Structure-function characterization of the transition zone in the intervertebral disc.

Understanding the structure-function relationship in the intervertebral disk (IVD) is crucial for the development of novel tissue engineering strategies to regenerate IVD and the establishment of accurate computational models for low back pain research. A large number of studies have improved our knowledge of the mechanical and structural properties of the nucleus pulposus (NP) and annulus fibrosus (AF), two of the main regions in the IVD. However, few studies have focused on the AF-NP interface (transition zone; TZ). Therefore, the current study aims to, for the first time, characterize the cyclic and failure mechanical properties of the TZ region under physiological loading (1, 3, and 5%s-1 strain rates) and investigate the structural integration mechanisms between the NP, TZ, and AF regions. The results of the current study reveal significant effects of region (NP, TZ, and AF) and strain rates (1, 3, and 5%s-1) on stiffness (p < 0.001). In addition, energy absorption is significantly higher for the AF compared to the TZ and NP (p <0.001) as well as between the TZ and NP (p <0.001). The current research finds adaptation, direct penetration, and entanglement between TZ and AF fibers as three common mechanisms for structural integration between the TZ and AF regions. STATEMENT OF SIGNIFICANCE: Despite a large number of studies that have mechanically, structurally, and biologically characterized the nucleus pulposus (NP) and annulus fibrosus (AF) regions, few studies have focused on the NP-AF interface region (known as Transition Zone; TZ) in the IVD; hence, our understanding of the TZ structure-function relationship is still incomplete. Of particular importance, the cyclic mechanical properties of the TZ, compared to the adjacent regions (NP and AF), are yet to be explored and the precise nature of the structural integration between the NP and AF via the TZ region is not yet known. The current study explores both the mechanical and structural properties of the TZ region to ultimately identify the mechanism of integration between the NP and AF.

Toward a mechanically biocompatible intervertebral disc: Engineering of combined biomimetic annulus fibrosus and nucleus pulposus analogs.

Intervertebral disc (IVD) degeneration and accompanying lower back pain impose global medical and societal challenges, affecting over 600 million people worldwide. The IVD complex fibrocartilaginous structure is responsible for the spine biomechanical function. The nucleus pulposus (NP), composed of swellable glycosaminoglycan (GAG), transfers compressive loads to the surrounding fiber-reinforced annulus fibrosus (AF) lamellae, which stretches under tension. Together, these substructures allow the IVD to withstand extremely high and complex loads. Key to mimic the complete disc must consider the properties of its substructures. This study presents three novel substructures-a biomimetic silk-reinforced composite lamella for the AF, a GAG analog for the NP, and a novel biomimetic combined AF-NP construct. The biomimetic AF demonstrates nonlinear, hyperelastic, and anisotropic behavior similar to the native human AF, while the NP analog demonstrates mechanical behavior similar to the human NP. The synergized biomimetic AF-NP demonstrates similar behavior to the unconfined NP, with significantly increased deformations indicating improved performance. Validation of the AF-NP construct mechanics using a finite element model yields results compatible with native human IVD under various physiological loadings. The ability of our AF-NP construct to mimic the native IVD offers a revolutionary concept for the potential development of a fully functional IVD.

The mechanical behavior of silk-fibroin reinforced alginate hydrogel biocomposites - Toward functional tissue biomimetics.

Soft tissues are constructed as fiber-reinforced composites consisting of structural mechanisms and unique mechanical behavior. Biomimetics of their mechanical behavior is currently a significant bioengineering challenge, emphasizing the need to replicate structural and mechanical mechanisms into novel biocomposite designs. Here we present a novel silk-based biocomposite laminate constructed from long natural silk and fibroin fibers embedded in an alginate hydrogel matrix. Controlling the mechanical features of these laminates were studied for different fiber volume fractions (VF) and orientations using unidirectional tensile tests. Three material systems were investigated having different fiber orientations: longitudinal (0°), transverse (90°), and cross-plied (0/90°). The general behavior of the biocomposite laminates was anisotropic hyperelastic with large deformations. Longitudinal fibroin laminates have shown a tensile modulus of 178.55 ± 14.46 MPa and tensile strength of 18.47 ± 2.01 MPa for 0.48 VF. With similar VF, cross-plied fibroin laminates demonstrated structural shielding ability, having a tensile modulus and tensile strength of 101.73 ± 8.04 MPa and 8.29 ± 1.63 MPa for only a third of the VF directed in the stretching direction. The stress-strain behavior was in a similar range to highly stiff native human soft tissues such as ligament and meniscus. These findings demonstrate the potential of the fibroin fiber-reinforced biocomposites to mimic the mechanics of tissues with a quantitatively controlled amount of fibers and designed spatial arrangement. This can lead to new solutions for the repair and replacement of damaged functional and highly stiff soft tissues.