Biomedical subjects

Abraham J Verbout

Publications and source records attributed to Abraham J Verbout.

12 recordsLinked to original sources

PubMed2006

Analysis of ectopic and orthotopic bone formation in cell-based tissue-engineered constructs in goats.

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.

Animals↗

PubMed2006

The effect of cell-based bone tissue engineering in a goat transverse process model.

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.

Animals↗

PubMed2006

Cement augmentation techniques in traumatic thoracolumbar spine fractures.

STUDY DESIGN: Review of human cadaveric and in vivo animal studies and clinical trial. OBJECTIVE: To develop less invasive surgical techniques for reconstruction of the anterior column in thoracolumbar fractures. SUMMARY OF BACKGROUND DATA: Persistent central endplate depression can cause anterior column insufficiency after posterior surgery for traumatic thoracolumbar fractures. Reduction of the central endplate followed by intravertebral cement augmentation could restore weight-bearing capacity. MATERIALS AND METHODS: In human cadaveric burst fracture models, balloon-assisted endplate reduction (BAER) and vertebroplasty techniques have been investigated in terms of their safety and biomechanical properties. The histologic properties of different cement polymers were studied in an animal vertebral body and endplate defect model. In addition, the clinical outcome of percutaneous cement augmentation in the setting of a burst fracture examining the BAER technique and vertebroplasty with adjunctive posterior pedicle screw fixation is reviewed. RESULTS: These techniques have proven to be safe and effective, although cement leakage outside the confines of the vertebral body may occur. Calcium phosphate cements are preferable over methylmethacrylate because of their in vivo histologic properties. Using the BAER technique and posterior pedicular fixation, anterior vertebral height restoration is possible. Following balloon removal, some loss of fracture height restoration is observed. Further loss of vertebral height reduction was not observed following cement curing clinically. CONCLUSIONS: These studies show that less invasive anterior vertebral reconstruction using percutaneous cement augmentation techniques is feasible following traumatic vertebral fractures.

Animals↗

PubMed2005

A new in vivo screening model for posterior spinal bone formation: comparison of ten calcium phosphate ceramic material treatments.

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.

Animals↗

PubMed2005

Balloon vertebroplasty in combination with pedicle screw instrumentation: a novel technique to treat thoracic and lumbar burst fractures.

STUDY DESIGN: Clinical trial (phase II). OBJECTIVES: To assess the feasibility and safety of balloon vertebroplasty after posterior short-segment reduction and fixation for the treatment of traumatic burst fractures. SUMMARY OF BACKGROUND DATA: Hardware failure and loss of reduction after posterior short-segment instrumentation are complications caused by insufficiency of anterior column support. This is due to migration of disc tissue through the endplate into the fractured vertebral body that cannot be restored with posterior instrumentation. METHODS: Patients with traumatic thoracolumbar burst fractures without neurologic deficits were included. After posterior reduction and fixation, bilateral transpedicular balloon reduction of the endplate was performed, and calcium phosphate cement was injected. Preoperative and postoperative Cobb angle and central and anterior height were assessed with radiographs and MRI. RESULTS: Twenty patients underwent surgery without technical difficulties, and a substantial reduction of the endplates could be achieved with the technique. All patients recovered uneventfully, and the neurologic examination revealed no deficits. The postoperative radiographs and magnetic resonance images demonstrated a good fracture reduction and filling of the bone defect without unwarranted bone displacement. The central and anterior height of the vertebral body could be restored to 78 and 91% of the estimated intact height, respectively. Complications were cement leakage in five cases without clinical implications and one wound hematoma. CONCLUSIONS: Transpedicular balloon vertebroplasty for the direct restoration of burst fractures seems feasible in combination with posterior instrumentation. Cement leakage occurred but had no clinical consequences.

Adolescent↗

PubMed2004

Optimization of bone-tissue engineering in goats.

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.

Animals↗

PubMed2004

Osteogenicity of autologous bone transplants in the goat.

BACKGROUND: Little is known about the specific mechanisms that make autologous graft bone (AG) superior to the current alternatives. A potential mechanism is the active bone formation by the osteoprogenitor cells within the AG. However, whether these cells survive the transplantation is questionable, especially in nonvascularized, clinically sized grafts. In the present study, we investigated the role of viability in AG implanted ectopically and orthotopically in the goat. METHODS: Eight goats were operated on twice. At the first operation, pieces of vital or devitalized autologous cortical bone were implanted in the paraspinal muscles. Eight weeks later, corticocancellous plugs were taken from the femoral condyles, morselized, and reimplanted as either vital or devitalized orthotopic grafts. The goats received fluorochrome labels at 5, 7, and 9 weeks after the first operation. At 12 weeks, the goats were killed, and the samples were examined histologically. RESULTS: Ectopically, new bone had formed in both the vital and devitalized grafts. In the vital grafts, all three fluorochrome labels were present, indicating an early osteogenic mechanism. Within the devitalized grafts, only the 9-week label was observed. Histomorphometry indicated significantly more new bone in the vital grafts (10.3% vs. 1.7% in the devitalized grafts, P <0.01). Orthotopically, both vital and devitalized grafts showed new bone. Again, graft viability was advantageous in terms of new bone formation (14.5% vs. 9.3%, P <0.02). CONCLUSION: The cells inside the autologous bone transplants most likely survived transplantation and were capable of initiating and sustaining new bone formation.

Animals↗

PubMed2004

Optimization of bone tissue engineering in goats: a peroperative seeding method using cryopreserved cells and localized bone formation in calcium phosphate scaffolds.

