Mirit Sharabi

A new class of bio-composite materials of unique collagen fibers

A novel collagen-based bio-composite was constructed from micro-crimped long collagen fiber bundles extracted from a soft coral embedded in alginate hydrogel matrix. The mechanical features of this bio-composite were studied for different fiber fractions and in longitudinal and transverse loading modes. The tensile modulus of the alginate hydrogel was 0.60±0.35MPa and in longitudinal collagen-reinforced construct it increased up to 9.71±2.80 for 50% fiber fraction. Ultimate tensile strength was elevated from 0.08±0.04MPa in matrix up to 1.21±0.29 for fiber fraction of 30%. The bio-composite demonstrated hyperelastic behavior similar to human native tissues. Additionally, a dedicated constitutive material model was developed to enable the prediction of the longitudinal mechanical behavior of the bio-composite. These findings will allow tailor-designed mechanical properties with a quantitatively controlled amount of fibers and their designed spatial arrangement. This unique bio-composite has the potential to be used for a wide range of engineered soft tissues.

The Vertebral Bone

Abstract The current chapter reviews the multiscale structure of the vertebral bone, with nested hierarchical microstructures along different length scales. The chapter also deals with the vertebral bone’s mechanical behavior, the different methods used to predict the mechanical properties, and experimental measurements, including density and microarchitecture. The final section reviews multiscale computational models used in biomechanical simulations of the vertebral bones and their performance.

The Mechanical Role of Collagen Fibers in the Intervertebral Disc

Abstract The current chapter reviews the mechanical role of the collagen fibers in the intervertebral disc, including the different roles of the collagen fibers in the different subparts of the disc and the integration between these subparts. Moreover, this chapter surveys the different collagen types, their role and location in the intervertebral disc, along with the changes that occur with aging. The final part of the chapter reviews finite element models and simulations that include structural representation of the collagen fibers in the intervertebral disc.

Unique Collagen Fibers for Biomedical Applications

The challenge to develop grafts for tissue regeneration lies in the need to obtain a scaffold that will promote cell growth in order to form new tissue at a trauma-damaged site. Scaffolds also need to provide compatible mechanical properties that will support the new tissue and facilitate the desired physiological activity. Here, we used natural materials to develop a bio-composite made of unique collagen embedded in an alginate hydrogel material. The collagen fibers used to create the building blocks exhibited a unique hyper-elastic behavior similar to that of natural human tissue. The prominent mechanical properties, along with the support of cell adhesion affects cell shape and supports their proliferation, consequently facilitating the formation of a new tissue-like structure. The current study elaborates on these unique collagen fibers, focusing on their structure and biocompatibility, in an in vitro model. The findings suggest it as a highly appropriate material for biomedical applications. The promising in vitro results indicate that the distinctive collagen fibers could serve as a scaffold that can be adapted for tissue regeneration, in support of healing processes, along with maintaining tissue mechanical properties for the new regenerate tissue formation.

The mechanical role of the radial fibers network within the annulus fibrosus of the lumbar intervertebral disc: a finite elements study

The annulus fibrosus (AF) of the intervertebral disc (IVD) consists of a set of concentric layers composed of a primary circumferential collagen fibers arranged in an alternating oblique orientation. Moreover, there exists an additional secondary set of radial translamellar collagen fibers which connects the concentric layers, creating an entangled fiber network. The aim of this study is to investigate the mechanical role of the radial fiber network. Towards that goal, a three-dimensional finite-element model of the L3-L4 spinal segment was generated, and calibrated to axial compression and pure moment loading. The AF model explicitly recognizes the two heterogeneous networks of fibers. The presence of radial fibers demonstrated a pronounced effect on the local disc responses under lateral bending, flexion and extension modes. In these modes, the radial fibers, in the disc region with axial compression stress, were in a tensile state. In addition, the circumferential fibers, on the opposite side of the IVD, were also under tension. The local stress in the matrix was decreased in up to 9% in the radial fibers presence. This implies an active fiber network acting collectively to reduce the stresses and strains in the AF lamellae. Moreover, the radial fibers reduce the sideways expansion in the matrix in 26.6% near the neutral bending axis of the disc. The proposed biomechanical model provided a new insight into the mechanical role of the radial collagen fibers in the AF structure. This model can be used in the design of future IVD substitutes.

Nonlinear Elasticity of the ECM Fibers Facilitates Efficient Intercellular Communication

Biological cells embedded in fibrous matrices have been observed to form intercellular bands of dense and aligned fibers through which they mechanically interact over long distances. Such matrix-mediated cellular interactions have been shown to regulate various biological processes. This study aimed to explore the effects of elastic nonlinearity of the fibers contained in the extracellular matrix (ECM) on the transmission of mechanical loads between contracting cells. Based on our biological experiments, we developed a finite-element model of two contracting cells embedded within a fibrous network. The individual fibers were modeled as showing linear elasticity, compression microbuckling, tension stiffening, or both of the latter two. Fiber compression buckling resulted in smaller loads in the ECM, which were primarily directed toward the neighboring cell. These loads decreased with increasing cell-to-cell distance; when cells were >9 cell diameters apart, no such intercellular interaction was observed. Tension stiffening further contributed to directing the loads toward the neighboring cell, though to a smaller extent. The contraction of two neighboring cells resulted in mutual attraction forces, which were considerably increased by tension stiffening and decayed with increasing cell-to-cell distances. Nonlinear elasticity contributed also to the onset of force polarity on the cell boundaries, manifested by larger contractile forces pointing toward the neighboring cell. The density and alignment of the fibers within the intercellular band were greater when fibers buckled under compression, with tension stiffening further contributing to this structural remodeling. Although previous studies have established the role of the ECM nonlinear mechanical behavior in increasing the range of force transmission, our model demonstrates the contribution of nonlinear elasticity of biological gels to directional and efficient mechanical signal transfer between distant cells, and rehighlights the importance of using fibrous gels in experimental settings for facilitating intercellular communication. VIDEO ABSTRACT.