Electrospun nanofibers for regenerative medicine
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Electrospun nanofibers represent a class of versatile scaffolds for tissue engineering applications owing to their ability to mimic the nanoscale features of the native extracellular matrix (ECM). In addition, nanofibers produced by electrospinning can be readily collected as uniaxially aligned assemblies to recapitulate the architecture of the ECM in tissues with anisotropic characteristics, such as tendon-to-bone insertions, tendons, and nerves. This dissertation focuses on the design, fabrication, functionalization, and assessment of various types of scaffolds consisting of aligned nanofibers, which can be used to augment regeneration in tissues with anisotropic structures. Briefly, for tendon-to-bone insertion repair, I assessed the capability of aligned nanofibers with a gradient in mineral content to induce spatially graded osteogenesis of adipose-derived mesenchymal stem cells (ASCs). I also developed an alternative approach to the production of a gradient in the density of osteoblasts. The graded pattern of osteoblasts generated using both approaches could mimic their distribution in the native tendon-to-bone insertion. To further enhance the stiffness of the scaffolds, a new solution was developed to coat the scaffold with a thicker mineral layer. In a third project, a novel method of generating crimp in aligned nanofibers was developed. A solvent plasticizer was employed to release the residual stress retained in the nanofibers during electrospinning, which led to the generation of crimp. Finally, the outgrowth of neurites derived from embryoid bodies (EBs) was studied using aligned nanofibers as the substrates. Depending on the strength of adhesion between nanofibers and neurites, two patterns of outgrowth--parallel and perpendicular (to the alignment)--were observed. Maturation of neurons derived from dissociated EBs was also investigated, as characterized by their extracellular action potential and the ability to form neuromuscular junctions with co-cultured muscle cells.