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Theo H Smit

Publications and source records attributed to Theo H Smit.

At least 19 recordsLinked to original sources

A biomechanical analysis of the self-retaining pedicle hook device in posterior spinal fixation.

Regular hooks lack initial fixation to the spine during spinal deformity surgery. This runs the risk of posterior hook dislodgement during manipulation and correction of the spinal deformity, that may lead to loss of correction, hook migration, and post-operative junctional kyphosis. To prevent hook dislodgement during surgery, a self-retaining pedicle hook device (SPHD) is available that is made up of two counter-positioned hooks forming a monoblock posterior claw device. The initial segmental posterior fixation strength of a SPHD, however, is unknown. A biomechanical pull-out study of posterior segmental spinal fixation in a cadaver vertebral model was designed to investigate the axial pull-out strength for a SPHD, and compared to the pull-out strength of a pedicle screw. Ten porcine lumbar vertebral bodies were instrumented in pairs with two different instrumentation constructs after measuring the bone mineral density of each individual vertebra. The instrumentation constructs were extracted employing a material testing system using axial forces. The maximum pull-out forces were recorded at the time of the construct failure. Failure of the SPHD appeared in rotation and lateral displacement, without fracturing of the posterior structures. The average pull-out strength of the SPHD was 236 N versus 1,047 N in the pedicle screws (P < 0.001). The pull-out strength of the pedicle screws showed greater correlation with the BMC compared to the SPHD (P < 0.005). The SPHD showed to provide a significant inferior segmental fixation to the posterior spine in comparison to pedicle screw fixation. Despite the beneficial characteristics of the monoblock claw construct in a SPHD, that decreases the risk of posterior hook dislodgement during surgery compared to regular hooks, the SPHD does not improve the pull-out strength in such a way that it may provide a biomechanically solid alternative to pedicle screw fixation in the posterior spine.

Animals↗

Lumbar body fusion with a bioresorbable cage in a goat model is delayed by the use of a carboxymethylcellulose-stabilized collagenous rhOP-1 device.

The purpose of this study was to evaluate the efficacy of recombinant human osteogenic protein-1 (rhOP-1) with a carboxymethylcellulose-stabilized collagenous carrier as a bone graft substitute for instrumented lumbar spinal fusion in an established goat model. Twenty goats received a resorbable poly-L-lactic acid (PLLA) interbody cage packed with either rhOP-1 and its carrier or autologous bone graft. The carrier material was bovine collagen type-1 stabilized with carboxymethylcellulose. The fusion segments were retrieved at 3 or 6 months postimplantation and evaluated by radiographic and histologic analyses. The rhOP-1 graft substitute, used in combination with the resorbable PLLA cage, showed inferior results as compared to autologous bone graft in the goat lumbar fusion model. Whereas four out of five segments from the autograft group were fused after 6 months, none of the four segments receiving the rhOP-1 graft substitute were fused at this time point. Bone ingrowth into the cage was delayed or absent in the experimental group, whereas all autograft specimens showed advanced bone ingrowth (3 months) or fusion (6 months). We suggest that the fusion process was inhibited, because cells were unable to penetrate the rhOP-1 graft material. This led to delayed bone formation and in some cases inadequate tissue formation.

Absorbable Implants↗

Collagen type V enhances matrix contraction by human periodontal ligament fibroblasts seeded in three-dimensional collagen gels.

Extracellular matrix components play an important role in modulating cellular activity. To study such capacities of the matrix, fibroblasts are frequently cultured in a three-dimensional gel and contraction is assessed as a measure of cellular activity. Since a connective tissue contains several types of collagen, we investigated the effect of gels composed of collagen I alone or in combination with 10% collagen III and/or 5% collagen V on contraction by human periodontal ligament fibroblasts. Gels containing collagen V contracted much faster than those without this type of collagen. Blocking of the integrin beta1-subunit with an activity-blocking antibody delayed (gels with collagen V) or almost completely blocked (gels without collagen V) contraction. Use of an antibody directed against integrin alpha2beta1 resulted in delay of gel contraction for gels both with and without collagen V. Anti-integrin alpha v beta3 or RGD peptides partially blocked contraction of gels containing collagen V, but had no effect on gels consisting of collagen I alone. The beta1-containing integrins are involved in the basal contraction by fibroblasts that bind to collagens I and III. The enhanced contraction, stimulated by collagen V, appears to be mediated by integrin alpha v beta3. We conclude that collagen V may play an important modulating role in connective tissue contraction. Such a modulation may occur during the initial stages of wound healing and/or tissue regeneration.

