Shady Elmasry

Modeling the role of IGF-1 on extracellular matrix biosynthesis and cellularity in intervertebral disc

The insulin-like growth factor-1 (IGF-1) is a well-known anabolic agent for intervertebral disc (IVD), promoting both proteoglycan (PG) biosynthesis and cell proliferation. Accordingly, it is believed that IGF-1 may play a central role in IVD homeostasis. Furthermore, the exogenous administration of IGF-1 has been proposed as a possible therapeutic strategy for disc degeneration. The objectives of this study were to develop a new computational framework for describing the mechanisms regulating IGF-mediated homeostasis in IVD, and to apply this numerical tool for investigating the effectiveness of exogenous administration of IGF-1 for curing disc degeneration. A diffusive-reactive model was developed for describing competitive binding of IGF-1 to its binding proteins and cell surface receptors, with the latter reaction initiating the intracellular signaling mechanism leading to PG production and cell proliferation. Because PG production increases cell metabolic rate, and cell proliferation increases nutritional demand, nutrients transport and metabolism were also included into the model, and co-regulated, together with IGF-1, IVD cellularity. The sustainability and the effectiveness of IGF-mediated anabolism were investigated for conditions of pathologically insufficient nutrient supply, and for the case of exogenous administration of IGF-1 to degenerated IVD. Results showed that pathological nutrients deprivation, by decreasing cellularity, caused a reduction of PG biosynthesis. Also, exogenous administration of IGF-1 was only beneficial in well-nourished regions of IVD, and exacerbated cell mortality in malnourished regions. These findings remark the central role of nutrition in IVD health, and suggest that adequate nutritional supply is paramount for achieving a successful IGF-based therapy for disc degeneration.

Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking.

Implications of Decompressive Surgical Procedures for Lumbar Spine Stenosis on the Biomechanics of the Adjacent Segment: A Finite Element Analysis

Surgeries for Lumbar Spinal Stenosis (LSS) aim at decompressing spinal nerves and relieving symptoms of radiculopathy or myelopathy. Frequently after surgery, stenosis may progress in adjacent spinal segments, but the etiology of adjacent segment degeneration is still unclear. It is hypothesized that surgical approaches for LSS may alter the normal biomechanics of adjacent segments, eventually contributing to the development of stenosis. This study investigated implications of established decompressive surgical approaches on adjacent segments biomechanics. A realistic finite element model of a L1-L5 human lumbar spine was used for assessing changes in spine segments’ biomechanics due to laminotomy and laminectomy surgeries. First, the model was validated by comparing its predictions to previously reported spine kinematic data obtained after multi-level laminotomy and laminectomy. Subsequently, using a hybrid loading protocol, segments’ kinematics, intradiscal pressure, and stress in flexionextension were investigated simulating single level (L4-L5) laminotomy and laminectomy procedures. Alterations of spine segments biomechanics due to laminotomy were minimal. In contrast, after laminectomy, the L3-L4 range of motion, intradiscal pressure, and stress increased up to 50%, 20%, and 120%, respectively. These results suggest that laminotomy represents a better approach than laminectomy for reducing risks of spine instability or mechanically-accelerated disc degeneration in adjacent segments.

A computational analysis on the implications of age-related changes in the expression of cellular signals on the role of IGF-1 in intervertebral disc homeostasis

Insulin-like growth factor-1 (IGF-1) is a well-known anabolic agent in intervertebral discs (IVD), promoting both proteoglycan (PG) biosynthesis and cell proliferation. Accordingly, it is believed that IGF-1 plays a central role in IVD homeostasis. The IGF-mediated anabolic activity in IVD occurs when the growth factor, free from binding proteins (IGFBP), binds to IGF cell surface receptors (IGF-1R). Previous studies reported that, with aging, cellular expression of IGFBP increases, while that of IGF-1R decreases. Both changes in cellular signals are thought to be among the factors that are responsible for the age-related decline in IGF-mediated PG biosynthesis, which ultimately leads to disc degeneration. In this study, a computational model describing the role of IGF-1 in the homeostasis of IVD was deployed in a parametric analysis to investigate the effects of age-related changes in expression of IGF-1R and IGFBP on the IGF-mediated upregulation of PG biosynthesis and cellular proliferation. It was found that changes in the expression of IGF-1R and IGFBP mostly affected the nucleus pulposus, while in the most external disc regions (annulus fibrosus and cartilage endplates) the IVD homeostatic balance was unaltered. It was shown that a decrease of IGF-1R expression caused reduction of both PG levels and cell density in the tissue. In contrast, increase in IGFBP expression increased both PG and cell concentration, suggesting that such change in cellular signaling may be a plausible defense mechanism from age-related IVD degeneration.

