Because endogenous healing is limited in injured musculoskeletal soft tissues, scaffoldbased regenerative medicine and tissue engineering strategies aim to synthesize new functional tissue to restore physiological function. However, fibrous scaffolds to date have had limited success in generating extracellular matrix that reproduces the structural and mechanical anisotropy of healthy tissue potentially due to an inability to reproduce complex geometries with both tissue-scale dimensions and physiological fiber size.

Therefore, the broad goal of the studies outlined in this dissertation was to demonstrate the ability of textiles- and additive manufacturing-based approaches to address these limitations. It was also the aim of this work to illustrate a method to reproducibly create scaffolds with (1) complex, anisotropic fibrous architectures, (2) tissue-scale dimensions, and (3) physiological fiber size. First, the ability to control the formation of aligned collagen fibers in vivo was investigated by varying geometric parameters in 3D-bioplotted scaffolds, namely interstrand distance from 100 – 400 µm. It was determined that after 12 weeks of implantation in subcutaneous pockets in rats, scaffolds with an interstrand distance of 100 µm formed the greatest amount and most highly oriented collagen fibers. Despite this result, 3D-bioplotted structures are limited to fiber sizes of 100 µm or greater, which is 1-2 orders magnitude greater than native collagen fiber diameter. Next, melt electrowriting was explored as a method to scale down these scaffold fibers while maintaining control over fiber deposition. In addition to producing fibers ranging in diameter from 23 – 89 µm, it was determined that the mechanical properties of continuously fabricated melt electrowritten structures with geometries relevant for tissue engineering can be controlled by varying process parameters. Specifically, tensile modulus was found to depend on translation speed of the collecting surface. Building upon these findings, the following study explored the feasibility of using melt electrowriting to create scaffolds with sinusoidal fibers that mimic crimp, a microstructural feature of collagen fibers. Although sinusoidal scaffolds were successfully made, it was unclear whether these fibers influence the morphology of seeded cells due to large interfiber spacing (0.8 mm). Scaffolds with interfiber spacing less than 0.8 mm resulted in less control over fiber deposition and scaffold repeatability. Lastly, 3D melt blowing was investigated for its potential to create tissue-scale, anisotropic structures composed of physiologically sized fibers with interfiber spacing smaller than that possible with melt electrowriting. Moreover, this technique’s compatibility with a biomedical polymer, poly(ε-caprolactone) (PCL), was demonstrated. The mechanical properties and degree of anisotropy of PCL scaffolds was found to vary with fiber diameter and orientation, demonstrating the potential of 3D melt blowing to address conventional challenges to musculoskeletal soft tissue scaffold fabrication.

This work demonstrates the potential and limitations of additive manufacturing- and textiles-based methods to create anisotropic, porous structures with fibers similar in scale to collagen fibers. While no single method can yet repeatably create complex architectures with tissue-scale dimensions and physiological fiber size, different fabrication techniques can be used to explore different questions about material properties and cell-material interactions.