Harnessing electrospun nanofibers to recapitulate hierarchical fibrous structures of meniscus

The meniscus has complex biomechanical functions endowed by the hierarchical fibrous structure of its extracellular matrix (ECM), which plays a central role in protecting the knee joint. However, it is challenging to recapitulate the ECM structure of the meniscus. Herein, we used electrospinning to prepare various scaffolds with distinct nanofibrous structures to approximate that of the heterogeneous ultrastructure of meniscus ECM. Our results showed that adjusting the deposition manner of nanofibers during electrospinning could effectively manipulate the architectures of resulting scaffolds. This approach led to electrospun scaffolds with random or aligned fibrous structures that reassemble the surface or superficial layers of the meniscus. We also showed that assembly of electrospun nanofibers into yarn-like configurations replicates the circumferentially aligned fibrous bundles of the inner part of the meniscus. These scaffolds exhibited distinct fibrous anisotropies and mechanical properties. In vitro studies indicated good cytocompatibility of scaffolds, especially, the yarn scaffold supported considerable meniscus cell infiltration. The meniscus cells, in turn, enhanced the mechanical properties of scaffolds. Taken together, these data imply that electrospun scaffolds may have potential in enhancing meniscus repair and regeneration.