Rapid advancements in medicine have been both driven by and require new technologies and materials. The use of fibrous polymers produced through electrostatic spinning has been employed in the development of fabricated extracellular matrices for tissue engineering and for drug delivery. Described herein is work towards the development of novel fibrous polymer matrices, with additional biological functionality imparted through the encapsulation of proteins and enzymes within the fibers.
Biphasic fibrous matrices containing encapsulated proteins were fabricated using a novel variation on traditional electrostatic spinning, known as suspension electrospinning. This fabrication method allowed for the formation of solid polymer fibers with diameters in the micron range, with encapsulated protein-loaded aqueous reservoirs along the fiber core. These biphasic fibrous materials were fabricated from various biocompatible polymers and characterized for morphology and protein localization, providing insight into the mechanistic formation of the matrices.
Suspension electrospinning was used to produce multifunctional scaffolding for two clinical-focused applications. Biphasic fibers containing matrix metalloproteinase were developed for retinal progenitor based therapies for age related macular degeneration. These scaffolds were used to deliver retinal progenitor cells to the subretinal space and to release the encapsulated enzyme to degrade away an inhibitory glial scar located on the retina. The use of the scaffolds was found to both eliminate the inhibitory environment and promote retinal progenitor cell infiltration into host tissue in a murine model of retinal degeneration.
Biphasic scaffolding was also developed for the use in heart valve tissue engineering. Vascular endothelial growth factor was encapsulated and delivered from biphasic fibers for the promotion of progenitor cell differentiation into appropriate cardiovascular phenotypes. Also, the mechanical properties of the biphasic scaffolds were evaluated for use as a synthetic heart valve, and a distinct correlation between increasing aqueous inclusions and decreasing mechanical properties was described.
The results from this body of work form a foundation for the further optimization of these biphasic fibrous materials. The successful implementation of protein-releasing biphasic polymeric fibers sets the stage for the application and implementation of this processing approach in a broad range of clinical settings, where there is a need for multifunctional scaffolding materials.