Examination of a lumbar spine biomechanical model for assessing axial compression, shear, and bending moment using selected Olympic lifts.

BACKGROUND/AIMS Loading during concurrent bending and compression associated with deadlift, hang clean and hang snatch lifts carries the potential for injury to the intervertebral discs, muscles and ligaments. This study examined the capacity of a newly developed spinal model to compute shear and compressive forces, and bending moments in lumbar spine for each lift. METHODS Five male subjects participated in the study. The spine was modeled as a chain of rigid bodies (vertebrae) connected via the intervertebral discs. Each vertebral reference frame was centered in the center of mass of the vertebral body, and its principal directions were axial, anterior-posterior, and medial-lateral. RESULTS The results demonstrated the capacity of this spinal model to assess forces and bending moments at and about the lumbar vertebrae by showing the variations among these variables with different lifting techniques. CONCLUSION These results show the models potential as a diagnostic tool.

A computational model for investigating the effects of changes in bioavailability of insulin-like growth factor-1 on the homeostasis of the intervertebral disc

Insulin-like growth factor-1 (IGF-1) is well-known for upregulating cell proliferation and biosynthesis of the extracellular matrix in the intervertebral disc (IVD). Pathological conditions, such as obesity or chronic kidney disease cause IGF-1 deficiency in plasma. How this deficiency impacts disc homeostasis remains unknown. Pro-anabolic approaches for the treatment of disc degeneration based on enhancing IGF-1 bioavailability to tissue-cells are considered, but knowledge of their effectiveness in enhancing cellular anabolism of a degenerated disc is limited. In this study, we developed a computational model for disc homeostasis specifically addressing the role of IGF-1 in modulating both extracellular matrix biosynthesis and cellularity in the IVD. This model was applied to investigate how changes in IGF-1 bioavailability, namely deficiency or enhancement of growth factor, affect disc health. In this study, it was found that IGF-1 deficiency mainly affects the biosynthesis of ECM components, especially in the most external regions of the IVD such as the cartilage endplates and the outer portion of annulus fibrosus. Also, a total of three approaches for increasing IGF-1 bioavailability as a therapy for degenerated IVDs were investigated. It was found that all these strategies are only beneficial to those disc regions receiving sufficient nutritional supply (i.e., the outmost IVD regions), while they exacerbate tissue degradation in malnourished regions (i.e., inner portion of the disc). This suggests that pro-anabolic growth factor-based therapies are limited in that their success strongly depends on an adequate nutritional supply to the IVD tissue, which is not guaranteed in degenerated discs.

Implications of spine fixation on the adjacent lumbar levels for surgical treatment of thoracolumbar burst fractures: a finite element analysis

Surgical correction with corpectomy and subsequent fusion of neighboring levels is a commonly practiced treatment for thoracolumbar burst fractures. Different fixation constructs are currently implemented to fuse the injured level. However, little is known about the implications of such constructs on the biomechanics of the adjacent spine segments. The objective of this study is to compare the biomechanical alterations at the adjacent segments due to implanted construct. A 3D nonlinear finite element model of the thoracolumbar spine (from T12 to S1) was used for assessing changes in the biomechanics of the adjacent spine segments. First, the vertebral body and the adjacent discs of the operated level (L1) were completely excised leaving only the posterior elements. Next, four constructs were implanted at the thoracolumbar junction (T12-L2): (1) 2RPC which includes two posterior rods, six pedicle screws, an expandable cage, and a transverse plate; (2) 1RPC which includes the same instrumentation of 2RPC with the exclusion of the posterior rod contralateral to the transverse plate; (3) 2RC which includes posterior rods, pedicle screws, and an expandable cage; (4) PC which includes the expandable cage and the transverse plate. Models were validated by comparing their predicted range of motion (ROM) to in vitro biomechanical tests. Subsequently, the stresses generated at all the adjacent levels (L2-L3, L3-L4, L4-L5, and L5-S1) were measured and compared. The results showed that the constructs including pedicle screws (2RPC, 1RPC, 2RC) yielded similar biomechanical performance being the stiffest. Moreover, the same constructs demonstrated comparable stress levels at the adjacent segments, generating 50% higher than that produced from the PC construct. Elevated mechanical stress is believed to be a cause of disc degeneration. Accordingly, the PC construct, although less reliable in stabilizing the injured segment, represented the most conservative approach for preventing potential development of adjacent disc degeneration. Correspondence to: Shihab Asfour, Department of Industrial Engineering, College of Engineering, University of Miami, Coral Gables, FL 33124-0621, USA, Tel: 3052842367; Fax: 3052844040; E-mail: sasfour@miami.edu

