Biomechanical study of pedicle screw construct and locking compression plate fixation for the treatment of posterior pelvic ring injuries: A finite element analysis

doi:10.21203/rs.3.rs-3132972/v1

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Biomechanical study of pedicle screw construct and locking compression plate fixation for the treatment of posterior pelvic ring injuries: A finite element analysis

https://doi.org/10.21203/rs.3.rs-3132972/v1

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Objective

The pedicle screw construct and locking compression plate have been clinically investigated for the treatment of posterior pelvic ring injuries. However, few studies are available that evaluate the biomechanical performance of these two pelvic fixation techniques. The aim of this study was to compare the construct stability, model displacement and stress distribution of two implants with a finite element (FE) method.

Methods

A three-dimensional FE model of spine-pelvis-femur complex with ligaments was reconstructed from computed tomography images. The unstable posterior pelvic ring injury was created, which was fixed with the pedicle screw construct or locking compression plate. A follower load of 400 N was applied to the upper surface of the vertebrae to simulate upper body weight, while the ends of the proximal femurs were fixed.

Results

The construct stiffness of the pedicle screw model was 2 times that of the plate fixation. The maximum displacement of the pedicle screw model decreased by 51.2% compared with the plate fixation. The peek stresses of the implant and pelvis in the pedicle screw model decreased by 80.4% and 25% when compared with the plate model (44.57 MPa and 34.48 MPa in the pedicle screw model, and 227.47 MPa and 45.97 MPa in the plate model).

Conclusions

The study suggested that the pedicle screw construct could provide better fixation stability compared with locking compression plate, and serves as the recommended fixation method for the treatment of posterior pelvic ring injuries.

Pelvic ring injuries

Pedicle screw

Locking plate

Fracture fixation

Finite element (FE) analysis

Pelvic ring injuries are severe, with an estimated frequency of 3% of all body fractures [1]. Unstable posterior pelvic ring injuries commonly involve the disruption of the sacrum, sacroiliac joint, ilium, or a combination [2], mostly lead to vertical and rotational instability of the pelvic ring. These fractures are typically suffered from high-energy traumas such as traffic accidents and falls from heights [3], associated with high rates of morbidity and mortality [4]. Due to destruction of the complex posterior pelvic structures, conservative treatment usually is not an effective therapeutic method. Surgical treatment for dealing with these unstable pelvic ring injuries has become a gold method in recent years [5]. However, the therapeutic outcomes of unstable pelvic ring injuries are far from satisfactory, problems include chronic pelvic pain and restricted activities of daily living inevitably exist [6]. Therefore, it remains a great challenge for orthopedic surgeons to choose an appropriate method of fixation for the treatment of unstable pelvic ring injuries.

A great variety of management methods have been investigated for posterior pelvic ring fixation, including external fixation, anterior sacroiliac joint plates, locking compression plate (LCP), transiliac sacral bars, percutaneous sacroiliac screws, and minimally invasive pedicle screw-rod fixators. Currently, open reduction internal fixation has been associated with high rates of wound complications. Close reduction with percutaneous sacroiliac screw fixation is one of the most popular techniques [7, 8]; it has been regarded as a standard method for the definitive treatment of unstable posterior pelvic ring injuries. However, due to the complex sacroiliac joint structure involving important blood vessels and nerves, the sacroiliac screw technique needs repeated fluoroscopy with high quality to confirm appropriate screw position and requires an experienced surgeon with great surgical skill to avoid neurovascular injuries [9]. Furthermore, many surgeons refuse to expose themselves to X-rays because they are afraid of great radiation. 3D navigation technology has advantages in reducing radiation exposure in surgery and improving accuracy in screw implantation [10]. However, the navigation equipment is expensive and requires a long learning curve, which makes it difficult to be widely used in various hospitals.

Currently, the primary concern is focus on how to treat unstable posterior pelvic ring injuries effectively by minimally invasive technique. The LCP may be an effective treatment alternative to stabilize the posterior pelvic ring due to the advantages of convenience, minimal surgical trauma, and sufficient stability [11]. In spite of these advantages, however, the LCP has also been associated with a higher incidence of symptomatic hardware [12], and the difficulty of pre-contour the plate according to the irregular structure of posterior pelvic ring [11]. To avoid these limitations, the minimally invasive pedicle screw-rod fixator has been employed for the treatment of posterior pelvic ring injuries [13]. The posterior fixator utilizes two pedicle screws connected to a transverse rod for structural stability of the posterior pelvic ring using percutaneous invasive technique. Clinical trials also demonstrated the good results of the posterior pedicle screw construct for unstable posterior pelvic ring injuries [14].

