Anisotropic hair keratin‐dopamine composite scaffolds exhibit strain‐stiffening properties

Abstract Human hair keratin (HHK) has been successfully explored as raw materials for three‐dimensional scaffolds for soft tissue regeneration due to its excellent biocompatibility and bioactivity. However, none of the reported HHK based scaffolds is able to replicate the strain‐stiffening capacity of living tissues when responding to large deformations. In the present study, strain‐stiffening property was achieved in scaffolds fabricated from HHK via a synergistic effect of well‐defined, aligned microstructure and chemical crosslinking. Directed ice‐templating method was used to fabricate HHK‐based scaffolds with highly aligned (anisotropic) microstructure while oxidized dopamine (ODA) was used to crosslink covalently to HHKs. The resultant HHK‐ODA scaffolds exhibited strain‐stiffening behavior characterized by the increased gradient of the stress–strain curve after the yield point. Both ultimate tensile strength and the elongation at break were enhanced significantly (~700 kPa, ~170%) in comparison to that of HHK scaffolds lacking of aligned microstructure or ODA crosslinking. In vitro cell culture studies indicated that HHK‐ODA scaffolds successfully supported human dermal fibroblasts (HDFs) adhesion, spreading and proliferation. Moreover, anisotropic HHK‐ODA scaffolds guided cell growth in alignment with the defined microstructure as shown by the highly organized cytoskeletal networks and nuclei distribution. The findings suggest that HHK‐ODA scaffolds, with strain‐stiffening properties, biocompatibility and bioactivity, have the potential to be applied as biomimetic matrices for soft tissue regeneration.