Hofmeister effect-enhanced gelatin/oxidized dextran hydrogels with improved mechanical properties and biocompatibility for wound healing

Compared with other types of hydrogels, natural derived hydrogels possess intrinsic advantages of degradability and biocompatibility. However, due to the low mechanical strength, their potential applications in biomedical areas are limited. In this study, Hofmeister effect-enhanced gelatin/oxidized dextran (Gel/O-Dex) hydrogels were designed with improved mechanical properties and biocompatibility to accelerate wound healing. Gel and O-Dex were chemically crosslinked through Schiff base reaction of aldehyde and amino groups. After soaking in kosmotrope solutions physical crosslinking domains were induced by Hofmeister effect including α-helix structures, hydrophobic interaction regions and helical junction zones among Gel molecular chains. The type of anions played different influence on the properties of hydrogels, which was consistent with the order of Hofmeister series. Particularly, H2PO4- treated hydrogels showed enhanced mechanical strength and fatigue resistance superior to that of Gel/O-Dex hydrogels. The underlying mechanism was that the physical crosslinking domains sustained additional mechanical stress and dissipated energy through cyclic association and dissociation process. Furthermore, Hofmeister effect only induced polymer chain entanglements without triggering any chemical reaction. Due to Hofmeister effect of H2PO4- ions, aldehyde groups were embedded in the center of entangled polymer chains that resulted in better biocompatibility. In the full-thickness skin defects of SD rats, Hofmeister effect-enhanced Gel/O-Dex hydrogels by H2PO4- ions accelerated wound healing and exhibited better histological morphology than ordinary hydrogels. Therefore, Hofmeister effect by essential inorganic anions is a promising method of improving mechanical properties and biocompatibility of natural hydrogels to promote medical translation in the field of wound healing from bench to clinic. STATEMENT OF SIGNIFICANCE: Hofmeister effect enhanced hydrogel mechanical properties in accordance with the order of Hofmeister series through physical crosslinking that induced α-helix structures, hydrophobic interaction regions and helical junction zones among Gel molecular chains. Due to the Hofmeister effect of H2PO4- ions, aldehyde groups were embedded in the center of entangled polymer chains that resulted in better biocompatibility. Hofmeister effect-enhanced Gel/O-Dex hydrogels through H2PO4- ions accelerated wound healing and exhibited better histological morphology than ordinary hydrogels. Therefore, Hofmeister effect by essential inorganic anions is a promising method to improve mechanical properties and biocompatibility of natural hydrogels for their medical applications..