Abstract
Nanofiber scaffolds have been well-documented for use in tissue engineering. These scaffolds are unique because they have a high surface area to volume ratio and can be specifically designed to mimic the naturally-occurring extracellular matrix, through both nanofiber diameter and alignment. Nanofiber scaffolds can be synthesized to mimic this structure by aligning the fibers through mechanical and electrostatic means. This dissertation is focused on controlling the alignment, fiber diameter, composition, and controlled drug release characteristics of nanofiber scaffolds for optimal tissue regeneration.
Aim 1 – Optimum alignment of nanofiber scaffolds for fibroblast response. Synthetic nanofiber scaffolds could be used to mimic the nanoscale extracellular matrix to speed up post-injury recovery time in nervous, bone, tendon, ligament, muscle, and arterial tissues. Aligned nanofiber scaffolds provide more directional cues for cellular response than random fibers, and are nanostructured similarly to nervous, ligament, muscle, and tendon extracellular matrices. Aligned nanofiber scaffolds can be readily synthesized by electrospinning onto a rotating mandrel. These experiments have yielded fibers with angular deviations that range from 3-60 degrees and diameters that range from 60nm to a few microns. Our first aim is to determine how to produce the nanofiber scaffold that would have the best characteristics for tissue regeneration applications. These characteristics include polymer composition, diameter, and alignment. In studying the production of nanofiber scaffolds, we observed that as nanofiber diameters decrease the fibers become more difficult to align using a mandrel. We will measure the alignment of nanofibers of different diameters and of different polymers. Alignment will be examined for decreasing fiber diameters as well as different types of polymer, such as PLGA, PCL, or PPHOS (see glossary). We will also determine what nanofiber diameter and alignment elicits the best PC12 and Schwann cell growth and alignment.
Aim 2- Characterizing release kinetics for coaxially electrospun fibers. Coaxially electrospun fibers with different polymers in the core and sheath are unique materials, not only because of their high surface area to volume ratio, but also because of their ability to elute encapsulated drugs – for instance growth factors – as the fiber degrades. This drug release, in combination with the micro- and nanotopographic cues provided by electrospun fibers can provide additional signaling factors to alter the proliferation and morphology of cells. The core and sheath can elute different drugs, so that one drug can be introduced from the scaffold in the first phase of healing and another drug can be released in a later phase to trigger an optimum cell response.
This improved understanding of the influence of alignment, fiber diameter, composition, and controlled release characteristics of nanofiber scaffolds on model cell systems, such as Schwann and PC12 cells, will enable the optimization of nanofiber scaffolds for tissue engineering applications.
