Ti-24Nb-4Zr-8Sn Alloy Pedicle Screw Improves Internal Vertebral Fixation by Reducing Stress-Shielding Effects in a Porcine Model

To ensure the biomechanical properties of Ti-24Nb-4Zr-8Sn, stress-shielding effects were compared between Ti-24Nb-4Zr-8Sn and Ti-6Al-4V fixation by using a porcine model. Twelve thoracolumbar spines (T12–L5) of 12-month-old male pigs were randomly divided into two groups: Ti-24Nb-4Zr-8Sn (EG, n = 6) and Ti-6Al-4V (RG, n = 6) fixation. Pedicle screw was fixed at the outer edge of L4-5 vertebral holes. Fourteen measuring points were selected on the front of transverse process and middle and posterior of L4-5 vertebra. Electronic universal testing machine was used to measure the strain resistance of measuring points after forward and backward flexion loading of 150 N. Meanwhile, stress resistance was compared between both groups. The strain and stress resistance of measurement points 1, 2, 5, 6, 9, and 10–14 in Ti-24Nb-4Zr-8Sn fixation was lower than that of Ti-6Al-4V fixation after forward and backward flexion loading (P < 0.05). The strain and stress resistance of measurement points 3, 4, 7, and 8 was higher in Ti-24Nb-4Zr-8Sn fixation than that of Ti-6Al-4V fixation (P < 0.05). Stress-shielding effects of Ti-24Nb-4Zr-8Sn internal fixation were less than that of Ti-6Al-4V internal fixation. These results suggest that Ti-24Nb-4Zr-8Sn elastic fixation has more biomechanical goals than conventional Ti-6Al-4V internal fixation by reducing stress-shielding effects.


Introduction
With global population aging, the incidence of degenerative lumbar degeneration has increased [1]. Vertebral fusion has become a gold standard for the treatment of lumbar degenerative diseases in spine surgeons [2,3]. Lumbar fusion of clinical application has been significantly improved in past decades, and rigid internal fixation technology has increased lumbar fusion rates [4,5].
Low back pain induced by degenerative diseases is often experienced by the individuals beyond middle age. The standard treatment is decompression and interbody fusion, which is followed by a pedicle screw-rod system to stabilize spine [6,7]. Conventional pedicle screw-rod system is made from the titanium alloy Ti-6A1-4V, which is biocompatible, corrosion resistant, bendable, and stiff enough to provide sufficient stability for spine [8]. However, the elastic modulus of Ti-6A1-4V (110 GPa) is much higher than that of cortical bone (18 GPa), and thus it changes spinal kinetics. After the implantation of Ti-6A1-4V, the motion of adjacent segments increases to compensate the reduced motion of implanted segments, which accelerate adjacent disc degeneration [9]. A stress-shielding effect, in which some stresses on vertebral bodies are shifted to pedicle-rod systems, decelerates intervertebral fusion and increases the looseness of pedicle screw. To eliminate these complications, some dynamic fixation systems have been developed. The most used one is the Dynesys Dynamic Stabilization System [10,11], in which titanium alloy rods are replaced with polymolecular cords and spacers. However, the long-term clinical outcomes are not much better than expected [12].
Furthermore, due to strong stress-shielding effects caused by internal fixation, bone stress stimulation was significantly reduced, leading to bone reconstruction and absorption [13].
Biomechanical measurement of fusion techniques shows that all fusion will increase the stress of adjacent vertebrae [14]. Animal experiments also confirmed that strong internal fixation could cause stress occlusion and osteoporosis [15].

BioMed Research International
The increase of the stress near the segment after strong internal fixation accelerates the degeneration of adjacent segment disc [16,17], which has become an urgent problem that needs to be solved after lumbar fusion.
In order to solve the problem caused by strong internal fixation, the researchers induce the concept of elastic fixation of spine and the premise of skeletal stability [18]. To reduce the load of the internal fixation and increase sharing load of spine, it is necessary to reduce the stress block and focus. At present, most researchers have applied intramedullary nailing or bone plate, joint replacement prosthesis implantation, and postoperative fixation of spine after internal fixation [19,20]. However, the degree of occlusion remains unclear [21,22]. The data show that there is no significant difference between the elastic internal and rigid internal fixation system in the therapy of lumbar degenerative lesions [23]. Low modulus beta-titanium alloys are hoped to provide good biocompatibility and alleviate stress-shielding effects. Titanium alloy Ti-6Al-4V is widely used for implants, which are characterized by high elastic modulus that may induce undesirable stressshielding effects and toxicity [24]. Ti-24Nb-4Zr-8Sn alloy, as a low modulus (49 GPa), has been approved to a potential bone load-bearing implant material without toxicity [25].
However, the effects of Ti-24Nb-4Zr-8Sn and Ti-6Al-4V fixation on shielding stress were seldom compared. To ensure biomechanical properties of Ti-24Nb-4Zr-8Sn, this experiment is performed to compare the effects of Ti-24Nb-4Zr-8Sn and Ti-6Al-4V fixation on shielding stress. Before and after internal fixation, the strain and stress resistance values of the two kinds of internal fixation on vertebra was compared under the same flexion load.