BACKGROUND: Bone tissue engineering by combining cultured bone marrow stromal cells with a porous scaffold is a promising alternative for the autologous bone graft. Drawbacks of the technique include the delay necessary for cell culture and the complicated logistics. We investigated methods to bypass these drawbacks. Furthermore, we investigated the localization of bone formation inside the scaffold. METHODS: Bone marrow stromal cells from seven goats were culture expanded and cryopreserved. One week before surgery, some of the cells were thawed, cultured, and seeded on porous calcium phosphate scaffolds. The constructs were cultured for another week until implantation. The remaining cryopreserved cells were thawed just before implantation and peroperatively resuspended in plasma before combining with the scaffold. Scaffolds impregnated with fresh bone marrow, devitalized cultured constructs, and empty scaffolds served as controls. All samples were implanted in the back muscles of the goats for 9 weeks. RESULTS: Histologic examination showed minimal (<1%) bone in the empty and devitalized scaffolds, 4.2 +/- 5.1 bone area percent in the bone marrow samples, and significantly more bone in both the cultured and peroperatively seeded constructs (11.7 +/- 2.5 and 14.0 +/- 2.0%). The peripheral 350 microm of the implants contained significantly less bone. CONCLUSION: Peroperative preparation of osteogenic constructs with cryopreserved cells is feasible. These constructs yield substantially more bone than the scaffolds alone or scaffolds impregnated with fresh bone marrow. Bone deposition is much less on the scaffold periphery.

Animals↗

PubMed2004

Bone tissue engineering in a critical size defect compared to ectopic implantations in the goat.

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.

Animals↗

PubMed2003

Temperature elevation after vertebroplasty with polymethyl-methacrylate in the goat spine.

Although the general complication rate for vertebroplasty is low, neural compression and thermal damage have been related to the use of polymethyl-methacrylate cement. This study focuses on the risk of thermal tissue damage after vertebroplasty. In this study, cavities were created by a transpedicular approach in the vertebral bodies (L3, L4, and L5) of four milk goats, and polymethyl-methacrylate cement was injected. In three locations (the bone-cement interface, the epidural space, and the disc space) the temperature was measured in regular intervals after injection of the cement. The mean injected volume was 0.8 ml, which accounted for a 22% volume fraction. The mean peak temperature of the bone-cement interface was 44.6 degrees C, while the maximum temperature at the epidural space and disc space was 37.0 and 37.5 degrees C, respectively. The local temperature measured after in vivo vertebroplasty did not reach values that are known to cause tissue necrosis.

Animals↗

PubMed2002

Clinical benefit of joint distraction in the treatment of severe osteoarthritis of the ankle: proof of concept in an open prospective study and in a randomized controlled study.

OBJECTIVE: Osteoarthritis (OA) is a degenerative, disabling joint disease that affects >10% of the adult population. No effective disease-modifying treatment is available. In the present study, we used joint distraction, a relatively new treatment in which mechanical contact between the articular surfaces is avoided while intraarticular intermittent fluid pressure is maintained, to treat patients with severe OA of the ankle. METHODS: Patients with severe ankle OA (n = 57) who were being considered for joint fusion (arthrodesis) were treated with joint distraction in an open prospective study. In addition, a randomized trial was performed in 17 patients to determine whether joint distraction had a better outcome than debridement. A standardized evaluation protocol (physical examination, assessment of pain, mobility, and functional ability) was used, and changes in radiographic joint space width and subchondral sclerosis were measured. Thirty-eight patients in the open study have been followed up for >1 year, with up to 5 years of followup in 7 of them (mean +/- SD followup 2.8 +/- 0.3 years). Patients in the randomized study have been followed up for 1 year. RESULTS: Significant clinical benefit was found in three-fourths of the 57 patients in the open prospective study. Most interestingly, the improvement increased over time. Radiographic evaluation showed increased joint space width and decreased subchondral sclerosis. Moreover, joint distraction showed significantly better results than debridement. CONCLUSION: The clinical benefit of joint distraction in the treatment of severe OA is proof of the concept. Although the followup remains relatively short and effects over time remain unpredictable, our study creates possibilities for the treatment of severe OA in general. Considering the high prevalence of OA and the lack of a cure for it, joint distraction as a treatment of severe OA may have great medical, social, and economic impact.

Adolescent↗

PubMed2002

The epidemiology of total hip replacement in The Netherlands and Sweden: present status and future needs.

By combining data from the Discharge registers and the census bureaus in The Netherlands and Sweden, we calculated the age-specific incidences of primary total hip replacement (THR), studied the demographic profile of the population receiving THR and predicted demands. In the period 1986-1997, the number of THRs increased by 20% in Sweden to 10,000 operations (113/100,000 inhabitants) and by 68% to 17,400 operations (112/100,000 inhabitants) in The Netherlands. Of this increase 3% and 15% could be explained by changes in the age-profile and size of the population, respectively. Although the overall incidence of THR was similar in both countries in 1997, we found that, after correction for differences in population structure, the incidence of THR was 20% higher in The Netherlands. In Sweden, relatively more men were operated on than in The Netherlands. We also found that in Sweden, but not in the Netherlands, relatively more older people were operated on in 1997 than in 1987. Assuming no further change in the age- and sex-specific arthroplasty rates, the predicted annual number of total hip replacements by the year 2020 will increase by at least one fourth in Sweden and almost one half in The Netherlands.

Adult↗