Fabrication and Evaluation of 3D-printed Dittany-infused Patches for Anti-inflammatory Dermatological Applications

This study aimed to validate the dermatological potential of <i>Origanum dictamnus</i> (dittany) infusion, traditionally recognized for its anti-inflammatory properties. To this end, 3D-printed hydrogel patches incorporating dittany were developed and evaluated for biocompatibility, wound-healing, anti-inflammatory activity, and effects on skin barrier. Hydrogel patches were fabricated via extrusion-based 3D printing using aloe vera gel, hydroxypropyl methylcellulose (HPMC), glycerol, and combinations of dittany infusion and panthenol. <i>In vitro</i> assays with HaCaT keratinocytes included cytotoxicity testing, scratch-wound healing, and qPCR-based analysis of inflammatory biomarkers. <i>In vivo</i> transepidermal water loss (TEWL) measurements were performed to assess skin barrier integrity and hydration after patch application. The traditional use of dittany infusion in skin ailments was confirmed, along with its relatively low cytotoxicity. Three 3D-printed gel types were evaluated <i>in vitro</i>, all showing superior performance to the raw plant extract. The optimal formulation contained 2% HPMC, 2% glycerol, 5% panthenol, and 0.06% dittany infusion (w/w% relative to aloe vera gel). At 3.25 mg/mL, this formulation achieved ~ 70% wound closure and significantly reduced IL-6 and TNF-<i>α</i> levels, indicating strong anti-inflammatory activity (p < 0.05). Both crude extract and patches show a trend toward reducing pro-inflammatory interleukins while simultaneously upregulating the anti-inflammatory cytokine IL-4. TEWL measurements indicated that none of the patches impaired the skin barrier function, confirming their compatibility with various skin types. This study provides the first scientific evidence that the incorporation of dittany infusion into 3D-printed hydrogels holds promise for safe, effective, plant-based topical therapies.