Abraham J Verbout

Utrecht University, Utrecht, Utrecht, Netherlands

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Publications (27)

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    [Show abstract] [Hide abstract] ABSTRACT: Study Design. Systematic literature reviewObjective. To assess the effect of total disc replacement for chronic low back pain due to lumbar degenerative disc disease compared to fusion or other treatment options.Summary of Background Data. There is an increasing use in disc replacement devices for degenerative disc disease, but their effectiveness compared to other interventions such as fusion of the motion segment or conservative treatment remains unclear.Methods. A comprehensive search in CENTRAL, MEDLINE, EMBASE, BIOSIS ClinicalTrials.gov, and FDA trials register was conducted. Randomized controlled trials (RCT) comparing total disc replacement with any other intervention for degenerative disc disease were included. Risk of Bias was assessed using the criteria of the Cochrane Back Review Group. Quality of evidence was graded according to the GRADE approach. Two review authors independently selected studies, assessed risk of bias and extracted data. Results and upper bounds of confidence intervals were compared against predefined clinically relevant differences.Results. We included seven RCT's with a follow-up of 24 months. There is risk of bias in the included studies due to sponsoring and absence of any kind of blinding. One study compared disc replacement against rehabilitation and found a significant advantage in favor of surgery, which, however, did not reach the predefined threshold. Six studies compared disc replacement against fusion and found that the mean Improvement in VAS back pain was 5.2 mm higher (2 studies, 95% CI 0.2 to 10.3) with a low quality of evidence. The improvement of Oswestry score at 24 months in the disc replacement group was 4.3 points more than in the fusion group (5 studies; 95% CI 1.85 to 6.68) with a low quality of evidence. Both upper bounds of the confidence intervals were below the predefined clinically relevant difference.Conclusions. Although statistically significant, the differences in clinical improvement were not beyond generally accepted boundaries for clinical relevance. Prevention of adjacent level disease and/or facet joint degeneration was not properly assessed. Therefore, because we believe that harm and complications may occur after years, we believe that the spine surgery community should be prudent about adopting this technology on a large scale, despite the fact that total disc replacement seems to be effective in treating low back pain in selected patients, and in the short term is at least equivalent to fusion surgery.
    Full-text Article · Sep 2012 · Spine
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    [Show abstract] [Hide abstract] ABSTRACT: Bone regeneration is a complex process regulated by a large number of bioactive molecules. Many growth factors and cytokines involved in the natural process of bone healing have been identified and tested as potential therapeutic candidates to enhance the regeneration process. Although many of these studies show an enhancement of the bone regeneration process by a single drug therapy, in vivo bone regeneration is the result of a complex interplay between the applied growth factor and various endogenous produced growth factors. To investigate these growth factor interactions, various studies have investigated the effect of growth factor combinations on bone regeneration. This review provides an overview of the growth factor and cytokine combinations tested in translational bone regeneration studies and shows that their interaction may result in an enhancement or inhibition of bone formation.
    Full-text Article · Nov 2010 · Tissue Engineering Part B Reviews
  • [Show abstract] [Hide abstract] ABSTRACT: Most current methods for cell monitoring on 3D porous scaffolds involve end-stage investigation of scaffolds. Repeated measurements on scaffolds, without disturbing cell vitality and proliferation, are needed to relate in vitro to in vivo data. Alamar Blue was used for this purpose. Two different Ca/P scaffolds were studied, using rat BMSCs with three different seeding densities [2.5 x 10(4) (SD1), 2.5 x 10(5) (SD2), 2.5 x 10(6) (SD3) cells]. Alamar Blue readings were done on days 1, 3, 5 and 7. After 7 days all 96 scaffolds (n = 16) were implanted in 16 mice for 4 weeks. Bone histomorphometry was performed. For both scaffolds, seeding efficiencies were highest with SD1 and SD2, cell proliferation was optimal in SD1, whereas SD3 resulted in an initial drop in vital cell number in the first 3 days. In vivo, upscaling from SD1 to SD2 lead to significantly more bone contact% in both scaffolds. Alamar Blue was shown to be a valuable tool in relating in vitro to in vivo data. Cell proliferation may differ depending on seeding density and scaffold type used. Seeding more cells may not necessarily result in more in vivo bone contact%.