Materials.
Twelve thoracolumbar spines (T12-L5) were obtained from 12-month male pigs. Before obtaining the specimens, all spines had no damage and deformity after being scanned by X-ray. All vertebra were randomly assigned into elastic Ti-24Nb-4Zr-8Sn (EG, = 6) and rigid Ti-6Al-4V (RG, = 6) fixation groups. Scalpel, posterior longitudinal ligament, anterior longitudinal ligament, and facet joint were removed by scalpel and spatula (Figure 1(a)). The specimens were numbered and basic dimensions were measured (Figures 1(b)-1(d)). Lumbar spine specimens were embedded and fixed with denture base resin solution. Figure 1(e) showed the embedded species. Strain measurement was performed in both groups. The resistance of strain gauge was 121.4 ± 0.1 and gauge sensitivity coefficient was 2.14. Two kinds of pedicle screws Ti-24Nb-4Zr-8Sn and Ti-6Al-4V were used to fix vertebra as Figures 1(f) and 1(g) showed.

The Establishment of Measuring Points.
With a finite element (FE) model and lumbar kinematic analysis according to earlier reports [26][27][28], biomechanical parameters with flexion loading were predicted. The geometry used in FE model of L4-5 was reconstructed across a porcine thoracolumbar spine. Before and after fixation at L4-5, the maximum strain and stress points were predicted after forward and backward flexion loading.
A total of 14 measuring points with possible high strain and stress resistance were predicted with a finite element (FE) model and lumbar kinematic analysis. Measuring points numbers 1 and 2 were found at left faces of L4-5 vertebra (Figure 2(a)). Measuring points numbers 3, 4, and 7-10 were found at middle faces of L4-5 vertebra (Figure 2(b)). Measuring points 5 and 6 were found at right faces of L4-5 vertebra (Figure 2(c)). Measuring points 11-14 were found at the posterior of L4-5 vertebra (Figure 2(d)). Figure 2(e) showed the measuring points used in Ti-24Nb-4Zr-8Sn group and Figure 2(f) showed measuring points used in Ti-6A1-4V group.

Measurement of Strain Resistance after Internal Fixation and Flexion
Load. The load was transmitted by the load cell with 300 N ranges, and the displacement was transmitted by photoelectric encoder. First of all, each specimen was installed in the test machine. Each specimen was loaded and unloaded 20 times for preconditioning processing. The strain gauge wire of each measuring point of the specimen was connected with the bridge arm of the dynamic resistance strain gauge junction box and bridged in a half way. The temperature compensation was adapted to the external condition. A load of 150 N was applied to the specimen at a load with increasing rate of 2 mm/min (the load applied in this experiment was within the physiological load range). The strain resistance of each measuring point was measured by dynamic resistance strain gauge. After forward and backward flexion load, strain resistance was measured before pedicle screw fixation (Figures 3(a) and 3(b)). After forward flexion load, strain resistance was measured in Ti-24Nb-4Zr-8Sn group (Figure 3(c)) and Ti-6A1-4V group (Figure 3(d)) after pedicle screw fixation. Strain resistance was also measured in. After backward flexion load, strain resistance was measured in Ti-24Nb-4Zr-8Sn group (Figure 3(e)) and Ti-6A1-4V group (Figure 3(f)) after pedicle screw fixation.

Each Group of Specimens of Pedicle Screw Fixation after
Internal Fixation. As Figure 3 showed, pedicle screw was fixed before application of flexion load. Two kinds of pedicle screw were manufactured by medical instrument company (Chunlizhengda Co., Beijing, China) by using titanium alloy Ti-24Nb-4Zr-8Sn (49 GPa) or Ti-6A1-4V (110 GPa). The lumbar posterior (L4, L5) was fixed with Ti-24Nb-4Zr-8Sn fixator or Ti-6A1-4V fixator. Ten points for pedicle screw fixation were determined. In order to measure the internal rod fixation and the junction of the strain, four additional points were selected for the internal fixation and pedicle screw at the junction (11-14 points). The measurement points were shown in Figure 2. The measuring points were the same between the EG and the RG groups (Figures 2(e) and 2(f)).
For the measurement of the strain gauge after pedicle screw fixation: the same model, batch, sensitivity coefficient, and resistance of strain gauge were used. The stress measurement was performed to measure the strain of the rats under the flexion load before the internal fixation of pedicle screw under flexion load. Ti-24Nb-4Zr-8Sn and Ti-6A1-4V fixation were performed under 150-N flexion load shown in Figures  2

Stress Calculation.
The stress formula is provided as follows: where is the stress, is the strain, and is the elastic modulus. In this experiment, the modulus of rigid internal Ti-6A1-4V fixation system is 110 GPa, and the modulus of the Ti-24Nb-4Zr-8Sn elastic internal fixation system is about 70 GPa [29], and the elastic modulus of the lumbar vertebrae is 19.2 GPa [29].
2.6. Statistical Analysis Methods. SPSS software package 16.0 SPSS (Chicago, IL, USA) was used for data analysis. The difference between the two types of variable data of variance was analyzed by using Scheffe method and paired t-test. < 0.05 for the statistical difference was significant.

