Naturally derived dual dynamic crosslinked multifunctional hydrogel for diabetic wound healing

Diabetic wound treatments remain a significant challenge for regenerative medicine due to the unicity of clinical dressings, which lack systemic multifunction with injectability, self-healing ability, moderate tissue adhesion, anti-inflammation and antibacterial abilities, and guidance of tissue repair. Herein, a naturally derived multifunctional hydrogel dressing composed of keratin, protocatechuic aldehyde (PA) and iron ions is fabricated through a simple mixing process, circumventing the use of any extra crosslinking agents or functional modification. Our findings showed that a dual dynamic crosslinked network was constructed through a dynamic thiolaldehyde addition reaction between thiol groups in keratin and aldehyde groups in PA, and catechol-metal ions coordination bonds between catechol groups in PA and Fe3+, and realized good injectability, mechanical performance, self-healing ability, tissue adhesion and antibacterial properties of the hydrogel. Moreover, the incorporation of phellopterin (PP), a natural compound derived from traditional Chinese herb Angelica dahurica endowed the hydrogel with anti-inflammation properties. The PP-loaded hydrogel shortened inflammation duration and accelerated wound repair in the full-thickness wounds of streptozotocin-induced diabetic mice, notably by promoting macrophage polarization towards anti-inflammatory phenotype and resolving local inflammation. The PP-loaded hydrogel achieved almost wound closure after only 10 days for a diabetic wound of 6 mm in diameter. This study demonstrated that the PP-loaded dynamic crosslinked multifunctional hydrogel had a great potential in the treatment of diabetic wounds.