Finite Element Study to Evaluate the Biomechanical Performance of the Spine After Augmenting Percutaneous Pedicle Screw Fixation with Kyphoplasty for the Treatment of Burst Fractures

Percutaneous pedicle screw fixation (PPSF) is a well-known minimally invasive surgery (MIS) employed in the treatment of thoracolumbar burst fractures (TBF). However, hardware failure and loss of angular correction are common limitations caused by the poor support of the anterior column of the spine. Balloon kyphoplasty (KP) is another MIS that was successfully used in the treatment of compression fractures by augmenting the injured vertebral body with cement. To overcome the limitations of stand-alone PPSF, it was suggested to augment PPSF with KP as a surgical treatment of TBF. Yet, little is known about the biomechanical alteration occurred to the spine after performing such procedure. The objective of this study was to evaluate and compare the immediate post-operative biomechanical performance of stand-alone PPSF, stand-alone-KP, and KP-augmented PPSF procedures. Novel three-dimensional (3D) finite element (FE) models of the thoracolumbar junction that describes the fractured spine and the three investigated procedures were developed and tested under mechanical loading conditions. The spinal stiffness, stresses at the implanted hardware, and the intradiscal pressure at the upper and lower segments were measured and compared. The results showed no major differences in the measured parameters between stand-alone PPSF and KP-augmented PPSF procedures, and demonstrated that the stand-alone KP may restore the stiffness of the intact spine. Accordingly, there was no immediate post-operative biomechanical advantage in augmenting PPSF with KP when compared to stand-alone PPSF, and fatigue testing may be required to evaluate the long-term biomechanical performance of such procedures.

Effectiveness of pedicle screw inclusion at the fracture level in short-segment fixation constructs for the treatment of thoracolumbar burst fractures: a computational biomechanics analysis

Abstract When treating thoracolumbar burst fractures (BF), short-segment posterior fixation (SSPF) represents a less invasive alternative to the traditional long-segment posterior fixation (LSPF) approach. However, hardware failure and loss of sagittal alignment have been reported in patients treated with SSPF. Including pedicle screws at the fracture level in SSPF constructs has been proposed to improve stiffness and reliability of the construct. Accordingly, the biomechanical performance of the proposed construct was compared to LSPF via a computational analysis. Pedicle screws at fracture level improved the performance of the short-segment construct. However, LSPF still represent a biomechanically superior option for treating thoracolumbar BF.

Examination of a lumbar spine biomechanical model for assessing axial compression, shear, and bending moment using selected Olympic lifts

BACKGROUND/AIMS Loading during concurrent bending and compression associated with deadlift, hang clean and hang snatch lifts carries the potential for injury to the intervertebral discs, muscles and ligaments. This study examined the capacity of a newly developed spinal model to compute shear and compressive forces, and bending moments in lumbar spine for each lift. METHODS Five male subjects participated in the study. The spine was modeled as a chain of rigid bodies (vertebrae) connected via the intervertebral discs. Each vertebral reference frame was centered in the center of mass of the vertebral body, and its principal directions were axial, anterior-posterior, and medial-lateral. RESULTS The results demonstrated the capacity of this spinal model to assess forces and bending moments at and about the lumbar vertebrae by showing the variations among these variables with different lifting techniques. CONCLUSION These results show the models potential as a diagnostic tool.