Adult↗

Radiographic, histologic, and chemical evaluation of bioresorbable 70/30 poly-L-lactide-CO-D, L-lactide interbody fusion cages in a goat model.

STUDY DESIGN: A study of lumbar interbody fusion using polylactic acid-based bioresorbable fusion cages in a goat model. OBJECTIVE: To evaluate the effect of polylactic acid polymer composition, and internal stabilization on the rate and quality of interbody fusion. SUMMARY OF BACKGROUND DATA: A spinal cage should provide an appropriate biomechanical environment to facilitate interbody fusion. Previous studies have shown that bioresorbable polylactic acid-based cages can provide adequate stability for spinal fusion. However, at present and to our knowledge, the best bioresorbable materials, optimal cage stiffness, and desired period over which the cage should biodegrade are unknown. METHODS: Interbody fusions were performed at L3-L4 level in 35 skeletally mature Dutch milk goats. Titanium and poly-L-lactide-CO-D,L-lactide (PLDLLA) cages were implanted at random as stand-alone cages. In addition, PLDLLA cages were implanted with anterior fixation. The goats were euthanized at 3, 6, or 12 months. Radiographic, magnetic resonance imaging, histologic, and histomorphometric analyses were performed on retrieved segments. Chemical analysis was used to assess degradation of the retrieved PLDLLA cages. Beforehand, chemical and mechanical degradation of the PLDLLA cages were assessed in vitro. RESULTS: At 3 months, bone graft was almost completely remodeled. Endochondral bone formation was observed in all specimens. At 6 months, 50% of the PLDLLA stand-alone cages and 83% of the PLDLLA anterior fixation cages were fused. At 12 months, 38% of the PLDLLA stand-alone and 83% of the titanium cages realized fusion. A very mild and dispersed foreign body reaction was seen in all PLDLLA specimens. E-beam sterilized PLDLLA cages degraded more rapidly in vivo as compared to both, PLDLLA cages in vitro, and ethylene oxide sterilized poly-L-lactic acid cages in vivo. CONCLUSIONS: Within the 3-6-month period, PLDLLA stand-alone cages provided insufficient mechanical stability, which manifested as cracking and deformation of the cages and lower fusion rates. This result implies that within this time, additional stabilization is required; supplemental internal fixation proved sufficient to obtain successful fusion. In all cases, only a mild host response was seen, indicating good biocompatibility.

Absorbable Implants↗

Primary spinal segment stability with a stand-alone cage: in vitro evaluation of a successful goat model.

BACKGROUND: Interbody cages have been developed to restore disk height and to increase stability of the spinal segment, and thereby enhance fusion. However, they often prove inadequate as a stand-alone device. It is unknown how much primary stability is required to facilitate fusion. In various goat studies, we have obtained spinal fusion routinely with a stand-alone cage device. However, data covering the mechanical conditions under which these fusions have been obtained are lacking. In this study, we addressed the issue of primary stability. METHODS: We used an established goat model for spinal fusion in vitro. 48 native lumbar spine segments were mechanically tested in flexion/extension, axial torsion (left/right), anterior/posterior shear, and left/right lateral bending. Then all segments were provided with a titanium cage using the exact surgical procedure of our earlier in vivo studies, and the mechanical tests were repeated. Under shear force and axial torsion, a significant loss of stiffness was seen in the operated segments as compared to nonoperated controls. No increase in stiffness was found in any of the loading directions. INTERPRETATION: Cage implantation in a lumbar spinal segment does not increase immediate postoperative stability as compared to the native segment in this goat model. This is attributable to both the annular damage during cage implantation and the subsequent loss of segment height. Yet previous in vivo studies using this goat model have generally shown fusion. This implies that high primary segment stability is not required for fusion or, alternatively, that the tested range of motion of the spinal segment in vitro does not occur at these magnitudes in vivo.

