Role of intra-lamellar collagen and hyaluronan nanostructures in annulus fibrosus on lumbar spine biomechanics: insights from molecular mechanics-finite element-based multiscale analyses.

Annulus fibrosus' (AF) ability to transmit multi-directional spinal motion is contributed by a combination of chemical interactions among biomolecular constituents-collagen type I (COL-I), collagen type II (COL-II), and proteoglycans (aggrecan and hyaluronan)-and mechanical interactions at multiple length scales. However, the mechanistic role of such interactions on spinal motion is unclear. The present work employs a molecular mechanics-finite element (FE) multiscale approach to investigate the mechanistic role of molecular-scale collagen and hyaluronan nanostructures in AF, on spinal motion. For this, an FE model of the lumbar segment is developed wherein a multiscale model of AF collagen fiber, developed from COL-I, COL-II, and hyaluronan using the molecular dynamics-cohesive finite element multiscale method, is incorporated. Analyses show AF collagen fibers primarily contribute to axial rotation (AR) motion, owing to angle-ply orientation. Maximum fiber strain values of 2.45% in AR, observed at the outer annulus, are 25% lower than the reported values. This indicates native collagen fibers are softer, attributed to the softer non-fibrillar matrix and higher interfibrillar sliding. Additionally, elastic zone stiffness of 8.61 Nm/° is observed to be 20% higher than the reported range, suggesting native AF lamellae exhibit lower stiffness, resulting from inter-collagen fiber bundle sliding. The presented study has further implications towards the hierarchy-driven designing of AF-substitute materials.

A multiscale investigation into the role of collagen-hyaluronan interface shear on the mechanical behaviour of collagen fibers in annulus fibrosus - Molecular dynamics-cohesive finite element-based study.

Multi-directional deformation exhibited by annulus fibrosus (AF) is contributed by chemo-mechanical interactions among its biomolecular constituents' collagen type I (COL-I), collagen type II (COL-II), proteoglycans (aggrecan and hyaluronan) and water. However, the nature and role of such interactions on AF mechanics are unclear. This work employs a molecular dynamics-cohesive finite element-based multiscale approach to investigate role of COL-I-COL-II interchanging distribution and water concentration (WC) variations from outer annulus (OA) to inner annulus (IA) on collagen-hyaluronan (COL-HYL) interface shear, and the mechanisms by which interface shear impacts fibril sliding during collagen fiber deformation. At first, COL-HYL interface atomistic models are constructed by interchanging COL-I with COL-II and increasing COL-II and WC from 0 to 75%, and 65%-75% respectively. Thereafter, a multiscale approach is employed to develop representative volume elements (RVEs) of collagen fibers by incorporating COL-HYL shear as traction-separation behaviour at fibril-hyaluronan contact. Results show that increasing COL-II and WC increases interface stiffness from 0.6 GPa/nm to 1.2 GPa/nm and reduces interface strength from 155 MPa to 58 MPa from OA to IA, contributed by local hydration alterations. A stiffer and weaker interface enhances fibril sliding with increased straining at the contact - thereby contributing to reduction in modulus from 298 MPa to 198 MPa from OA to IA. Such reduction further contributes to softer mechanical response towards IA, as reported by earlier studies. Presented multiscale analysis provides deeper understanding of hierarchical structure-mechanics relationships in AF and can further aid in developing better substitutes for AF repair.

Insights into the role of water concentrations on nanomechanical behavior of type I collagen-hyaluronan interfaces in annulus fibrosus: A molecular dynamics investigation.

Multi-faceted deformation capabilities of Annulus Fibrosus (AF) results from an intricate mechanical design by nature. Wherein, organization and interactions between the constituents, collagen type I (CI), collagen type II (C2), hyaluronan, aggrecan, and water are instrumental. However, mechanisms by which such interactions influence AF mechanics at tissue-scale is not well understood. This work investigates nanoscale interfacial interactions between CI and hyaluronan (CI-H) and presents insights into their influence on tissue-scale mechanics of AF. For this, three-dimensional molecular dynamics (MD) simulations of tensile and compressive deformation are conducted on atomistic model of CI-H interface at 0%, 65%, and 75% water concentrations (WC). Results show hyaluronan lowers local hydration around CI component of interface, owing to its hydrophilic nature. Analyses show that increase in WC from 65% to 75% leads to increased interchain sliding in hyaluronan, which further lowers tensile modulus of the interface from 2.1 GPa to 660 MPa, contributing to softening observed from outer to inner AF. Furthermore, increase in WC from 65% to 75%, shifts compressive deformation from buckling-dominant to non-buckling-dominant which contributes towards lower radial bulge at inner AF. Findings provide deeper insights into mechanistic interactions and mechanisms at fundamental length-scale which influence the AF structure-mechanics at tissue-scale.

Impact of Variations in Water Concentration on the Nanomechanical Behavior of Type I Collagen Microfibrils in Annulus Fibrosus.