    Article · Jan 2010 · Journal of Biomedical Materials Research Part A
  • [Show abstract] [Hide abstract] ABSTRACT: The aim of this study was to investigate the effect of implant location on bone formation in goats using autologous bone marrow-derived stromal cells in porous calcium phosphate scaffolds. Intramuscular locations were compared to posterolateral spine fusion locations in eight goats. As scaffolds, we used biphasic calcium phosphate porous blocks of 5 x 5 x 5 mm. Cell-seeded implants were compared to empty controls. Bone marrow-derived stromal cells were seeded at 8 million cells per cm(3) scaffold and cultured for 1 week. The follow-up time was 12 weeks. Fluorochromes were administered intravenously at 4, 6, and 8 weeks. Ectopic implants showed 21 +/- 3.6% bone formation for the cell seeded and 2.0 +/- 3.0% for the controls (p < 0.001). Paraspinal implants, however, showed 0.10 +/- 0.13% in the cell seeded compared to 0.023 +/- 0.027% in the control group (p = 0.09). A benefit of the cells was only found in the area closest to the paraspinal muscles (p < 0.01). Bone formation in the control samples was of later onset compared to the cell-seeded implants. In conclusion, cell-based bone tissue engineering in an ectopic environment was clearly effective. Similar constructs implanted in a posterolateral spine fusion location hardly showed any effect.
    Article · Sep 2009 · Tissue Engineering Part A
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    [Show abstract] [Hide abstract] ABSTRACT: Data from literature showed that a new type of metallic silver PMMA cement had good results in infection prophylaxis. This study investigated the in vivo efficacy of silver cement in the prevention of methicillin-sensitive Staphylococcal infections, compared to plain and tobramycin-containing cement. In 48 rabbits, 0.6% silver, 1% silver, plain, or tobramycin PMMA cement was injected into the femoral medullary canal after contamination with 10(5), 10(6), or 10(7) colony forming units (CFU) Staphylococcus aureus. After 14 days, bone was collected for bacteriology and histopathology. All plain and silver cement rabbits were infected, whereas only two tobra rabbits were infected (p < 0.001). The number of bacteria cultured ((10)logCFU) from bone adjacent to the cement, was 6.4 +/- 0.3 and 6.1 +/- 0.3 for the 0.6% and 1% silver rabbits. For the rabbits with plain and tobra cement, this was 6.2 +/- 0.2 (p > 0.95) and 0.0 +/- 0.0 (p < 0.001), respectively. Two tobra rabbits had a positive culture of a distal bone sample. Histological sections of plain, 0.6%, and 1% silver rabbits all showed signs of infection; these signs were absent in the tobra rabbits. Silver and plain cement were not effective in preventing infection, whereas tobra cement was effective. As silver cement predominantly exhibits an antimicrobial effect at the direct cement surface, this cement seems less useful in situations where there are bacteria present in surrounding tissues, like revision surgery. Whether silver cement has relevance in the prevention of bacterial colonization of cement remains to be determined.
    Full-text Article · Aug 2009 · Journal of Orthopaedic Research
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    [Show abstract] [Hide abstract] ABSTRACT: No options are available for local antibiotic delivery from uncemented implants. By loading a porous titanium implant with a biomimetic HA-coating (PeriApatite, PA) with antibiotics, we could obtain adequate local antibiotic concentrations and reduce infection susceptibility. This study investigated the efficacy of a tobramycin-loaded PA-coated titanium foam implant in preventing infection, as well as the effects on osseointegration. In 72 New Zealand White rabbits, an uncoated (Ti), PA-coated (PA), or Tobramycin-PA-coated (PA-tobra) titanium foam rod was implanted intramedullary in the left tibiae after contamination of the implant bed with none (control), 10(3), 10(4) or 10(5) CFU Staphylococcus aureus. PA-tobra implants were loaded with 2.4 mg tobramycin. After 28 days analysis was done by bacteriology, histopathology and histomorphometry. Six percent of the contaminated PA-tobra rabbits were infected, whereas this was 53 and 67% for PA and Ti, respectively (p < 0.001). Quantitative cultures were also significantly lower in the PA-tobra group (p = 0.003). None of the control rabbits were infected. Histopathological and histomorphometrical scores were both better for the PA-tobra group, although only significant compared to Ti. No significant differences were observed between PA and Ti rabbits. We conclude that the application of tobramycin to PA-coated titanium foam implants appears to be an effective local antibiotic strategy for uncemented implants for infection prophylaxis and has a beneficial effect on implant fixation, which will result in improved long-term implant survival.