At present, few studies are available that compare the biomechanical performance of these two pelvic fixation techniques. Owing to the variations in bone quality and anatomy, fracture patterns, and fixation location [15], it is very difficult to compare the biomechanical stability of different implants for the treatment of posterior pelvic ring injuries. In recent years, finite element (FE) analysis has been commonly used to study the advantages and disadvantages of different fixation techniques, which is beneficial in improving clinical results [16]. In the current study, FE analysis was performed to study the biomechanical stability of unstable posterior pelvic ring injuries with the posterior pedicle screw construct and the locking compression plate, and to provide a reference for appropriate selection of fixation devices.

Finite element modeling

A 31-year-old healthy male volunteer (height, 176 cm; weight, 70 kg) with no history of bone diseases, traumas or deformities was selected and signed the informed consent for the current study. The spine-pelvis-femur complex, including L1-L5 lumbar spine, full pelvis, and upper one-third of the femurs was scanned using 128-slice spiral computed tomography (CT) (Philips Brilliance, Philips Healthcare, Netherlands). The slice thickness was 1 mm. The DICOM data were imported into Mimics 21.0 software (Materialise, Leuven, Belgium) to reconstruct the geometry of the spine-pelvis-femur based on the segmentation of the CT images (Fig. 1). Smoothing and noise reduction were processed using the reverse engineering software Geomagic Studio 2017 (3D System, USA). The normal model was established and modified using software SolidWorks 2017 (Dassault Systemes, USA). The lumbar spine consisted of the vertebrae (cortical bone, cancellous bone, and posterior elements), intervertebral discs (annulus fibrosus and nucleus pulposus). The full pelvis consisted of the left ilium, sacrum, right ilium, and pubic symphysis, and the bone was segmented into the cortical and cancellous bone. The femurs were composed of upper one-third of the left femur and right femur, and the bones were segmented into two partitions, the cortical layer and cancellous core. The spine was connected to the pelvis via articular cartilage in the sacroiliac joint and the femurs were connected to the pelvis via articular cartilage in the hip joint. To simulate normal condition, thirteen ligaments were constructed: anterior sacroiliac ligament, posterior sacroiliac ligament, interosseous sacroiliac ligament, sacrospinous ligament, sacrotuberous ligament, superior pubic ligament, arcuate pubic ligament, inguinal ligament, iliolumbar ligament, anterior longitudinal ligament, posterior longitudinal ligament, intertransverse ligament, supraspinous ligament.

The three-dimensional geometric models of two implants (pedicle screw construct, and locking compression plate) were reconstructed according to the manufacturer's specifications using SolidWorks 2017 software. The pedicle screw construct was realized by using two titanium pedicle screws connected to a transverse rod. The two pedicle screws were modeled as 7-mm diameter and 55-mm length solid cylinders. The rod was modeled as 6-mm diameter. Plate fixation was carried out with a titanium locking plate and six locking screws. The locking plate was 4 mm in diameter and 147 mm in length. The six locking screws had a diameter of 3.5 mm and a length of 20 mm.

To simulate unstable posterior pelvic ring injuries, the anterior sacroiliac ligament, posterior sacroiliac ligament, interosseous sacroiliac ligament and articular cartilage of the left sacroiliac joint were removed (Fig. 2). The implants were then positioned according to clinical experience of an experienced orthopedic surgeon. For the pedicle screw fixation, two pedicle screws were positioned in the direction from the bilateral posterior superior iliac spine (PSIS) to the anterior inferior iliac spine (AIIS) as demonstrated in Fig. 3a. For the locking plate fixation, the plate was positioned on the surface of the bilateral PSIS, and the six screws did not penetrate into the sacroiliac joint as shown in Fig. 3b.

The models were imported to the FE software ANSYS Workbench 17 (ANSYS, Inc., USA), through which the models were assembled and meshed with three-dimensional ten-node tetrahedron elements. The number of nodes and elements of the two models are shown in Table 1. A mesh convergence test was conducted by adjusting the optimum element size.

