3D-Printed Multifunctional Hydrogels with Phytotherapeutic Properties: Development of Essential Oil-Incorporated ALG-XAN Hydrogels for Wound Healing Applications

Thisstudy aimed to develop three-dimensional (3D)-printed hydrogelscontaining phytotherapeutic agents as multifunctional wound dressings.In this regard, 3D-printed sodium alginate (ALG)-xanthan gum(XAN) hydrogels incorporated with different clove essential oil (CLV)concentrations were produced by the extrusion-based 3D-printing technology.Rheology measurements, filament fusion, and filament collapse analysesindicated that XAN's blending overcame the challenges associatedwith ALG's printability and shape fidelity. Attenuated totalreflection-Fourier-transform infrared (ATR-FTIR) spectra and totalphenolic content assay confirmed the presence of CLV in the 3D-printedhydrogels. Additionally, the releasing profile showed that CLV exhibitedlong-term release for up to 28 days. Furthermore, the incorporationof CLV increased 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicalscavenging while reducing the S. aureus and E. coli relative bacterial viability;thereby, the CLV incorporation enhanced the 3D-printed ALG-XANhydrogel antioxidant and antibacterial activity. In addition, anti-inflammatoryactivity was assessed using Raw 264.7 macrophage-like cells, and theresults demonstrated that CLV reduced nitric oxide (NO) concentrationin medium, indicating a potential anti-inflammatory effect. Moreover,in vitro cytotoxicity results showed that the incorporation of CLVhas no toxic effect on NHDF cells, whereas the proliferation of NHDFcells exhibited a dose-dependent response. In conclusion, the presentstudy shows not only the development of a new ALG-XAN biomaterialink but also the potential benefit of natural phytotherapeutics incorporatedinto 3D-printed hydrogels as a multifunctional wound dressing.