The Strain Resistance Values of Measuring Points between
Ti-24Nb-4Zr-8Sn Internal Fixations Were Similar with Ti-6A1-4V before Internal Fixation. The strain resistance of Ti-24Nb-4Zr-8Sn fixation and Ti-6A1-4V fixation group was compared after flexion loading. Before alloy fixation, there was no significantly statistical difference for strain resistance after forward flexion loading (Table 1) or backward flexion loading (Table 2) between the EG and the RG groups ( > 0.05). The results suggested that the specimens were similar with the same strain resistance values of measuring points between the EG and the RG groups.

Discussion
The strain and stress resistance of the Ti-24Nb-4Zr-8Sn and Ti-6A1-4V fixation increased after flexion load, but the increase in Ti-6A1-4V group was greater than that of Ti-24Nb-4Zr-8Sn group. Strain resistance of 10 measuring points in Ti-6A1-4V group was higher than that of Ti-24Nb-4Zr-8Sn group (Tables 3 and 4, < 0.05). Similarly, stress resistance of Ti-24Nb-4Zr-8Sn was also lower than that of Ti-6A1-4V group (Tables 5 and 6, < 0.05). Normally, bone material with low modulus elasticity is less resistant to outside stress, while the material with high-modulus elasticity is more resistant to outside stress. The results showed that the stressshielding effects of Ti-24Nb-4Zr-8Sn fixation were small. Stress conduction can be caused by lumbar degeneration [16], whereas back pain and other symptoms can be reduced or even disappear if lumbar dynamic internal fixation system precisely limits the activities of the vertebral body [30]. Theoretically, lumbar dynamic stability system reduces adjacent segment degeneration and the stress on the intervertebral bone graft and promotes bone healing and spine recovery. However, high-level stress will cause spinal cord compression and induce nerve tissue damage [31]. Lumbar Ti-24Nb-4Zr-8Sn fixation system is a dynamic stability system made of titanium alloy and polyether ether ketone (PEEK) materials [32]. The materials are safe for patient health and have high strength, excellent mechanical properties, good self-lubricating, corrosion resistance, wear, and other characteristics [33]. Its ultralow elastic modulus in a simple bar-shaped design can achieve a satisfactory dynamic fixation effect. Ti-24Nb-4Zr-8Sn fixation system can reduce the stress resistance of titanium pedicle screw when the stress resistance acts on the elastic connecting rod with certain microaction because polyethylene fiber elastic connecting rod instead of rigid connecting rod with titanium alloys is used. The system reduces vertebral osteoporosis and pedicle screw loosening, fracture, and other risks and maintains intervertebral space and active function.
The load of the segment slows down the degeneration of adjacent segment discs. After the internal fixation of the spine, biomechanical properties of the column are restored, the load sharing of the internal fixation system is reduced, and the reduction of internal fixation load is important to avoid fixation failure [34]. Selective stress occlusion is another way to address stress-induced osteoporosis [35]. Vertebral compression stress stimulates bone growth and strengthens. Selective stress occlusion makes the internal fixation mainly against lateral bending, rotation and shear stress, reducing the compressive stress on internal fixation, thereby increasing the compressive stress of the vertebral body and compressive stress of vertebra. All these results can improve mechanical performance. Ti-24Nb-4Zr-8Sn fixation improved patient's postoperative symptoms significantly when compared with fusion surgery with Ti-6A1-4V [36]. Lumbar Ti-24Nb-4Zr-8Sn internal fixation system has the following advantages: retaining motion function of the surgical segment while reducing the stress resistance of adjacent segments, delaying the occurrence of degeneration and even less damage to the disc, providing sufficient stability while retaining a certain degree of activity of lumbar spine, and delaying the occurrence of adjacent segment degeneration. This experiment is done by establishing a biomechanical model with Ti-24Nb-4Zr-8Sn fixation. The results showed that the effects of stress occlusion caused by Ti-24Nb-4Zr-8Sn fixation were less than those caused by Ti-6A1-4V fixation.
Limitations of the Present Work. There were some limitations of the present study: Ti-24Nb-4Zr-8Sn fixation lacks longterm randomized controlled outcome, and long-term clinical stability, screws loosening, fatigue of screw, and connecting rods remain unclear; the specimens used for the lumbar spine may cause different results when compared with other specimens; only Ti-24Nb-4Zr-8Sn and Ti-6A1-4V fixation were used to compare stress-shielding effects. In the posterior extension, compression, left and right bending, and stress need to be further analyzed in the future.