Table 1

Number of nodes and elements of the two groups of models
	Pedicle screw constrcut	Locking compression plate
Node Element	365285 197740	372010 201452

Material properties

All materials involved in the models were regarded as homogeneous, isotropic, and linear elastic. The ligaments were modeled as tension-only spring elements, and the stiffness coefficient is shown in Table 2. The pedicle screws, rod, locking plate and screws were made of titanium alloy. The material properties of the spine-pelvis-femur complex and implants were obtained from previous published reports [17–19] and are listed in Table 3.

Table 2

Material properties of the pelvic and lumbar ligaments
Ligaments	Stiffness coefficient K (N/mm)
Anterior sacroiliac ligament Posterior sacroiliac ligament Interosseous sacroiliac ligament Sacrospinous ligament Sacrotuberous ligament Superior pubic ligament Arcuate pubic ligament Inguinal ligament Iliolumbar ligament Anterior longitudinal ligament Posterior longitudinal ligament Intertransverse ligament Supraspinous ligament	700 1400 2800 1400 1500 500 500 250 1000 23.75 26.15 9.8 9.8

Table 3

Material properties of the spine-pelvis-femur complex and implants
Materials	Young’s modulus (Mpa)	Poisson’s ratio
Lumbar cortical bone Lumbar cancellous bone Pelvis cortical bone Pelvis cancellous bone Femur cortical bone Femur cancellous bone Annulus fibrosus Nucleus pulposus Posterior elements Pubic symphysis Sacroiliac cartilage Articular cartilage Titanium alloy	12,000 100 12,000 100 15,000 100 1 1 3500 5 54 100 110,000	0.3 0.2 0.3 0.2 0.3 0.2 0499 0.499 0.25 0.45 0.4 0.3 0.3

Boundary and loading conditions

The ends of the proximal femurs were fixed in all degrees of freedom to simulate a standing state with a double-leg stance. The facet joints and spinous processes were considered to be perfectly bonded. The sacroiliac joint and symphysis pubis were assumed to have frictionless contact. The hip joints were modeled as fully bonded. The implants were fully tied to the bone; the pedicle screws were fully locked to the rod; the locking screws were fully tied to the locking plate. A follower load of 400 N was applied to the upper surface of L1 to simulate upper body weight [17].

Evaluation criteria

The FE analysis was conducted using the ANSYS Workbench 17 software. The biomechanical stability was represented by construct stiffness and maximum displacement of the sacrum. The construct stiffness was defined by the ratio of the maximum vertical displacement of the sacrum to the applied load. In addition, the von Mises stress distribution and peak value of the implants and pelvises were also analyzed.

Model validation

To validate our FE models, we reconstructed an intact spine-pelvis-femur FE model and 500 N vertical loading was applied to the surface of the vertebrae. For the intact model, the von Mises stress distribution was symmetrical in the sagittal plane, and the stress was concentrated at the greater sciatic notch, and posterior and superior of the acetabulum. The peek von Mises stress and the concentration were in agreement with previous report [17], the peek stress of this study was 22.0 Mpa, and the value of the reported data was 13.5 ~ 25.7 MPa under the same loading. For the injured mode (Fig. 2), the construct stiffness of our FE model was 180.03 N/mm, which was comparable to the cadaveric model (193.0 ± 33.06 N/mm) [20]. The results of the intact and injured models demonstrated good agreement with the existing findings, showing that our FE models were satisfactorily validated.

Construct stiffness

The pedicle screw construct fixation model provided the higher construct stiffness (435.14 N/mm) compared with the plate fixation model (217.01 N/mm). The construct stiffness of the pedicle screw model was 2 times that of the plate fixation.

Model displacement

Table 4 and Fig. 4 showed the model displacement distribution of the two models. The maximum displacement of the pedicle screw construct model was located at the top of the sacrum on the intact side, while that of the plate fixation model appeared at the top of the sacrum on the injured side. The pedicle screw model showed smaller maximum displacement compared with the plate model. The maximum amount of displacement of the pedicle screw and the plate model was 1.413 mm and 2.895 mm, respectively. The maximum displacement of the pedicle screw construct decreased by 51.2% compared with the plate fixation.