    Full-text Article · Jun 2009 · Journal of Orthopaedic Research
  • [Show abstract] [Hide abstract] ABSTRACT: Improvement of tissue-engineered grafts is still a challenge in the field of regenerative medicine. Using multipotent stromal cells (MSCs), which have immunosuppressive qualities in an allogeneic situation, off-the-shelf implants can be created. This study compared allogeneic and autologous MSCs at an orthotopic (L1 transverse process model) and ectopic (intramuscular) implantation location in 2-year-old goats. Further, the possible additional effect of platelet-leukocyte gel (PLG) as a source of growth factors on bone formation was investigated. For the orthotopic implantation, cassettes were implanted in nine goats bilaterally on the lumbar transverse processes, either with PLG-seeded or with plasma-seeded constructs. To assess the onset of bone formation, fluorochromes were administered at weeks 3, 5, and 9. Their incorporation in newly formed bone indicated that seeded cells enhanced bone formation in the first weeks. Nevertheless, after 16 weeks no beneficial effects of cells were found in the cassettes in contrast to the ectopic location. No effect of PLG on bone formation was shown at either location. Finally, we show no significant difference in bone formation between autologous and allogeneic MSCs, an important finding when considering the use of allogeneic cells as an off-the-shelf component in tissue-engineered bone in goats.
    Article · May 2009 · Tissue Engineering Part A
  • Ruth E Geuze · Moyo C Kruyt · Abraham J Verbout · [...] · Wouter J.A. Dhert
    [Show abstract] [Hide abstract] ABSTRACT: Construction of bone grafts for regenerative medicine would highly benefit from off-the-shelf components, such as allogeneic bone marrow stromal cells (BMSCs) and blood-derived growth factors from platelet concentrate. Although allogeneic BMSCs are considered immunosuppressive, their use in transplantation studies is still cautioned. In this study, we used off-the-shelf goat allogeneic BMSCs, per-operatively aspirated bone marrow (BM) and platelet gel (PLG). Ten goats received six different hybrid constructs consisting of biphasic calcium phosphate scaffolds seeded with PLG or plasma that were mixed with BM, allogeneic BMSCs or left without cells. All constructs were implanted in the paraspinal muscles for 9 weeks. Fluorochromes were administered at 2, 3, and 5 weeks to assess onset of bone formation. Analysis revealed that the scaffolds without cells yielded small amounts of bone. Allogeneic BMSCs had a positive effect on the amount and early onset of bone formation. Fresh BM did not enhance ectopic bone formation. The PLG, which contained higher levels of transforming growth factor beta than plasma, did not result in more bone either. Fluorochrome incorporation results indicate that the presence of seeded cells in the constructs accelerates bone formation. This study shows a potential role of allogeneic BMSCs in bone tissue-engineering research.
    Article · Aug 2008 · Tissue Engineering Part A
  • [Show abstract] [Hide abstract] ABSTRACT: Bone marrow stromal cells (BMSCs) have been shown to proliferate and produce matrix when seeded onto braided poly(L-lactide/glycolide) acid (PLGA) scaffolds. Mechanical stimulation may be applied to stimulate tissue formation during ligament tissue engineering. This study describes for the first time the effect of constant load on BMSCs seeded onto a braided PLGA scaffold. The seeded scaffolds were subjected to four different loading regimes: Scaffolds were unloaded, loaded during seeding, immediately after seeding, or 2 days after seeding. During the first 5 days, changing the mechanical environment seemed to inhibit proliferation, because cells on scaffolds loaded immediately after seeding or after a 2-day delay, contained fewer cells than on unloaded scaffolds or scaffolds loaded during seeding (p<0.01 for scaffolds loaded after 2 days). During this period, differentiation increased with the period of load applied. After day 5, differences in cell content and collagen production leveled off. After day 11, cell number decreased, whereas collagen production continued to increase. Cell number and differentiation at day 23 were independent of the timing of the mechanical stimulation applied. In conclusion, static load applied to BMSCs cultured on PLGA scaffolds allows for proliferation and differentiation, with loading during seeding yielding the most rapid response. Future research should be aimed at elucidating the biomechanical and biochemical characteristics of tissue formed by BMSCs on PLGA under mechanical stimulation.