Animals↗

Bone cell responses to high-frequency vibration stress: does the nucleus oscillate within the cytoplasm?

Mechanosensing by cells directs changes in bone mass and structure in response to the challenges of mechanical loading. Low-amplitude, high-frequency loading stimulates bone growth by enhancing bone formation and inhibiting disuse osteoporosis. However, how bone cells sense vibration stress is unknown. Hence, we investigated bone cell responses to vibration stress at a wide frequency range (5-100 Hz). We used NO and prostaglandin E2 (PGE2) release, and COX-2 mRNA expression as parameters for bone cell response since these molecules regulate bone adaptation to mechanical loading. NO release positively correlated whereas PGE2 release negatively correlated to the maximum acceleration rate of the vibration stress. COX-2 mRNA expression increased in a frequency-dependent manner, which relates to increased NO release at high frequencies, confirming our previous results. The negatively correlated release of NO and PGE2 suggests that these signaling molecules play different roles in bone adaptation to high-frequency loading. The maximum acceleration rate is proportional to omega3 (frequency=omega/2pi), which is commensurate with the Stokes-Einstein relation for modeling cell nucleus motion within the cytoplasm due to vibration stress. Correlations of NO and PGE2 with the maximum acceleration rate then relate to nucleus oscillations, providing a physical basis for cellular mechanosensing of high-frequency loading.

3T3 Cells↗

Does bioresorbable cage material influence segment stability in spinal interbody fusion?

To reduce long term complications associated with nonresorbable interbody fusion cages, bioresorbable cages are being developed. We investigated the influence of bioresorbable cage material on segment stability, intervertebral disc height and fusion in vivo using radiostereometric analysis comparing 70/30 poly(L-lactide-co-D,L-lactide) (PLDLLA) cages with titanium cages. Twenty-eight goats were randomized to receive PLDLLA (n = 21) or a titanium control (n = 7) cage at L3-L4. Range of motion for flexion and extension and change in intervertebral disc height were measured before and after surgery and at followup (3, 6, and 12 months). Fusion was graded with a validated radiographic score. Although the PLDLLA cage could not provide the optimal environment for a successful high fusion rate, the range of motion of the PLDLLA segments gradually decreased in time and was similar to the titanium control group at 12 months. In addition the decrease of intervertebral disc height was similar for both PLDLLA (1.4 +/- 0.8 mm) and titanium (1.3 +/- 1.0 mm) specimens. Both results showed a bioresorbable cage does not lead to less decrease of motion or more loss of intervertebral disc height in time compared to titanium. This study therefore supports further development of a bioresorbable cage concept.

Absorbable Implants↗

Bio imaging of intracellular NO production in single bone cells after mechanical stimulation.

