologically instructive properties by changing the basic parameters of the material. In this study we compared a novel tricalcium phosphate ceramic (TCP) to iliac crest autograft and allograft, in instrumented posterolateral fusions in a goat model. A total of nine goats were included, who underwent a two-level lumbar fusion. Each side of the spine was randomized into one type of graft: iliac crest autograft; fresh-frozen allograft; TCP alone; or TCP combined with local autograft (50:50). The fusion rates after 16 weeks were comparable between the groups (autograft 3/8, allograft 4/8, TCP 4/8, TCP/local autograft 5/8). Calculation of the fusion volume on CT images, showed significantly greater volume in the control groups (autograft 7.8mL; allograft 8.9mL) compared to the groups with TCP (TCP 6.1mL; TCP/local autograft 6.0mL). No adverse tissue response was seen on histological analysis and TCP was almost completely resorbed. The results demonstrate that TCP is capable of achieving fusion at a similar rate to iliac crest autograft in posterolateral fusions, while almost completely resorbing within 16 weeks. Despite the lower fusion volume, the TCP is a promising alternative circumventing the disadvantages of autograft and allograft.
    Tissue Engineering Part C Methods 03/2013; · 4.64 Impact Factor

Publication Stats

2k Citations
364.88 Total Impact Points

Institutions

  • 1995–2014
    • University Medical Center Utrecht
      • • Department of Orthopedics
      • • Image Sciences Institute
      • • Orthopedic Surgery
      Utrecht, Utrecht, Netherlands
  • 2013
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 2011–2013
    • Leiden University Medical Centre
      • Department of Neurosurgery
      Leiden, South Holland, Netherlands
  • 1998–2013
    • Utrecht University
      • Department of Clinical Sciences of Companion Animals
      Utrecht, Utrecht, Netherlands
  • 2009
    • Radboud University Nijmegen
      • Department of Orthopaedics
      Nijmegen, Provincie Gelderland, Netherlands
  • 2007
    • University of British Columbia - Vancouver
      • Department of Orthopaedics
      Vancouver, British Columbia, Canada
  • 2006
    • University of Toronto
      Toronto, Ontario, Canada
  • 2005
    • Thomas Jefferson University
      • Department of Orthopaedic Surgery
      Philadelphia, PA, United States
    • Radboud University Medical Centre (Radboudumc)
      Nymegen, Gelderland, Netherlands