3D-printable hyaluronic acid/gelatin double-network hydrogels for stretchable and adhesive wound patches

초록

Achieving rapid hemostasis and effective scavenging of reactive oxygen species at wound sites is crucial for designing wound patches to accelerate the skin wound healing process, while considering their tissue biocompatibility and adhesive features. To address these challenges, we propose integrating natural polymer-based double-network hydrogels with multiple functionalities for the 3D printing of wound dressing materials. Natural polymer-based double-network hydrogels comprising oxidized diol-modified hyaluronic acid (HA), hydrazide-modified HA, and cold-water fish gelatin (G) were enhanced with gallic acid (GA) to confer antioxidant and tissue-adhesive properties on them. The odHA/hHA/G hydrogels exhibited excellent stretchability (~2.5-fold extension relative to original length), and their storage shear modulus and toughness were 1.7- and 1.3-fold higher, respectively, than those of odHA/hHA hydrogels, without compromising self-healing. In vitro evaluation demonstrated that G significantly lowered blood clotting index and shortened clotting time, while GA coating markedly increased radical-scavenging activity. The GA-coating also increased tissue adhesion by ~3-fold and maintained robust attachment under wet conditions. In vivo studies using a rat wound model demonstrated that 3D-printed hydrogel patches accelerated wound healing, as evidenced by nearly complete wound closure by day 15 and enhanced tissue regeneration and neovascularization. Overall, this study highlights the potential of 3D-printable, natural polymer-based double-network hydrogels as multifunctional wound patches by combining hemostasis, tissue adhesion, antioxidant activity, and mechanical compliance which offers a practical strategy to improve skin wound repair.

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