3D printed personalized wound dressings using a hydrophobic deep eutectic solvent (HDES)-formulated emulgel

Abstract

Curcuminoids, known for their antibacterial, anti-inflammatory, and wound healing properties, face challenges in medical applications due to their limited water solubility, resulting in poor bioavailability and clinical efficacy. This study introduces a novel approach to formulating 3D printing ink for personalized wound dressings by utilizing hydrophobic deep eutectic solvents (HDES) to incorporate poorly water-soluble compounds from Curcuma longa (i.e., curcuminoids and ar-turmerone) into hydrogels. The use of HDES, comprising either acetic acid or octanoic acid combined with menthol in a 2 : 1 molar ratio, significantly improved the solubility of curcuminoid derivatives and ar-turmerone by approximately 10 to 600 times, depending on the intrinsic chemical polarities of each compound, compared to conventional extraction solvents (i.e., ethanol and water). By formulating an emulgel using HDES as the oil phase in a gelatin methacryloyl (GelMA) solution stabilized by a biocompatible surfactant, we achieved a 3D biocompatible printing ink with preserved rheological characteristics, enabling the production of personalized wound dressings using a custom-designed, syringe-based 3D printer. The emulgel constructs exhibited regulated swelling profiles, prolonged release of curcuminoids over 60 days as monitored by a Franz cell diffusion assay, and promoted human dermal fibroblast proliferation in vitro. Additionally, the emulgel components worked synergistically with curcuminoids to significantly enhance anti-biofilm activity against Staphylococcus aureus, offering an effective strategy to prevent wound infections. Our findings have demonstrated, for the first time, the formulation of biochemical ink for 3D printing harnessing HDES, providing a new pathway for developing advanced wound dressings with relatively high concentrations of poorly soluble plant bioactive compounds tailored for chronic wound management.