UNLABELLED: We show the intracellular upregulation of NO production after mechanical stimulation, an essential chemical signal in bone remodeling. This is done in real time using the fluorescent chromophore DAR-4M AM. Differences in cellular response to mechanical stimulation of different regions of a single cell were observed. INTRODUCTION: Osteocytes are the most abundant bone cells that are believed to be the mechanosensors of bone, responding to mechanical stresses in interstitial fluid flow through the canaliculi. Under mechanical load, chemical signals such as NO play a key role in the activity of osteoblasts/osteoclasts that regulate bone remodeling. Despite the importance of NO in signaling, its real-time detection has proved challenging. This is largely because of the short NO half-life (typically approximately 0.1-5 s). Here, we show the upregulation of intracellular NO production in single osteocytes under localized mechanical stimulation. MATERIALS AND METHODS: We used the chromophore DAR-4M AM for NO detection. This is loaded into surface-attached MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells that are subjected to a localized mechanical stimulation using optical tweezers or a microneedle tip. DAR-4M AM is membrane-permeable and chelates NO, forming a stable, fluorescent compound, which is visible with a rhodamine filter. RESULTS: Nonstimulated MLO-Y4 and MC3T3-E1 cells showed basal NO production levels, as indicated by a gradual increase in their fluorescence intensity. Localized mechanical stimulation of single MC3T3-E1 cells and MLO-Y4 cells by optical tweezers (150-550 pN, 0.5-3 Hz, 1 minute) showed a nearly 15-30% increase, whereas MLO-Y4 cells stimulated by a microneedle (10-20 nN, 1 minute) showed nearly 15-16% increase relative to their nonstimulated state. Furthermore, stimulation of a single cell process by a microneedle resulted in a 2-10% increase in the fluorescence intensity. CONCLUSIONS: NO is essential for mechanically induced bone remodeling and is a meaningful parameter for measuring bone cell activation after mechanical loading. Here we show NO upregulation in individual bone cells after a localized mechanical stimulation. We also show that both the cell body and the cell processes might be involved in mechanosensing. This technique allows characterization of the mechanosensitivity of different parts of a single osteocyte. This opens up the possibility to uncover the complexities and function of single osteocytes in the dynamic process of bone remodeling.

Animals↗

Flow-related mechanics of the intervertebral disc: the validity of an in vitro model.

STUDY DESIGN: An in vitro mechanical study on porcine motion segments. OBJECTIVES: To test the validity of in vitro studies of the flow-related mechanics of the intervertebral disc and, in particular, to investigate whether fluid flows back into the disc during unloading after a loading cycle. SUMMARY OF BACKGROUND DATA: In vivo studies show both the inflow and outflow of fluid in the intervertebral disc. The resistance to flow out of the disc is higher than to inflow. The fluid flow is regulated via unbalance between the external load and the osmotic pressure of the nucleus pulposus. MATERIALS: There were 8 porcine lumbar motion segments (without posterior elements) and 8 isolated discs tested in a physiologic saline bath (39 degrees C). The specimens were preloaded at 0.025 MPa for 15 minutes. Three 15-minute loading periods at 2.0 MPa were applied, each followed by an unloading period of 30 minutes. Loads, axial displacements, and nucleus pressure were recorded online. RESULTS: Over the 3 loading and unloading periods, all specimens showed a net loss of height and mass. The time series of specimen height during the 3 unloading periods showed virtually identical responses. The pressure in the nucleus decreased in the subsequent loading periods and showed no increase during unloading. CONCLUSION: The data show the limitations of an in vitro model for studying fluid flow-related intervertebral disc mechanics. During loading, outflow of fluid occurred, but inflow appears to be virtually absent during unloading. Poro-elastic behavior cannot be reproduced in an in vitro model.

Animals↗

Initial stress-kick is required for fluid shear stress-induced rate dependent activation of bone cells.

The shear stress induced by the loading-mediated flow of interstitial fluid through the lacuno-canalicular network is a likely stimulus for bone cell adaptive responses. Furthermore, the magnitude of the cellular response is related to the rate of mechanical loading rather than its magnitude. Thus, bone cells might be very sensitive to sudden stress-kicks, as occuring e.g., during impact loading. There is evidence that cells change stiffness under stress, which might make them more sensitive to subsequent loading. We studied the influence of a stress-kick on the mechanosensitivity of MC3T3-E1 osteoblast-like cells under different peak shear rate conditions, as measured by nitric oxide production. MC3T3-E1 bone cells were treated with steady or pulsating fluid shear stress (PFSS) for 5 min with different peak rates (9.70, 17.5, and 22.0 Pa Hz) using varying frequencies (5 and 9 Hz), and amplitudes (0.70 and 0.31 Pa). PFSS treatment was done with or without fluid flow pretreatment phase, which removed the initial stress-kick by first applying a slow fluid flow increase. Nitric oxide production in response to fluid shear stress was rate dependent, but necessitated an initial stress-kick to occur. This suggests that high-rate stimuli condition bone cells to be more sensitive for high-frequency, low-amplitude loads.

Bone Marrow Cells↗

Dynamic shear stress in parallel-plate flow chambers.