Table 4

Parameters results
Parameters	Pedicle screw constrcut	Locking compression plate
The maximum displacement of the model (mm) The peak von Mises stress of the implant (Mpa) The peak von Mises stress of the pelvis (Mpa)	1.413 44.57 34.48	2.895 227.47 45.97

Stress distribution

The von Mises stress distributions of the two implants were illustrated in Table 4 and Fig. 5. In the pedicle screw construct, the peak von Mises stress appeared at the junction of the pedicle screw and the rod on the injured side. In the plate fixation, the peak stress was concentrated at the junction of the plate and the locking screw around the fracture site. The results showed that the pedicle screw model had the smaller peek von Mises stress compared with the plate model. The magnitude of peek von Mises stress in the pedicle screw and plate model was 44.57 MPa and 227.47 MPa, respectively. The peek von Mises stress of the pedicle screw construct decreased by 80.4% when compared with the plate fixation.

The von Mises stress distribution of the pelvis was shown in Table 4 and Fig. 6. In the pedicle screw construct, the peak von Mises stress was concentrated at the pedicle screw hole on the intact side. In the plate fixation, the peak von Mises stress was concentrated at the middle locking screw hole on the intact side. The pedicle screw model had the smaller peek von Mises stress compared with the plate model, and the magnitude was 34.48 MPa and 45.97 MPa, respectively. The peak von Mises stress of the pedicle screw construct was 25% less than that of the plate fixation.

Currently, posterior pelvic ring injuries remain a challenge for orthopedic surgeons and surgical treatment is necessary for treating these injuries. There are various internal fixation methods have been described [8, 9, 11]. However, each technique owns its advantages and disadvantages, and no consensus has been reached pertaining to the optimal method for these injuries. The introduction of percutaneous minimally insertion of sacroiliac screw with limited soft tissue exposure is probably the most common method, however, this technique is technically demanding and limited by potential vascular and neural injuries [21]. The LCP technique is an effective treatment of choice for posterior pelvic ring injuries in view of its convenience and minimal trauma. The retrospective data of Tang et al. [11] found that in posterior pelvic ring injuries, LCP fixation could achieve satisfactory radiological and functional results. However, the disadvantages of the LCP include limited reduction potential, damage to the threads of screw holes during pre-contouring the plate, and potential injury to the nerve and blood vessels when the soft tissue is stripped off [6, 11]. To address these limitations, the pedicle screw construct was introduced as an alternative to treat posterior pelvic ring injuries [13]. Bi et al. [5] clinically compared the pedicle screw construct versus the LCP in a retrospective study and observed that the size of incision, operation duration and bleeding volume were statistically smaller in the pedicle screw group than those in the LCP group.

However, as far as we know, few biomechanical studies using FE simulation method have compared the posterior pedicle screw construct with the dorsal LCP fixation in the management of unstable posterior pelvic ring injuries. It is difficult to evaluate the biomechanical performance of an implant by means of clinical trials. FE analysis is the preferred method used to compare the biomechanics of different implants for the treatment of posterior pelvic ring injuries [16–18]. In the current study, we constructed the three-dimensional model of sacroiliac joint injury treated with the pedicle screw construct or LCP fixation to evaluate the differences in biomechanical properties. The results of this study found that the two pelvic fixation techniques, i.e., pedicle screw construct, and LCP fixation, had great differences on the construct stiffness, model displacement and stress distribution under the follower load condition. Our results suggested that the construct stiffness of the pedicle screw model was much higher than that in the plate model. Moreover, the maximum displacement in the pedicle screw model was much smaller than that in the plate model. Additionally, the peak stresses of the implant and pelvis in the pedicle screw model were much lower than those in the plate model.

