Modulating electrospun fibrous scaffolds to mimic native meniscus properties and engineer an in vitro injury model

Abstract

Electrospun fibrous scaffolds can be produced and optimized for creating models of the fibrous connective tissues found in the body. Fibrous tissues, like the meniscus, are made up of highly complex and organized collagen fibers which aid their ultimate functionality. However, these tissues, and the meniscus in particular, are prone to injury and demonstrate poor regenerative outcomes. By optimizing the production of highly aligned electrospun polymer fibers with and without small molecules, like non-ionic surfactants, more effective and reproducible in vitro models of meniscal tissue may be built. These scaffolds can be used in conjunction with a tensile bioreactor to investigate how an altered microenvironment affects mechanically sensitive signaling pathways and meniscal cell phenotypes post-injury. In this work we present a detailed analysis of the primary driving factors of electrospun fiber alignment in rotating mandrel systems and how non-ionic surfactant can alter collection of random or aligned electrospun fibers at a macromolecular or macroscopic scale. To demonstrate the utility of surfactant for modifying properties, the concentration-based effects on scaffold physical properties and interactions with primary meniscal cells were assessed. Finally, a tensile bioreactor was used in conjunction with both unaligned and aligned polymer scaffolds to establish an injury model system. The work herein has shown that optimal alignment of micron scale fibers occurs with collection of a large diameter mandrel and surfactant has a destabilizing effect on collection of aligned fibers in systems with smaller diameter mandrels. These studies indicate that surfactant may be a powerful tool for modulating mechanical properties and primary meniscal cell response to fibrous scaffolds. Further, aligned scaffolds can be successfully used as an extracellular matrix-mimetic material in a meniscal injury tear model in a modified bioreactor system. This work sets the stage for reproducibly investigating the response of primary meniscal cells to fibrous scaffolds with altered force transmission.