Hyaluronic acid nanofibers crosslinked with a nontoxic reagent

The poor water resistance of the eletrospun hyaluronic acid (HA) nanofibers prevents their biomedical applications. In this manuscript, we crosslinked HA nanofibers with the periodate oxidation - adipic acid dihydrazide (ADH) crosslinking strategy. Quantification results showed that ∼ 57 % of aldehydes in oxidized HA were crosslinked by ADH and the crosslinking density could reach 75.7 %. Correspondingly, the crosslinked HA nanofiber mats exhibited wet tensile strength up to 0.88 MPa and could maintain their nanofibrous morphology after 14 days in simulated body fluid. Although ∼ 28 % of the aldehydes in oxidized HA were unreacted, the crosslinked HA nanofibers did not cause toxicity to L929 fibroblast cells, possibly because that the unreacted aldehyde groups were linked on macromolecular fragments and could not go across cell membranes. The water resistant and biocompatible HA nanofibers are expected to seek extensive applications in biomedical fields such as wound healing, adhesion prevention, and tissue engineering.