There is evidence that the pedicle screw construct can provide sufficient biomechanical stability in the treatment of unstable posterior pelvic ring injuries. Song et al. [16] compared the pedicle screw fixation with two anterior reconstruction plates in the treatment of Tile C1 pelvic fractures (unilateral sacroiliac joint injury combined with superior and inferior pubic ramus fractures) by FE simulation technology and the results showed that the maximum displacements of the ilium and implant in the pedicle screw model were smaller than those of the plate model. Our results found that the maximum displacement of the sacrum in the pedicle screw model decreased by 51.2% compared with the plate fixation. The smaller maximum displacement of the pelvis represents better fixation stability [17], and thus, the author came to the conclusion that the posterior pelvic ring injuries fixed with the pedicle screw construct could achieve sufficient mechanical stability. Dienstknecht et al. [22] used freshly frozen human pelvis to simulate AO type C injury model (unilateral sacroiliac joint disruption combined with pubic symphysis displacement) to compare the pedicle screw construct, two sacroiliac screws and two ventral compression plates, and observed that differences in the three-dimensional displacement did not reach statistical significance. The study revealed that the pedicle screw construct had similar biomechanical stability to other two internal fixations, and it was considered that the pedicle screw construct might be an alternative to the other implants for unstable posterior pelvic ring injuries. In another biomechanical study on pelvic bones [23], unilateral sacral fractures were simulated and fixed with a modified dual pedicle screw construct or a conventional posterior plate, and the results demonstrated that the mean maximum loads, the loads applied to the construct at displacements of 5 mm and 7.5 mm, and the mean stiffness in the pedicle screw group were significantly higher compared with the posterior plate group, which led the authors to conclude that the usage of a modified dual pedicle screw construct was biomechanically stronger than conventional posterior plate fixation in unstable vertical sacral fracture. In our unilateral sacroiliac joint injury model, the construct stiffness of the pedicle screw model was 2 times that of the plate fixation. The construct stiffness of a fixation device is a main determinant of fracture site motion that affects the progression of fracture healing [24], and clinical studies demonstrated that the substantial increase in construct stiffness did not seem to interfere with fracture healing [9, 14]. Using FE model to simulate Denis II type fracture to compare the pedicle screw construct and two sacroiliac screws, Salášek et al. [25] proved that the pedicle screw construct could achieve higher stiffness in comparison with sacroiliac screws. In detail, the mean stiffness ratio medially and laterally in the pedicle screw model were 75.22% and 57.88%, while the values in sacroiliac screws model declined to 46.54% and 44.74%, respectively.

The lower peek stress of the fixation devices represents a lower risk of implant failure [17]. In this study, the von Mises stress distributions of the two implants were also evaluated. The stress in the pedicle screw construct was concentrated at the junction of the pedicle screw and the rod, and the stress concentration for the plate fixation was found at the junction of the plate and the locking screw. The peek von Mises stress of the implant in the pedicle screw construct decreased by 80.4% when compared with the plate fixation. From the biomechanical point of view, the pedicle screw model had lower risk of fatigue failure than the plate model. Nevertheless, it is worth noting that the yield strength of the used titanium alloy was 921 MPa [26], while the peek von Mises stress in the pedicle screw and plate model was 44.57 MPa and 227.47 MPa, respectively. The peek stress of the implant was lower than the yield stress in both models, therefore suggesting that the two methods of fixation for the treatment of unstable pelvic ring injuries could be safe. The results were in concordance with the data of Song et al. [16] who conducted a biomechanical study in the treatment of Tile C1 pelvic fractures and found that the maximum stresses of the ilium and implant in the pedicle screw model were less than those in the plate model. In another biomechanical study, Salášek et al. [24] apparently demonstrated that the pedicle screw construct experienced the lower stress compared with two sacroiliac screws. In detail, the von Mises stress ratio of the pedicle screw construct was 139.27%, while the value in sacroiliac screws increased to 565.35%.

Recent studies have found that the pedicle screw construct could obtain satisfactory clinical results in treating unstable posterior pelvic ring injuries. In a retrospective study, Hua et al. [14] reported that in unstable pelvic ring injuries, 23 patients were treated with a minimally invasive anterior internal pelvic fixator (INFIX) with or without a posterior pedicle screw construct, and the authors found an excellent or good rate of 82.6% in postoperative radiographic outcomes according to the Matta criteria and 87% in clinical results at 6 months postoperatively according to the Majeed scores. The results were in concordance with the data of Wu et al. [27] who conducted a retrospective analysis in 23 unstable pelvic ring injuries using INFIX with or without a posterior pedicle screw construct and observed that an excellent or good rate of 87% was acquired according to the radiological Matta criteria and 91.3% in clinical results at 12 months postoperatively according to the Majeed scores. Similar retrospective data of Wang et al. [9] found that the excellent and good rate of 89.7% in both radiological Matta criteria and clinical Majeed scores in a series of 29 posterior pelvic ring instabilities with the pedicle screw construct. The results were compatible with the data of Bi et al. [5] who performed a retrospective analysis in unstable posterior pelvic ring fractures and found that an excellent rate of 83.3% in clinical Majeed scores when the pedicle screw-rod fixator was used. In a prospective study, Salášek et al. [28] reported that in a series of 64 Tile C1 pelvic fractures, no significant difference in the clinical Majeed scores was found between the pedicle screw construct group and two sacroiliac screws group. However, two developed iatrogenic neurological injuries in sacroiliac screws, while no intraoperative complications were associated with the pedicle screw construct.