An in vitro model using a parallel-plate fluid flow chamber is supposed to simulate in vivo fluid shear stresses on various cell types exposed to dynamic fluid flow in their physiological environment. The metabolic response of cells in vitro is associated with the wall shear stress. However, parallel-plate flow chambers have not been characterized for dynamic fluid flow experiments. We use a dimensionless ratio h / lambda(v), in determining the exact magnitude of the dynamic wall shear stress, with its oscillating components scaled by a shear factor T. It is shown that, in order to expose cells to predictable levels of dynamic fluid shear stress, two conditions have to be met: (1) h / lambda(v) < 2, where h is the distance between the plates and lambda(v) is the viscous penetration depth; and (2) f(0) < f(c) / m, where the critical frequency f(c) is the upper threshold for this flow regime, m is the highest harmonic mode of the flow, and f(0) is the fundamental frequency of fluid flow.

Animals↗

The role of dorsal shear forces in the pathogenesis of adolescent idiopathic scoliosis--a hypothesis.

The pathogenesis of adolescent idiopathic scoliosis (AIS), a condition exclusive to man, has been the subject of many studies, but remains little understood. Previous work has shown that backward inclination of vertebrae in the sagittal plane has prognostic significance in the progression of AIS, and that certain regions of the human spine may be subject to dorsal shear forces, depending on posture, unlike what is found in other vertebrates. We postulate that these dorsal shear forces, acting exclusively upon specific regions of the human spine, may contribute to rotational instability of the spine. Asymmetric loading of the posterior parts of the vertebrae then would lead to asymmetrical growth in all three planes of specific parts of vertebrae, according to Hueter-Volkmann's law. Asymmetrical growth of the neurocentral cartilage of the vertebra, for instance, has been shown to lead to AIS-like deformities in growing pigs, and could explain the development and progression of the deformity in humans.

Adolescent↗

Four-year follow-up of poly-L-lactic Acid cages for lumbar interbody fusion in goats.

BACKGROUND: New applications of bioabsorbable polymer implants demand for histologic evaluation because a host tissue response is elicited and late complications after polymer implantation have been reported. Furthermore, in load-bearing regions an accelerated polymer degradation and foreign body reaction may be observed. METHODS: Lumbar interbody fusion procedures were performed using poly-L-lactic acid (PLLA) and titanium cages in 43 goats. At 3, 6, 12, 24, 36, and 48 months after surgery, sequential histologic analysis of instrumented motion segments, lymph nodes, and nervous structures was performed. Blood samples were retrieved for laboratory analysis. RESULTS: No adverse local or distant histologic or systemic effects were observed during the absorption of the poly-L-lactic acid cages. Interbody fusion was maintained, and only a very mild inflammatory response was observed. In half the specimens complete absorption was observed, and in the remaining specimens an estimated 1-10% of the original PLLA was present at the 3-year follow-up. At the 4-year follow-up, five out of seven PLLA specimens showed no PLLA particles under polarized light microscopy. In the remaining two specimens an estimated 1% of the original PLLA could be observed. CONCLUSIONS: Poly-L-lactic acid cages are feasible for lumbar interbody fusion, and the biocompatibility under high load bearing conditions is excellent during the complete absorption of the PLLA interbody fusion cages.

Absorbable Implants↗

Nitric oxide production by bone cells is fluid shear stress rate dependent.

Shear stress due to mechanical loading-induced flow of interstitial fluid through the lacuno-canalicular network is a likely signal for bone cell adaptive responses. Moreover, the rate (determined by frequency and magnitude) of mechanical loading determines the amount of bone formation. Whether the bone cells' response to fluid shear stress is rate dependent is unknown. Here we investigated whether bone cell activation by fluid shear stress is rate dependent. MC3T3-E1 osteoblastic cells were subjected for 15 min to fluid shear stress of varying frequencies and amplitudes, resulting in peak fluid shear stress rates ranging from 0 to 39.6 Pa-Hz. Nitric oxide production, a parameter for bone cell activation, was found to be linearly dependent on the fluid shear stress rate; the slope was steepest at 5 min (0.11 Pa-Hz(-1)) and decreased to 0.03 Pa-Hz(-1) at 15 min. We conclude that the fluid shear stress rate is an important parameter for bone cell activation.