    Article · Aug 2008 · Tissue Engineering Part A
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    [Show abstract] [Hide abstract] ABSTRACT: A center parallel cohort study with blinded inclusion based on clinical equipoise. To compare outcomes of nonoperative and operative treatment strategies in terms of quality of life and neurologic and functional status. Despite a considerable body of literature, sound evidence regarding the optimal treatment for traumatic thoracic and lumbar spine fractures is lacking. Medical records of patients hospitalized for traumatic spinal fractures between 1991 and 2002 were identified in 2 trauma centers in the same country with established and different treatment strategies. Eligibility was retrospectively assessed for each case by a panel of orthopaedic surgeons who were representative of the 2 medical centers, and who were blinded to the treatment actually administered. Patients were included in the study when there was disagreement on the suggested treatment method. Thus, 2 comparable groups were identified undergoing nonoperative or operative treatment. Outcome assessment and comparison across groups focused on quality of life, residual pain, neurologic recovery, and employment in the middle-long-term follow-up. Discordance in regards to choice of treatment was identified in 190 (95 treated nonoperative, 95 operative) of 636 potentially eligible patients. Patients were comparable regarding baseline characteristics, except for a somewhat higher proportion of males and neurologic impairment in the operative group. Seventeen percent of the nonoperative and 21% of the operative group developed complications and 3 patients displayed neurologic deterioration for which a treatment change was considered necessary. Follow-up was complete in 79%; mean follow-up time was 6.2 years with a minimum of 2 years. Pain scores, disability indexes, and general health outcome were comparable at follow-up. Compared with matched population norms, outcomes were poorer regardless of treatment method. Neurologic recovery was better in the operative group, but this difference did not reach statistical significance. Multivariate regression analyses revealed that female gender and neurologic impairment were independent predictors of poor functional outcome. Eighty-eight and 83% of the nonoperatively and operatively treated patients were employed at some point after a rehabilitation period. Overall outcome of nonoperative and operative treatment in middle-long-term follow up is comparable, although there seems to be a difference in neurologic recovery patterns. Studies on the cost-effectiveness of treatment options and the patterns of recovery within 2 years after injury would assist in guideline development and stimulate interest for future research.
    Full-text Article · May 2008 · Spine
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    [Show abstract] [Hide abstract] ABSTRACT: The efficacy and benefits of high-dose antibiotic cement spacers compared with beads in the treatment of an infected prosthesis have been shown. However, in clinical practice, commercial, low-dose antibiotic bone cement is often used. This study investigated the in vitro antibiotic release of hip spacers made from Refobacin-Palacos-R or Antibiotic-Simplex-P cement compared with Septopal beads. Antibiotic concentrations were measured during 6 weeks. All carriers showed a burst release, but spacers showed little additional release after the first week. Cumulative release was 27.5 +/- 2.3 mg for Palacos, 23.8 +/- 0.2 mg for Simplex, and 188.3 +/- 9.3 mg for Septopal (P < .001). Despite the efficacy of high-dose antibiotic bone cement spacers, we believe one should be cautious toward using low-dose antibiotic bone cement for spacers because this could result in an unsuccessful eradication of infection.
    Full-text Article · Mar 2008 · The Journal of arthroplasty
  • Natalja E Fedorovich · Joost R De Wijn · Abraham J Verbout · [...] · Wouter J.A. Dhert
    [Show abstract] [Hide abstract] ABSTRACT: Organ or tissue printing, a novel approach in tissue engineering, creates layered, cell-laden hydrogel scaffolds with a defined three-dimensional (3D) structure and organized cell placement. In applying the concept of tissue printing for the development of vascularized bone grafts, the primary focus lies on combining endothelial progenitors and bone marrow stromal cells (BMSCs). Here we characterize the applicability of 3D fiber deposition with a plotting device, Bioplotter, for the fabrication of spatially organized, cell-laden hydrogel constructs. The viability of printed BMSCs was studied in time, in several hydrogels, and extruded from different needle diameters. Our findings indicate that cells survive the extrusion and that their subsequent viability was not different from that of unprinted cells. The applied extrusion conditions did not affect cell survival, and BMSCs could subsequently differentiate along the osteoblast lineage. Furthermore, we were able to combine two distinct cell populations within a single scaffold by exchanging the printing syringe during deposition, indicating that this 3D fiber deposition system is suited for the development of bone grafts containing multiple cell types.
