Fabrication and Analysis of Complex Electrospun Scaffolds and Constructs

摘要

Tissue construct mechanics are of pivotal importance in mechanically active tissues, particularly where the construct must assume a functional role immediately upon implantation and during the remodeling period. While numerous methods exist to generate porous scaffolds for tissue engineering, electrospinning has become increasingly applied as a means of generating microfibrillar scaffolds that provide surface structures roughly comparable in scale to that seen with ECM proteins such as collagen. Simple mechanical relationships have been explored in electrospun scaffolds such as simple fiber alignment to achieve planar anisotropy, however more thorough structure-function characterization has not been pursued to date. Further, the effect of cellular or other component incorporation has not been studied. An understanding of cellular function within scaffolds is critical for the design of seeded tissue constructs. For these reasons, this research aimed to gain an understanding of how structural and compositional modifications to electrospun scaffolds can result in a change in mechanical function and host response. This research question was approached through a series of directed modifications to the electrospinning process designed to alter the microenvironment within the scaffold. These micro-scale changes were related to tissue-level changes in both planar biaxial and flexural mechanical response. This knowledge was used to fabricate cellularized constructs for cardiac right ventricular outflow tract replacement in order to discern the fate and function of implanted cells within electrospun scaffolds. The results from this research can be combined with structural deterministic modeling in order to gain a more complete understanding of the mechanical and biological function of cellularized electrospun constructs and therefore help guide future work in the rational design of engineered tissues.