Radial variation in water concentration from outer to inner lamellae is one of the characteristic features of annulus fibrosus (AF). In addition, water concentration changes are also associated with intervertebral disc (IVD) degeneration. Such changes alter the chemo-mechanical interactions among the biomolecular constituents at molecular level, affecting the load-bearing nature of IVD. This study investigates mechanistic impacts of water concentration on the collagen type I microfibrils in AF using molecular dynamics simulations. Results show, in axial tension, that increase in water concentration (WC) from 0% to 50% increases the elastic modulus from 2.7 GPa to 3.9 GPa. This is attributed to combination of shift in deformation from backbone straightening to combined backbone stretching- intermolecular sliding and subsequent strengthening of tropocollagen-water (TC-water-TC) interfaces through water bridges and intermolecular electrostatic attractions. Further increase in WC to 75% reduces the modulus to 1.8 GPa due to shift in deformation to polypeptide straightening and weakening of TC-water-TC interface due to reduced electrostatic attraction and increase in the number of water molecules in a water bridge. During axial compression, increase in WC to 50% results in increase in modulus from 0.8 GPa to 4.5 GPa. This is attributed to the combination of the development of hydrostatic pressure and strengthening of the TC-water-TC interface. Further increase in WC to 75% shifts load-bearing characteristic from collagen to water, resulting in a decrease in elastic modulus to 2.8 GPa. Such water-mediated alteration in load-bearing properties acts as foundations toward AF mechanics and provides insights toward understanding degeneration-mediated altered spinal stiffness.

Effect of aggrecan degradation on the nanomechanics of hyaluronan in extra-fibrillar matrix of annulus fibrosus: A molecular dynamics investigation.

Intervertebral Disc (IVD) Degeneration is one of the primary causes of low back pain among the adult population - the most significant cause being the degradation of aggrecan present in the extra-fibrillar matrix (EFM). Aggrecan degradation is closely associated with loss of water content leading to an alteration in the mechanical behaviour of the IVD. The loss in water content has a significant impact on the chemo-mechanical interplay of IVD biochemical constituents at the fundamental level. This work presents a mechanistic understanding of the effect of hydration, closely associated with aggrecan degradation, on the nanoscale mechanical behaviour of the hyaluronan present in the EFM of the Annulus Fibrosus. For this purpose, explicit three-dimensional molecular dynamics analyses of tensile and compressive tests are performed on a representative atomistic model of the hyaluronan present in the EFM. To account for the degradation of aggrecan, hydration levels are varied from 0 to 75% by weight of water. Analyses show that an increase in the hydration levels decreases the elastic modulus of hyaluronan in tension from ~4.6 GPa to ~2.1 GPa. On the other hand, the increase in hydration level increases the elastic moduli in axial compression from ~1.6 GPa in un-hydrated condition to ~6 GPa in 50% hydrated condition. But as the hydration levels increase to 75%, the elastic modulus reduces to ~3.5 GPa signifying a shift in load-bearing characteristic, from the solid hyaluronan component to the fluid component. Furthermore, analyses show a reduction in the intermolecular energy between hyaluronan and water, under axial tensile loading, indicating a nanoscale intermolecular debonding between hyaluronan and water molecules. This is attributed to the ability of hyaluronan to form stabilizing intra-molecular hydrogen bonds between adjacent residues. Compressive loading, on the other hand, causes intensive coiling of hyaluronan molecule, which traps more water through hydrogen bonding and aids in bearing compressive loads. Overall, study shows that hydration level has a strong influence on the atomistic level interactions between hyaluronan molecules and hyaluronan and water molecules in the EFM which influences the nanoscale mechanics of the Annulus Fibrosus.

Measurement of strain in the rod for lumbar pedicle screw fixation: An experimental and finite element study.

Spinal fusion with pedicle-screw-rod is being used widely for treating spinal deformities diseases. Several biomechanical studies on screw rod based implant failure through screw pullout, bending, screw breakage have been performed. But few studies are available regarding the effect of strain for breakage of rod. So, the purpose of the present study is to observe strain at the rod connected with the pedicle screw for different loading condition. The strain in stainless steel (SS) connecting rods for pedicle screw fixation were measured using strain gauge. In order to investigate the bio-mechanical response of lumbar spine with reference to strain in the rod, a simple experimental setup was developed using a specimen of L1-S spine segment. SS rods were used for pedicle screw implant on prototyped lumbar Spine. Prior to testing with pedicle screw, the lumbar spine specimen was also compared with FE results. The strain measured using strain gauges at L3-L4 level on SS rod were within a range of 85 to 310 microstrain under 6, 8, 10 Nm flexion and extension, and for L4-L5 level, these values were within a range of 95 to 440 microstrain. It was found that FE result was higher than the strain gauge result and the error varied between 10.5% to 33% with average error of 22.8%. However similar stain behavior was observed by the FE analysis. The proposed method, as well as the qualitative data, might be helpful for the researchers to understand biomechanical behavior of pedicle-screw implanted spine.