The transiliacal internal fixator, which was initially described by Füchtmeier et al. [29] in a prospective study including 31 patients with vertical shear injuries of the pelvis, using two 7.0 mm pedicle screws connected to a transverse rod, and the fixator was proven to be a minimal invasive technique with a very low rate of neurovascular injuries for stabilization of sacroiliac joint ruptures and sacral fractures. In Füchtmeier’s study, the pedicle screws were placed into the PSIS in cranio-caudal direction and parallel to the superior gluteal line. To obtain sufficient biomechanical stability by internal fixation with a pedicle screw rod system, the greater diameter of pedicle screws was recommended [16]. In a radiographic morphometric study, Schildhauer et al. [30] found that the supraacetabular bone canal from the PSIS to the AIIS to place pedicle screws did demonstrate the optimal path for lumbopelvic fixation in treating spinal and pelvic ring injuries. The bone corridor allowed placement of the implant with a length of 141 mm in male and 129 mm in female patients, and screws with 8-mm diameter in male and 6- to 7-mm in female patients. Schmitz et al. [31] confirmed the results of Schildhauer and proved that Schanz screws were placed into the supraacetabular bone canal could reach a length of up to 135mm (mean 100mm ± 20mm), which led the authors to conclude that placement of the Schanz screws from the PSIS to the AIIS could provide a greater mechanical stability for fragility fractures of the pelvis with vertical and rotational instability. In our study, two 7.0 mm pedicle screws with 55-mm length were inserted in the direction from the PSIS to the AIIS.

However, there were some limitations in this study. Firstly, the material properties of the bones and implants were simplified into homogeneous, isotropic, and linearly elastic. Secondly, muscles were not included in the models, which could not fully reflect the real conditions. Finally, only static loads were applied to the spine-pelvis-femur complex for FE analysis. The spine-pelvis-femur, in reality, is exposed to complex forces and moments during normal activity. Despite this, the FE model used in this study was comparable to those used in previous in vitro studies.

The current study compared the biomechanical properties of the pedicle screw construct and LCP fixation in unstable posterior pelvic ring injuries. According to the FE analysis, the use of pedicle screw fixation could increase construct stiffness, decrease the displacement, and reduce the stresses in the implant and pelvis. Therefore, the pedicle screw construct could provide better fixation stability compared with LCP fixation, and serves as the recommended fixation method for the treatment of posterior pelvic ring injuries.

Finite element

LCP

Locking compression plate

PSIS

Posterior superior iliac spine

AIIS

Anterior inferior iliac spine

INFIX

Anterior internal pelvic fixator

Acknowledgements

I would like to thank all authors for help and support in the process of data analysis and article writing.

Authors’ contributions

JZ, YW and BQY designed and participated in the whole process of the study. GDL helped in the design of the study. JW analyzed the data. JZ and YW drafted the manuscript. BQY reviewed the manuscript. All authors read and approved the final manuscript.

Funding

This study was funded by the Characteristic Program of Pudong New Area Health Commission (PWZzb2022-15).

Availability of data and materials

The authors declare that all the data supporting the findings of this study are available within the article.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Pudong New Area People’s Hospital. Informed consent was obtained from the individual participant included in this study.

Consent for publication

For manuscripts that include details, images, or videos relating to individual persons, written informed consent for the publication of these details has been obtained from the patients.

Competing interests

The authors declare that they have no competing interests.

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No competing interests reported.

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Biomechanical study of pedicle screw construct and locking compression plate fixation for the treatment of posterior pelvic ring injuries: A finite element analysis

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Abstract

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Introduction

Methods

Finite element modeling

Material properties

Boundary and loading conditions

Evaluation criteria

Results

Model validation

Construct stiffness

Model displacement

Stress distribution

Discussion

Conclusion

Abbreviations

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