    Article · Feb 2008 · Tissue Engineering Part A
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    [Show abstract] [Hide abstract] ABSTRACT: A retrospective cohort study on patients with traumatic vertebral fractures who underwent fusion with iliac crest bone. To evaluate the influence of low back surgery on donor site attributed pain, we compared donor site pain between patients who underwent high and low level fusions. The most common complication of posterior iliac crest bone graft harvesting is postoperative pain at the donor site. The incidence of donor site pain after bone graft harvesting from the posterior iliac crest is mainly reported from studies in patients who underwent low lumbar or lumbosacral surgery. The close proximity of the primary surgery to the iliac crest could interfere with the reported incidence of donor site pain. Questionnaires regarding the iliac crest morbidity were sent to patients who underwent instrumented posterolateral fusion after traumatic spinal fractures. The incidence of donor site attributed pain was compared between patients whose fusion was between T2 and L2, with patients whose fusion extended to L3 or more caudally. In patients with a fusion of high levels, the donor site pain was significantly lower compared with patients with fusion of low levels (14.3% vs. 40.9%). Patients probably cannot differentiate between donor site pain and residual low back pain. The reported incidence of pain related to posterior iliac crest bone graft harvesting may therefore be overestimated.
    Full-text Article · Sep 2007 · Spine
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    [Show abstract] [Hide abstract] ABSTRACT: Culture remains the gold standard in the diagnosis of bacterial infection, but molecular biological techniques have yielded promising results. In this study, we validated a combined polymerase chain reaction and reverse line blot hybridization protocol for identifying musculoskeletal infections. Samples were obtained from seventy-six patients undergoing orthopaedic surgery for various aseptic and septic indications. The diagnosis of infection was based on a review of all available clinical and culture data. In addition to routine culture for aerobic and anaerobic growth, samples were analyzed with a broad-range 16S rRNA polymerase chain reaction and subsequent reverse line blot hybridization with use of twenty-eight group, genus, and species-specific oligonucleotide probes. An infection was diagnosed on the basis of patient data in thirty-one patients. All but one of the patients with a clinical diagnosis of infection had a positive result of the polymerase chain reaction-reverse line blot hybridization. Five of the forty-five patients in whom an infection was not suspected on the basis of patient data had at least one positive result of the polymerase chain reaction-reverse line blot hybridization. Cultures demonstrated microorganisms in twenty-five patients with an infection and in two patients in whom an infection was not suspected on the basis of the patient data. Staphylococcus aureus was the most common organism grown on culture. The species identified by the polymerase chain reaction-reverse line blot hybridization was in full accordance with that grown on culture in all but one patient. Polymerase chain reaction-reverse line blot hybridization performed well in detecting and identifying the various bacterial species and was more sensitive than routine culture. It identified Staphylococcus aureus as the most frequently found microorganism. Five patients in whom an infection was not suspected on the basis of the patient data had a positive result of the polymerase chain reaction, which may have been caused by contamination of the samples. However, three of these patients had aseptic loosening of a total hip prosthesis, suggesting the presence of a low-grade bacterial infection that remained undetected by the culture but was detected by the polymerase chain reaction-reverse line blot hybridization. Diagnostic Level III.
