(352f) STEP Enabled Ordered Polymeric Micro/Nanofiber Scaffolds for Tissue Engineering

Fibrous scaffolds mimicking native extra-cellular matrix (ECM) provide a direct route to study cellular behavior, which can then be used to develop scaffold based tissue engineering therapies. The hierarchical nature of ECM along with the inherent topological constraints provides different pathways for living cells to adapt and conform to the surrounding environment. Numerous studies have indicated the importance of key engineered parameters: fiber diameter, fiber alignment, geometrical fiber spacing, scaffold mechanical strength, fiber roughness and topological constraints of scaffolds. These parameters constituting a vast design space with limited available information on their engineering limits along with their interdependency rules lead to a currently loose framework for designing fibrous biomaterial scaffolds. Using our previously reported Spinneret based Tunable Engineered Parameters (STEP) technique; we are able to fabricate and deposit high aspect ratio (length/diameter) fiber arrays of different polymeric systems (Diameter: sub-50 nm-sub-micron and Length: several mm-cm) in single and multiple layers at tunable geometrical spacing's within the same scaffold. Significant efforts are then devoted towards understanding the mechanisms of cellular mechanics in the vicinity of topological cues, the findings of which are implemented towards understanding the mechanisms of attachment, proliferation and differentiation of different cell lineages for regenerative medicine applications. Specifically, the fabricated scaffolds are then cultured with pluripotent mouse C2C12, rat hepatocytes and rat neural stem cells. C2C12 cells on the scaffolds are observed to elongate resembling myotube morphology along the fiber axis, spread along intersecting layers and fuse into bundles at the macroscale. Hepatocytes are observed to form monolayers on criss-cross networks and are healthy in culture for over four weeks. Neural stem cells on the customized scaffolds are observed to differentiate predominantly into neurons and high degree of alignment along the fiber axis is observed. Current ongoing studies are aimed at determining the effects of fiber diameter and fiber spacing on cellular adhesion and migration, which are envisioned to aid in the design of future scaffolds for tissue engineering applications.