Multi-Lamellar and Multi-Axial Maturation of Cell-Seeded Fiber-Reinforced Tissue Engineered Constructs

The architecture of load-bearing fibrous tissues is optimized to enable a specific set of mechanical functions. This organization arises from a complex process of cell patterning, matrix deposition, and functional maturation [1]. In their mature state, these tissues span multiple length scales, encompassing nanoscale interactions of cells with extracellular matrix to the centimeter length scales of the anatomic tissue volume and shape. Two structures that typify dense fibrous tissues are the meniscus of the knee and the annulus fibrosus (AF) of the intervertebral disc (IVD). The mechanical function of the wedge-shaped knee meniscus is based on its stiff prevailing circumferential collagen architecture that resists tensile deformation [2,3]. Adding to its complexity, radial tie fibers and sheets are interwoven amongst these fibers, increasing stiffness in the transverse direction and binding the tissue together [4]. In the annulus fibrosus, multiple anisotropic lamellae are stacked in concentric rings with their prevailing fiber directions alternating above and below the horizontal axis in adjacent layers [5]. The high circumferential tensile properties of this laminate structure allow it to resist bulging of the nucleus pulposus with compressive loading of the spine. Given their structural properties, unique form, and demanding mechanical environments, the knee meniscus and the AF region of the IVD represent two of the most challenging tissues to consider for functional tissue engineering.