    Full-text Article · Jul 2007 · The Journal of Bone and Joint Surgery
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    [Show abstract] [Hide abstract] ABSTRACT: In this cross-sectional magnetic resonance imaging study, vertebral rotation was measured in the transverse plane of the normal, nonscoliotic spine of persons with a complete mirror image reversal of the internal body organs, called situs inversus totalis. To determine if a pattern of rotation exists in the normal spine of persons with situs inversus totalis, opposite of what was found in humans with normal organ anatomy. In humans, as well as in quadrupeds, the mid and lower thoracic vertebrae of the normal, nonscoliotic spine show a pre-existent pattern of rotation to the right side. This rotational pattern is similar to what is seen in the most prevalent types of adolescent idiopathic scoliosis and, therefore, probably plays an important role in determining the direction of spinal curvature once scoliosis starts to develop. The cause of this pre-existent rotation, however, is unknown. Magnetic resonance imaging scans of the thorax and abdomen of 37 persons with situs inversus totalis and a normal, nonscoliotic spine were acquired to measure axial vertebral rotation from T2 to L5 with a previously developed computer-based measurement method. The results of this study showed a predominant rotation to the left side of the mid and lower thoracic vertebrae, and to the right side of the upper thoracic and lumbar vertebrae. The mean vertebral rotation angles differed significantly from zero degrees rotation at the mid and lower thoracic levels, with a maximum rotation of 2.7 degrees at level T7 (P < 0.001). The normal spine of humans with a situs inversus totalis shows a pre-existent pattern of vertebral rotation opposite of what is seen in humans with normal organ anatomy. This study shows a relation between the asymmetrical position of the thoracic organs and pre-existent vertebral rotation in the normal spine.
    Full-text Article · Jun 2007 · Spine
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    [Show abstract] [Hide abstract] ABSTRACT: Despite decades of extensive research, the application of cell-based bone tissue engineering in clinically relevant models remains challenging. To improve effectiveness, a better understanding of how the technique should work is crucial. In the current study, we investigated the onset time, rate, location and direction of bone formation in ectopically and orthotopically implanted clinically sized tissue-engineered constructs to gain insight the mechanism behind it. Bone marrow stromal cells (BMSCs) were obtained from 10 goats, culture expanded and cryopreserved. Porous biphasic calcium phosphate (BCP) disks of 17mmx6mm were per-operatively seeded with BMSCs or left empty. Both conditions were implanted intramuscularly and in bilateral critical-sized iliac wing defects. Fluorochromes were administered at 3, 5 and 7 weeks and samples were retrieved after 9 weeks. Histology showed abundant and homogeneous bone formation throughout the intramuscular BMSC samples and little bone in the controls. Histomorphometry and measurements of the fluorochrome labels of the ectopical BMSC samples indicated that osteogenesis started at the periphery and subsequent osteoconduction filled the whole scaffold within 7 weeks. In the orthotopically implanted disks, there was good integration with the surrounding bone, but minimal bone in the center of the implants, in both conditions. Bone was only derived from the interface with the surrounding bone, there was no early bone at the surfaces in contact to soft tissue as was seen in the ectopical samples. Apparently cell survival was minimal and insufficient for relevant additional bone formation. However, the speed of integration with surrounding bone and subsequent bone apposition on the BMSC-seeded orthotopic scaffolds were found to be significantly enhanced, which may be relevant especially in challenging environments.
    Full-text Article · May 2007 · Biomaterials
  • [Show abstract] [Hide abstract] ABSTRACT: A disadvantage of traditional posterolateral spinal fusion models is that they are highly inefficient for screening multiple conditions. We developed a multiple-condition model that concentrates on the initial process of bone formation from the transverse process and not on a functional fusion. The effect of bone marrow stromal cells (BMSCs) in four different porous ceramic scaffolds was investigated in this setting. Polyacetal cassettes were designed to fit on the goat transverse process and house four different ceramic blocks, i.e: hydroxyapatite (HA) sintered at 1,150 degrees and 1,250 degrees; biphasic calcium phosphate (BCP) and tricalcium phosphate (TCP). Goat BMSCs (n=10) were cultured and per-operatively seeded autologeously on one of two cassettes implanted per animal. The cassettes were bilaterally mounted on the dorsum of decorticated L2-processes for 9 weeks. To asses the dynamics of bone formation, fluorochrome labels were administered and histomorphometry focused on the distribution of bone in the scaffolds. A clear difference in the extent of bone ingrowth was determined for the different scaffold types. An obvious effect of BMSC seeding was observed in three of four scaffold types, especially in scaffold regions adjacent to the overlying muscle. Generally, the BCP and TCP scaffolds showed better osteoconduction and an increased response to BMSCs administration. In conclusion the model provides a reliable and highly efficient method to study bone formation in cell-based tissue engineering. An effect of cell administration was obvious in three of the four scaffold materials.
