Silk fibroin-hyaluronic acid nanofibers for peripheral nerve regeneration

Peripheral nerve injuries are common and a major source of pain that can lead to debilitating loss of function. Current treatments are limited, with autologous nerve grafts being the gold standard treatment for nerve injuries. However, autografting is not always successful and can lead to increased debilitation through donor site morbidity. Tissue engineering seeks to improve nerve injury treatment though the use of nerve conduits. Conduits made from a functional biomaterial can be implanted into a nerve injury site encouraging and controlling axonal regrowth without causing additional harm to the patient. Both silk fibroin (SF) and hyaluronic acid (HA) have been proven successful in the field of neural tissue engineering. SF has excellent mechanical properties and is biocompatible. HA is part of the extracellular matrix and had been used in nerve regeneration applications. This study developed aligned combination SF-HA nanofibers through electrospinning that could be used within a nerve conduit. Both materials were methacrylated to allow for photocrosslinking and additional control over material properties. Methcrylated SF-HA was tested alongside a material containing only methacrylated HA that has already proven to be effective in literature. When characterizing the materials, it was found that through chemical methacrylation HA was substituted at 60% while SF reported a 30% substitution. Electrospun SF-HA nanofibers were found to have a greater diameter than HA fibers; however, SF-HA was found to be more aligned with greater surface hydrophobicity. Mechanically, it was found that both materials exceeded the elastic modulus of native tissue, but SF-HA far exceeded HA in elasticity and overall fiber extension. Furthermore, human Schwann cells attached, proliferated, and released more pro-regenerative growth factors on SF-HA than HA. Dorsal root ganglia neurons also displayed longer neurite extensions on SF-HA fibers. We concluded that SF-HA nanofibers have potential as a nerve conduit material.