Bioinspired Multifunctional Hydrogels for Deep Learning-Enabled Wound pH Visual Monitoring and Treatment

Smart wound dressings capable of real-time environmental monitoring and therapeutic intervention are crucial for managing difficult-to-heal wounds. Herein, we report a bioinspired, enzyme cascade-initiated multifunctional hydrogel (EVQ) that integrates pH-responsive visual monitoring, broad-spectrum antimicrobial activity, and mechanical adaptability for intelligent wound healing. The hydrogel is formed via an in situ redox-initiated polymerization catalyzed by a glucose oxidase (GOx)–hemin cascade, enabling rapid gelation within ∼30 s under physiologically relevant glucose levels and yielding an injectable matrix that conforms to irregular wound geometries. Incorporation of quaternized chitosan (QCS) enhances both tensile performance and interfacial adhesion, increasing tensile strength by ∼60% compared to QCS-free gels, while maintaining an elongation at break comparable to commercial dressings (68–134%) and providing robust wet adhesion to porcine skin. The EVQ hydrogel also exhibits excellent moisture management, remaining hydrated for at least 24 h and swelling to ∼10-fold its dry weight. Antibacterial assays demonstrate >90% bacterial inhibition against Escherichia coli and S. aureus over pH 5.5–8.5, with L929 cell viability consistently above 80%, confirming good cytocompatibility. For real-time wound pH monitoring, phenol red is embedded in the hydrogel matrix, producing a distinct colorimetric transition and a pH-dependent absorbance response at 560 nm across pH 5–9 with <2% interference from common wound exudate components. A deep learning model based on ResNet34, trained on 1000 colorimetric hydrogel images, achieves 93.25% classification accuracy for pH levels between 5 and 9. In a S. aureus -infected murine wound model, EVQ treatment leads to almost complete wound closure by day 12 (residual area <0.5%), compared to ∼15% residual area in untreated controls, and is accompanied by enhanced collagen deposition, increased CD31/VEGF expression, and reduced IL-6 levels. Collectively, these results establish EVQ as a bioinspired multifunctional hydrogel platform that couples in situ forming mechanics, potent antimicrobial and adhesive properties, and deep learning-enabled pH sensing for next-generation intelligent wound management.