BME MS Defense: Alice Chou
Optimization of Electrospun Collagen Scaffolds for Tendon Tissue Engineering
Supervised by Professor Hani Awad
It has been estimated that tendon injuries comprise of roughly 45% of the 33 million musculoskeletal injuries in the United States. As the percentage of aging population engaging in physical activities continues to rise, these numbers are projected to increase. The traditional surgical treatments for tendon and ligament the injuries such as autografts and allografts have disadvantages including donor site morbidity and limited long-term function, respectively. Therefore, tendon tissue engineering has emerged as a promising alternative to biological grafts.
One strategy in tissue engineering is to create scaffolds, which mimic tendon extracellular matrix, onto which cells can be seeded. Tendon is comprised primarily of type I collagen such that the fibers are densely arranged in parallel bundles along the longitudinal axis of the tendon with a distinct hierarchical structure. Electrospinning is a fabrication method in which the architecture of the scaffold may be controlled via process parameters. The major goal of this project is to demonstrate the feasibility of producing transversely isotropic electrospun collagen type I scaffolds for tendon repair and evaluate the mechanical, biomechanical and biological properties in vitro. Using a custom-designed electrospinning apparatus, we first optimized the fabrication parameters of electrospun collagen type I scaffolds to enhance the homogeneity of the fiber diameters and alignment. We then tested the hypothesis that fibroblasts cultured on these electrospun scaffolds with a transverse-isotropic fiber alignment will have a greater degree of alignment compared to cells seeded on randomly oriented scaffolds. Microscopy images reveal that fibroblasts seeded on aligned fiber scaffolds elongated in the direction of the fibers. This has important biological consequences for the cellâs responsiveness to mechanical loading. We further hypothesized that fibroblasts seeded in aligned scaffolds and subjected to physiological mechanical stretch will have enhanced metabolism and increased synthesis of de novo extracellular matrix. Dynamic tensile stretch increased gene expression of collagen I, collagen III, decorin, scleraxis, and tenascin-C in tendon fibroblasts seeded on the electrospun collagen scaffolds. The advantages of electrospinning collagen scaffolds stem from the ability to control both the macro and micro scaffold architecture to recreate the extracellular matrix of the tendon. The data suggest that these electrospun scaffolds can be used to study the biological responses of tendon fibroblasts under mechanical stretching. Additionally, this tissue engineering approach may be scalable for future clinical applications in tendon repair.