Animals↗

The use of high-resolution magnetic resonance imaging for monitoring interbody fusion and bioabsorbable cages: an ex vivo pilot study.

OBJECT: Interbody fusion is a gradual process of graft resorption and tissue formation, ideally resulting in a bone bridge between two adjacent vertebral bodies. Initially, fibrous tissue and cartilage are formed, which subsequently are replaced by bone through the process of endochondral ossification. When cages and/or their contents are made of resorbable polymers like lactic or glycolic acids, there is a simultaneous process of implant degradation, which is eventually accompanied by reactions in the surrounding tissues. The purpose of this study was to explore the use of highresolution magnetic resonance (MR) imaging for monitoring tissue differentiation, spinal fusion, cage degradation, and eventually tissue reactions as a function of time. METHODS: Lumbar vertebral segments obtained in 14 goats with 3, 6, and 12 months of follow up (three, four, and seven animals, respectively) were available from a study of the feasibility of poly(L,D-lactic acid) cages for spinal fusion. Plain x-ray films, MR images, and histological sections were used to evaluate spinal fusion and cage resorption. The first follow-up tests revealed that MR imaging noninvasively provided three-dimensional information on cage placement, cage degradation and bone formation, and that it has potential to differentiate between the various soft tissues. CONCLUSIONS: Although the magnetic field strength and thus the resolution used were higher than normal in clinical practice, MR imaging appears to be a promising modality for the noninvasive clinical follow up of patients who undergo fusion with resorbable cages. Tissue reactions were not encountered in this study, and thus could not be evaluated.

Absorbable Implants↗

Centrifuges and inertial shear forces.

Centrifuges are often used in biological studies for 1 x g control samples in space flight microgravity experiments as well as in ground based research. Using centrifugation as a tool to generate an Earth like acceleration introduces unwanted inertial shear forces to the sample. Depending on the centrifuge and the geometry of the experiment hardware used these shear forces may contribute as much as 99% to the total force acting on the cells or tissues. The inertial shear force artifact should be dealt with for future experiment hardware development for Shuttle and the International Space Station (ISS) as well as for the interpretation of previous spaceflight and on-ground research data.

Cell Adhesion↗

Changes in bone architecture during spinal fusion: three years follow-up and the role of cage stiffness.

STUDY DESIGN: A morphometrical analysis of microcomputed tomography-based reconstructions of bone from the fusion zone in spinal cages. OBJECTIVE: To describe the architectural changes of the fusing bone tissue in time and to study the effect of cage stiffness on the development of the bone architecture within the cage. SUMMARY OF BACKGROUND DATA: Interbody fusion within spinal cages is routinely evaluated as either successful or not successful. The quality of the fusion, however, strongly depends on the architecture (i.e., structure and density) of the bone tissue within the cage. Bone architecture obviously changes during the fusion process, and cage stiffness is known to play a pivotal role. METHODS: Nine bone samples were available from a long-term in vivo study on resorbable spinal cages in Dutch milk goats described elsewhere. Follow-up periods of 3, 6, 12, 24, 30, and 36 months were considered for cages made of titanium or Poly L-Lactic Acid. The specimens were scanned with a resolution of 13 microm in a microcomputed tomography system. From the resulting reconstructions, the bone density; trabecular thickness, spacing, and number; connectivity density; and structure model index were assessed. RESULTS: We found a homogenization of all bone structure indexes along the spinal axis with time, and remarkably faster in the Poly L-Lactic Acid cages than in the titanium cages. After longer follow-up periods, a coarser bone structure with larger trabecular thickness and intertrabecular spacing was found. The structure model index appeared to be sensitive for nonunions. CONCLUSIONS: More "mature" spinal fusions showed a coarser and more homogeneous bone structure. High cage stiffness had a deteriorating effect on the fusion rate. The structure model index appears to be an interesting parameter for quantifying the quality of bone in the fusion zone.

Animals↗