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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., Competing Interests: This work declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Using phantom samples, we investigated the feasibility of spatially-offset Raman spectroscopy (SORS) as a tool for monitoring non-invasively the mineralization of bone tissue engineering scaffold in-vivo . The phantom samples consisted of 3D-printed scaffolds of poly-caprolactone (PCL) and hydroxyapatite (HA) blends, with varying concentrations of HA, to mimic the mineralisation process. The scaffolds were covered by a 4 mm layer of skin to simulate the real in-vivo measurement conditions. At a concentration of HA approximately 1/3 that of bone (~0.6 g/cm 3 ), the characteristic Raman band of HA (960 cm -1 ) was detectable when the PCL:HA layer was located at 4 mm depth within the scaffold (i.e. 8 mm below the skin surface). For the layers of the PCL:HA immediately under the skin (i.e. top of the scaffold), the detection limit of HA was 0.18 g/cm 3 , which is approximately one order of magnitude lower than that of bone. Similar results were also found for the phantoms simulating uniform and inward gradual mineralisation of the scaffold, indicating the suitability of SORS to detect early stages of mineralisation. Nevertheless, the results also show that the contribution of the materials surrounding the scaffold can be significant and methods for subtraction need to be investigated in the future. In conclusion, these results indicate that spatially-offset Raman spectroscopy is a promising technique for in-vivo longitudinal monitoring scaffold mineralization and bone re-growth., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Aim: To investigate the role of urokinase plasminogen activator (uPA) in cholangiocarcinoma (CCA) invasion and its correlation with clinicopathological parameters., Methods: uPA expression in CCA tissue was determined by immunohistochemistry. The level of uPA from two CCA cell lines (HuCCA-1 and KKU-M213) and a non-cancer immortalized cholangiocyte cell line (H69) was monitored by plasminogen-gelatin zymography and western blotting, whereas that of plasminogen activator inhibitor type 1 (PAI-1) protein and uPA receptor (uPAR) mRNA was monitored by western blotting and quantitative real-time reverse transcriptase polymerase chain reaction, respectively. Two independent methods were employed to suppress uPA function: a synthetic uPA inhibitor (B428) and silencing of uPA gene expression using siRNA. In vitro invasion of the uPA-disrupted cells was assessed by Matrigel-coated Transwell assay., Results: The immunohistochemical study showed that 75.3% (131/174) of CCA tissues expressed uPA. High uPA expression was correlated with lymphatic invasion and metastasis of CCA patients. Plasminogen-gelatin zymography of the conditioned media and cell-surface eluates showed that both CCA cell lines, but not H69, expressed both secreted and membrane-bound forms of uPA. Although the two CCA cell lines, HuCCA-1 and KKU-M213, expressed a relatively high level of uPA and uPAR, the latter exhibited a much lower degree of in vitro invasiveness, correlating with a high expression of PAI-1 in the latter, but not in the former. Suppressing uPA function with a specific uPA inhibitor, B428, or with siRNA against uPA reduced in vitro invasiveness of KKU-M213 cells, demonstrating the requirement for uPA in the invasiveness of CCA cells. Therefore, our in vivo and in vitro studies suggest that uPA is an important requirement for the invasion process of CCA., Conclusion: uPA expression correlates with lymphatic invasion and metastasis in vivo and is required for CCA cell invasion in vitro, suggesting its potential as a therapeutic target.