Fetal milieu-simulating hyaluronic acid-dopamine-chondroitin sulfate hydrogel promoting angiogenesis and hair regeneration for wound healing

Wound regeneration with complete functions and skin appendages is still challenging in wound dressing application. Inspired by the efficient wound healing in the fetal environment, we developed a fetal milieu-mimicking hydrogel for accelerating wound healing simultaneously with hair follicle regeneration. To mimic the fetal extracellular matrix (ECM), which contains high content of glycosaminoglycans, hyaluronic acid (HA) and chondroitin sulfate (CS) were selected to fabricate hydrogels. Meanwhile, dopamine (DA) modification endowed hydrogels with satisfactory mechanical properties and multi-functions. The hydrogel encapsulated atorvastatin (ATV) and zinc citrate (ZnCit), namely HA-DA-CS/Zn-ATV, exhibited tissue adhesion, self-healing capacity, good biocompatibility, excellent anti-oxidant ability, high exudate absorption, and hemostasis property. In vitro results revealed that hydrogels exerted significant angiogenesis and hair follicle regeneration efficacy. In vivo results confirmed that hydrogels significantly promoted wound healing, and the closure ratio reached over 94 % after 14 days of hydrogels-treatment. The regenerated skin exhibited a complete epidermis, dense and ordered collagen. Furthermore, the number of neovessels and hair follicles in the HA-DA-CS/Zn-ATV group were 1.57- and 3.05-fold higher than those of the HA-DA-CS group. Thus, HA-DA-CS/Zn-ATV serves as multifunctional hydrogels for simulating the fetal milieu and achieving efficient skin reconstruction with hair follicle regrowth, exhibiting potential in clinical wound healing.