    Article · Nov 2006 · Biomaterials
  • [Show abstract] [Hide abstract] ABSTRACT: This study presents a new screening model for evaluating the influence of multiple conditions on the initial process of bone formation in the posterior lumbar spine of a large animal. This model uses cages designed for placement on the decorticated transverse process of the goat lumbar spine. Five conduction channels per cage, each be defined by a different material treatment, are open to both the underlying bone and overlying soft tissue. The model was validated in ten adult Dutch milk goats, with each animal implanted with two cages containing a total of ten calcium phosphate material treatments according to a randomized complete block design. The ten calcium phosphate ceramic materials were created through a combination of material chemistry (BCP, TCP, HA), sintering temperature (low, medium, high), calcination and surface roughness treatments. To monitor the bone formation over time, fluorochrome markers were administered at 3, 5 and 7 weeks and the animals were sacrificed at 9 weeks after implantation. Bone formation in the conduction channels was investigated by histology and histomorphometry of non-decalcified sections using traditional light and epifluorescent microscopy. According to both observed and measured bone formation parameters, materials were ranked in order of increasing magnitude as follows: low sintering temperature BCP (rough and smooth) approximately medium sintering temperature BCP approximately = TCP > calcined low sintering temperature HA > non-calcined low sintering temperature HA > high sintering temperature BCP (rough and smooth) > high sintering temperature HA (calcined and non-calcined). These results agree closely with those obtained in previous studies of osteoconduction and bioactivity of ceramics thereby validating the screening model presented in this study.
    Article · Jan 2006 · Biomaterials
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    [Show abstract] [Hide abstract] ABSTRACT: Since the application of the autologous bone graft, the need for an alternative has been recognized. Tissue engineering (TE) of bone by combining bone marrow stromal cells (BMSCs) with a porous scaffold, is considered a promising technique. In this study we investigated the potential of tissue engineered bone to heal a critical sized defect in the goat. Orthotopic bone formation was compared to ectopic bone formation in comparable constructs. TE constructs were prepared from goat BMSCs and porous biphasic calcium phosphate ceramic scaffolds. These constructs and scaffolds without cells were implanted paired in critical sized iliac wing defects. Comparable samples were implanted intramuscularly. After 9 (n=7) and 12 (n=8) weeks implantation, the samples were analyzed histomorphometrically. After 9-weeks implantation in the iliac wing defect, significantly more bone apposition was found in the TE condition. After 12 weeks, the defects were almost completely filled with bone, but no significant advantage of TE was determined anymore. This contrasted with the intramuscular samples where TE implants showed significantly more bone at both time points. In conclusion, bone TE is feasible in critical sized defects. However, when appropriate osteoconductive/inductive materials are applied the effect of cell seeding may be temporary.
    Full-text Article · Jun 2004 · Journal of Orthopaedic Research
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    [Show abstract] [Hide abstract] ABSTRACT: Successful bone-tissue engineering (TE) has been reported for various strategies to combine cells with a porous scaffold. In particular, the period after seeding until implantation of the constructs may vary between hours and several weeks. Differences between these strategies can be reduced to (a) the presence of extracellular matrix, (b) the differentiation status of the cells, and (c) the presence of residual potentially immunogenic serum proteins. These parameters are investigated in two types of calcium phosphate scaffolds in a goat model of ectopic bone formation. Culture-expanded bone-marrow stromal cells from eight goats were seeded onto two types of hydroxyapatite granules: HA60/400 (60% porosity, 400-microm average pore size) and HA70/800. Scaffolds seeded with cells and control scaffolds were cultured for 6 days in medium containing autologous or semisynthetic serum, in the presence or absence of dexamethasone. Other scaffolds were seeded with cells just before implantation in medium with or without serum. All conditions were implanted autologously in the paraspinal muscles. After 12 weeks, bone had formed in 87% of all TE constructs, as demonstrated by histology. Histomorphometry indicated significantly more bone in the HA70/800 scaffolds. Furthermore, a significant advantage in bone formation was found when the constructs had been cultured for 6 days. In conclusion, both scaffold characteristics (porosity) and TE strategy (culturing of the constructs) were demonstrated to be important for bone TE.
    Full-text Article · May 2004 · Journal of Biomedical Materials Research Part B Applied Biomaterials