Continuous Nanofiber: From Structural Composite to Tissue Engineering

Continuous nanofibers produced by electrospinning are an emerging class of nanomaterials. Despite high expectations, mechanical properties of nanofibers have been reported inferior. Work on mechanical optimization of nanofibers was further hindered by the lack of direct experimental techniques to test and analyze structure of individual nanofibers. The first objective of this dissertation is to explore the mechanical properties of different individual nanofibers from novel organo-soluble polyimide and silkworm silk, and investigate their structure-properties relationship. Individual as-spun nanofibers were mechanically tested until failure with a unique testing protocol. Dramatic size effects with extraordinary properties i.e., simultaneous improvement of strength, modulus, and toughness of fine nanofibers were observed. Pioneering explanation of structural mechanisms of unusual properties and size effects was proposed and further verified with the unique structure analysis protocol. These studies on mechanical optimization of these nanofibers might help to avoid the classical strength-toughness trade-off, and these nanofibers can be used as inexpensive reinforcement for next generation structural supernanocomposites and other safety-critical structures. Nanofibers have also demonstrated great potential as novel scaffolds for tissue engineering. But, regardless of advancements, very little is known about cell-nanofiber interaction mechanisms. Therefore, the second objective of this dissertation is to reveal the underlying cellular and molecular mechanism of cell sensing and adaptation to nanofibers. The regulatory role of RhoA kinase (ROCK) and focal adhesion kinase (FAK), each representing key molecular mechanosensors of cytoskeletal tension and focal adhesion, in mesenchymal stem cells (MSCs) alignment and morphology on nanofibers were tested. To test this, both ROCK and FAK expression and activation by MSCs on aligned and random nanofibers were assessed. Then, the effects of ROCK and FAK silencing via small hairpin RNA (shRNA) on MSC alignment and spreading on test substrates were examined. MSCs with ROCK-shRNA and FAK-shRNA displayed significantly impaired responses in nanofiber-guided cell alignment and spreading, suggesting a crucial role of ROCK and FAK in controlling MSC sensing and response to nanofibers. These findings may provide a new insight for nanofiber-based tissue engineering