Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

Abstract

Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation.

Anisotropic Fibrous Scaffolds for Articular Cartilage Regeneration

“…9,10 Fiber size, in particular, plays a crucial role in determining the mechanical properties of the bulk scaffold. By varying the fiber size, the resultant pore size and mechanical strength can be varied over a wide range.…”

“…10,11 In addition, fiber orientation can be varied by modifying collector geometry or rotating collector speed, yielding fibrous scaffolds that vary from randomly oriented scaffolds to highly aligned networks with concomitant variations in tensile strength. 9,12,13 Nevertheless, such homogenous, electrospun scaffolds still lack cartilage's zonal organization, and are therefore unable to regenerate this native tissue's anisotropic mechanical properties, collagen fiber orientation, biochemical gradients, and cellular distribution. 14,15 Biodegradable scaffolds that are functionally graded in terms of organization, porosity, pore size, and mechanical properties may provide distinct advantages over scaffolds that feature uniform properties and homogeneous compositions.…”

Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation

“…In this process, a high voltage applied to a viscous polymer solution results in the formation of fibers via electrostatic charge repulsion; these fibers collected en masse result in a 3D fibrous network. An extensive library of polymers can be electrospun, spanning a range of stiffness and fiber diameters (50 nm to several microns), capturing the biologic diversity of fiber diameters within the cellular microenvironment (6,7). Importantly, the alignment of electrospun fibers can also be controlled, generating scaffolds that mimic the organization of tissues where direction dependence (structural and mechanical anisotropy) is essential for function, including cardiac (8), neural (9), and orthopaedic tissues (6).…”

Biaxial mechanics and inter‐lamellar shearing of stem‐cell seeded electrospun angle‐ply laminates for annulus fibrosus tissue engineering

“…We have previously adopted an electrospinning-based approach to generate scaffolds for multi-lamellar AF tissue engineering. 8,[13][14][15] Scaffolds can be formed with a highly aligned fibrous structure that instructs alignment of cells and their subsequent matrix deposition. 16 Seeding these scaffolds with mesenchymal stem cells (MSCs) and culture in chemically defined conditions leads to marked increase in biochemical content and mechanical properties.…”